ANDREA FODOR MD2013.03.27.

Important facts 1.Important facts 1.

Lung cancer is the most frequent solid tumour.

The early diagnosis is problematic, screening is unsolved.

The lethality of Lung cancer is high, survival low.

It’s tightly related to smoking.

Important facts 2.Important facts 2.

The incidence and mortality of Lung cancer is increasing all over the world, except of some developed countries.

Hungary is on the top of mortality rank of all malignant diseases.

Lung cancer is incurable without radical surgery.

LUNG CANCER in the world (estimated LUNG CANCER in the world (estimated incidence by WHO, 2000)incidence by WHO, 2000)

Lung cancer ……………….1.200.000Breast cancer…..…………..1.000.000Colorectal cc..………………940.000Gastric cancer ….……………870.000Primary hepatic cancer……….560.000Cervical cancer……………….470.000Esophageal cc..……………….410.000

5 years survival of Lung Cancer

14%

Leading sites of new cancer cases and deaths—2003 estimates.

Each year the American Cancer Society estimates the total number of new cancer cases and deaths .

In 2003, there were an estimated 171,900 new lung cancer cases and 157,200 deaths, making it the most common killer from cancer in men and in women.

Lung cancer is the leading cause of cancer death in both men and women.

Risk factors of lung cancer:Risk factors of lung cancer:

1. Smoking , including secondhand!

Smoking is responsible for 90% of lung cancer cases !!!!!!

Risk factors of lung cancer:Risk factors of lung cancer:2. Other pulmonary diseases:

TuberculosisCOPDSilicosis, Fibrosis

3. Compounds of Cr, Ni, As, asbestos4. Irradiation (external source, incorporated

source, e.g. radon)5. Other air pollution (industry, traffic)6. Genetic factors

Key to succesful therapy:Key to succesful therapy:

Early detection!

Conventional diagnostic methods :

Anamnesis: Detection of

risk factors and common signs and symptoms caused by the tumor and it’s metastasis.

Signs and Symptoms of Lung Cancer

CoughHemoptysisWheeze and stridorDyspnoea Chest painPneumoniaEsophageal compression with dysphagiaWeightloss

Signs and Symptoms of Lung Cancer

Sings of pareses: Phrenic nerve paralysis with hemidiaphragm elevation ,

Recurrent laryngeal nerve paralysisSympathetic nerve paralysis with Horner's syndrome

Palpable (lymph) nodes Enlarged collateral veins : Superior vena cava

syndrome from vascular obstruction

Headache, vertigo, nausea – because of cerebral metastasis

Paraneoplastic syndromes:

• The cancer produces hormone-like substances The cancer produces hormone-like substances that enter the blood and cause problems in that enter the blood and cause problems in other organs or tissue. other organs or tissue.

• The symptoms paraneoplastic syndrome The symptoms paraneoplastic syndrome causes are not a direct result of cancerous causes are not a direct result of cancerous cells, but they are sometimes the first cells, but they are sometimes the first symptoms of lung cancersymptoms of lung cancer. .

• These symptoms often do not generate an These symptoms often do not generate an immediate lung cancer diagnosis because they immediate lung cancer diagnosis because they do not affect the lung.do not affect the lung.

• Tumors may produce signs and symptoms Tumors may produce signs and symptoms distant from the primery site or its metastasis.distant from the primery site or its metastasis.

Paraneoplastic syndromes :

1.) Migrating thrombophlebitis 2.) Deep venous thrombosis 3.) SIADH –Syndrome of Inappropriate

Antidiuretic Hormone Production : causing hyponatraemia

4.) Digital clubbing5.) Neuropathy6.) Myopathy7.) Hypercalcaemia

Diagnostic methods - Imaging:

1.) chest X-ray:Normal Posterior to Anterior (PA) Chest X-ray

Diagnostic methods - Imaging:

• Chest X-ray :Normal Lateral Chest X-ray

LUNG CANCER, central type

LUNG CANCER, peripheral typeLUNG CANCER, peripheral type

Diagnostic methods - Imaging:

2.) Computed tomography

Diagnostic methods - Imaging

3. ) PET-CT

Searching for metastasis:

4,) abdominal USG

5.) bone scintigraphy

Searching for metastasis:

6.) MRI : Spinal canal,

evaluation of paravertebral tumor

brain MRI

Diagnostic methods

Diagnosis of malignancy can be obtained by cytologic examination of bronchial brushing and washing specimen or can be obtained by cytological or histological examination of the tumor.

