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MANAGEMENT OF THYROID CANCER
By
Salah Mabruok Khalaf
South Egypt Cancer Institute2012
Local seminar Medical Oncology department
Epidemiology
bull Thyroid Cancer accounts for 15 of all cancers
bull The most common endocrine malignancy (95 of all
endocrine cancers)
bull Sex Female to Male Ratio 251 except anaplastic
carcinoma
bull Age most common after age 30
Risk Factors for Thyroid Cancer1 Neck irradiation
The only well-established risk factor for differentiated thyroid cancer
2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited
syndromes including iFamilial adenomatous polyposis
iiGardners syndrome
iiiCowdens disease
2 Medullary carcinoma in MEN syndrome
3 Other risk factors i History of goiter
ii family history of thyroid disease
iii Female gender
iv Asian race
Clinical Manifestation
bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule
bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease
bull Cervical lymph node enlargement
Investigations
bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in
detecting non palpable nodule and solid versus
cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of
a nodule
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Epidemiology
bull Thyroid Cancer accounts for 15 of all cancers
bull The most common endocrine malignancy (95 of all
endocrine cancers)
bull Sex Female to Male Ratio 251 except anaplastic
carcinoma
bull Age most common after age 30
Risk Factors for Thyroid Cancer1 Neck irradiation
The only well-established risk factor for differentiated thyroid cancer
2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited
syndromes including iFamilial adenomatous polyposis
iiGardners syndrome
iiiCowdens disease
2 Medullary carcinoma in MEN syndrome
3 Other risk factors i History of goiter
ii family history of thyroid disease
iii Female gender
iv Asian race
Clinical Manifestation
bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule
bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease
bull Cervical lymph node enlargement
Investigations
bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in
detecting non palpable nodule and solid versus
cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of
a nodule
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Risk Factors for Thyroid Cancer1 Neck irradiation
The only well-established risk factor for differentiated thyroid cancer
2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited
syndromes including iFamilial adenomatous polyposis
iiGardners syndrome
iiiCowdens disease
2 Medullary carcinoma in MEN syndrome
3 Other risk factors i History of goiter
ii family history of thyroid disease
iii Female gender
iv Asian race
Clinical Manifestation
bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule
bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease
bull Cervical lymph node enlargement
Investigations
bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in
detecting non palpable nodule and solid versus
cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of
a nodule
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Clinical Manifestation
bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule
bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease
bull Cervical lymph node enlargement
Investigations
bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in
detecting non palpable nodule and solid versus
cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of
a nodule
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Investigations
bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in
detecting non palpable nodule and solid versus
cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of
a nodule
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull FNAC indicationsISonar-based criteria
Solid nodule
1 More than 1 cm if associated with sonographic suspious features
2 More than 15 cm in absence of sonographic suspicion
Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features
2 More than 2 cm in absence of sonographic suspicion
Spongiform nodule (microcystic component gt 50 of nodules
IHigh risk Clinical feature
RT exposure
Genetic predisposition
Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA
bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Classification and Incidence ofThyroid Cancer
Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma
Tumors of Parafollicular cells Medullary 5
Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Papillary Cancer
1Histologic1 Psammoma bodies
2 Orphan Ann nucleus
2Multicentric 30-50
3Spread via Lymphatics- propensity for cervical node involvement
4Invasion of adjacent structures and distant mets uncommon
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types
1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell
8Rarely associated with radiation exposure
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Huumlrthle Cell Neoplasms
1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)
2Less affinity for I131
3Need to differentiate from benignmalignant
4Metastasis may be more sensitive to I131 than primary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy
2 It can also be diagnosed by fine-needle aspiration biopsy
microscopically typically
3 Family members should be screened for calcitonin
elevation andor for the RET proto-oncogene mutation
4 Not associated with radiation exposure
5 Residual disease (following surgery) or recurrence can be
detected by measuring calcitonin
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Medullary Thyroid Cancer Occurs in Four Clinical Settings
I- Sporadic
180 of all cases of medullary thyroid cancer
2Typically unilateral
3No associated endocrinopathies
4Peak onset 40 - 60
5Females predominance 32 ratio
6One third will present with intractable diarrhea
Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to
the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
II-MEN II-A (Sipple Syndrome)
(Multiple Endocrine Neoplasia II A)
1Sipple syndrome has
[1] bilateral medullary carcinoma
[2] pheochromocytoma
[3] hyperparathyroidism
2This syndrome is inherited in an autosomal dominant fashion
Because of this males and females are equally affected
3Peak incidence of medullary carcinoma in these patients is in the
30s
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
III-MEN II B
1This syndrome has
