management of carcinoma hypopharynx
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Management of carcinoma hypopharynx
By- Dr. Isha JaiswalModerator- Dr. Shantanu Sapru
Date: 10th December 2014
Topics to be covered:
• Pre-treatment evaluation• Staging• Treatment overview
• Evidence based treatment• NCCN guidelines
Surgery Radiotherapy Chemotherapy Biological therapy
Evaluation of patients with suspected hypopharyngeal cancer
Clinical Exanimation of head & neckFiber optic laryngopharyngoscopy & biopsy of primary tumorContrast enhanced CT scan face and neckContrast enhanced MRI face & neckChest X RayBlood investigations
Optional investigationsCECT chestPET ScanBarium swallow
Fiber-optic direct laryngoscopy• used routinely to complement the laryngeal mirror examination. • assessment of extent of primary tumor & mobility of vocal cords.• critical in assessing the superficial spread of neoplasm• superior to any imaging modality in detecting mucosal spread• can be attached to a photographic device• biopsy of the tumor is done for histopathological confirmation.
Typical findings of hypopharyngeal cancer on endoscopy:Ulceroproliferative/infiltrative growth.mucosal ulceration.pooling of the saliva in the pyriform fossa.oedema of the arytenoids. fixation of the cricoarytenoid joint, or true vocal cords or both.
CECT Scan Face & Neck• Timing: should be done before biopsy of to avoid post biopsy oedema.• Advantages: aids in staging by detection of:
Limitations
invasion into larynx. extra laryngeal/extra pharyngeal spread. paraglottic space spread. spread to retropharyngeal space. clinically occult metastatic lymphadenopathy.
Failure to detect small superficial tumours & early laryngeal cartilage involvement. Underestimating ulcerative and infiltrative lesions overestimating tumor extent due to inflammation/ oedema & distortion of adjacent normal
structures
MRI Face & Neck• Compared to CECT shows better soft tissue contrast & less artifact from
dental fillings.• An important adjunct study in three situations:
• Disadvantages :
Determining cartilage invasion :shown by increase T2 signal & post contrast enhancement.
Determining extent of extralaryngeal/paraglottic space involvement Determining oesophageal involvement shown by increased T2 signal, wall thickening
and effaced fat planes
motion artefacts. overestimating tumour extent :inflammation/ oedema /distortion
In detection of unknown /small primary tumorIn evaluating clinically occult nodal involvementIn follow up to differentiate between treatment sequelae & tumor
recurrence/residual
Role Of 18FDG PET-CT
Impact Of FDG-PET On Staging &Management of H&N SCC*
A multicenter study of 233 H&N SCC patients (including 46 hypopharyngeal cancer)
TNM staging and therapeutic decisions were first determined based on conventional workup & then FDG-PET data was used to restage the patients & reanalyse their management.
PET and conventional workup revealed discordant TNM staging in 100 patients (43%).
PET was deemed significantly more accurate than conventional staging & improved the staging in 20% of patients.
Incorporation of PET data ultimately impacted management in 32 patients (13.7%).
*Lonneux M, Hamoir M, Reychler H, et al. Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study. J Clin Oncol 2010;28:1190–1195.
CONCLUSIONS: FDG-PET is a reliable imaging procedure in the detection of clinically occult primary tumor/node and recurrent/residual carcinomas localized in the head and neck.
it cannot as yet replace other diagnostic procedures in pretreatment planning but does contribute valuable complementary diagnostic information.
TNM STAGING- AJCC 7TH edition (2010)*T1: Tumour limited to one subsite of hypopharynx and ≤ 2 cm in greatest dimension.
T2: Tumour invades more than one subsite or adjacent site or measures >2cm but ≤ 4 cm without fixation of hemilarynx.
T3: Tumours > 4 cm or with fixation of hemilarynx or extension into esophagus
T4a: Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, central compartment of soft tissue.T4b: Tumor invades prevertebral fascia, encases the carotid artery or involves mediastinal structures.
*Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging handbook, 7th ed. New York: Springer, 2010.*
TNM STAGING- AJCC 7TH edition (2010)*
• N0: No regional LN• N1: Single ipsilateral LN ≤ 3cm• N2a: Single ipsilateral LN 3-6cm b: Multiple ipsilateral LNs ≤ 6cm c: Bilateral or contralateral LNs ≤ 6cm• N3: Any LN more than 6cm
• M stage: • Mx- cannot be assessed, • M0- no distant metastasis, • M1- distant metastasis
Stage groupingStage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1, T2T3T3
N1N0N1
M0M0M0
Stage IV A T1,T2,T3T4a
N2N0,N1,N2
M0M0
Stage IV B Any TT4b
N3Any N
M0M0
Stage IV C Any T Any N M1
Treatment options Surgery Types IndicationsEvidence
Targeted therapyTypes IndicationsEvidence
ChemotherapyTypes IndicationsEvidence
Radiotherapy TypesIndicationEvidence
Multi modality treatment
General Treatment Recommendations Based On Hypopharynx Tumor Stage*
*Perez & Brady's Principles and Practice of RadiationOncology
Single Modality:• – Surgery or RT
Choice depends on• – Tumor: site, extension• – Patient: preference, comorbidities• – Expertise of the multidisciplinary team, available resources Equally effective: however no randomised trials for surgery vs. RT.
Each modality can salvage the other if local recurrence.
EARLY STAGE (I-II)(T1-T2, N0)
ADVANCED STAGE:(III/IV)T1-2, N1-3 / T3-4, N0-N+
Multi Modality: • Radiotherapy with altered fractionation schedules • Radiotherapy with chemotherapy• Radiotherapy with biological therapy• Neoadjuvant chemotherapy f/b surgery• Surgery f/b RT/CT-RT
Choice depends on• Tumor: site, extension• Patient: preference, comorbidities• Expertise of the multidisciplinary team, available resources
Treatment options
Surgery ± neoadjuvant/adjuvant
chemo/radiotherapy
Voice preserving
surgeryRadical surgery
RadiotherapyConventional/altered #
± chemotherapy
± biological
therapy± salvage
surgery
RADIATION THERAPY
Definitive RT• conventional fractionation• hyper fractionation • accelerated radiotherapy
Preop-RTPost-op RT
Benefits of RT over surgery• Probability of functional morbidity or cosmetic defects is reduced.• Risk of a major postoperative complication is avoided• Elective neck RT can be included with little added morbidity.• Surgical salvage of RT failure is supposed to have better outcome than the RT salvage
of a surgical failure.
Indications for primary radiotherapy• small sized tumor• larynx/voice preservation• those who refuse surgery
CAUSE-SPECIFIC AND OVERALL SURVIVAL FOR CARCINOMA OF THE PYRIFORM SINUS TREATED WITH RADIATION ALONE
2001
As stage increases 5 years survival with RT alone
decreases
Radiation treatment intensification
2. Addition of chemotherapy to RT
1. Altered fractionation RT
3.Chemotherapy +Altered fractionation RT
4. Addition of biological therapy to RT
*2Horiot JC. Controlled clinical trials of hyperfractionated and accelerated radiotherapy in otorhinolaryngologic cancers [in French].Bull Acad Natl Med 1998;182(6)*#Cummings B, O’Sullivan B, Keane T. 5-year results of a 4 week/twice daily radiation schedule: the Toronto Trial. Radiother Oncol2000
*2
*3
TRIALS OF HYPERFRACTIONATION
1992 EORTC 22791
TRIALS OF PURE ACCELERATED FRACTIONATION
*!Jackson et al. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer.Radiother Oncol 1997*2Skladowski Ket al. 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer—. Radiother Oncol 2000;55*3Overgaard J,. The DAHANCA 6 and 7 trial: a study of 5 versus 6 fractions per week of conventional radiotherapy of (SCC) of the head and neck. Radiother Onco *4Hliniak AZ.. Radiother Oncol 2000;56:S5.
*1
*2
*3
*4
Aim: to find whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma.