1.) Pleural fluid cytology2.) Fiberoptic bronchoscopy

Fiberoptic bronchoscopy

Endoscopic view of a central type LC

Other biopsies:

3.) transthoracic needle biopsy- we can examin cytological or histological sample

4.) mediastinoscopy - for evaluate

mediastinal lymph nodes for metastasis5.) biopsy thoraco(pleuro)scopy

SCLC NSCLC

Small cell lung cancer

About 15 -20% of lung cancer patients.

Most patient with SCLC have clinically detectable metastasis at diagnosis:

-bone involvement-hepatic and adrenal lesions-brain metastasis

Non- small cell lung cancer

About 80 -85 % of lung cancer patients.

1,) adenocarcinoma 30-40%14 subtypes,e.g. Bronchoalveolar carcinoma

2,)Squamosus cell carcinoma 20-30 %3,) Large cell carcinoma 4-6%4,) Others

Staging and Diagnosis

In 1985, the American Joint Committee on Cancer, the International Union Against Cancer, and the Japanese Cancer Committee established a worldwide

TUMOR-NODE-METASTASIS (TNM) staging system,

which was rapidly adopted and extensively used in the management of lung cancer.

A revised staging system was accepted in 2009.

• Stages are : I- IV• ( Stage I, II and III are divided into A and B subgroups)

• Stage is determined by 3 components:– T1-4= Tumor size– N1-3= Lymph node involvement– M0-1= Absence or presence of metastases

5-year survival depending on the stage of disease at diagnosis !

Staging and Diagnosis

In the current staging system, the primary tumor is subdivided into four categories (T1 to T4) depending on size, site, and local involvement.

T3:two malignant nodules in the same lobe on PET CT scans

Staging and Diagnosis

• Lymph node involvement has been subdivided Lymph node involvement has been subdivided into bronchopulmonary (N1), into bronchopulmonary (N1),

• ipsilateral mediastinal (N2), ipsilateral mediastinal (N2), • and contralateral or supraclavicular disease and contralateral or supraclavicular disease

(N3).(N3).

TNM classification 7 th edition:

• Distant Metastasis (M)• M0 No distant metastasis• M1 Distant metastasis• M1a Separate tumor nodule(s) in a

contralateral lobe, tumor with pleural nodules or malignant pleural (or pericardial) effusion2

• M1b Distant metastasis (in extrathoracic organs)

The lung cancer therapy depends on:

• The tumor related factors: histology (small cell or not small cell lung

cancer) molecular pathology: KRAS mutation status, EGFR mutation status• TNM• The patient related factors: comorbidities, performance score age

• Karnofsky: 100%: fully active 0: dead.

• WHO: 0: fully active5: dead

• Zubrod=WHO=ECOG

• The Eastern Cooperative Oncology Group (ECOG), was established in 1955.

51

Grade

ECOG

0 Fully active, able to carry on all pre-disease performance without restriction

1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours

3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours

4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair

5 Dead

Stage Description Treatment options

I. Single tumor. Surgery

II. Spread to the lymph node of the lung, ipsilateral side or the tumor is bigger than 5 cm.

Surgery and after surgery adjuvant chemotherapy recommended.

IIIA. Spread to the lymph node in the tracheal area, chest wall, diaphragm region, ipsilateral side.

Chemotherapy or chemo-radiotherapy followed by surgery.

IIIB. Spread to the lymph node of opposite site or in the neck.

Combination of chemotherapy and radiation.

IV. Tumor has spread beyond the chest.

Palliative therapy with or without chemo-therapy/radiotherapy.

• Surgery is the standard of care.• Lobectomy has been regarded by most

thoracic surgeons as the gold standard for resection of early stage NSCLC.

• Analysis of hilar and mediastinal lymph node must be performed to exclude occult lymph node metastasis to ensure accurate staging in determining the need of adjuvant chemotherapy.

Adjuvant chemotherapy:

In Stage II adjuvant (after surgery) chemotherapy is recommended.

Adjuvant chemotherapy: Controls micro-metastases that may be responsible

for systemic recurrence after “successful” surgery.The chemotherapy is cisplatin based.

Adjuvant chemotherapy:

• The Lung Adjuvant Cisplatin Evaluation (LACE) pooled analysis. Disease-free survival (A) and overall survival (B) curves (see text). (From Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant Cisplatin Evaluation [LACE]: a pooled analysis of five randomized clinical trials including 4,584 patients LACE meta-analysis. J Clin Oncol 2008;26:3552:3559.)

