International Atomic Energy Agency What Radiation Effects are Possible? (besides skin injuries) L3

Radiation Protection in Cardiology Lecture 3: Radiation effects 2 Educational Objectives Effects other than skin injuries Their probability in interventional cardiology practice Special concerns in children, young & pregnant females

Radiation Protection in Cardiology Lecture 3: Radiation effects 3 What can radiation do? It can bring a smile on the faces of people of all ages

Radiation Protection in Cardiology Lecture 3: Radiation effects 4 What can radiation do? Cancer Genetic effects Skin injuries Cataract Infertility Death Non-neoplastic Effects NB. In this lecture, we shall predominantly deal with cancer & genetic effects

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Radiation Protection in Cardiology Lecture 3: Radiation effects 6 Main Point Threshold Preventable

Radiation Protection in Cardiology Lecture 3: Radiation effects 7 Dose Effect Deterministic effects Cataract infertility erythema epilation Cancer Genetic Prob  dose Stochastic

Radiation Protection in Cardiology Lecture 3: Radiation effects 8 Stochastic and Deterministic Effects A stochastic effect is one where the severity of the result is the same but the probability of occurrence increases with radiation dose, e.g., development of cancer. There is no threshold for stochastic effects. A deterministic effect is one where the severity depends upon the radiation dose, e.g., skin burns. There is a threshold for deterministic effects.

Radiation Protection in Cardiology Lecture 3: Radiation effects 9 You mean I can get cancer even if I am working with small amount of radiation? This requires discussion on how radiation effects occur Cardiologist

Radiation Protection in Cardiology Lecture 3: Radiation effects 10 Is there RADIATION in this room?

Radiation Protection in Cardiology Lecture 3: Radiation effects 11 Radiation from Natural Sources Normally 1-3 mSv/year In areas of high background, 3-13 mSv/year

Radiation Protection in Cardiology Lecture 3: Radiation effects 12 Interventional Cardiology CT Radiography

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International Atomic Energy Agency Nucleus Double membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome. Chromosomes

Radiation Protection in Cardiology Lecture 3: Radiation effects 15 Induction of DNA changes

International Atomic Energy Agency

Radiation Protection in Cardiology Lecture 3: Radiation effects 17 radiation hits a cell nucleus! No change DNA mutation

Radiation Protection in Cardiology Lecture 3: Radiation effects 18 DNA Mutation p  a D Cell survives but mutated Stoch.eff. Mutation repaired Unviable Cell Viable Cell Cell death

Radiation Protection in Cardiology Lecture 3: Radiation effects 19 Deterministic effects caused by cell death: burns, organ failure, death Deterministic effects caused by cell death: burns, organ failure, death

Radiation Protection in Cardiology Lecture 3: Radiation effects 20 Normal process Altered process due to mutated genes

Radiation Protection in Cardiology Lecture 3: Radiation effects 21 Altered process due to mutated genes

Radiation Protection in Cardiology Lecture 3: Radiation effects 22 Stochastic effects  Cancerogenesis  Hereditary effects  Effects in the embryo/foetus

Radiation Protection in Cardiology Lecture 3: Radiation effects 23 Carcinogenesis

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Radiation Protection in Cardiology Lecture 3: Radiation effects 25 So now that you have scared me with this information, what should I do? It is not our intent to scare you with these facts, but to educate about potential long-term risks.

Radiation Protection in Cardiology Lecture 3: Radiation effects 26 OK, Agree that Radiation can cause cancer, But how do I know if I will get cancer!!!

