Lung Cancer

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Lung Cancer: Diagnosis, Staging, and Treatment:

Lung Cancer: Diagnosis, Staging, and Treatment By Chest Department Ainshams University

Lung Cancer:

Lung Cancer Most common cause of cancer death in US Overall 5 year survival of 15% More deaths by lung cancer than the next four most common cancers combined (Colorectal, Breast, Prostate, & Pancreas)

Lung Cancer Risk Factors:

Lung Cancer Risk Factors Gender Smoking history Older age Presence of airflow obstruction Genetic predisposition Occupational exposures

Lung Cancer and Gender:

Lung Cancer and Gender Male predilection, but changing rapidly Increase in women smokers In 2007: 55% Men 45% Women

PowerPoint Presentation:

LUNG CANCER Tobacco Percent active 85-87 passive 3-5 Etiology Relationship to Smoking

Lung Cancer and Smoking:

Lung Cancer and Smoking ~90% of lung cancers attributed to smoking However, only 20% smokers will develop lung cancer in their lifetime. ? Death from other causes ie. CAD, COPD Genetic predisposition Risk decreases when stop smoking Yet, 50% of new cases are former smokers

Occupational Exposures Linked to 3 - 15% of Lung Cancers Proven Suspected :

Occupational Exposures Linked to 3 - 15% of Lung Cancers Proven Suspected Arsenic Asbestos Bischloromethyl ether Chromium Mustard gas Nickel Polycyclic aromatic hydrocarbons Ionizing radiation Acrylonitrile Beryllium Vinyl chloride Silica Iron ore Wood dust

Asbestosis & Lung Cancer:

Asbestosis & Lung Cancer Prolonged heavy exposure has relative risk between 2 - 10 of causing lung cancer. Peak incidence 15 - 24 years after exposure. Fiber type is important: Crocidolite & amosite > chrysotile & anthophyllite.

Asbestosis & Lung Cancer:

Asbestosis & Lung Cancer Risk of smoking & asbestos exposure is multiplied. Mortality ratio: Nonsmoking asbestos worker: 5.17 Smoker: 10.85 Smoker & asbestos worker: 53.24

Relative Risk of Developing Lung Cancer:

Relative Risk of Developing Lung Cancer

Lung Cancer: Symptoms at Presentation:

Lung Cancer: Symptoms at Presentation Due to primary tumor: Cough, hemoptysis, chest pain, wheezing, dyspnea, & fever. Thoracic extension of tumor: Chest pain, SVC syndrome, hoarseness, & dysphagia.

Lung Cancer: Symptoms at Presentation:

Lung Cancer: Symptoms at Presentation Metastases: Lymph node enlargement, bone pain, neurologic deficits, skin & subcutaneous lesions. Systemic symptoms: Anorexia, weight loss, weakness, & paraneoplastic syndromes Patients often present with advanced disease due to lack of symptoms at early stages.

Lung Cancer: Findings on Chest X-ray:

Lung Cancer: Findings on Chest X-ray Nodule (< 3cm) vs. Mass (>= 3cm). Location: Peripheral (Adenocarcinoma) vs. Central (Squamous). Single or multiple (metastases). Endobronchial obstruction. Atelectasis of lobe or lung. Pneumonia.

Lung Cancer: The Chest X-ray:

Lung Cancer: The Chest X-ray Hilar and mediastinal adenopathy. Pleural effusions. Elevated hemidiaphragm.

Lung Cancer: CT Scan of Thorax:

Lung Cancer: CT Scan of Thorax Nodule details: Calcification, spiculation etc.. Evaluate extension into adjacent structures: Endobronchial, great vessels, pericardium etc.. Evaluation of adenopathy. Upper abdominal pathology: Metastatic lesions in liver, adrenals, & kidneys.

Lung Cancer: Sputum Cytology:

Lung Cancer: Sputum Cytology Helpful for central lesions. With three samples: 80% detection rate of centrally located tumors. 50% detection rate of peripheral lesions.

Lung Cancer: Video Flexible Bronchoscopy:

Lung Cancer: Video Flexible Bronchoscopy Excellent to evaluate endobronchial disease. Brushings and bronchial biopsies are high yield for visible lesions. Transbronchial biopsies of large peripheral lesions +/- fluoroscopic guidance. Evaluation of obstruction for stent placement & brachytherapy.

