Estimated Cancer Deaths, U.S., 2019 Men Women Lung & bronchus - - PDF document

Steven Markowitz MD, DrPH Barry Commoner Center, CUNY Updates In Environmental and Occupational Medicine

UCSF School of Medicine

March 7, 2020

Use of Low Dose CT Scanning for Early Lung Cancer Detection Among High Risk Workers Disclosure

Funded by the United States Department of Energy for medical screening, including lung cancer screening

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Estimated Cancer Deaths, U.S., 2019

Men Lung & bronchus 76,650 Prostate 31,620 Colon 27,640 Pancreas 23,800

Liver 21,600

Women Lung & bronchus 66,020 Breast 41,760 Colon 23,380

Pancreas 21,950 Ovary 13,980

Source: Adapted from Table 1. American Cancer Society. Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 2019.

Lung cancer mortality remains high, because most cases are diagnosed at advanced stages when successful treatment is limited.

Occupational lung cancer

• 1. Contributes to 10% to 15% of lung cancer

~10,000 to 20,000 deaths annually in U.S.

• 2. Accounts for 40% to 60% of all occupational cancers
• 3. Main exposures: asbestos, silica, diesel exhaust,

welding fumes

Rushton 2010; Labreche 2019; Steenland. AJIM, 2005

Global Burden of Disease Study, 2015 525,000 annual lung cancer deaths due to 9 occupational lung carcinogens

GBD 2015 Risk Factors Collaborators, Lancet 2016

86,000 chemicals in EPA TSCA Inventory ~ 1,000 evaluated by IARC

Total chemicals used in U.S. and evaluated by IARC

Agents Classified by the IARC Monographs, Volumes 1-125

120 83 314 500 Group 3 Not classifiable as to its carcinogenicity to humans Group 1 Carcinogenic to humans Group 2B Possibly carcinogenic to humans Group 2A Probably carcinogenic to humans

IARC Lung Carcinogens

Group 1 Group 2A Agent Arsenic and inorganic arsenic compounds Asbestos (all forms) Beryllium and beryllium compounds Bis(chloromethy)ether; chloromethyl methyl ether (technical grade) Cadmium and cadmium compounds Chromium(VI) compounds Coal, indoor emissions from household combustion Coal tar pitch Engine exhaust, diesel Nickel compounds Outdoor air pollution Painting Particulate matter in outdoor air pollution Plutonium Radon-222 and its decay products Silica dust, crystalline Soot Tobacco smoke, secondhand Welding fumes X-radiation, gamma-radiation Biomass fuel (primarily wood), indoor emissions from household combustion of Bitumens, occupational exposure to

• xidized bitumens and their

emissions during roofing alpha-Chlorinated toluenes and benzoyl chloride (combined exposures) Cobalt metal with tungsten carbide Creosotes Diazinon Hydrazine IARC Monographs Volumes 1-125

IARC Lung Carcinogens identified since 2010 (*)

Group 1 Group 2A Agent Arsenic and inorganic arsenic compounds Asbestos (all forms) Beryllium and beryllium compounds Bis(chloromethy)ether; chloromethyl methyl ether (technical grade) Cadmium and cadmium compounds Chromium(VI) compounds Coal, indoor emissions from household combustion Coal tar pitch Engine exhaust, diesel* Nickel compounds Outdoor air pollution Painting Particulate matter in outdoor air pollution* Plutonium Radon-222 and its decay products Silica dust, crystalline Soot Tobacco smoke, secondhand Welding fumes* X-radiation, gamma-radiation Biomass fuel (primarily wood), indoor emissions from household combustion of* Bitumens, occupational exposure to

• xidized bitumens and their

emissions during roofing* alpha-Chlorinated toluenes and benzoyl chloride (combined exposures) Cobalt metal with tungsten carbide Creosotes Diazinon* Hydrazine*

In occupational medicine, have we had any opportunity to arrest and cure lethal

• ccupational diseases?

Screening for Lung Cancer

Why prioritize blue collar workers for lung cancer screening?

• 1. Exposed to lung carcinogens at work.
• 2. Smoke at high rates.
• 3. Workplace as a basis to inform

and screen.

Source: Syamlal G. J Occup Environ Med, 2016. SOC high-level aggregation codes are used. 5 10 15 20 25 30 Management, Business, Science, and Arts Others Sales and Office Service Production, Transportation, and Material Moving Construction, Maintenance, and Natural Resources Prevalence (%)

Prevalence of Cigarette Smokers by Occupation, United States, 2012‐2014

10% 12% 17% 21% 25% 27%

The majority of lung cancers in the U.S. occur among former smokers.