[1] medullary carcinoma
[2] Pheochromocytoma
[3] mucosal ganglioneuromas and Marfanoid habitus
2Inheritance is autosomal dominant as in MEN IIA (m=f)
3Pheochromocytomas must be detected prior to any operation
4The idea here is to remove the pheochromocytoma first to remove
the risk of severe hypertensive episodes while the thyroid or
parathyroid is being operated on
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
IV-Inherited medullary carcinoma without associated endocrinopathies
This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is
between the ages of 40 and 50
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Anaplastic cancer
1)Peak onset age 65 and older
Very rare in young patients
2)Males more common than females by 2 to 1 ratio
3)Undifferentiated
4)May arise many years (gt20) following radiation
exposure
5)Neck mass usually large diffuse and very hard
6)Rapidly growing often inoperable highly recurrent
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
7) Invade locally metastasize both locally and distantly
(to lungs or bones)
8) Cervical metastasis are present in the vast majority
(over 90) of cases at the time of diagnosis
9) Mean survival 6 months
10) Often requires the patient to get a tracheostomy to
maintain their airway
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
STAGING OF THYROID CANCER
In differentiated thyroid carcinoma several classification and
staging systems have been introduced However no clear
consensus has emerged favoring any one method over another
bull AMES systemAGES SystemGAMES system
bull TNM system
bull MACIS system
bull University of Chicago system
bull Ohio State University system
bull National Thyroid Cancer Treatment Cooperative Study
(NTCTCS)
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)
solitary tumor or (b) multifocal tumor)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor le 2 cm limited to the thyroid
T2 Tumor gt 2 cm but le4 cm limited to the thyroid
T3 Tumor gt 4 cm limited to the thyroid or any tumor with
minimal extrathyroid extension (eg extension to
sternothyroid muscle or perithyroid soft tissues)
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve
bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically
unresectable
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper
mediastinal lNs)
bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis
bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)
bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
AJCC Stage Groupings Papillary or follicular thyroid cancer
bull Younger than 45 yearsbull Stage I
bull Any T any N M0 bull Stage II
bull Any T any N M1
bull Age 45 years and olderbull Stage I
bull T1 N0 M0bull Stage II
bull T2 N0 M0 bull Stage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Papillary or follicular thyroid cancer
Age 45 years and older
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
Stage I
T1 N0 M0
Stage II
T2 N0 M0
Stage III
T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Medullary thyroid cancer bullStage I
bull T1 N0 M0 bullStage II
bull T2 N0 M0bullStage III
bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0
Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T any N M1
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Anaplastic thyroid cancer
bull All anaplastic carcinomas are considered stage IV
bull Stage IVA bull T4a any N M0
bull Stage IVB bull T4b any N M0
bull Stage IVC bull Any T any N M1
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
PROGNOSIS
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
PROGNOSIS
Prognostic schemes GAMES scoring (PAPILLARY amp
FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )
Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated
bull Age lt40 gt40
bull Mets None Regional or Distant
bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal
bull Sex Female Male
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival
lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Treatment
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this
complication may be reduced when a small amount of tissue remains on the contralateral side
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
II-Lobectomy
bull Rationale
1048708 Most patients are low risk and excellent prognosis
1048708 Role of adjuvant treatment not defined
1048708 Complications of Total
1048708 Occult multicentric tumor not clinically significant
1048708 Most local recurrences treated with surgery
1048708 Excellent outcome with lobectomy in low risk patients
bull Disadvantage
bull approximately 5 to 10 of patients will have a recurrence
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Indications for total Thyroidectomy OR lobectomy (all present)
bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension
Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Node removal
bull Selective node removal can be performed and radical
neck dissection is usually not required
bull This results in a decreased recurrence rate but has not
been shown to improve survival
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Thyroid carcinoma after lobectomy for benign lesions
I-Completion of thyroidectomy
bull gt 4 cm
bull Positive margins
bull Extra-thyroidal invasion (T3 or T4(
II- Completion of Thyroidectomy or follow
up
bull Clinically suspicious lymph node
contralateral lesion or perithyroidal node
bull Aggressive variant
bull Macroscopic multifocal disease
bull ge1 cm in diameter
III- follow up
bull Negative margins
bull No contralateral lesion
bull lt 1 cm in diameter
bull No suspicious lymph
node
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
POSTSURGICAL EVALUATION AFTER THYROIDECTOMY
I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +
antithyroglobulin antibodies)
II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan
Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT
bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas
Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Pretherapy whole body iodine scan
bullIf performed a pretherapy scan should use a low dose of 131I
(1 to 5 mCi) or 123I
bull To detect residual thyroid tissue thyroid cancer and metastatic foci
bull To reduce the potential for sublethal radiation stunning of thyroid tissue that
prevents optimal uptake of future 131I therapy
bullStunning is defined as a reduction in uptake of the 131I
