““No Air”No Air”Management of Lung CancerManagement of Lung Cancer

Elaine Bouttell, MD FRCPCElaine Bouttell, MD FRCPCMedical oncologyMedical oncology

GRRCCGRRCC

• Disclosures:– Advisory board for Novartis, RCC

ObjectivesObjectives• 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

OverviewOverview

• 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

OverviewOverview• Staging system for SCLC (15%)

• Life expectancy depending on stage

• Management of SCLC– Limited stage– Extensive stage

• Follow-up

• Complications and Paraneoplastic conditions

StatisticsStatistics• 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 FactorsRisk 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 Second Hand Smoke causes Lung CancerCancer

• 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 SmokersLung 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 Risk Reduction after Quitting SmokingSmoking

• 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 DetectionScreening 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 TreatmentBest Treatment

• 1. Prevention

• 2. Prevention

• 3. Prevention

Non Small Cell Lung CancerNon Small Cell Lung Cancer

StagingI T1-2 N0II 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 Management of Potentially Resectable Stage I, II, IIIA NSCLCResectable Stage I, II, IIIA NSCLC

• Surgery

Life Expectancy by StageLife 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 IIMedically 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 Adjuvant Therapy Post-Surgical ResectionResection

• 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 IIIBUnresectable 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 TreatmentFollow-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 Metastatic Non-Small Cell Lung CancerCancer

• 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 Metastatic Non-Small Cell Lung CancerCancer

• 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 StagingSmall Cell Lung Cancer Staging

• Limited – potentially curable

• Extensive - incurable

Small Cell Lung CancerSmall 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 CancerSmall 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 Small Cell Lung Cancer ManagementManagement

• 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 TreatmentFollow-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 Small Cell Lung Cancer ManagementManagement

• 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-upFollow-up• Symptoms of concern:

– 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 SyndromesParaneoplastic Syndromes

• Non-Small Cell Lung Cancer– Hypercalcemia

• Squamous cell > adeno > small cell

– Clubbing, Hypertrophic pulmonary osteoarthropathy

• Adeno

– DVT/PE• Adeno

Paraneoplastic SyndromesParaneoplastic Syndromes

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

Complications Treated with Complications Treated with Palliative RadiationPalliative Radiation

• Brain metastases

• Spinal cord compression

• Hemoptysis

• SVCO

• Painful bone metastases

• Airway obstruction (+/- postobstructive pneumonitis)