Lancet. 2003
randomised trial between January, 1992, and December, 1999,
1485 patients treated with primary radiotherapy alone,1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions per week at the same total dose and fraction number (66-68 Gy in 33-34 fractions)
TWO SUBPROTOCOLS: DAHANCA 6, which included all glottic carcinomas, and DAHANCA 7, included tumours of the supraglottic larynx,pharynx, and oralcavity
The only difference in the two subprotocols was that DAHANCA 6 dealt only with the fractionation effect,whereas the DAHANCA 7 also included treatment with the hypoxic radiosensitiser nimorazole.
More than 97% of the patients received the planned total dose. Median overall treatment times were 39 days (six-fraction group) and 46 days (five-fraction group).
Primary locoregional tumour control as function of number of fractions per week
Overall 5-year locoregional control rates were 70% and 60% for the six-fraction and five-fraction groups, respectively (p=0.0005).
primary tumour control (76 vs 64% for six and five fractions, p=0.0001), but was non-significant for neck-node control
Disease specific survival Overall survival
Disease-specific survival improved (73 vs 66%) for six and five fractions but not overall survival
Early and late radiation-related morbidity Acute morbidity was significantly more frequent with six than with five fractions, but was transient.
CONCLUSIONAccelerated radiotherapy applied to squamous-cell carcinoma of the head and neck yields better locoregional control than does a conventional schedule with identical dose and fractionation.
2010 IAEA-ACC
*1 Dische, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 1997; *2 Poulsen, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV SCCHN: aTTROG Radiother Oncol 2001; *3 Bourhis, et al. Preliminary results of the GORTEC 96–01 randomized trial, comparing very accelerated radiotherapy versus concomitant radio-chemotherapy for locally inoperable HNSCC. Int J Radiat Oncol Biol Phys 2001;
*1
*2
*3
1997
2010
.
• Patients with stage III or IV SCC (n=1076) were randomized to 4 treatment arms:
2000
(1) Standard fractionation
70 Gy/35 daily fractions/7 weeks
(2) Hyper fractionation
81.6 Gy/68 twice-daily fractions/7 weeks
(3) Accelerated fractionation with split
67.2Gy(1.6bid)/42 fractions/6 weeks
with a 2-week rest after 38.4 Gy
(4) Accelerated fractionation with concomitant boost 72 Gy/42 fractions/6 weeks.(1.8Gy/f with 1.5 Gy /f boost on last 12 fractions)
RTO 90-03 Results: at 2years• LRC:• significant improvement in 2 yr locoregional control for
the hyper fractionation and concomitant boost arms .• DFS:• trend toward improved disease-free survival (p = 0.067
and p = 0.054 respectively for the hyper fractionation and concomitant boost arms
• OS: difference in overall survival was not significant.
• TOXICITY:• altered fractionation regimens were associated with
higher incidence of grade 3 or worse acute mucosal toxicity, but no significant difference in overall toxicity at 2 years following completion of treatment.
2006GORTEC 9402
CHEMOTHERAPY
• NEOADJUVANT• CONCURRENT• ADJUVANT
1996EORTC 24891
EORTC trial 24891 compared PF (cisplatin and 5-FU) induction chemotherapy followed by radiation therapy (RT) versus total laryngectomy, radical neck dissection, and postoperative RT in patients with hypopharyngeal cancer
Role of NACT for larynx preservationNACT-RT Vs Surgery-RT
Survival Disease free survival
Metastasis free survival Larynx preservation
• Treatment failures occurred at approximately the same frequencies in both arms.
• Fewer failures at distant sites in the induction-chemotherapy arm
• The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm
• The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction chemotherapy arm were 42% and 35% respectively.
CONCLUSION OF EORTC 24891
Choice of chemotherapy regimen:2 drug vs.3 drug regimen
2007: TAX323/EORTC 24971
PATIENT CHRACTERISTICS:
29%pts of ca hypopharynx
Aim :compare TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.