Radiation Protection in Cardiology Lecture 3: Radiation effects 27 Life Insurance Agent Malpractice Insurance Probability

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Radiation Protection in Cardiology Lecture 3: Radiation effects 29Radiosensitivity Probability of a cell, tissue, or organ suffering an effect per unit dose Will be greater if the cell: Is highly mitotic Is undifferentiated

Radiation Protection in Cardiology Lecture 3: Radiation effects 30 Life Span Study Massachusetts Children in (LSS) of Ankylosing tuberculosis patients Israel irradiated Japanese atomic Spondylitis given chest for ringworm UK National Registry bomb survivors Study (ASS) fluoroscopies of the scalp Radiation Workers Parameter (Shimizu et al) (Weiss et al) (Boice et al) (Ron et al) (Kendall et al) Population 86, size (with DS86 doses) Period of 5-55 years Up to over Up to over 50 years Up to 32 years Up to 40 years follow-up following exposure 50 years (mean 25.2 (mean 30 years) (mean 26 years) years) Ranges of: (a) ages at All Virtually all Under 15 to over years years exposure  15 years (b) sexes Similar numbers of 83.5% male Female Similar number of 92% male males and females males and females © ethnic Japanese Western (UK) Western (N. American) African and Asian Western (UK) groups Setting in War Medical: ther- Medical:diagnostic Medical:therapy Occupational which apy for non- for non-malignant exposure malignant disease was received disease Features of some epidemiological studies of radiation-induced cancer risks

Radiation Protection in Cardiology Lecture 3: Radiation effects 31 Life Span Study Massachusetts Children in (LSS) of Ankylosing tuberculosis patients Israel irradiated Japanese atomic Spondylitis given chest for ringworm UK National Registry bomb survivors Study (ASS) fluoroscopies of the scalp for Radiation Workers Parameter (Shimizu et al) (Weiss et al) (Boice et al) (Ron et al) (Kendall et al) Range of All All (but Mainly breast & lung mainly brain, All organs mainly those bone marrow, irradiated in proximity thyroid, skin to spine and breast Availability Organ doses: Mean organ Organ doses: Brain, thyroid & Individual whole-body of dose individual basis doses: indiv. Individual basis skin doses: external doses estimates only for red individual basis bone marrow at present Range dose Mainly 0-4 Gy Mainly 0-20 Gy Mainly 0-3 Gy Brain: 0-6 Gy Mainly Sv (mean 1.5 Gy) (mean Sv) Thyroid:0-0.5 Gy (mean 0.09 Gy) Dose rate High High High, but highly High Low fractionated Radiation Mainly low-LET Low-LET Low-LET Low-LET Mainly low-LET Quality Features of some epidemiological studies of radiation-induced cancer risks

Radiation Protection in Cardiology Lecture 3: Radiation effects 32 LIFE SPAN STUDY LIFE SPAN STUDY Excess absolute risk for solid cancer mortality

Radiation Protection in Cardiology Lecture 3: Radiation effects 33 LIFE SPAN STUDY Atomic Bomb Survivors Cancer risk estimate: 4–6% per 1000 mSv (depending on projection method) ! Note: The probability best applies to group of people and is not suitable for individual case

International Atomic Energy Agency Hereditary Effects

Radiation Protection in Cardiology Lecture 3: Radiation effects 35 Heritable effects Effects to be observed in offspring born after one or both parents had been irradiated prior to conception.

Radiation Protection in Cardiology Lecture 3: Radiation effects 36 Hereditary effects Descendents of Hiroshima and Nagasaki survivors were studied but no statistical abnormalities were detected.

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Radiation Protection in Cardiology Lecture 3: Radiation effects 38 A cohort of 31,150 children born to parents who were within 2 km of the hypocenter at the time of the bombing was compared with a control cohort of 41,066 children. No indicator was significantly modified by parental radiation exposure.

Radiation Protection in Cardiology Lecture 3: Radiation effects 39 In the absence of human data the estimation of hereditary effects is based on animal studies.

Radiation Protection in Cardiology Lecture 3: Radiation effects 40 UNSCEAR 2001 Report HEREDITARY EFFECTS OF RADIATION Risks to offspring following prenatal exposure: Total risk = % per mGy to the first generation (3000 to 4700 cases per gray per one million progeny) Includes multifactorial diseases 1/10 the risk of fatal carcinogenesis Constitutes % of baseline frequency

Radiation Protection in Cardiology Lecture 3: Radiation effects 41 …above …above the prevalent background dose, an increment in dose results in a proportional increment increment in the probability of hereditary effects effects of 0.0005% per mSv of dose.

