ML23207A114

W14 Million Person Study Boice RIC 2023

ML23207A114
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Issue date:	03/15/2023
From:	Boice J, Flora R NRC/RES/DSA, Vanderbilt Univ
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RIC 2023 - Navigating the Nuclear Future Million Person Study - Human Health Radiation Risk Assessment in the Nuclear Power & Industrial Radiographer Worker Cohorts --- March 15, 2023 (W14)

Overview of the Million Person Study and Relevance to NRC John D Boice Jr Vanderbilt University, Department of Medicine National Council on Radiation Protection & Measurements (NCRP)

John.Boice@ncrponline.org

Good Science = Informed Regulations =

Protection of Workers The study of low dose and low-dose rate exposure is of immeasurable value in understanding the possible range of health effects from prolonged exposures to radiation. The Million Person Study of low-dose health effects was designed to evaluate radiation risks among healthy American workers and veterans who are more representative of today's populations than are the Japanese atomic bomb survivors exposed briefly to high-dose radiation in 1945..

Overview of the Million Person Study and Relevance to NRC John Boice, Director of Science/Professor of Epidemiology, National Council on Radiation Protection and Measurements/Vanderbilt University Medical Center Million Person StudyHuman Health Radiation Risk Assessment in the Nuclear Power and Industrial Radiographer Cohorts Lawrence Dauer, Attending Physicist, Memorial Sloan Kettering Cancer Center The Importance of Radiation Epidemiology to Space Exploration Steve Blattnig, Technical Advisor, National Aeronautics and Space Administration

April 2022 IJRB Special Issue - Million Person Study 24 Peer-Reviewed Articles The Million Person Study, Whence it Came Reviews Relevance to Space Exploration A Million Persons, a Million Dreams and Vision for NCREB Obtaining Vital Status and Cause of Death Methods Statistical Modeling Approaches Dosimetry and Uncertainty Approaches Dosimetry Dosimetry for Atomic Veterans Dosimetry for Medical Radiation Workers Dose Reconstruction for Internal Emitters Mortality Among Nuclear Power Plant Workers Original Articles Mortality Among Medical Workers Mortality Among Mallinckrodt Workers Mortality Among Los Alamos National Laboratory Workers Mortality Among Tennessee Eastman Corporation Workers Sex-Specific Lung Cancer Risks among MPS Cohorts Radium Dial Painters Editors: Andre Bouville, John Boice, Larry Dauer, Ashley Golden, Richard Wakeford

Boice et al. A Million Persons, A Million Dreams IJRB 2022;98(4):795-821

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary

• Future

Why another study?

Much is Known about Radiation Health Effects When Exposure is Received All at Once (Briefly)

The Major Gap in Understanding is Health Effects from Exposures Received Gradually Over Time Needed to accurately access risks related to:

Accidents Occupation Space and High Medicine or Terrorism Environment Altitude Travel Protection Guidelines, Compensation, Risk Assessment/Projection, Representativeness, Specific Relevance, Responsibility to Workers and their Families

Why a Study of a Million Radiation Workers?

To provide the Statistical power (ability) to address:

- low dose effects

- rare cancers

- intakes of radionuclides (and associated high-LET health effects)

- differences between women and men

- other conditions (CVD, CeVD, Dementia, and even Cognition)

Who is Being Studied?

No.

Cohort (Source) Workers Manhattan Project and other cohorts (DOE) 300,000 Robert Oppenheimer, General Leslie Atomic Veterans (DOD) 114,270 Groves, Enrico Fermi, Hans Bethe, Theodore Hall Nuclear Power Plant Workers (NRC) 135,193 Industrial Radiographers (NRC) 123,556 Medical Radiation Workers (Landauer) 109,019 Nuclear Submariners & Other (US Navy) 210,000 Radium Dial Workers (DOE) 3,200 Boice et al. The Million Person Study, Whence it Came and Why. IJRB April 2022

Dosimetry is the Key to Good Epidemiology Roadmap for Dauer All (Report 178)-2019 LT et al. Int Medical J Rad Biol Nov 19, 2018 Workers (Commentary 30) Internal Emitters - Brain (Commentary 31)-2022

TRACING is Another Key to Good Epidemiology The Pope visits 1 Million People in Philadelphia 2015 AP Photo Personal Identifiers - 30 cohorts - to Trace for Vital Status ( Some last known alive 1940s) ; Obtain Cause of Death; Obtain All occupational exposures; Estimate organ doses; Analyze and combine

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary

• Future

A unique feature of the Million Person Study is incorporating organ-specific doses from intakes of radionuclides in the dose-response analyses.