Primary end point :PFS
358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group
ARM A (N=177) ARM B(N=181) TOTAL P value
CONCLUSION OF TAX 323
At a median follow-up of 32.5 months, the median PFS was 11.0 months in the TPF group and 8.2 months in the PF group .
There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group.
2007: TAX 324
15% patients of ca hypopharynx
Aim: compare induction chemotherapy with docetaxel plus cisplatin and fluorouracil(TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy for treatment of SCCH& N
Results of TAX 324more patients survived in the TPF group than in the PF group
estimates of overall survival at 3 years were 62% in theTPF group and 48% in the PF group,
median overall survival was 71 months and 30 months, respectively (P = 0.006).
better locoregional control in the TPF group than in the PF group (P = 0.04)
incidence of distant metastases in the two groups did not differ significantly (P = 0.14)
Rates of neutropenia and febrile neutropenia were higher in the TPF group;
chemotherapy was more frequently delayed because of hematologic adverse events in the PF group
2009 GORTEC 2000-01
CONCURRENT CHEMORADIOTHERAPY
An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable
Squamous Cell Head and Neck Cancer.
J Clin David J. Adelstein Oncol 21:92-98. 20032003CTRT VS RT ALONE
which one is better in unresectable HNSCC?
ARM C
CTRT of 2 Gy/d, was split between the first CT course (30 Gy) & third CT course (30 to 40 Gy).
A total dose of 60 to 70 Gy was given
The radiation therapy break was planned to allow for the possibility of surgical resection in those patients rendered resectable after the first two courses of chemotherapy and the first30 Gy of radiation.
Patients who had achieved a complete response after this induction or who remained unresectable proceeded, without surgery, tocomplete chemoradiotherapy.
2003, 2006,2012Forastiere et al
•RT Vs. CTRT Vs. NACT-RT which one is better?
J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 2
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Vol 24, No 18S (June 20 Supplement), 2006: 5517
2012 Radiotherapy Alone Vs. Concurrent CTRT Vs. Sequential NACT-RT
J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 2
Loco regional control Overall survival
Larynx preservation
2012 UPDATE
No Published Phase 3 Trial Study Have Tested
Induction Chemotherapy f/b chemoradiotherapy
Vs Upfront Chemoradiotherapy
ALTERED FRACTIONATION± CHEMO-RADIOTHERAPY
Lancet Oncol. 2012 Feb;13(2):145-53. doi: 10.1016/S1470-2045(11)70346-1. Epub 2012 Jan 18
2012
aimed to assess the efficacy and safety of a combination of approaches.
STAGE III/IV, M0 HNSCC
n=840
RANDOMIZED
Arm AConventional
chemo radiotherapy
RT – 70Gy/6w 1st 40Gy 2Gy/#/d, 5#/w
Next 30Gy (off the spinal cord) 1.5Gy/#/BD
CT – 2 cycles of 5days each, 4w apart.
Carboplatin 70mg/sqm/d + 5FU 600mg/sqm/d
RT – 70Gy/35#/7w at 2Gy/#, 5#/w
CT – 3 cycles of 4days each, 3w apart.
Carboplatin 70mg/sqm/d + 5FU 600mg/sqm/d
RT – 64.8Gy/3.5w at 1.8Gy/#/BD,
5#/w
Arm AConventional
chemoradiotherapy
Arm BAccelerated RT with
concomitant CT
Arm CVery
Accelerated RT
. Median follow-up was 5·2 years
Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy or very accelerated radiotherapy
conventional chemoradiotherapy improved PFS compared with very accelerated chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy.
More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001).
(60%) of patients in the conventional chemoradiotherapy group, (64%) of patients in the accelerated radiotherapy-chemotherapy group, and (70%) of patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045).
Results of GORTEC 9902
CONCLUSION OF GORTEC 9902
1. Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy.
• 2. Acceleration of radiotherapy cannot compensate for the absence of chemotherapy.
• 3. Acceleration of radiotherapy is probably not beneficial in concomitant chemo-radiotherapy schedules.