Disease free survival:

Overall survival:

Stage Description Treatment options

I. Single tumor. Surgery

II. Spread to the lymph node of the lung, ipsilateral side or the tumor is bigger than 5 cm.

Surgery and after surgery adjuvant chemotherapy recommended.

IIIA. Spread to the lymph node in the tracheal area, chest wall, diaphragm region, ipsilateral side.

Chemotherapy or chemo-radiotherapy followed by surgery.

IIIB. Spread to the lymph node of opposite site or in the neck.

Combination of chemotherapy and radiation.

IV. Tumor has spread beyond the chest.

Palliative therapy with or without chemo-therapy/radiotherapy.

Platinium based regimens• Overall 1-year survival with platinum-based versus

non-platinum chemotherapy regimens. There was a 2.94% survival benefit at 1 year for patients treated with a platinum-based chemotherapy doublet.

• First line:• platinum + third generation drug: gemcitabin docetaxel paclitaxel vinorelbine pemetrexed • Cisplatinum is beneficial generally, carboplatinum is beneficial

for brain metastases or renal dysfunction (less nephrotoxicity)

• The triplets have more toxic side effects as doublets but no better therapeutic efficiency

• Phase cycle No: 4-6.

• We can combine chemotherapy with radiotherapy for greater therapeutic effect .

DiagnosisComplete remissionPartial remissionStable disease

Progressiv disease

There is more time untill progression

CLASSIC TREATMENT

NEWAPPROACH

Diagnosis Complete remissionPartial remissionStable disease

Progressiv

disease

Maintenance therapy

Advanced NSCLC – stage III.B-IV.

First line treatmentPlatinum based combination(4–6 cycle)

No treatment

Second or third line treatment

Maintenance therapy with bevacizumab

• VEGF inhibitor bevacizumab ( monoclonal antibody) in first line therapy with platinum for advanced NSCLC at 4-6 cycle –

• after this treatment we can give bevacizumab alone untill progression as a maintenence therapy.

Agents targeting the vascular endothelial growth factor (VEGF)

( TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor. pathway. TKIs, tyrosine kinase inhibitors;)

)

Effects of bevacizumab

EARLY EFFECTS CONTINUED EFFECTS

1 Regression Normalisation2 Inhibition3

Decreases tumour

size

Improves delivery of chemother

apy

Suppresses new vessel

growth

Enables metastectomyIncreases PFSIncreases OS

Suppresses regrowth via

vessel ‘scaffolds’

Willett, et al. Nat Med 2004; Gerber, Ferrara. Cancer Res 2005

TARGETED THERAPY:Bevacizumab ( Avastin) and

tyrosine kinase inhibitors ( Iressa and Tarceva)

• Targeted therapy is a type of medication that blocks the growth of

cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth,

rather than by simply interfering with rapidly dividing cells (e.g. with traditional chemotherapy).

• Targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.

• Therapy: primary systemic chemotherapy for resectable cases too!

• After 4 cycle chemotherapy

• In any stage have to use chemotherapy: platinum + etoposid.• Second line we can use : topotecan.

• Irradiation• Drugs: bisphosphonates

• LMWH• EPO• GCS

• Cancer pain: painkillers

• Endoscopic possibilities:– Laser– Stent

• Brachyterapy

• Sharplan Nd-YAG• 10-150W• Coagulation,

vaporisation

Laeser therapy

• The predominant tissue effects of Nd:YAG lasers are thermal necrosis and photocoagulation. Thermal necrosis uses higher energy levels to destroy tissue,causing the formation of eschar. The problem with this approach is the significant vascularity of most lung cancers. In destroying tissue with laser energy,large blood vessels can also be destroyed. These blood vessels can be perforated with the tissue destruction,leading to significant hemorrhage

Airway stents

A selection of the currently available airway stents.

Prevention

Primary profilaxis:Primary profilaxis:• Exposition profilaxis (quitting smoking)Exposition profilaxis (quitting smoking)

Secondary prophylaxis: Secondary prophylaxis: • Early detectionEarly detection

Conditions of early detection

• 1. Diagnostic methods more sensitive and more 1. Diagnostic methods more sensitive and more effective than we use todayeffective than we use today

• 2. Screening more effective than we use today 2. Screening more effective than we use today • Low-dose CT scanning is a new and potentially Low-dose CT scanning is a new and potentially

efficacious method for early detection of lung efficacious method for early detection of lung cancer.cancer.

This noninvasive technique, which creates an This noninvasive technique, which creates an image of the entire thorax during a single held image of the entire thorax during a single held breath with a low radiation dose. breath with a low radiation dose.