Relevance: Environmental Risk Assessment Leggett RW et al. Methods of improving brain dose estimates for internally deposited radionuclides. . J Radiol Prot 42 (3), 2022

Manhattan Project and other Workers Radionuclide Intakes Los Alamos National Laboratory, NM (1942) Pu, H-3 Rocky Flats (1951), Savannah River (1950) Pu, H-3 Hanford, WA (1943) Pu, Am, U, H-3 Atomics International / Rocketdyne, CA (1948) Po, Pu, Am Mound Laboratory, OH (1947) Po, Pu, H-3 Mallinckrodt, KS (1942), Middlesex, NJ (1943) Ra, U Fernald, OH (1951) Ra, U

Women in the Million Person Study Nuclear Power 5,000 Industrial Radiographers 13,000 Mound 2,000 Los Alamos 6,629 Rocky Flats 5,000 Hanford 8,000 K-25 (ORNL) 9,000 Other DOE 40,000 TEC (Oak Ridge) 13,000 Medical 60,000 Radium Dial Painters 3,200 Total already >160,000 Number of adult Japanese female atomic bomb survivors in 1945 ~30,000

Tennessee Eastman Corporation Women 13,951 Women employed 1943-1947 (Uranium dust) 652 cases of lung cancer Boice et al. Mortality among TEC uranium processing workers. IJRB 2023

Radium Dial Painters - Reactivated !

Radium Girls (n=3,200)

• Reactivated (Martinez et al. IJRB 2022)

• Lifetime follow-up - 66% alive in 1980

• Improved dosimetry and risk assessment

• Bone cancer, leukemia, breast, nasal sinuses, lung, dementia, cognition

• Lifespan shortening

• Accelerated ageing, DNA methylation

• WARP - training for the future

• Back to the Future - The legacy continues Relevance: Training Radiation Professionals for Future Martinez et al. IJRB April 2022 Thanks to DOE for financial support 18

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary

• Future

Atomic Veterans, Health and Consequences Atomic Veterans - Health Studies - 115,000 - From TRINITY 1945 to HARDTACK 1958 Desert Rock VI exercise (TEAPOT), NTS, 1955 20

Ischemic Heart Disease (n=16,709)

Among Atomic Veterans 113,806 Men ERR per 100 mGy -.001 (-0.12, 0.11) 0.1 Hazards Ratio - 1 0

-0.1 0 10 20 30 40 50 Dose to Heart (mGy)

Boice et al. Nuclear Weapons Test Participants. Int J Radiat Biol 2022

Navy Personnel (~300,000) in the Million Person Study

• Nuclear weapons test participants 70,300

• Other Navy Personnel, e.g., shipyard ~60,000 Insert sub picture

• Nuclear submariners 169,000 Total ~300,000

SUBMARINER STUDY - NASA COLLABORATION

• To examine: multiple occupational stressors: Environmental (radiation, air contaminants);

Psychological (confinement, isolation, hostile environnent): Physical (fatigue, high workload, circadian rhythm disruption, sleep deprivation) -- and any interaction with continuous radiation.

• A range of neurological, behavioral, and cognitive impairment disorders will be evaluated, e.g.,

mortality and incidence for Parkinsons disease

• Incidence data already have been obtained for over 67,000 sailors from Medicare records

• Cognitive function scores are available for all submariners admitted to nursing homes

• Other outcomes include heart disease, sleep disruption, cataracts and many others Relevance: Possible Cognition Impairment due to stress and low dose radiation Slide thanks to Robin Elgart, NASA

Epidemiologists will go to any DEPTH in the Public Interest USS Montpelier -

Attack Nuclear Sub At 600 feet

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Novel Findings - neurobehavioral

• Summary Findings

• Future

Medical Radiation Workers 109,019 Medical Workers employed 1965-1994 General or Interventional Radiography, Nuclear Medicine, Radiation Oncology 370 cases of lung cancer in Women, 480 cases of lung cancer in men 53,801 Women 55,218 Men ERR per 100 mGy = 0.09 (95% CI -0.19, 0.36) ERR per 100 mGy = 0.16 (95% CI 0.01, 0.32)

Relevance: How important is sex-specific risk Boice et al. Sex-specific lung cancer risk. IJRB 2022 Yoder et al. Dosimetry medical radiation workers. IJRB 2022 differences?

Harmonizing Lung Cancer Risks Cohort No. Workers ERR at 100 mGy (90% CI)

Nuclear Power Plant 135,193 -0.04 (-0.10, 0.01)

Industrial Radiographers 123,556 0.09 ( 0.04, 0.19)

Medical Radiation Workers 109,019 0.15 (0.02, 0.27)

NPP + IR + Medical 367,722 0.02 (-0.03, 0.07)

Atomic Veterans 113,806 0.08 (-0.06, 0.22)

Mound 4,954 0.01 (-0.02, 0.04)

Mallinckrodt 2,514 -0.06 (-0.18, 0.06)

Rocketdyne 5,801 0.06 (-0.50, 1.23)

Atomic Bomb Survivor Estimates Los Alamos 26,328 0.00 (-0.16; 0.17)

F: ERR per 100 mGy 0.11 (0.07, 0.16)

TEC (women) 13,951 0.01 (-0.12, 0.15)

M: ERR per 100 mGy 0.04 (0.02, 0.07)

To date, Little evidence for an effect for fractionation exposures and data appear inconsistent with estimates from atomic bomb survivor study 27

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Novel Findings - neurobehavioral

• Summary Findings

• Future

NCRP - NRC Commentary and Report Collaborations How are the NRC Cohorts Different from the Other MPS Cohorts?