2000Lancet. 2000 Mar 18;355(9208):949-552007Radiother Oncol. 2007 Oct;85(1):156-70. Epub 2007 May 4.2009Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 142011Radiother Oncol. 2011 Jul;100(1):33-40. doi: 10.1016/j.radonc.2011.05.036. Epub 2011 Jun 16
ABSOLUTE BENEFITS- oral cavity-8.9% oropharynx-8.1% larynx-5.4% hypopharynx-4%
2011 update
platinum based regimen more effective.no significant difference efficacy between mono and multi drug platinum regimens
• LEVEL 1 EVIDENCE OF ADDITION OF CT IN TERMS OF OVER ALL SURVIVAL.• ADDITION OF CT-ABSOLUTE BENEFIT IN SURVIVAL-5%IN 5 YRS.• INDUCTION/ADJUVANT-2% SUVIVAL BENEFIT• CONCURRENT CTRT 8% 5YR SURVIVAL BENEFIT• BENEFIT MORE IN CONCURRENT CTRT• BENEFIT DECREASES WITH INCREASING AGE.• ABSOLUTE BENEFITS-oral cavity 8.9% oropharynx-8.1% larynx-5.4%
hypopharynx-4%
MACH- NC-CONCLUSIONS
MARCH META-ANALYSIS
20062010
The Lancet, Volume 368, Issue 9538, Pages 843 - 854, 2 September 2006
15 Randomized Trials of Varied Fractionation (1970-1998)
PATIENT CHARACTERISTICS7073 patientsTumours sites: mostly oropharynx and larynx 74% patients had stage III—IV disease
hyper fractionated
accelerated
accelerated with total dose reduction
Overall survival was the main endpoint
median follow up:6 yr
benefit Conventional vs Altered Hyper fractionation vs Accelerated fractionation
Locoregional control
Loco regional control 6.4 %times higher
benefit was higher with hyper fractionated radiotherapy
( OS 8% at 5 years) than with accelerated radiotherapy
(2% with accelerated fractionation without total dose reduction and 1·7% with total
dose reduction at 5 years, p=0·02)
Survival benefit absolute benefit of 3·4% at 5 years with altered
fractionated radiotherapy,
RESULTS OF MARCH META-ANALYSIS:There was a significant survival benefit in altered fractionation.(3.4%at 5 years)There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6·4% at 5 years; p<0·0001The benefit was significantly higher in the youngest patients
InterpretationAltered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit
Role of biological therapy
• Cetuximab with RT• Bonner et al- • 424 patients• Locally advanced SCCHN• 15% pt : Ca hypopharynx
Bonner et al, 2006
Drawback: in control arm RT alone given (not a standard treatment for stage III and IV HNSCC)
• LOCOREGIONAL CONTROL • OVERALL SURVIVAL
Bonner et al 2010 update: 5 years follow up
subgroups analysis demonstrated effect of cetuximab was pronounced in patients with
oropharyngeal carcinoma, T1-T3 disease,concomitant boost radiation, N1-N3,KPS 90-100 ,male patients, EGFR expression ≤ 50%, ≤65 years.