CASE REPORTS

2012.03.21.

CASE 1 • The female patient was born in 1941.• In 2007 the brest cancer was diagnosed at her.• In 2007 left brest segment resection and

axillary lymphadenectomy was made and she got chemotherapy and radiotherapy after the operation.

• In 2010 left pulmonectomy was made because of the 7 cm large Sarcomatoid carcinoma of left upper lobe.

• Patient didn’t accept adjuvant therapy.

CASE 1: Chest X- ray 8 weeks after left pulmonectomy

CASE 2

• The male patient was born in 1936.• In 1994 he had prostatectomy because of the

tumor.• In 2010 there was a central infiltration in his

screening chest X-ray. He had no complaints.• In 2010 right lower lobe resection was made

with hilar lymph nodes.

CASE 2

CASE 2

• Diagnosis: Adenocarcinoma bronchogenes invasivum pulmonis

• The tumor size was 31 x 23 mm with metastasis in hilar lymph nodes. ( T2a N1 Mo)

• He got 6 cycle adjuvant chemotherapy:cisplatin and vinorelbin

CASE 3 : PA CHEST X- RAY

CASE 3: LATERAL CHEST X - RAY

CASE 3

• The male patient was born in 1953.• The tumor is visable only on the lateral chest X – ray and on the computed tomography

images. It reached the lateral chest wall therefore thoracic surgery wasn’t recommended. Neoadjuvant chemotherapy ( Taxotere – Cisplatin ) and thoracic radiotherapy started. After the successful neoadjuvant therapy surgery may be the next step.

CASE 4

• The female patient was born in 1953.• Her father and her brother died of lung

cancer.• Her symptoms started in December 2010

with swelling of her face and neck.• She was sent to an Allergist, but

antihistamines didn’t help, so further medical tests was done: there was an infiltration in right upper lobe on her chest X-ray.

CASE 4

• Bronchoscopy showed a tumor mass in right upper lobe bronchus and computed tomography scans showed a tumor mass in the mediastinum, which compresses the Superior Vena Cava.

• Urgent chest radiotherapy started.• The histology sample showed neuroendocrin

carcinoma.

CASE 4: typical symptom of SVC syndroma

• Superior vena cava syndrome in a person with bronchogenic carcinoma. Note the swelling of his face first thing in the morning (left) and its resolution after being upright all day (right).

CASE 4

• She got chemotherapy also: Taxotere- Carboplatin

• She got steroids, diuretics, LMWH .

• And the stent was taken into the Superior Vena Cava.

CASE 4: Stent in the Superior Vena Cava

CASE 5• The male patient was born in 1952.• He is a heavy smoker.• He has COPD and advanced atherosclerosis in

lower limbs with AFS occlusion on both sides.• The femoro- popliteal bypass was done, but

the bypass occlusion have occurred.• He got pentoxyfillin infusions regularly,but he

can not walk, just roll the wheelchair.

CASE 5 : chest X-ray before the treatment

CASE 5• We could not verify the tumor with bronchoscopy .

( It’s a periferial type.)Transthoracic needle biopsy we couldn’t make because of his impaired lung function.

• ( He has COPD .) Complication could be pneumothorax and it could be dangerous with an impaired lung function.

• We verified the Adenocarcinoma with needle biopsy from the metastatic supraclavicular lymphnode.

•

CASE 5

• The patient got only chest radiotherapy.

• After the chest radiotherapy we can see good tumor regression.

CASE 5 : chest X-ray after the chest radiotherapy

CASE 6

• The female patient was born in 1962.• In december 2010 she had vertigo, nausae,

she was unable to walk.• CT of the brain and brain MRI showed

multiplex brain metastasis.• Chest computed tomography scans showed a

big tumor and lymphnodes conglomerate in left hilus.

CASE 6

CASE 6

• She got whole brain radiotherapy ( WBRT )and after the radiotherapy we started

• Taxotere- Cisplatin- Avastin chemotherapy.

CASE 7

• The male patient was born in 1930.• He had no complaint.• The chest X-ray and computed tomography

scans showed a tumor in the right upper lobe and infiltration in both upper lobe.

CASE 7

CASE 7

• The sputum examination showed Mycobacterium tuberculosis.

• Oncological team didn’t recommend any activ oncotherapy, they recommend first antituberculotic therapy.

• After tumor progression only chest radiotherapy would be recommended while also taking the antituberculotic drugs.

Thanks for Your attention!