therapy dose induced by a pretreatment diagnostic dose
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Dose of RAI
bullThe dosing of 131I for ablation is somewhat controversial
bullLow-dose ablation with less than 30 mCi administered on
an outpatient basis
bull For low-risk young patients
bullHigh-dose ablation with100 to 200 mCi
bull For high-risk patients
bull300 mCi
bull For all patients with metastatic disease that treated with repeated
therapeutic doses of 131I
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Replacement therapy
bullPostoperative treatment with exogenous thyroid hormone
in doses sufficient to suppress thyroid-stimulating hormone
(TSH) with development of thyrotoxic manifestations
decreases incidence of recurrence
bullAdministration of Thyroid Hormone
To suppress TSH and growth of any residual thyroid
To maintain patient euthyroid
o Maintain TSH level 01uUml in low risk pts
o Maintain TSH Level lt 01uUml in high risk pts
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Stage III Papillary and Follicular
A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease
B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Stage IV Papillary and Follicular 1) Adequate uptake of I131
bull I131
1) Inadequate uptake or not sensitive to I131
i Localized lesions
1) Radiation therapy
2) Resection of limited metastases dont uptake of I131
iiDisseminated disease
1) TSH suppression with thyroxine is effective
2) Chemotherapy has been reported to produce occasional complete
responses of long duration
3) Clinical trials testing new approaches to this disease
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Medullary Thyroid Cancer treatment
bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck
dissections Why
bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival
advantage
bull Radioactive iodine has no place in the treatment of patients with MTC
bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease
bull No single drug regimen can be considered standard
bull Some patients with distant metastases will experience prolonged survival and can
be observed until they become symptomatic
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Anaplastic Thyroid Cancer bull Surgery
bull Tracheostomy is frequently necessary
bull If the disease is confined to the local area which is rare total
thyroidectomy is warranted to reduce symptoms caused by the
tumor mass
bull Radiation therapy
bull Used in patients who are not surgical candidates or whose tumor
cannot be surgically excised
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Anaplastic Thyroid Cancer bull Chemotherapy
bull Produce partial remissions in some patients
bull Approximately 30 of patients achieve a partial remission with
doxorubicin
bull The combination of doxorubicin plus cisplatin appears to be more
active than doxorubicin alone and has been reported to produce
more complete responses
Treatment options under clinical evaluation
bull The combination of chemotherapy plus radiation therapy in patients following
complete resection may provide prolonged survival but has not been compared to
any one modality alone
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30
bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common
site of distant metastasis is the lung
bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Treatment of recurrent thyroid cancer
The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Adequate I131 uptake
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull I131 ablation
bull RT
bull Disseminated
bull I131 ablation
bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has
been reported to produce occasional objective responses usually of short
duration
Treatment of recurrent thyroid cancer
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Inadequate I131 uptake or insensitive to I131
bull Localized
bull Surgery with or without I131 ablation can be useful in controlling local
recurrences regional node metastases or occasionally metastases at other
localized sites
bull RT
bull Disseminated
bull Systemic chemotherapy
Treatment of recurrent thyroid cancer
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Systemic chemotherapy
bull Doxorubicin alone
bull Cisplatin and doxorubicin (better)
bull BAP Cisplatin doxorubicin and bleomycin
bull CVD cyclophosphamide vincristine and dacarbazine
bull Dacarbazine and 5-fluorouracil
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy
bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT
bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)
bull Improve OS and decrease RR
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
BAP regimenbull Schedule
bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5
bull Cell typebull Several histologic types of thyroid carcinoma responded but the
best responses were observed in medullary and anaplastic giant-cell carcinomas
bull Effectivenessbull BAP regime can achieve reasonable palliation and probably
increases survival in poor-prognosis thyroid cancers
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
CVD regimenbull Schedule
bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks
bull Cell typebull Medullary thyroid carcinoma
bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in
patients with advanced MTC
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Dacarbazine and 5-fluorouracil
bull Schedule
bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and
12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks
Six cycles
bull Cell type
bull MTC
bull Effectiveness
bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to
have significant activity and was well tolerated
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Target therapy
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Take home messagesbull FNAC is not adequate for definite diagnosis of follicular
carcinomabull Because the mixed papillary-follicular variant tends to
behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis
bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer
bull Once medullary carcinoma is diagnosed familial predisposition should be checked up
bull If I131 is indicated stunning effect should be avoided
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
Take home messages
All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary
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