“No Air” Management of Lung Cancer Elaine Bouttell, MD FRCPC Medical oncology GRRCC

Disclosures: Advisory board for Novartis, RCC

Objectives Review the diagnosis, treatment, and palliation of lung cancer Review the types and demographics of lung cancer Identify the differences between primary and secondary lung cancer Function of the DAU Screening and early diagnosis of lung cancer Review differences between curative and non-curative treatment Treatment modalities: surgery, chemotherapy, radiation therapy

Overview Review statistics (incidence, death rates) Etiology Staging system for NSCLC (85%) Life expectancy depending on stage Management of NSCLC Resectable Stage I, II, IIIA Unresectable Stage IIIA, IIIB Incurable Stage IV

Overview Staging system for SCLC (15%) Life expectancy depending on stage Management of SCLC Limited stage Extensive stage Follow-up Complications and Paraneoplastic conditions

Statistics In 2008: 23,900 Canadians will be diagnosed with lung cancer 20,200 will die of lung cancer (more deaths than colorectal, prostate, and breast cancer combined) 1 in 12 men will develop lung cancer, 1 in 13 will die of it (incidence and death rates decreasing) 1 in 16 women will develop lung cancer, 1 in 18 will die of it (incidence and death rates increasing)

Risk Factors Smoking (including second hand smoke exposure)– 80-90% Previous radiation therapy Previous diagnosis of lung cancer Exposure to asbestos, arsenic, chromium, nickel (especially in smokers), radon gas Family history of lung cancer Air pollution?

Second Hand Smoke causes Lung Cancer Meta-analysis of 52 studies prepared for the Surgeon General’s report in 2006 concluded that the odds ratio for spouse of smoker is 1.21-1.37 (dose response) SHS exposure in the work place, OR 1.22 Exposure to children leads to OR 1.10, >25 smoker-years doubled the risk, <25 smoker-years did not appear to increase the risk

Lung Cancer in Never Smokers Percentage of never-smokers among lung cancer patients appears to be increasing incidence in never smokers increasing, or prevalence of never-smokers in the population increasing? US women age 40-79: 14.4-20.8/100,000 person-years US men: 4.8-13.7 adenocarcinoma, different biology

Risk Reduction after Quitting Smoking Cutting back from 1ppd to ½ ppd decreased risk 27% Risk of lung cancer falls over 15 years after quitting then remains about 2x risk of a never smoker Risk reduction appears to be related to age at quitting

Screening for Early Detection No test in asymptomatic patients (CXR, sputum cytology, CT scan) shown to reduce mortality from lung cancer Reasonable to do CXR in any smoker presenting with symptoms

Best Treatment 1. Prevention 2. Prevention 3. Prevention

Non Small Cell Lung Cancer Staging I T1-2 N0 II T1-2 N1 T3 N0 IIIA T1-2 N2 T3 N1-2 IIIB T N3 T4 N0-3 IV T N M1 “wet” IIIB

Management of Potentially Resectable Stage I, II, IIIA NSCLC Surgery

Life Expectancy by Stage 5 year overall survival rates for surgically resected: Stage I 60-75% Only 57% clinical stage I are pathologic stage I, and 13% are actually pathologic stage IIIA Stage II 36-60% Stage IIIA 3-34%

Medically Inoperable Stage I and II Radiation therapy alone 11-43% die of non-cancer causes 70% 5 yr OS for Stage I 60% 3 yr OS for Stage II

Adjuvant Therapy Post-Surgical Resection Radiation: consider if close/positive margin, ?N2 Chemotherapy (4 months weekly vinorelbine + cisplat d1 d8) Overall increase in cure rate 5-15% stage II and IIIA controversial for stage IB (?benefit if T>4cm) no proven additional benefit for stage IA

Unresectable Stage IIIA and IIIB Treatment with curative intent vs Palliation Curative Intent: Sequential chemo followed by RT better than RT alone Concurrent chemo/RT better than sequential (4 yr OS 21% vs 14%) 10 early (within 6 mths) toxic deaths in concurrent arm vs 3 in the sequential arm ?PCI (prophylactic cranial irradiation) Decreased brain mets as first site of failure at 5 yrs 35% to 8%

