Reducing Deaths from Occupational Lung Cancer Laura Welch MD Center for Construction Research and Training

Fraction of cancer attributable to occupation in Great Britain, for IARC group I carcinogens Site % attributable in men % attributable in women total Leukemia 0.3% 0.5% 0.2% Bladder 1.3% 0.6% 1% Non-melanoma skin cancer 11.8% 3% 8.4% Lung 16.5% 4.5% 11.6% Attributable fraction here is very similar to what Steenland published in 2003. Will list the group 1 carcinogens in subsequent slide Rushton et al. 2008. Burden of cancer at work. Occup Env Med 65:789-800

Fraction of cancer attributable to occupation in Great Britain, for IARC groups I and strong 2A carcinogens Site % attributable in men % attributable in women total Leukemia 2.7% 0.8% 1.7% Bladder 11.3% 2% 8.3% Non-melanoma skin cancer 11.8% % 8.4% Lung 21.6% 5.5% 15% Rushton et al. 2008. Burden of cancer at work. Occup Env Med 65:789-800

Brown et al Br J Ca 2012. Occupational cancer in Britain. 107:S56-S70 This does not display all the Group 1 agents but shows the ones with the largest attributable fractions. Asbestos exposure was widespread in US and parts of Europe through the 1970s, and with a long latency those exposures are still causing disease but should begin to decline. You can see from this slide that we might concentrate screening to specific occupations with these high risk exposures. Brown et al Br J Ca 2012. Occupational cancer in Britain. 107:S56-S70

Risk from occupational exposure in non-smokers Study author Study design Exposure RR Pohlabeln Case control, non smokers Ever worked in list A occupation 1.52 Kruezer Case control, non smokers, men only 2.4 Neuberger Case control, non smokers, women only Occupational exposure to asbestos 4.38 Frost Cohort study 1.9 Zeka Ever exposed to silica 1.76 Cassidy Occupational exposure to silica 1.51 Tse 3.09 Studies are limited by small numbers of lung cancers in non smokers, but most studies show increased risk from occupation in non smokers. CI’s are wide for these estimates, and other studies do not show an increased RR

NCCN Guidelines High-risk, category 1: High-risk, category 2B: 55 to 74 years old at least a 30 pack-year history of smoking smoking cessation for less than 15 years High-risk, category 2B: at least 50 years old 20 or more pack-year history of smoking 1 additional risk factor: COPD, occupational exposures, radon exposure, family history You are all familiar with these recommendations. Category 2B starts screening at an earlier age and does not specify recent smoking, as long as there is another risk factor present NCCN guidelines do not give any guidance how to incorporate occupational exposure.

American Association of Thoracic Surgery Annual LDCT screening for smokers and former smokers aged 55-79 with 30 pack year history Annual LDCT screening for smokers and former smokers aged 55-79 with 20 pack year history and additional co-morbidity that produces a cumulative risk of lung cancer >5% over subsequent 5 years Annual screening for lung cancer survivors This differs from NCCN: starts at age 55 for everyone. Specifies a risk for lung cancer over 5% - do we have models that will let us calculate those risks? An approach that allows calculation of individual risk is preferable, as long as the data going into it is sound and precise. For discussion, is that 5% number the right one, or is it arbitrary?

Who’s eligible for BTMed lung cancer screening? Age 50-79 years old Current or former smoker with significant smoking history (20 Pack years with no restriction on time since quit) CXR shows asbestosis, may be eligible without meeting smoking criteria Worked Construction or DOE work > 5 years CXR shows pleural plaques or COPD on spirometry (must also meet smoking criteria, but does not have to meet > 5 yrs work history)

Exclusion criteria Spirometry with FEV1 < 40% Previously diagnosed with lung cancer or have another cancer that has been diagnosed or treated within past 5 years. Symptoms suspicious for lung cancer Health problem that substantially limits life expectancy or unwillingness to have curative surgery.

Model of continuum of care from Lung Cancer Alliance - Overview Provide clear information on risks and benefits of the screening process in language appropriate to the candidate. Follow comprehensive standards for screening quality, radiation dose and diagnostic procedures such as those from ACR, NCCN and IELCAP Work with a multi-disciplinary clinical team to carry out a coordinated continuum of care for screening, diagnosis and disease management: Experienced radiologists, pathologists and pulmonologists to evaluate the images/specimens; Trained thoracic surgeons with experience in minimally invasive techniques; Oncologists and radiation oncologists experienced in lung cancer; Nurses and support staff who will assist patients with lung cancer; Include a comprehensive smoking cessation program in screening and continuum of care program based on best practices evidence.

Model of continuum of care from Lung Cancer Alliance – a specific example Lung cancer screening consistent with Level 1A data and NCCN/IELCAP guidelines. Pulmonary medicine with bronchoscopy, image guided biopsy (SuperD), EBUS services. Thoracic surgery with expertise in VATS procedures and VATS lobectomy with complete staging through lymphadenectomy, subscribing to the STS General Thoracic Surgery Database. Medical oncologic treatment consistent with NCCN guidelines and with access to clinical trials for all stages. Radiation oncology with state-of-the-art technology and CyberKnife therapy. Pathology with specific pulmonary expertise and access to genomic tissue profiling. Diagnostic and interventional radiology have direct interface with multi-disciplinary team for nodule evaluation.