Radiation Protection in Cardiology Lecture 3: Radiation effects 42 OK, Understood that these radiation effects have a probability But, I want to know about ME, if I will get these

Radiation Protection in Cardiology Lecture 3: Radiation effects 43 Do you worry about? Not really Yes Yes, Very much

Radiation Protection in Cardiology Lecture 3: Radiation effects 44 Do you worry about?

Radiation Protection in Cardiology Lecture 3: Radiation effects 45 If you work in such a manner that you adhere to prescribed dose limits of 20 mSv per year for whole working life of 18 to 65 years, your chance of excess cancer is 1 in Note: The probability calculations are for a group of people and not for individual case

Radiation Protection in Cardiology Lecture 3: Radiation effects 46 That sounds interesting. Is it possible to work in such a manner that I remain within 20 mSv/yr. It should be possible to achieve conditions so that you do not exceed ≈ 3 mSv/yr. Just wait for Topic No. 7 in this course

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Radiation Protection in Cardiology Lecture 3: Radiation effects 48 Are there reports of increased cancer incidence among Cardiologists ? One, Last Question!!!

Radiation Protection in Cardiology Lecture 3: Radiation effects 49 Let us look into the data for other professional groups like radiologists… (Because cardiologists have traditionally not interacted with safety and radiation effects professionals)

Radiation Protection in Cardiology Lecture 3: Radiation effects 50 Radiologists & radiological personnel: Eight cohorts 1.3 from US (radiologists, Army X ray Technologists, radiological technologists 2.1 each from China, Canada, Denmark, Japan & UK Variety of data pertaining to cancer incidence for different sites, mortality data (cancer), now also to other diseases such as cardiovascular Variation from Healthy worker effect to small increase

Radiation Protection in Cardiology Lecture 3: Radiation effects 51 UK Radiologists Around 2700 male radiologists, registered from Standardized mortality ratio (SMR) Annual exposure, 0.1 Sv before 1950, 0.05 Sv in early 1950’s Compared mortality rates and death from Circulatory disease: Observed number of deaths were generally close to or lower than expected.

Radiation Protection in Cardiology Lecture 3: Radiation effects 52 US Radiological Technologists Over 146,000, predominantly females, 73% Total cancer death rates were lower than expected in general population Risks higher for those <1950 Relative risk of mortality from circulatory disease higher for those starting work in earlier years [<1940=1.22, 1940’s=1.00, 1960+=1.00]

Radiation Protection in Cardiology Lecture 3: Radiation effects 53 US Radiologists Study : Cohort with highest exposure, 15% higher mortality from cardiovascular disease than other physicians., after age 55. No information about smoking and other risk factors.

Radiation Protection in Cardiology Lecture 3: Radiation effects 54

Radiation Protection in Cardiology Lecture 3: Radiation effects 55

Radiation Protection in Cardiology Lecture 3: Radiation effects 56 May involve small children, young females and pregnant patients

Radiation Protection in Cardiology Lecture 3: Radiation effects 57 Radiosensitivity In Children and Young Patients Age is a primary determinant of radiosensitivity– the younger the patient, the higher the radiosensitivity Breast of 15 year old is 15 times more sensitive to radiocarcinogenesis than the breast of 45 year old

Radiation Protection in Cardiology Lecture 3: Radiation effects 58 Z Kardiol Aug;92(8): Radiation-induced coronary artery disease. Mert M, Arat-Ozkan A, Ozkara A, Aydemir NA, Babalik E. Istanbul University, Institute of Cardiology, Istanbul, Turkey. It was realized that mediastinal radiotherapy due to Hodgkin's disease at 10-year of age (causative) 36 year man, no coronary artery risk factor. Unstable angina..1 month. Angio-Total occlusion of the left anterior descending artery and 70% stenosis of the proximal right coronary artery