Lung Cancer: Transbronchial Needle Aspiration (TBNA):

Lung Cancer: Transbronchial Needle Aspiration (TBNA) Allows biopsy of subcarinal & paratracheal lymph nodes during flexible bronchoscopy. Helpful for staging. Minimal risk to patient.

Lung Cancer: CT - Guided Transthoracic Needle Biopsy:

Lung Cancer: CT - Guided Transthoracic Needle Biopsy Peripheral lesions away from diaphragm. 25% pneumothorax risk. May be beneficial for poor operative candidates. Remember: Negative needle biopsy result may be false negative.

Lung Cancer: PET Scan:

Lung Cancer: PET Scan Marker of active glucose metabolism. Can detect lesions to 0.8cm. ~90% sensitivity & ~85% specificity. Indications: Staging lung cancer. Solitary pulmonary nodule.



Lung Cancer: Other Diagnostic Tests:

Lung Cancer: Other Diagnostic Tests Thoracentesis. Surgical resection: Thoracotomy vs. VATS.

Staging of the Mediastinum:

Staging of the Mediastinum Mediastinoscopy: Mediastinal lymphadenopathy staging. Central lesions. Large peripheral lesions. “Gold Standard.”

Newer Technologies:

Newer Technologies Endobronchial Ultrasound (EBUS) Endoscopic Ultrasound (EUS)

Histology of Lung Cancers in U.S.:

Histology of Lung Cancers in U.S.


Adenocarcinoma Most common cell type in US. Peripheral location. Glandular formation. Mucin production.

Bronchoalveolar Cell Carcinoma:

Bronchoalveolar Cell Carcinoma Subtype of adenocarcinoma. Preservation of alveolar architecture. Spread through the airways. May present as unresolving pneumonia.

Squamous Cell Carcinoma:

Squamous Cell Carcinoma Cavitation. Centrally located along airways. Intravascular invasion. Intercellular bridging. Keratinization.

Squamous Cell Carcinoma:

Squamous Cell Carcinoma Keratin pearls. Nests of cells.

Large Cell Carcinoma:

Large Cell Carcinoma A poorly differentiated carcinoma. Diagnosis of exclusion. Large cells. Abundant cytoplasm. Large nuclei with prominent or vesicular nucleoli.

PowerPoint Presentation:

T definitions 6th ed. descriptor 7th ed. descriptor Tumors = 2 cms. T1 T1a Tumors > 2 cms and = 3 cms. T1 T1b Tumors > 3cms and = 5cms. T2 T2a Tumors > 5 cms and = 7 cms. T2 T2b Tumors > 7 cms . T2 T3 Separate nodule(s) in the primary lobe. T4 T3 Separate nodule(s) in a different ipsilateral lobe. M1 T4 Malignant pericardial effusion. T4 M1a Pleural dissemination. T4 M1a

PowerPoint Presentation:

Nodal Zone Lymph node station Upper zone Low cervical, supraclavicular, sternal notch (1R – 1L) Upper paratracheal (2R – 2L) Prevascular (3a) and retrotracheal (3p) Lower paratracheal (4R – 4L) Aortopulmonary zone Subaortic (aortopulmonary window - 5) Para-aortic (ascending aorta or phrenic nerve - 6) Subcarinal zone Subcarinal (7) Lower zone Paraesophageal (8) Pulmonary ligament (9) Hilar zone Hilar (10) Interlobar superior (11s) and inferior (11i) Peripheral zone Lobar (12) Segmental (13) Subsegmental (14)

PowerPoint Presentation:

M factor definitions 6th ed descriptor 7th ed descriptor Metastasis cannot be assessed. MX M0 Malignant pericardial effusion. T4 M1a Pleural dissemination (malignant pleural effusions, pleural nodules). T4 M1a Additional nodules in the contralateral lung (same histology). M1 M1a Distant metastasis. M1 M1b

PowerPoint Presentation:

PL category Definition T status PL0 Tumor within the subpleural parenchyma or, invading superficially into the pleural connective tissue below the elastic layer. PL0 is not a T descriptor and the T component should be assigned on other features. PL1 Tumor invades beyond the elastic layer. pT2 Indicates VPI PL2 Tumor invades to visceral pleural surface. PL3 Tumor invades the parietal pleura. pT3