Follow-up Post Curative Treatment Non-small cell lung cancer post surgery +/- adjuvant chemotherapy, or concurrent chemo/RT No proven survival benefit to ANY routine investigations in asymptomatic patients Recurrent disease rarely curable, unless second primary lung cancer Directed history and physical +/- CXR q 3 mth x 2 yr, then q 6mth x 3 yr, then annual

Metastatic Non-Small Cell Lung Cancer Palliative chemotherapy vs BSC Response rate 30% Survival benefit (30 vs 20% 1 year OS) with no adverse effect on QOL (BLT JCO 2005) if wt loss <10% and ECOG PS <2 PS 0 No activity restrictions PS 1 Strenuous physical activity restricted PS 2 Capable of self care, no work, up and about >50% waking hours PS 3 Confined to bed or chair >50% PS 4 Confined to bed or chair

Metastatic Non-Small Cell Lung Cancer Survival benefit with chemo: Previously 2 months (incr from 7 mth to 9) 30% 1 year survival Now 35-50% 1 year survival, up to 25% 2 yr survival with treatment First line cisplatin/carboplatin + gem (squamous), vin, taxane Second line taxotere, pemetrexed (adeno), erlotinib Third line erlotinib

Small Cell Lung Cancer Staging Limited – potentially curable Extensive - incurable

Small Cell Lung Cancer Limited Stage Disease encompassable within a radiation field Response rate to chemotherapy 80-90% Median survival 15-20 mth with treatment, 12 mth without Potentially curable 3 yr OS 20%, 5 yr OS 15%

Small Cell Lung Cancer Extensive Stage (metastatic) Median survival 8-13 mth with treatment vs 7 mth without Response rate to first line chemo 60-80% ECOG PS not as important, often poor due to disease, improves with treatment

Small Cell Lung Cancer Management Limited Stage Concurrent Chemo/RT, ideally RT (3 wk) starting with cycle 1 Cisplatin/etoposide daily x 3d x 4 cycles (3 mth) Response rate 80-90% PCI results in decrease in symptomatic brain mets at three yrs from 59% in untreated to 33% in patients treated with PCI PCI increases 3yr OS from 15% to 20%

Follow-up Post Treatment Limited Stage Small Cell Lung Cancer No proven survival benefit to ANY routine investigations in asymptomatic patients Recurrent disease rarely curable, unless second primary lung cancer Most recurrences occur within first yr Relapses more rapidly progressive Consider directed history and physical + CXR q 2-3 mth for first year, q 3 mth for second yr, q 6 mth for yr 3-5, then annually

Small Cell Lung Cancer Management Extensive Stage Palliative chemotherapy Response rate to first line 60-80% Cis/etop, carbo/etop, oral etoposide x 3 mth PCI decreases symptomatic brain mets at 1 yr from 40% to 15%, increases 1 yr OS from 13% to 27% Second line treatment depends on time to progression

Follow-up Symptoms of concern: Complications to consider: New or worsening SOB, cough, hoarseness, dysphagia, chest pain, lightheadedness/syncope, peripheral edema, RUQ pain, wt loss, bone pain (back pain, cord compression symptoms), headache/CNS symptoms Complications to consider: DVT/PE SVCO Pleural, Pericardial effusion Cord compression Brain mets Paraneoplastic syndrome

Paraneoplastic Syndromes Non-Small Cell Lung Cancer Hypercalcemia Squamous cell > adeno > small cell Clubbing, Hypertrophic pulmonary osteoarthropathy Adeno DVT/PE

Paraneoplastic Syndromes Small Cell Lung Cancer SIADH Cushing’s syndrome Lambert-Eaton myasthenic syndrome Limbic encephalitis Cerebellar degeneration Peripheral sensory neuropathy

Complications Treated with Palliative Radiation Brain metastases Spinal cord compression Hemoptysis SVCO Painful bone metastases Airway obstruction (+/- postobstructive pneumonitis)