Radiation Protection in Cardiology Lecture 3: Radiation effects 59 Such case reports are not possible for cancer Risk factors for cardiac- known, ruling them out helps a lot ( because of long latent period and many others factors in life which can cause cancer)

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Radiation Protection in Cardiology Lecture 3: Radiation effects 62 CONCLUSIONS: This finding is compatible with current knowledge about the carcinogenic effect of low-dose irradiation but differs in the occurrence of an excess of lymphoma in the absence of an excess of leukemia, which has not been reported before. Pediatrics, 1983 Feb; 71(2): [contd.]

Radiation Protection in Cardiology Lecture 3: Radiation effects children who underwent cardiac catheterization due to congenital anomalies, between the years Expected number of malignancies for all sites was 4.75, while the observed number was 11.0 Of the 11 cancer cases, 4 lymphomas were observed (0.63 were expected, SIR = 6.3; 95% CI : ). One of these was Hodgkin's Disease. There were also three cases of melanoma as opposed to 0.62 expected (SIR = 4.9; 95% CI : ).

Radiation Protection in Cardiology Lecture 3: Radiation effects 64 may potentially cause a small increase in the lifetime risk of fatal malignancy, with lung malignancy being most likely

Radiation Protection in Cardiology Lecture 3: Radiation effects 65 Non-neoplastic effects of Radiation Risk of Cardiovascular Diseases following Radiation Exposures

Radiation Protection in Cardiology Lecture 3: Radiation effects 66 Does radiation exposure… …induce cardiovascular system damage?, e.g. congestive heart failure, arrhythmia, angina pectoris, or myocardial infarction …or …does it accelerate arteriosclerosis?

Radiation Protection in Cardiology Lecture 3: Radiation effects 67 Chernobyl workers, atomic bomb survivors, and radiotherapy patients…

Radiation Protection in Cardiology Lecture 3: Radiation effects 68 From Radiotherapy literature: Survivors of Hodgkin’s disease, non Hodgkin's disease, esophageal carcinoma, thymoma, lung cancer, breast cancer and metastatic seminoma Hodgkin’s:Most data comes from the cohort study of 2232 pediatric and adult patients irradiated during at Stanford University Medical Centre JAMA 270 (16), , Increased relative risk (RR) of cardiovascular disease demonstrated

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Radiation Protection in Cardiology Lecture 3: Radiation effects 71 Who is at risk? Children or teens who received spinal radiation, chest radiation (Hodgkin’s, non- Hodgkin’s lymphoma), left flank (Wilms), or radiation directly to the heart are possibly at risk.

Radiation Protection in Cardiology Lecture 3: Radiation effects 72Pregnancy

Radiation Protection in Cardiology Lecture 3: Radiation effects 73 Circulation 2001 Aug 21; 104(8): CONCLUSIONS : A typical catheter ablation procedure results in a very small increase in risk of harmful effects to the conceptus. However, estimation of conceptus dose from catheter ablation procedures is always needed to assess the risk to the individual developing in utero.

Radiation Protection in Cardiology Lecture 3: Radiation effects 74 Exposure before age 20 was associated with higher ERR(1Sv) compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR(1Sv) was observed to decline with increasing attained age, with by far the largest drop around age 35.

Radiation Protection in Cardiology Lecture 3: Radiation effects 75 Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years = 1.4, 95% confidence interval (CI) = ), This increased risk was observed only among women with a history of benign breast disease.

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Radiation Protection in Cardiology Lecture 3: Radiation effects 77Re-Cap 1.What can radiation do? 2.Effect that have threshold 3.No threshold effect- cancer, genetic 4.Effects at the level of Cell, DNA.. 5.Probability of Cancer, genetic effects 6.Individual risk 7.Radiologists, Technologists 8.Patients- Children, young & pregnant female