PowerPoint Presentation:

6th ed 7th ed N0 N1 N2 N3 T/M descriptors T1 (=2cm) T1a IA IIA IIIA IIIB T1 (>2 cm =3 cm) T1b IA IIA IIIA IIIB T2 (>3 cm =5 cm) T2a IB IIA IIIA IIIB T2 (>5 cm = 7 cm) T2b IIA IIB IIIA IIIB T2 (>7 cm) T3 IIB IIIA IIIA IIIB T3 (direct invasion) IIB IIIA IIIA IIIB T4 (same lobe nodules) IIB IIIA IIIA IIIB T4 (extension) T4 IIIA IIIA IIIB IIIB M1 (ipsilateral nodules) IIIA IIIA IIIB IIIB T4 (pleural effusion) M1a IV IV IV IV M1 (contralateral nodules) IV IV IV IV M1 (distant) M1b IV IV IV IV

NonSmall Cell Cancer N Stage:

NonSmall Cell Cancer N Stage N0: No nodes. N1: Ipsilateral hilar or peribronchial. N2: Ipsilateral mediastinal, subcarinal. N3: Contralateral hilar, contralateral mediastinal or supraclavicular/scalene.

Neuroendocrine Lung Tumors:

Neuroendocrine Lung Tumors Small cell carcinoma. Atypical carcinoid. Typical carcinoid. Malignant Intermediate Benign

Small Cell Carcinoma:

Small Cell Carcinoma Aggressive tumor. Smokers. Centrally located. Bulky adenopathy is common. Distant metastases common on presentation.

Small Cell Carcinoma:

Small Cell Carcinoma Small cells. Fine chromatin pattern. Abundant mitosis. Scant cytoplasm. Tends to smudge on microscopy. Synaptophysin & chromogranin.


Carcinoid Typical carcinoid: Usually endobrochial. Present with postobstructive pneumonia. Surgical resection is curative. Atypical carcinoid: More aggressive. May require surgery with chemotherapy.

Small Cell Lung Cancer: Staging:

Small Cell Lung Cancer: Staging Limited: 30-40% of small cell lung cancers. Confined to the hemithorax, mediastinum, and ipsilateral supraclavicular lymph node. Within the confines of radiation port. Extensive: 60-70% of small cell lung cancers. Any distant spread.

Lung Cancer Why the Poor Prognosis?:

Lung Cancer Why the Poor Prognosis? Survival statistics reveal the advanced stage at time of diagnosis Presentation is often after the patient becomes symptomatic Usually Stages IIIA/B or IV These stages have poor long term survival < 10% at 5 years

Lung Cancer Why the Poor Prognosis?:

Lung Cancer Why the Poor Prognosis? Successful surgical resection and cure are only possible at early stages In U.S. only 20-25% of newly detected lung cancer is Stage I

Non Small Cell Lung Cancer Treatment:

Non Small Cell Lung Cancer Treatment Stage IA: Lobectomy is treatment of choice. T1N0, lobectomy has 70% 5 year recurrence free survival. If inoperable: 30% cure rate with XRT alone. Stereotactic radiosurgery (CyberKnife). Radiofrequency ablation.

Non Small Cell Lung Cancer Treatment:

Non Small Cell Lung Cancer Treatment Stage 1B: Lobectomy. Adjuvant chemotherapy adds a 4-12% survival benefit. Best in tumors > 4 cm. NEJM 2004. ASCO 2004.

Non Small Cell Lung Cancer Treatment:

Non Small Cell Lung Cancer Treatment Stage II: Lobectomy is treatment of choice. Adjuvant chemotherapy now standard. Consider adjuvant XRT to mediastinum

Non Small Cell Lung Cancer Treatment:

Non Small Cell Lung Cancer Treatment Stage III: Combination chemotherapy with XRT is treatment of choice. Surgery has yet to be established consistently as benefit in randomized trials. Neoadjuvant therapy followed by surgical resection is option in IIIA.

Non Small Cell Lung Cancer Treatment:

Non Small Cell Lung Cancer Treatment Stage IV: Chemotherapy.