Synergy in Risk of Lung Cancer Tobacco and Occupation

• Asbestos
• Silica
• Arsenic
• Radon

Tobacco and Occupation

Screening for Lung Cancer

1970’s-1980’s

Failure of CXR and sputum cytology RCT’s to show lung cancer mortality reduction (Mayo Clinic, MSKCC, and John Hopkins)

Henschke et al. Lancet 1999

Early Lung Cancer Action Project

David Yankelevitz MD Claudia Henschke MD Henschke et al. Lancet 1999

ELCAP (1992 ) Screened 1,000 smokers, > 60 years old, > 10 pack-years Detected 27 lung cancers (2.7%) on baseline scan 23/27 (85%) were Stage I lung cancer

Lung cancer: usual stage at diagnosis

CA: A Cancer Journal for Clinicians, Volume: 70, Issue: 1, pp: 7-30, 2020,

Stage Distribution for Lung Cancer, U.S., 2009-2015

National Lung Screening Trial

2000 →

National Cancer Institute

National Lung Screening Trial (NLST)

• Three annual screening rounds (2002‐2004)

up to 7.4 years follow‐up

• Largest RCT to date; > 53,000 people

33 major medical centers

• $250 million cost
• ~26,700 in each arm: LDCT versus CXR

NLST eligibility criteria

• 55‐74 y.o.
• ≥ 30 pack years smoking history
• quit within past 15 years

Why these screening criteria? To identify a large high risk group that, if low dose CT scan is effective, is likely to show an appreciable reduction in death from lung cancer in a few years.

NLST results, 2011

Screening yield: T0: 1% had lung cancer T1: 0.68% had lung cancer T2: 0.88% had lung cancer

NLST results

Lung cancer stage distribution (three CT screening rounds combined) Stage 1: 63.0% Stage 2: 7.2% Stage 3: 17.0% Stage 4: 12.8%

NLST Research Team. NEJM 2011

NLST results

Lung cancer mortality reduction = 20% in CT versus CXR arm Overall mortality reduction = 6.7%

NELSON Trial

(Dutch‐Belgian trial)

De Koning et al. NEJM. January 29, 2020

• Four screening rounds at varied intervals

(1 year, 2 years, 2.5 years) up to 10 years follow‐up

• 2nd largest RCT to date; ~15,800 people
• ~6,600 in each arm: LDCT versus No imaging

NELSON Eligibility criteria

De Koning et al. NEJM. January 29, 2020

• 50‐74 y.o.
• > 15 cigs/day for > 25 years or

> 10 cigs/day for > 30 years (15 to 18.75 pack‐years)

• quit within past 10 years

NELSON, 2020

Screening yield: T0: 0.9% had lung cancer T1: 0.7% had lung cancer T2: 1.1% had lung cancer T3: 0.8% had lung cancer

NELSON results, 2020

Lung cancer stage distribution (in men)

(CT‐detected cancers; four CT screening rounds combined)

Stage 1: 58.6% Stage 2: 9.3% Stage 3: 16.3% Stage 4: 9.4% (unknown: 6.4%)

NLST Research Team. NEJM 2011

NELSON Results, 2020

De Koning et al. NEJM. January 29, 2020

Lung cancer mortality reduction 24% in men and 33% in women in CT versus control arm

USPSTF Recommendation, 2013

Endorsed annual LDCT screening for lung cancer Eligibility criteria: 55‐80 y.o. ≥ 30 pack years smoking history quit within past 15 years Occupation? Medicare (CMS), Decision memo, 2015 Eligibility criteria: 55 to 77 years old > 30 pack‐years smoking < 15 years since smoking cessation

Medicare (CMS), Decision Memo, 2015

Requires:

• Smoking cessation advice
• Shared decision‐making clinical visit
• National registry of CT data

Occupation?

Eligibility criteria Age- and smoking-based risk vs. Aggregate risk

2014 National Comprehensive Cancer Network (NCCN)

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NCCN Criteria #1: NCI/Medicare criteria Criteria #2: > 50 years old > 20 pack‐years smoking 1 other risk factor for lung cancer : total risk > 1.3%, 6 years

• Wood. NCCN, 2018

NCCN Criteria #1: NCI/Medicare criteria Criteria #2: > 50 years old > 20 pack‐years smoking 1 other risk factor for lung cancer: total risk > 1.3%, 6 years

• Wood. NCCN, 2018

NCCN Criteria #2 Other risk factors for lung cancer

• Occupational exposures

(asbestos, silica, diesel exhaust)

• Family history
• COPD, other respiratory diseases
• Radon exposure

Lung cancer risk calculators

MSKCC: age, gender, pack-years, #quit-years, asbestos AATS: age, gender, BMI, FH, EM education, pk-yrs, quit- years, asbestos ALA, ATS: age, pk-years, #quit-years

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Occupational studies

Worker Health Protection Program

Early Lung Cancer Detection

Required DOE to: “establish and carry out a program for the identification and

• ngoing medical evaluation of current and former Department
• f Energy employees who are subject to significant health

risks as a result of exposure of such employees to hazardous

• r radioactive substances during such employment”

1993 Defense Authorization Act Section 3162

Department of Energy Worker Health Protection Program

City University of New York United Steelworkers, Atomic Trades and Labor Council

Paducah GDP Portsmouth GDP K25 GDP Mound Fernald ORNL/Y-12 INL NTS WIPP CA Labs

Features

• Former nuclear weapons workers
• Non-urban areas
• Age, smoking history, occupational history
• Centralized CT reading
• Community-based diagnosis and treatment

Worker Health Protection Program ELCD 2000 - present Screened ~14,000 workers >50,000 CT scans

WHPP ELCD

Excellent participation!