ELCD Screening results Outcome All scans Baseline 1st annual 2nd+ annual 1290 Follow-up 356 236 57 63 Annual 1659 898 761 Indeterminate 194 154 30 18 Suspicious 117 76 20 23 Non small cell Stage 1 17 13 2 Stage II 3 1 Stage III Stage 4 6 5 Small cell 4

614 Referred for non-cancer findings Renal cancer Liver cancer Thyroid nodules/ thyroid cancer Esophageal cancer Throat cancer Breast nodules Adrenal tumors Aortic aneurysm Emphysema/ COPD Interstitial lung disease Asbestosis Pleural plaques Pancreatitis Coronary artery plaque Aorta & heart valve calcification Enlarged lymph nodes Degenerative bone Kidney stones & gallstones

IARC group 1 occupational lung carcinogens Dust: Asbestos Silica Metals: Beryllium Nickel Chromium Cadmium Arsenic Diesel exhaust, combustion products Uranium, plutonium, radon and other radioactive materials PAH Environmental tobacco smoke Working as painter or welder

This is based on the Bach model, I couldn’t find an on-line version for LLP model. You see that this nomogram include occupational exposures, but in a limited fashion

Definition of asbestos exposure in Memorial/Sloan on-line model Work in one or more of the following occupations: asbestos worker, insulator, lagger, plasterboard worker, dry waller, plasterer, ship scaler, ship fitter, rigger, shipyard boilermaker, shipyard welder, shipyard machinist, shipyard coppersmith, shipyard electrician, plumber/pipefitter, steamfitter, or sheet metal worker. Worked in this job for at least 5 years and began working in this job at least 15 years ago. These are high risk tasks that were defined for the CARET study – this was a large multi-center randomized intervention trial to test the hypothesis that B-carotene (vit A) would prevent lung cancer (it didn’t). CARET included a subset of individuals with a high risk of lung cancer from asbestos exposure. Bach used CARET to develop risk model from smoking and also incorporated asbestos exposure. So a “yes” exposure to asbestos is not any asbestos, it is 5 years of work in a high risk trade before 1980. Given that workers in these jobs usually started after high school, a 55 year old today would have started before 1980, most before 1970 This list does not include all high exposure asbestos work – you can see it focuses on shipyard work and construction trades. That was based on the participating institutions and the populations they could recruit for the trial.

Risk model from Memorial/Sloan Kettering, based on Bach model with assumed synergy between RR of exposure and risk of smoking AGE YEARS SMOKED CIGARETTES PER DAY YEARS SINCE QUIT ASBESTOS 10 YR RISK IF CONTINUES TO SMOKE 10 YR RISK IF QUITS NOW OR IS NON SMOKER 50 25 20 10 Yes No -- 2% 1% 35 60 6% 3% 45 14% 7% 10% 5% 65 40 20% I carried over correction from last slide, 2% to 1% in second row of second example. Here I have assigned a RR of 2 for asbestos exposure based on Steenland estimate, and simply multiplied the risk from smoking in the Bach model by 2. You can see how much it changes the risk for some of the workers, and would move those 60 yr olds into groups that need to be screened even if is an ex smoker

Projected 5 year absolute from LLP model (men) Age Yrs smoked FH lung ca Any cancer? pneumonia asbestos 5 yr risk 64 42 Late onset* No 9.53% 66 53 Yes 8.75% 67 Early onset* 3.16% 73 59 Late onset 27.09% 77 Early onset 3.17% Liverpool Lung Project, taken from tables in cited publication This model also includes FH of lung cancer, history of pneumonia Authors set asbestos exposure as yes/no for simplicity sake, but their underlying population had high exposures, likely similar to CARET Walk thru examples – show the high risk one who is 73, heavy current smoker In this model a non-smoker comes close to warranting screening – last line * Early = < 60 yrs at diagnosis, Late = 60+ years at diagnosis Cassidy et al 2008. The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer 98:270-276

Deval et al BMCPH 2017 Agent RR for agent Estimated risk level with smoking < 20 p-y 20-29 p-y > 30 p-y Tobacco alone 10 20 30 Asbestos med < 10 yr 1.5 15 45 Asbestos high > 5 yr 3 60 90 Silica

Deval et al: Definition of high-risk subjects (55 to 74 years)   Agent Cumulative level Cumulative duration Active/quit < 15 y Asbestos Intermediate ≥10 years ≥30 PY High <5 years ≥30 PY High ≥5 years ≥20 PY Asbestosis ≥20 PY Pleural plaques ≥30 PY Other carcinogenic agents ≥10 years ≥30 PY Co-exposure 2 carcinogenic agents ≥10 years ≥20 PY ≥ 3 carcinogenic agents ≥10 years ≥10 PY

Workers with occupational risk often are current smokers MMWR September 30, 2011 / 60(38);1305-1309 Working adults (millions) Smoking prevalence (age adjusted) NHIS 2004-2010 Smoking prevalence (age adjusted) 2000 IARC carcinogens Construction and extraction 8.4 31.4% 41.3% Asbestos, silica, almost all group I Transportation 8.1 28.7% 40.5% Diesel exhaust Food preparation and serving 7 30% 39.8% ETS Installation, repair 5 27.2% Similar to construction Production 9 26.1% 36.2% Varies by industry Management 13.2 16.3% 19.9% ?? Education 8.9 8.7% 9.6% So if screening programs target the workers with high rates of smoking may also be capturing the occupational risk as well!

Conclusions 20% of lung cancer in men are attributable to occupational exposures (esp asbestos, diesel and silica) High risk occupations are well known 50% of lung cancer in construction workers is attributable to occupation We currently have the knowledge to develop a risk assessment tool for occupational exposures Those high risk workers should be recruited for LDCT screening

Reaching high risk workers using continuum of care BTMed is using partnerships between NCI regional cancer centers and local hospitals in rural areas Outreach through retiree clubs, union newsletters, public meetings Other ideas?