Surgical options in operable Ca hypopharynxVoice preservation surgeryin early hypopharynx cancer
Supraglottic laryngectemyHemilaryngectomyPartial laryngopharyngectomy
Radical Laryngectomy in advanced stages
Total laryngectomyTotal laryngopharyngectomy
Primary Surgery• T1 and T2 Tumors: voice
conservation surgery• INDICATIONS
• CONTRAINDICATIONS
voice conservation approaches possible refuse radiation
vocal fold fixation, cartilage invasion, postcricoid invasion, deep pyriform sinus invasion, extension beyond the larynx
• T3 / T4 Tumors• INDICATIONS
dysfunctional larynxpt. with bulky destructive tumor that
severely compromise airway or destroy cartilage, bone, soft tissue undergo immediate laryngopharyngectomy and post op radiation
operation indication parts removed contraindication
hemilaryngectomyhorizontal partial
supraglottic laryngectomy(SGL)
T1/T2 pyriform sinus tumor
voice preservation for early supraglottic extension
epiglottis aryepiglottic fold false cords upper 1/3-1/2 of
thyroid cartilage ±hyoid bone
preserves one or both arytenoids & true vc
thyroid,cricoid cartilage invasion
arytenoid involvement vocal fold fixation postcricoid invasion deep pyriform sinus invasion extension beyond the larynx fixed neck nodes inadequate pulmonary
function
extended supraglottic laryngectomy
supraglottic lesion with<1cm base of tongue invasion
same as SGL with removal of i/l bot upto circumvallete papillae
operation indications removes contraindication
partial laryngopharyngectomy
used for small medial and anterior pyriform sinus lesion
false vocal cord epiglottis aryepiglottic fold pyriform sinus,
tvc are preserved
transglottic extension, cartilage invasion vocal cord paralysis, pyriform apex invasion, postcricoid invasion extralaryngeal spread poor pulmonary reserve
total laryngectomy
Advanced pyriform sinus lesion
cartilage invasion
removes hyoid, thyroid, cricoid cartilage, epiglottis strap muscle. Patient left with a permanent tracheostoma and pharynx reconstruction
total laryngopharyngectomy
for more advanced hypopharyngeal lesion
total laryngectomy plus removal of varying
amount of pharyngeal wall
Advances in surgery
• In recent years, advancements in organ preservation surgery have included the use of
• Transoral laser microsurgery • Transoral robotic surgery. • AdvantageLess morbidityavoiding tracheostomy and the use of feeding tubes
Transoral Laser Surgery: Inclusion Criteria *
Complete endoscopic visualization of the growthTumor extension to the contralateral VC < 3mmAbsence of arytenoid involvement (except vocal process)Subglottic extension < 5mmSupraglottic extension no further than lateral extension of ventricleMobile vocal foldsNo cartilage involvement
*Motamed M, et. al. Salvage conservation laryngeal surgery after irradiation failure for early laryngeal cancer. Laryngoscope 2006; 116:451-455
ADJUVANT RADIOTHERAPY IN
OPERATED HNSCC
Preoperative RT Vs postoperative RT: RTOG 73-03
Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries
duration of follow-up was 9-15 years, Loco-regional control& absolute survival was estimated & compared
1987
N=277 patients.Operable stage T2-T4 /N± oral cavity(14%) Oropharynx(17%) Supraglottic larynx(26%) Hypopharynx(43%)
Postoperative stage III or IV SCCHN
R
ANDOMIZE Arm 2:Post-op RT 60 Gy.
n= 141
Arm 1: Pre-op RT 50 Gyn=136
Long-term Follow-up Of RTOG Study 73-03
*(Tupchong L et al. Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):21-8.)
outcome preopRT postopRT
LRC 58% 70%
LRF within 2 years 59% 58%
LRF after 2years 27% 8%
Overall survival similar
toxicity similar
• Post op RT is better than preop RT for LRC
1991
Indications for post operative radiotherapy
Primary: Large primary - T4 or T3 with soft tissue
infiltration Close or positive margins of excision Deep infiltrative tumour High grade tumour Lympho-vascular and perineural invasion
Lymph nodes: Bulky nodal disease N2 / N3 Extra nodal extension Multiple level involvement
POSTOPERATIVE RADIOTHERAPYIs PO CTRT better than PORT alone?
RANDOMIZE Cisplatin
100 mg/m2 d 1, 22, 43
XRT
XRT
Cooper et al, 2004; Bernier et al, 2004.
SURGERY
RTOG 95-01459 patients
EORTC 22931 334 patients
EORTC (66 Gy over 6 ½ wks)RTOG (60–66 Gy over 6-6 ½ wks)
Postoperative Chemoradiotherapy
• RESULTS OF POSTOP CHEMORADIATION TRIAL
EORTC 22931 only
Bernier et alN=334
EORTC 22931 and RTOG 9501
RTOG 9501 only
Cooper et al.2004N=459
stage III/IV disease
margin+ ≥2positive l.n
ECE+ ECE + ECE +
margin +margin+
PNI+embolism
NCCN GUIDELINES
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