Enrollment 69% (n=5,121, 2014-2018) Show rate 89% (n=33,807 scans, 2007-2018)

All WHPP ELCD Sites Number (%) of People with Suspicious Nodules/Lung Cancer 11/1/00 to 9/30/19 Site Number of Individuals Screened Number (%) with Suspicious Nodules Number (%) Diagnosed with Lung Cancer TOTAL 13,807 429 (3.1% ) 185* (1.3%) ALL WHPP ELCD SITES Number (%) of Lung Cancers by Stage 8/8/00 to 9/30/19 Site Number of Lung Cancers (# staged) Number (%) Stage 1 * Number (%) Stage 2 Number (%) Stage 1 and 2 Number (%) Stage 3 and 4 TOTAL 185 (175 staged) 111 (63.4%) 15 (8.6%) 126 (72%) 49 (28%)

*Stage 0 (in situ) and limited small cell lung cancer are counted as Stage

• 1. Advanced small cell is counted as late stage (Stage IV).

WHPP ELCD Cases

NCCN Criteria #1: NCI/Medicare criteria Criteria #2: > 50 years old > 20 pack-years smoking 1 other risk factor for lung cancer: total risk > 1.3%, 6 years

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• Wood. NCCN, 2018

Eligibility criteria NLST-based risk vs. Aggregate risk

• AJPH. September 2018

DOE DOE Cons Construc truction tion Wo Worker Study udy (B (BTM TMed)

CT‐screened 1,260 construction workers NCCN Group #2 Criteria: age + smoking + [5 years of construction work, or CXR evidence of asbestosis or pleural plaques, or COPD] Results: Stage distribution: Stage 1 (57%) or 2 (10%) 1.7% lung cancer screening yield (baseline) < ½ participants met NLST criteria

Welch et al. OEM 2018

LDC LDCT studies dies in in Asbes Asbestos‐Exposed Exposed Wo Workers

9 studies (> 150 participants) “Asbestos exposure” variably defined

½ studies used 1 or 5 years of exposure as criterion

Screening yield: ever smokers: 86 LC’s/5,548, or 1.55% never smokers: 6 LC’s/1,787, or 0.33%

Markowitz, under review

Harms of LDCT

• 1. Radiation exposure
• 2. Anxiety
• 3. Smoking behavior
• 4. Over-diagnosis
• 5. Incidental findings: unnecessary testing
• 6. False positives: unnecessary procedures

Humphrey et al. Ann Intern Med. 2013;159:411-420.

Who is getting screened for lung cancer? 2013: USPSTF approves LDCT for lung cancer screening 2015: 3.9% of eligible individuals had LDCT (NHIS) 2017: 14.4% of eligible individuals had LDCT (BRFSS 2017: Insured vs uninsured 15.2% vs. 4.0% COPD vs no COPD 23.7% vs. 8.5%

Zahnd and Eberth AJPM 2019

Don’t ask, don’t screen

Occupation: Who should be screened?

• Age: 50 to 80 years
• Smoking: > 20 pack-years
• Occupational exposure to known lung carcinogens on

regular basis for > 5 years, factoring in latency

• Consider screening others with shorter but more intense

exposure Consider other LC risk factors (FH, chronic lung disease)

Challenges

• 1. Prioritize educational campaigns for high risk

populations

• 2. Inform and motivate public and private
• rganizations
• 3. Overcome financial barriers to screening
• 4. Document effectiveness of aggregate risk

approach to LDCT

Amy Manowitz MPH Jim Frederick Ashlee Fitch Garry Whitley Ray Beatty Amaka OnyekeluEze United Steelworkers and ATLC coordinators Albert Miller MD Brittany Dickens Jeffrey Miller MD Brett Siegel Samantha Haibi Leslie-Ann Williams Jennifer Morris Jennifer Stuckey Jonathon Corbin Mary Krutz Sharon Peyser

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Acknowledgements: WHPP

smarkowitz@qc.cuny.edu

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Thanks!

Low dose CT screening for lung cancer has been shown to do all EXCEPT the following:

• 1. Detect lung cancers at any early stage.
• 2. Lead to long-term survival of people whose CT-detected lung

cancers have been treated.

• 3. Reduce lung cancer mortality.
• 4. Detect all lung cancers that occur in the screened population.

Common occupational human lung carcinogens include all EXCEPT the following:

• 1. Diesel exhaust
• 2. Trichloroethylene
• 3. Silica
• 4. Outdoor air pollution (particulate matter)

The most important potential harm associated with low dose CT screening for lung cancer is:

• 1. Radiation exposure
• 2. Stress associated with finding of lung nodules on a CT

scan

• 3. Surgical intervention for nodules that turn out to be

benign

• 4. Financial cost to participant