• The Dosimetry is Exceptional REIRS Personal Dose Equivalents NCRP Report 178 to Convert to Organ Dose

• The Follow-up is Exceptional (>99%) for 258,749 Nuclear Power Plant Workers Industrial Radiographers

• Career Doses obtained from DOE REMS, US Navy, Landauer, other Mumma MT et al. Int J Radiat Biol 2022

Generic Letter 1994 https://www.nrc.gov/docs/ML1204/ML12047A243.pdf

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary

• Future

MPS - Selected Results

• Leukemia

• Ischemic Heart Disease

• Parkinsons Disease

Leukemia (non-CLL) - Dose Response Nuclear Power Plant Workers ERR = Excess Relative Risk; i.e., RR -1 Boice et al. Mortality among nuclear power plant workers. IJRB 2022

Leukemia Radiation Risks - Meta-analysis - 8 Studies Boice et al. A Million Persons, A Million Dreams. IJRB 2022

MPS - Selected Results

• Leukemia

• Ischemic Heart Disease

• Parkinsons Disease

Ischemic Heart Disease (n=9,888)

Nuclear Power Plant + Industrial Radiographers (n=258,703)

Ischemic Heart Disease Risk Estimates Relevance: Based on MPS to date, heart disease should Not be included in a system of radiation protection

MPS - Selected Results

• Leukemia

• Ischemic Heart Disease

• Parkinsons Disease

Its not going to do any good to land on Mars if were stupid. -

Ray Bradbury Place logo or company name here

Parkinsons Disease Mayak Workers 42 Azizova T et al. Occupational exposure to chronic radiation. Int J Epidemiol 2020

Parkinsons Disease (n=367,722)

Nuclear Power Plant + Industrial Radiographers + Medical Workers (n=354)

Boice et al. A Million Persons, A Million Dreams. IJRB 2022

Parkinsons Disease Risk Estimates Relevance: Is Parkinsons a radiation effect?

Surprising if so and needs to be confirmed.

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary

• Future

Conclusions - Findings to Date

• Chronic exposures cause leukemia (not surprising)

• Chronic exposures below 0.5 Gy do not cause IHD

• Chronic exposures are associated with Parkinsons disease - a new finding with complex implications if confirmed

• Chronic exposures may be associated with lung cancer but at a lower level than acute exposures

• Further follow-up & combination with other MPS cohort studies will provide more definitive conclusions Place logo or compan y name here

U.S. National Effort Past and Present - Funding Current: DOE, NASA, US Navy. CDC, and in kind from others

Acknowledgments

• Laurence Dauer, Michael Bellamy, Memorial Sloan Kettering

• Sarah Cohen, EpidStrategies Linda Walsh, University of Zurich

• Mike Mumma, Ben French Vanderbilt University Medical Center

• VUMC & Brown University (Laura Keohane, Loren Lippworth; Julie Lima, Kali Thomas)

• ORNL (Rich Leggett, Keith Eckerman, Caleigh Samuels, Derek Jokisch, Nicole Martinez, Nolan Hertel)

• ORAU (Betsy Ellis, Ashley Golden, Dave Girardi, Sara Howard)

• Risk Assessment Corporation (John Till, Harold Beck, Emily Caffrey, Helen Grogan)

• Landauer (Craig Yoder)

• National Council on Radiation Protection and Measurements (NCRP) (Kathy Held)

Funding from NASA, DOE, US Navy, NRC, NCI (NNX15AU88G) (80NSSC17M0016) (NNX16AG04G) (80NSSC19M0161)

Topics

• Background

• DOE Cohorts

• Military Cohorts

• Medical Cohort

• NRC Cohorts

• Recent Findings

• Summary Findings

• Future

Future

• Complete Studies DOE Worker, Radium Dial and Submariner Studies

• Complete Studies on Dementia, Depression, Cognition - Brave New World

• Harmonize (combine) ensemble/biologically-based models beyond meta-analyses

• Medicare Claims Files for Incidence and Smoking Hx

• Extend Follow-up 10 years for Nuclear Power, Industrial Radiographers

• Consider Workers exposed to Neutrons, Tritium - LANL, Rocky Flats, Hanford

• Consider AI, Machine Learning - BIG DATA - handling ~billions of data points

• Provide evidence on appropriateness of LNT-model for radiation protection

• Seek collaborators - radiation professionals needed for future

• Vision: The National Center for Radiation Epidemiology and Biology A Million Dreams are Keeping me Awake (and not retired)

- The Greatest Showman

Educational Videos -- Radiation Epidemiology for Public Health Decision Making URL: https://www.cdc.gov/nceh/radiation/emergencies/radiation-epidemiology-videos.htm Boice JD, Held KD, Shore RE. Radiation epidemiology and health effects following low-level radiation exposure. J Radiol Prot. 2019 Jul 4;39(4):S14-S27.

2023 NCRP Annual Meeting:

March 27 - 28, 2023 Integration of Physics, Biology and Epidemiology in Radiation Risk Assessment Eric J. Grant, Chair Emily A. Caffrey, Vice Chair