Non Small Cell Lung Cancer Contraindications to Surgical Resection:

Non Small Cell Lung Cancer Contraindications to Surgical Resection Stage IIIB or IV. Extensive invasion into surrounding structures: Vena cava or atrium involvement. Recurrent laryngeal or phrenic nerve involvement. SVC obstruction, malignant effusion, pericardial tamponade. Contralateral lymph nodes.

Non Small Cell Lung Cancer Contraindications to Surgical Resection:

Non Small Cell Lung Cancer Contraindications to Surgical Resection Medically unfit: Poor cardiac or pulmonary status. Predicted postoperative FEV1% < 40%. Predicted postoperative DLCO% < 40%. Exercise studies for marginal candidates.

Chemotherapy Drugs:

Chemotherapy Drugs Non small cell: Two drug regimen. Cis/Carbo platin + 1 other (Taxol/Taxotere/Gemcitabine) Small cell: Cisplatin / Etoposide

Biologic Agents:

Biologic Agents Avastin Angiogenesis inhibitor. Added to chemo. Bleeding risk. Contraindicated in squamous cell carcinoma.

Biologic Agents:

Biologic Agents Tarceva Epidermal growth factor inhibitor. Second line therapy. Asian, never smoking, women, adenocarcinoma / bronchoalveolar cell CA. PO. Rash, diarrhea.

Small Cell Lung Cancer Treatment:

Small Cell Lung Cancer Treatment Untreated: 1.5 - 3 month median survival Limited: Chemotherapy with XRT. 10-20 month median survival. 5 year survival ~10% Extensive: Chemotherapy. 7-11 month median survival. 5 year survival < 1%.

Small Cell Lung Cancer Brain Irradiation:

Small Cell Lung Cancer Brain Irradiation For known metastatic lesions. Prophylaxis in both Limited & Extensive disease. Decreases the risk of developing brain metastases. Improved survival.

Evaluation of the Solitary Pulmonary Nodule:

Evaluation of the Solitary Pulmonary Nodule 25% have symptoms of cough, chest pain, or hemoptysis. 75% asymptomatic. Benign nodules: 23% Tubercular lesions 14% Benign tumors (Hamartoma, neurogenic tumors, bronchial adenoma, mesothelioma) 13% Others (Chronic pneumonia, echinoccoccal cyst, bronchogenic cyst, aspergilloma etc.)

Evaluation of the Solitary Pulmonary Nodule:

Evaluation of the Solitary Pulmonary Nodule Malignant nodules 49% of all SPN’s: Primary lung cancer 38%, metastatic cancer 9% Incidence of malignancy increases with age: Ages 35-39 : 3% are malignant. Ages 40-49 : 15% Ages 50-59 : 42% Ages 60+ : 50%

Evaluation of the Solitary Pulmonary Nodule:

Evaluation of the Solitary Pulmonary Nodule Malignant Characteristics: Spiculations. Irregular contour. Eccentric calcifications. > 3 cm. Benign Characteristics: Smooth & round. Well circumscribed. Central, densely calcified, laminated, or “popcorn.” < 3 cm.

Evaluation of the Solitary Pulmonary Nodule:

Evaluation of the Solitary Pulmonary Nodule Comparison to prior films: New? Enlarging? Change in shape? Likely benign if no change in 2+ years. CT scan for better detail. Removal if new, bigger, or changing. CT-guided biopsy if not surgical candidate. Sampling error may require surgical biopsy.

Evaluation of the Solitary Pulmonary Nodule:

Evaluation of the Solitary Pulmonary Nodule Close follow up (3 months) if benign appearance may be an option. Consider PET scan. Risk of waiting - may spread if malignant & decrease survival. Future? Superdimension 3D electromagnetic tracking/ virtual bronch

NCI Cooperative Study Results: Mortality Rates/1,000/year:

NCI Cooperative Study Results: Mortality Rates/1,000/year No significant change in mortality was noted Screening should not be offered to general population However, CXR may be of benefit in an individual high risk patient

Lung Cancer Screening: Spiral CT Scan:

Lung Cancer Screening: Spiral CT Scan In preliminary studies, spiral CT detected higher numbers of Stage I lung cancers in patients at high risk. However, many benign nodules were also discovered and required close follow up. Some patients had surgery for benign disease as a result. Three large studies look promising!

