Lung Cancer Screening

Transcription

1 Lung Cancer Screening Ravi Salgia, M.D., Ph.D. Professor and Chair Medical Oncology and Therapeutics Research City of Hope

2 Nothing to disclose Disclosure

3 Lung Cancer 2016 >200,000 cases projected >160, deaths projected Leading cause of cancer related death: USA, Western Europe, and Japan

4 Lung Cancer: More research needed Every three minutes someone is diagnosed with lung cancer Men have a lifetime risk of 1 in 13 and women 1 in 17 In 2015, the federal government spent (NCI): $674 million/breast cancer, $288 million/prostate cancer, $349 million/lung cancer

5 Estimated Cost of Lung Cancer Treatment 2010: $230,000,000, : $450,000,000,000 21Juil/MTA/5

6 Salgia, et al, 2003

7 Salgia, et al, 2003

8 Lung Cancer Salgia, et al, 2003

9 LOCATION OF LUNG CANCER CENTRAL/HILAR Squamous cell carcinoma Small cell carcinoma PERIPHERAL Adenocarcinoma

10 Small Cell Carcinoma Histology

11 NON SMALL CELL LUNG CANCER Incidence of major histologic i types* Small-cell carcinoma Adenocarcinoma 15% Large-cell carcinoma * Numbers do not sum to 100% because of differences in diagnostic criteria. Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 5th ed. 1997;

12 NON SMALL CELL LUNG CANCER Stages at presentation 7% Stage II 31% Stage III 24% Stage I 38% Stage IV Fry WA, et al. Cancer. 1996;77:

13 Lung Cancer Survival

14 Lung Cancer: Who is at Risk? Patients that are former (or current) smokers with COPD/Emphysema Patients with prior lung, esophageal, head/neck cancers Patients with ihpulmonary fibrosis i Patients with pulmonary asbestosis

15 Lung Cancer risk factors Relative Risk Population Frequency Active Cigarette Smoking (>20PY) Passive Cigarette Smoking (>40-80PY) % % Asbestos Exposure 15.1? COPD (FEV1<70%) % Diet (Fruits and Vegetables >5 servings/day) % Selenium (>0.63 µg/g) % Family History (Parent/Child/Sib) %

16 National Lung Screening Trial Trial Design and Initial Results Prospective, randomized trial comparing low dose helical CT screening to chest x ray screening in high h risk participants i with the endpoint of lung cancer specific mortality Eligibility Age Asymptomatic current or former smoker; 30 pack year smoking history Former smokers: quit within preceding 15 years No prior lung cancer diagnosis No evidence of other cancer within preceding 5 years

17 NLST primary endpoint Helical CT vs. CXR Lung cancer-specific mortality 20% difference α 5% Power 90% Compliance Contamination Size 85% CT arm 80% CXR arm 5% CT arm 10% CXR arm 25,000 / arm

18 NEJM: NLST 20% reduction in mortality

19 Screen Positivity Rate by Annual Screening Round and Trial Arm Screen Round 1 LDCT CXR Number Number Percent Number Number Percent Screened Positive i Positive i Screened Positive i Positive i 26,314 7, ,049 2, Screen 24,718 6, ,097 1, Round 2 Screen Round 3 24,104 4, ,353 1, All Rounds 75,136 18, ,499 5, LDCT resulted in 649 cancer (3.6% of the positive screens) LDCT resulted in 649 cancer (3.6% of the positive screens) while CXR resulted in 279 cancers (5.5% of the positive screens.

20 Analysis of Primary Endpoint Reported on October 20, 2010 Trial Arm Person Years (PY) Lung Cancer Deaths LC Mortality per 100,000 PY Reduction in Lung Cancer Mortality LDCT 144, CXR 143, ***All cause mortality was reduced by 6.9% in the LDCT group.

21 Timeline Approval Screening --December 2013: USPTF designed screening LDCT B recommendation -Age years of age -At least 30 pack year history of smoking -Current smokers or former smokers who have quit within the past 15 years --February 2015: Center for Medicare and Medicaid Services (CMS) accepted coverage for screening Age years of age --Under Affordable Care Act, prevention measures given A or B grade are included in Essential Health Benefit beginning January, 2015

22 Courtesy G. Rogalski, 2016

23 Courtesy G. Rogalski, 2016

24 Lung Rads Overview

25 NON INVASEVE DIAGNOSTIC BIOMARKERS

26 Potential biomarkers for lung cancer screening

27 mirnas in Lung Cancer Diagnostic Fig. 2. Publications on mirnas in cancer and NSCLC Sheervalilou et al. Diagnostic Cytopathology DOI /dc

28 Conclusions: Early detection candidate biomarkers exist but only few of them are validated or tested in screening settings. The priority is now to validate existing candidates. Biomarkers should provide knowledge about added value and therefore should be integrated to clinical, laboratory and imaging g (LDCT) routine data. To demonstrate clinical utility requires significant investment in effort and resources towards prospective biomarkers driven clinical trial.

29 Prognostic mirnas in Lung Cancer Barger&Nana Shinkam Respiratory Medicine (2015) 109, 803e812

30 Predictive and prognostic value of circulating tumor cell detection in lung cancer

31 The Structure of the Lung is Fractal The tree like structure of the lung can be constructed by simple recursive branching rules Glenny, RW. J.Appl Physiol, 2011 Goldberger et al., PNAS, 2002 Weibel ER. Swiss Med Wkly 2009

32 Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data Szigeti et al. BMC Medical Imaging (2016) 16:14

33 SUMMARY Lung Cancer Lung cancer is a common malignancy In spite of novel therapeutics, the overall survival remains poor LDCT Screening is now standard of care for at risk population p Prevention and biomarker strategies have to be developed for better survival

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