Ionizing Radiation, Cancer, and Causation James P. Seward, MD MPP FACOEM Clinical Professor of Medicine, UCSF American Occupational Health Conf May 4, 2015 Ionizing Radiation, Cancer, and Causation James Seward, MD MPP I have no conflicts of interest or disclosures related to this lecture Core Concepts in Radiation Exposure Absorbed Dose measures the energy transfer from radiation in Grays (1 Gy= 100 RADs) Equivalent Dose adjusts for the resulting tissue damage (Absorbed dose x Quality Factor) o 1 Sievert (Sv) = 100 REM o For X-Ray, Gamma and Beta Quality Factor =1 o For Alpha Quality factor = 10 1
Environmental Pathways for Radiation Exposure: External, Internal, and Contamination Internal Dose from radioactive materials in the air 4 Source: WHO: Prelim Dose Assessment Natural Background Radiation 3 Natural background radiation dose approx 2 msv/year (range 1 10 msv) without known health effects 0.38 msv 2.3 msv In the USA average total background is about 6mSv when man made (e.g., medical) sources are added 5 Scientific Causation: Ionizing Radiation is Carcinogenic IARC Class I Carcinogen Meets Bradford Hill Criteria Key considerations for specific exposed groups: o Dose and dose response curve o Type/source of radiation (internal, external, α,β,γ,x, neutron) o Cancer site o Latency Period 2
What is the dose response relationship for radiation induced cancers? Linear No Threshold ( High Energy)._._._ Linear No Threshold (Low Energy) Linear Quadratic (leukemias) Linear with Threshold Source: BEIR VII 7 Linear No-Threshold Hypothesis (LNT) for Cancer Causation Assumes that cancer risk is proportionate to dose No threshold for risk beyond background exposure Errs on safe side Used in radiation safety standard setting 8 Biological Effects of Ionizing Radiation Committee (BEIR VII) of the National Research Council The Committee concludes that the current scientific evidence is consistent with the hypothesis that there is a linear, no threshold relationship between exposure to ionizing radiation and the development of cancer in humans. 3
Ionizing Radiation and Cancer The No Threshold model and uncertainty Can be + 10% Cancer mortality +4.1% +0.4% +0.04% Can be + 1% 10mSv Can be + 0% = No risk Can be + 4% 100mSv Can be + 0% = No risk Can be less than 1% 1000mSv 1 REM 10 REM 100 REM Human Epidemiology Supports Linear Dose Response for solid tumors above 100mSv (10 REM) Solid Tumors in Hiroshima and Nagasaki long term survivors Cancer radiotherapy Excess Lifetime risk of Fatal Cancer 4 5%/Sv (100 REM) Extrapolated Fatal Cancer Risks: o at US annual occ. exposure limit : 50 msv (5 REM) is ~0.2% (1/500) o From abdominal CT (~10 msv, 1 REM) is ~.04% (1/2500) Support for Low Dose Radiation cancer effects (below 100mSV or 10 REM) is found in recent human studies Linear Cancer trend among Hiroshima & Nagasaki survivors with lower exposures o 80% exposed to doses below 100mSv (10 REM) Techa River study (Siberia Preston et al.) shows cancer trend at dose below 100 msv (10 REM) 4
Concerns about the linear no threshold model Studies in areas with higher background radiation show no increased cancer rates Biologic repair of DNA may reduce risk UNSCEAR: does not recommend multiplying low dose by large numbers of individuals to estimate numbers of radiation induced health effects Is the cancer risk of 1 Sievert (100 REM) to 10 people the same as.01 Sv (1 REM) to 1,000 people? Human Epidemiology Shows Increased Cancer Risk Above 100 msv Linear No Threshold ( High Energy)._._._ Linear No Threshold (Low Energy)? Linear Quadratic (leukemias) Linear with Threshold 100 msv 10 REM Modified from: BEIR VII 14 Cancer Site and Radiation Type Different radiation sources may be associated with specific tumors o Organ specific deposition of nuclides o Route of entry o Physicochemical form IARC Monograph on Radiation o Good review of rad source and cancerspecific epidemiology o e.g., Plutonium bone, liver, lung 5
Excess Relative Risk for Solid Tumors in Atomic Bomb Survivors Study Source: Preston et al. Radiation Research 160(4): 381 407 (2003) Latency: Excess Cancer Deaths in Atomic Bomb Survivors by Year Source: Douple E et al: Disaster Med and Pub Hlth 2011;5(01)S122 S133 Childhood Thyroid Cancer Incidence after 1986 Chernobyl disaster Papillary thyroid cancer excess began within 4 years after meltdown Sources: UNSCEAR 2008 and WHO 6