NSCLC: Treatment and Outcomes:

NSCLC: Treatment and Outcomes CHT: chemotherapy RT: radiotherapy Surgery CHT Surgery +/- pre-operative CHT, RT+/- CHT 40-70% 5 yr survival 15-30% 5 yr survival 30 – 35% 1 yr survival CHT + RT or CHT followed by RT CHT with 2 agents for 3-4 cycles 10-20% 5 yr survival NSCLC: Treatment and outcomes according to stage Stages IIIa resectable Stages IIIa /b unresectable Stages IIIb / IV Stages I & II Spira and Ettinger, New Engl J Med 2004; 350: 379

Adjuvant Therapy:

Adjuvant Therapy Administered following definitive local therapy with the intent to improve outcome Overall survival Disease-free survival Local recurrence rate

Adjuvant Therapy:

Adjuvant Therapy General principles Occult, viable cancer cells present following surgery account for risk of disease relapse Treatments with proven effectiveness against the cancer are available Risk-benefit ratio for therapy must be favourable for individuals who may remain asymptomatic for their natural life expectancy after tumour resection

JBR.10 - Conclusions Adjuvant VbP in Stage IB/II NSCLC :

JBR.10 - Conclusions Adjuvant VbP in Stage IB/II NSCLC Adjuvant VbP safe (59% 3+ cycles) Absolute benefit 15% at 5 years, p=0.0022 30% reduction risk of death, p=0.012 Subgroup analysis stage IB, p=0.79 no effect of stage by treatment, p=0.13 # events less than planned Winton, NEJM 2005

CALGB 9633 - Conclusions Adjuvant PacCb in Stage IB NSCLC:

CALGB 9633 - Conclusions Adjuvant PacCb in Stage IB NSCLC Adjuvant PacCb safe (85% 4 cycles) Overall Survival Absolute benefit 12% at 4 years 38% reduction risk of death, p=0.028 Lung Cancer Specific Mortality Absolute reduction 11% at 4 years 49% reduction risk of death, p=0.018 Strauss, ASCO 23:7019, 2004

Adjuvant Chemotherapy :

Adjuvant Chemotherapy Why are the NCIC/CALGB results better? Patient Selection Earlier stage disease Uniform patient population ? More women, more adenocarcinoma Therapy 2 drug regimen Inclusion of 3rd generation agent: no pneumotoxins Better compliance (CALGB) Lack of radiation

Current BC Cancer Agency Recommendations:

Current BC Cancer Agency Recommendations PORT Not considered routine Discussion with patients with N2 disease or close margins Adjuvant chemotherapy Routine recommendation to appropriate post-thoracotomy patients Eligibility Completely resected stage IB to IIIA disease Lobectomy or pneumonectomy preferred ECOG performance status 0-1 Able to start chemotherapy within 2 months of surgery No upper limit age restriction


PET for NSCLC PET image courtesy of Dr Nevin Murray, BC Cancer Agency

Concurrent Chemoradiation:

Concurrent Chemoradiation Theoretically improves local control by sensitizing the tumour to radiation, while treating systemic disease Early definitive local therapy potential benefits Decrease metastatic events Decrease accelerated repopulation Decrease emergence and spread of chemotherapy resistance elements. Decrease radiotherapy resistance “Destroy as much cancer as quickly as possible”

PowerPoint Presentation:

Long Term Survival Comparison between Sequential and Concurrent Chemoradiation Therapy WJLCG % 5 yr OS 9 % 19 % RTOG 9410 % 4 yr OS 12 % 21 %

Chemotherapy and Surgery:

Chemotherapy and Surgery Depierre, JCO 20(1):247, 2002 355 stage I (except T1N0), II, IIIA PS 0-1, age <75 Chemo Chemo Surgery Surgery mitomycin 6mg/m2 d 1, ifosfamide 1.5 g/m2 d 1-3, cisplatin 30mg/m2 d1-3 q 21d x 2 cycles Chemo responders 60Gy over 7 weeks pT3 or pN2 disease and/or those with incomplete surgery Radiation

PowerPoint Presentation:

Treatment Regimens for NSCLC: Historical Context % 1-Yr Survival Supportive Care CDDP-combos Pre-1995 New Single Agents Cis + NVB/Txtr/Gem Carbo + Txl 3

Newer 2-agent Platinum-based Combination Therapies:

Newer 2-agent Platinum-based Combination Therapies Cisplatin Carboplatin Docetaxel Gemcitabine Irinotecan Paclitaxel Topotecan Vinorelbine Haura E: Cancer Control 2001; 8(4):326-36.

