5/12/2016. a seasoned clinician s perspective

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1 a seasoned clinician s perspective Thomas J Gross, MD Professor of Internal Medicine Pulmonary, Critical Care, & Occupational Medicine Carver College of Medicine Street cred: Medical Director Pulmonary Outpatient Clinics Pulmonary Proceduralist and Advanced Bronchoscopist Senior Pulmonary Member Multidisciplinary Lung Cancer Group ALA in IA Board Member I have no financial or intellectual conflicts of interest with material discussed today OBJECTIVES By the end of this performance, the engaged learner will: 1) Understand the recent trends in lung cancer rates ALA take a bow for reduced smoking rates! 2) Explore the complex epidemiology of lung cancer in the modern era do not back off smoking cessation efforts! 3) Appreciate the evolving paradigm for lung cancer biology most disease advanced when found, increasing focus on personalized tumor management Surveillance, Epidemiology, & End Results 1

2 Who gets it? 2

3 Risks for Lung Cancer: Age Percent of U.S. Women Who Develop Lung Cancer over 10, 20, and 30 Year Intervals According to Their Current Age, Current Age 10 Years 20 Years 30 Years N/A Percent of U.S. Men Who Develop Lung Cancer over 10, 20, and 30 Year Intervals According to Their Current Age, Current Age 10 Years 20 Years 30 Years N/A >>>>>>>>>>>>>>>> TOBACCO SMOKE Environmental Exposures Host Factors Epidemiology of Lung Cancer:Diagnosis and Management of Lung Cancer, 3rd ed: ACCP Evidence Based Clinical Practice Guidelines. Chest May; 143(5 Suppl): e1s e29s. doi: /chest

4 ACTIVE SMOKING 80 to 90% attributable risk with no clear safe threshold (nonsmoker = < 100 cigs/lifetime) Risk increased by BOTH time and dose 20X nonsmoker risk at 40 pack years Evolution in cig design with shift Squamous to Adeno Ca deeper, smaller Cigar & tobacco via hookah with elevated, albeit lower risk Marijuana & vapor devices less well studied Passive Smoke risk hard to isolate Estimated at 1.2 to 1.5 X Environmental Exposures Occupational maybe 10% total cases? Coke oven workers tar/soot from coal burning Heavy metals arsenic (oral too), chromium, nickel Diesel exhaust not clear maybe 1.3 X baseline Silica not clear in absence smoking or silicosis Asbestos 5X risk, synergistic with smoking (80X), independent of asbestosis Radiation exposure atomic bomb survivors (1.6X), Uranium miners (1.5 to 3X) harder to show for nuc plants, TB screening, XRT Environmental Exposures Domestic Radon radioactive products of similar potency to uranium mines Lower doses/longer exposures Pooled estimated risks on order 1.2 to 1.6 X unexposed Seems synergistic with smokers?passive smoke Unclear when critical exposure occurs childhood, adulthood Fairly easy to remediate, very common, will be real estate requirement soon everywhere get er done. 4

5 Environmental Exposures Air Pollution fossil fuel > other fuels Lung Cancer risk increased 1.5 X in US cities with worst air quality Similar data in Europe and Asia Indoor Air Quality primarily a developing world issue Soft coal and Biomass burning indoors for cooking or heat Indoor coal burning in Asia with 5X risk nonsmoking women Can cut risk in half with improved ventilation or stove design Biggest lung cancer risk in China after smoking if cut indoor burning in half for next 15 years, prevent 0.5 BILLION lung cancers Host Factors Genetics Family history of lung cancer in a first degree relative 1.4 to 1.7 X increase risk independent of smoking. 2 family members with lung cancer, 3X risk Acquired Lung Disease COPD lung cancer more common in smokers with COPD than similar smoking dose without COPD Non smoking COPD less clear 1.5 X risk in A1AT carrier Fibrotic Lung Diseases pneumoconiosis (asbestosis, silicosis, black lung ), Idiopathic Pulmonary Fibrosis (7X), Scleroderma (3 to 5X), Old TB, Prior Chest Radiation Immunodeficiency loss of tumor surveillance HIV (2.5X), Organ/Stem cell TXP (increased risk vs. more rapid ds) 5

6 Advanced disease at presentation Ineffective therapies for advanced disease 10 mm? T1a 2cm Solitary Pulmonary Nodule: A flawed paradigm? Dandelion vs. Canada Thistle Lung Cancer is more like breast cancer. Tumor stem cells? Multifocal field effect? One tumor predicts more? Tumor biology may trump staging 6

7 In lung cancer, like many others, small may not imply early stage. No tool yet ready to differentiate tumor behavior how do we distinguish over diagnosis from aggressive disease? Screening is important, but unlikely to lead to longer survivals alone. Lung cancer needs interventions aimed at managing a chronic disease. Focus shifting to blocking tumor growth and boosting host immune response. Roles for less radical surgery, smaller field radiation, and targeted ablation is evolving Growth Factor Receptors and downstream paths 65 to 80% of NSCLC have abnormal regulation Activating mutations, over expression, dysregulation Small molecule inhibitor drugs most are oral Better tolerated than standard chemo, higher response rates, prolonged survival 100% eventual failure due to acquired resistance new drugs Immunotherapy Exposing tumors to native tumor surveillance poor response to tumor vaccines and T cell boosting check point inhibitors are one such approach Uncover the tumor to immune system tumor killing Early studies show high response rates, good tolerance, prolonged median and overall survival Reports of autoimmune like illnesses The more genetically aberrant the tumor, the more robust the response Lung Cancer rates are falling good news!! Still the leading cancer death in US and most of developed world Will see an uptick as screening catches on and more citizens have healthcare Epidemiology based on 3 primary factors: Tobacco smoke Inhaled toxins passive tobacco smoke, air pollution, radon, occupational Host factors genetics, pre existing lung disease, immune competence Lung Cancer is deadly > 50% present at advanced stage + noncurative Rxfor advanced disease. Lung Cancer heterogeneous and small tumors may not be early. Prognosis and treatment better guided by tumor genetics and biology, than size. Increasing focus on managing as chronic disease, targeting unique tumor features. 7

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