폐암검진, 누구에게 필요한가? 분당서울대병원 내과 윤 호일

무료 폐암검진 시범사업 2017.4- 국립암센터 등 전국 9개 지역암센터, 서울대학교병원 55~74세 30갑년 이상의 흡연력 현재 흡연자 또는 금년한지 15년 이내의 과거흡연자 저선량 CT + 금연상담

Lung cancer worldwide The proportion of lung cancer patients in developing nations increased from 31% to 49.9% in the last two decades 15% of men and 53% of women with lung cancer worldwide are never smokers Geographic differences: the proportion of lung cancer of never smoking women: 83% in Asian countries, 15% in US IRAC, 2002, Global Cancer Statistics Geographic proportion of LC among never smoker women: Curr Poin Oncol 2009; 21: 99-104

Screening: why ? Goal: cancer mortality reduction Detect asymptomatic cancers Asymptomatic cancers = better prognosis (?)

폐암검진의 역사 1960-London CxR – No mortality difference 1970’s – MSKCC, Johns Hopkins, Mayo CxR/Sputum – No benefit of adding sputum cytology 1990;s – PLCO- No benefit of CxR screening ELCAP – LDCT better than CxR at detecting cancer Mayo – LDCT better than CxR 2002-2004- NLST – 20%reduyction in mortality LDCT 2010 – AFB, genomic, proteomic analysis, seruum molecular markers

CDC guideline for lung cancer screening Yearly screening with LDCT for people who- Have a history of heavy smoking (>30PY), and Smoke now or have quit within the past 15 years, and Are between 55 and 80 years old

Lung Cancer Screening Tools Sputum Cytology Chest X-ray Bach, ACCP guidelines, Chest 2007;132:69S-77S

Computed Tomography (CT) of the Chest Routine Low-dose 938mGy/cm 15.9 mSv 88mGy/cm 1.5 mSv Computed Tomography (CT) of the Chest -- Routine (Left) versus Low Dose (Right). The surveillance of small pulmonary nodules is a common indication for chest CT, and several protocols can be used for these studies. Routine chest CT (Panel A) is associated with a radiation dose to the patient that is 10 times that of low-dose chest CT (Panel B) (dose-length product, 938 mGy per centimeter vs. 88 mGy per centimeter; effective dose, 15.9 mSv vs. 1.5 mSv) -- yet each shows the small pulmonary nodule equally well (Panels A and B, arrows). The pulmonary parenchyma and upper abdomen are better visualized on the higher-dose routine scan (Panels A and C, respectively) than the low-dose scan (Panels B and D, respectively), but these areas are irrelevant to follow-up of a small pulmonary nodule. A recent survey of radiologists who perform chest CT showed that low-dose CT was not routinely used for examinations performed solely for the purpose of nodule follow-up and that most radiologists were unaware of the CT settings used for initial versus follow-up CT.1 Standardization of CT protocols could result in substantial reduction in patients' radiation doses without loss of diagnostic accuracy. Images courtesy of Dr. Michael J. Flynn, Department of Radiology, Henry Ford Health Systems. Smith-Bindman, N Engl J Med 2010;10.1056

Screening with Low-dose CT It works ? 31,567 subjects (1993-2005) 481 lung cancers detected 85% stage I (n=412) ELCAP, NEJM 2006;355:1763-71

National Lung Cancer Screening Trial (NLST) smokers ex-smokers ≥ 30 PA Age 55-74 LDCT Chest PA Years 1 2 RANDOM I S A T ON NLST, NEJM 2011; 365(5):395-409

NNS to prevent 1 lung cancer death = 320… 55 to 74 yrs, > 30P-Y, active or stop<15 yrs n « Positive » (diam>=4mm) Lung cancers Lung cancer deaths Risk reduction Low-dose CT 26.455 18.146 (68.5%) 1.060 346 (1.3%) 20,0% Chest X-ray 26.232 5.043 (19.2%) 941 425 (1.6%) NNS to prevent 1 lung cancer death = 320… NLST, NEJM 2011; 365(5):395-409

NLST: Highly selected population Probably healthier vs. base population < 65 years 73% vs 65% in the base population Less current smokers 48% vs 57% Better educated 6% with less than a high school education vs 21% NLST, JNCI 2010

European Screening Trials Overview NELSON DLCST ITALUNG LUSI DANTE MILD Nr rounds 4 5 10 or 5 Enrollement 15,464 4,104 3,206 3,551 2,472 3,581 Completed Y N Baseline detection 0.9% 0.8% 1.5% 1.0% 2.2% Incidence 0.5% 0.6% 0.4% - de Koning, ECCO-ESMO meeting, Sept. 2011

How many screen rounds? Lung cancer was diagnosed frequently after the third low-dose CT screening This observation suggests that continuing to screen high-risk individuals annually will provide a net benefit.

잠재적 이득 잠재적 손실 폐암사망율 20% 감소 방사능 노출 사망율 7% 감소 그릇된 안도 정상일 경우 안도감 over diagnosis 금연치료에 도움 위양성

Linear non-threshold model CT with an effective dose of 10 mSv Increased risk of fatal cancer of 1 in 2000 Natural incidence of fatal cancer 400 in 2000 (in the US population)

Radiation dose in adults Procedure Approximate effective dose Comparable natural background radiation Abdomen and pelvic CT 10 mSv 3 years Abdomen and pelvic CT, pre- and post contrast 20 mSv 7 years Brain CT 2 mSv 8 months Chest CT 7 mSv 2 years Low dose CT 1.5 mSv 6 months Chest PA 0.1 mSv 10 days Coronary CT 12mSv 4 years DEXA 0.001mSv 3 hours PET/CT 25mSv 8 years Mammography 0.4mSv 7 weeks

non-smoking lung cancer patients Adenocarcinoma, especially bronchioloalveolar carcinoma Asian ethnicity Female Better response to Epithelium Growth Factor Receptor (EGFR) Tyrosine Kinase (TK) inhibitors, such as erlotinib and gefitinib Iressa – AstraZeneca Tarceva - Genentech

Etiologic and molecular features Several etiologic factors have been proposed: Occupational and environmental factors: exposure to radon, asbestos, heavy metals Cooking fumes Environmental tobacco smoke Human papilloma virus (HPV) infection Inherited genetic susceptibility Molecular features EGFR mutations, p53 mutations, K-ras mutations

Exposure to cooking fumes A meta-analysis reported an increased risk of lung cancer in China Exposure to domestic coal for heating and cooking Indoor exposure to coal dust and chronic exposure to cooking oil vapor, though publication bias might affect these two factors More cooking dish-years, higher the OR of lung cancer Different frying methods: deep-frying have the highest risk Chinese women have higher proportion of non-smoking related lung cancer

Subsolid nodules

폐암검진, 누구에게 필요한가? 반드시 필요 (금연 교육과 함께) 55-74세 >30 갑년 흡연력 <15년 금연기간 고위험군이 아니더라도 폐암검진이 도움이 될 수 있다. 하지만 이 경우 대상연령이나 검사 기간 등은 차이가 있을 가능성이 있다.

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