Clinical Predictors of EGFR Tyrosine Kinase Inhibitors:

Clinical Predictors of EGFR Tyrosine Kinase Inhibitors Adenocarcinoma with BAC Features Lifetime non-smoking status Females Southeast Asian Origin

SCLC - Background:

SCLC - Background SCLC Incidence: ACS 2007: All Lung CA incidence: 213,000 13% of all lung CA (~27,000)

Natural History of SCLC:

Natural History of SCLC SCLC is distinguished from NSCLC by its rapid doubling time, high growth fraction, and the early development of widespread metastases Although considered highly responsive to chemotherapy and radiotherapy, SCLC usually relapses within two years despite treatment Overall, only three to eight percent of all patients with SCLC (10 to 13 percent of those with limited disease) survive beyond five years

SCLC Histology:

SCLC Histology SCLC is a “small blue round cell tumor” from neuroendocrine cells Classifications: oat cell (lymphocyte-like), fusiform, polygonal OR classical, large cell neuroendocrine, combined SCLC/NSCLC “crush” artifact Immunohisto tests: TTF1+ (adeno & SCLC)

Lymph Node Stations:

Lymph Node Stations 1 2 3a 3b 4 5 6 7 8 9 10 11-14 highest mediastinal upper paratracheal pretracheal retrotracheal lower paratracheal AP window Para-Aortic (above 5) subcarinal esophageal pulmonary ligament hilar interlobar, lobar, segmental, subsegmental

Lymph Node Stations:

Lymph Node Stations

Clinical Presentation of SCLC:

Clinical Presentation of SCLC Smokers (almost exclusively) Cough 75% Hemoptysis in 50% Dyspnea and chest pain 40% Constitutional symptoms 10 to 15% Clubbing 16 to 29% pneumonia, weight loss

SCLC Paraneoplastic Syndromes:

SCLC Paraneoplastic Syndromes SIADH ectopic ACTH production- Cushing’s synd Eaton-Lambert Myasthenic syndrome proximal muscle weakness that improves on repetition (“facilitation”) Hypercalcemia Peripheral Neuropathy


Workup Labs: CBC, chem, LFTs, LDH CT chest/abd/pelvis Brain imaging (CT or MRI) (up to 30% have brain mets at presentation)

SCLC Staging:

SCLC Staging Limited Stage (1/3) confined to 1 hemithorax disease fits within a tolerable radiation port Extensive Stage (2/3) doesn’t fit Recommend also use TNM staging, as for NSCLC

Where does SCLC metastasize to? “BALLS”:

Where does SCLC metastasize to? “BALLS” Brain (30%) Adrenal (20-40%) Liver (25%) Lung Skeleton (35%)

Prognostic Factors:

Prognostic Factors The host factors of poor performance status and weight loss Stage (limited versus extensive). In extensive disease, the number of organ sites involved is inversely related to prognosis Metastatic involvement of the central nervous system, the marrow, or the liver is unfavorable compared to other sites, although these variables are confounded by the number of sites of involvement. In most trials, women fare better than men, although the reasons for this are not known. The presence of paraneoplastic syndromes is generally unfavorable


Survival Limited Stage: Median OS: 14-24 months 5-yr OS: 20% Extensive Stage: MedianOS: 6-11 months 5-yr OS: 2%

Treatment – Limited Stage SCLC:

Treatment – Limited Stage SCLC Concurrent chemoradiation Chemo: cisplatin/etoposide q3wks Radiation: 150 cGy BID to 4500 cGy (Turrisi) OR 180 QD to 50-70Gy. (54Gy?) Sequential chemo, then RT. If CR, then PCI 2500/10, 3000/15, or 2400/8 Auperin (NEJM 99)

Treatment – Extensive Stage:

Treatment – Extensive Stage Chemo RT for palliation only

Treatment Fields for SCLC:

Treatment Fields for SCLC Cover primary disease & known positive LNs w/ 1.5-2cm margin. Do you cover elective mediastinal nodes for SCLC? Cord limit @ BID: <36Gy Lung V20 < 20-30% Heart D50 < 25-40Gy

Turrisi (NEJM 340(4):265-271, 1999):