What are the cancer risks? WHO Preliminary Dose Reconstruction Whole Body All Key Radioisotopes High Areas: 10 50 msv (1.0 5.0 REM) effective dose mostly external Lower areas: 1 10 msv (0.1 1.0 REM) effective dose mostly internal Source: WHO Preliminary dose estimation from the nuclear accident after the 2011 Great East Japan Earthquake Radio Iodine Exposures near Fukushima much lower than Chernobyl WHO models predict some Infants may have received >100mGy (10 RAD) to thyroid Measured doses lower than WHO Models have predicted Absolute risk for thyroid cancer in most highly exposed female infants increases 0.75% to 1.25% ( Lifetime attributable risk of 70%) Source : WHO Health Risk Assessment from the Nuclear Accident After the 2011 Great East Japan Earthquake and Tsunami 7
Exposure Concerns for >25,000 Fukushima Workers No Rad related fatalities Initial delay in iodine tabs for workers 12 workers high radio iodine thyroid exposure (up to 12 Gy, 1200 RAD) 75 workers get external dose over 100mSv (10 REM) o Some reach emergency exposure std: 250mSV (25 REM) o Uncertainty of dose measurements o Psychological concerns Health monitoring ongoing Source : UNSCEAR 2013 Summary Report to UN General Assembly 22 Medico legal Causation Most radiation related cancer claims are in the federal domain US Military Veterans o radiation risk activities and other jobs with radiation exposure Radiation Exposure Compensation Act (RECA 1990) Apology plus compensation to: o Uranium miners and ore transporters o Downwinders in parts of NV, UT, and AZ Energy Employees Occupational Illness Compensation Program Act (EEOICPA 2002) 8
Veterans Atmospheric Atomic tests Service in Hiroshima or Nagasaki (prior to July,1946) Presumptive compensation for any of 21 specified cancers Other cancer at least as likely as not a result of exposure VA uses Interactive RadioEpidemiologic Program for claims adjudication Uranium Miners RECA Lung Ca from exposure to Radon Daughters Presumptive if o Non smoker >200 WLM o Smoker >300 WLM age<45 >500 WLM any age $100K for lung CA & pneumoconioses Downwinders RECA Eligible for $50K if: Lived in area for 2 yrs during 1951 8 or July 1962 Develops leukemia or one of a specified list of cancers 9
Energy Employees Occupational Illness Compensation Program Act Dept. of Energy employees, contractors, and some vendors o $150K Compensates workers at certain facilities a priori if they develop specified cancers o Rad workers at gaseous diffusion plants o Amchitka Alaska atomic tests Compensates other workers for cancers that are as likely as not work related Specified radiogenic cancers EEOICPA and RECA Leukemia (except CLL) Bone Cancer* Renal Cancers* Multiple Myeloma Non Hodgkins Lymphoma Thyroid Breast Esophagus Stomach Pharynx Small Intestine Pancreas Bile Ducts Gall Bladder Liver *EEOICPA only Causal Determination under EEOICPA (and Veterans Claims) As Likely as not Probability of Causation (PC) 50% Radiation Risk PC = X 100 Radiation Risk + Baseline Risk 99% uncertainty level used for compensation 10
Factors Considered in NCI/NIOSH Interactive Radio Epidemiologic Program (IREP) Cancer type (specific models for many cancer types) Radiation dose and type (and acute v. chronic) Age at exposure Age at diagnosis Gender Smoking history (the only lifestyle factor included) Steps in determination of eligibility for compensation Dose Reconstruction (NIOSH for EEOICPA) Data entered into Interactive RadioEpidemiologic Program ( IREP) o Developed and updated by NCI o Models for specific cancers based on Japan Survivors and other studies o Calculates probability (PC) with a distribution based on uncertainties in dose, cancer model, and other factors o Upper 99% of credibility limit gives benefit of doubt to claimant References NRC (BEIR VII phase 2) Health Risks from Exposure to Low Levels of Ionizing Radiation 2006 Douple et al. Long term Radiation Related Health effects in a Unique Human Population Atomic Bomb Survivors. Dis Med and Pub Hlth Prep 2011(5)S122 S133 Shore R; Low Dose Radiation Studies:Status and Issues. Health Phys. 2009 (97)481 486 Preston D et al. Solid Cancer Incidence in Atomic Bomb Survivors 1958 1998. Rad Res. (2007) 168:1 64 WHO; Health Risk Assessment from the Nuclear Accident After the 2011 Great East Japan Earthquake and Tsunami. 2013 Krestinina L et al.; Leukaemia incidence in the Techa River Cohort 1953 2007. Br H Cancer 2013 Nov 26;109(11);2886 93 International Agency for Research on Cancer Monograph100D Radiation 2012 11