Turrisi (NEJM 340(4):265-271, 1999) “Twice-Daily Compared With Once-Daily Thoracic Radiotherapy In Limited Small-Cell Lung Cancer Treated Concurrently With Cisplatin and Etoposide”

Turrisi - Methods:

Turrisi - Methods 419 pts (’89-’92) with LS-SCLC Concurrent Chemo x4c (cis/etopo) q3w Radiation Group 1: 1.8 Gy QD to 45 Gy Group 2: 1.5 Gy BID to 45 Gy Bilateral mediastinal and ipsilateral hilar adenopathy Prophylactic Cranial Irradiation if CR 25 Gy/ 10 fx

Turrisi – Survival :

Turrisi – Survival 2 y 5 y

Turrisi - Conclusions:

Turrisi - Conclusions BID more effective than QD Benefit: 10% absolute increase in overall survival @ 5yrs Cost: 15% increase in high grade esophagitis

Auperin Meta-Analysis of PCI (NEJM 1999):

Auperin Meta-Analysis of PCI (NEJM 1999) PCI for LS-SCLC if CR after chemo Meta-analysis of 7 trials (1965-95) Dose Fx: 800x1 to 4000/20. Improved 3yr OS 20.7% v 15.3%. Incidence of brain mets decreased from 58% to 33% @ 3yrs. Better if PCI <4mo from chemo start No assessment of neurocognitive fxn

But what about PCI for ES-SCLC?:

But what about PCI for ES-SCLC? Slotman, EORTC, ASCO 2007 RCT, 286 pts w/ ES-SCLC If any response to chemo x4c, then randomized to +/- PCI PCI reduced risk of symptomatic brain mets 14.6% v 40.4% at 1 yr. Improved 1-yr OS 27.1% vs 13.3%.

PowerPoint Presentation:

Sequential changes during lung cancer pathogenesis Early Intermediate Late Normal epithelium Hyperplasia Dysplasia CIS Invasive carcinoma ~80% 3p LOH/small telomeric deletions 3p LOH/contiguous deletions ~50% Microsatellite alterations ~70% 9p21 LOH ~80% Telomerase dysregulation Telomerase upregulation ~60% myc overexpression ~80% 8p21-23 LOH ~40% Neoangiogenesis ~40% Loss of Fhit immunostaining ~70% p53 LOH p53 mutations ~80% Aneuploidy ~100% Methylation ~30% 5q21 APC-MCC LOH ~20% K-ras mutation Hirsch et al 2001

Treatment Strategies for Lung Cancer:

Treatment Strategies for Lung Cancer NSCLC: Treatment based on stage: Early stage (Stage I/II) – surgery Regional spread –combined modality (chemoradiation) Metastatic – chemotherapy, radiation as needed for local control Small cell lung cancer: chemotherapy (+radiation for limited stage)

Controversies in NSCLC Treatment:

Controversies in NSCLC Treatment Adjuvant therapy IALT study – small, but real (4.1%) improvement in survival with 3-4 cycles cisplatin (ASCO 2003) UFT x 2 yrs in stage I adenoca – 2.5% improvement in survival (ASCO 2003) Neoadjuvant therapy BLOT-phase II study, stage Ib-IIIA, induction taxol/carbo followed by surgery post-op chemo, 3 yr survival 63% superior to historical control (J Thor Cardio Surg 119:429, 2000) Adjuvant radiation PORT meta-analysis – not for early stage, probably not for regional disease (Lancet 352:257, 1998)

Controversies in NSCLC Treatment:

Controversies in NSCLC Treatment Choice of agents? Platinum vs. not (probably yes) Single vs. two vs. three agents (probably 2) Treatment of elderly – Yes if good performance Length of treatment – probably no more than 6 cycles of cytotoxic conventional chemo Second line treatment – yes Taxotere better than supportive care Iressa (EGFR inhibitor) approved after cisplatin/taxotere failure

Agents currently under development :

Agents currently under development Inhaled budesonide Zileuton (5-lipoxygenase inhibitor) Celecoxib, rofecoxib (COX-2 inhibitor) Pioglitazone (PPAR  agonist) Green tea polyphenols ACAPHA (herbal extract) Myo-inositol (dietary supplement) Selenium Sulindac sulfone (Exisulind)

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