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

International Atomic Energy Agency

What Radiation Effects are What Radiation Effects are Possible?Possible?

(besides skin injuries)(besides skin injuries)L3

Lecture 3: Radiation effects 2Radiation Protection in Cardiology

Educational ObjectivesEducational Objectives

• Effects other than skin injuries• Their probability in

interventional cardiology practice

• Special concerns in children, young & pregnant females


What can radiation do?

It can bring a smile on the faces of people of all ages


What can radiation do?

CancerGenetic effectsSkin injuriesCataractInfertilityDeathNon-neoplastic Effects

NB. In this lecture, we shall predominantly deal with cancer & genetic effects



Main PointMain Point

Threshold

Dose

Eff

ect

Deterministic effects

Cataractinfertility

erythema

epilation

CancerGeneticProb dose

500 mSv cataract 150 mSv for sterility (temporary-males)2500 mSv for ovarian

Preventable


Dose

Eff

ect

Deterministic effects

Cataract infertilityerythema

epilation

CancerGeneticProb dose

Stochastic


Stochastic and Deterministic EffectsStochastic 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.


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


Is there RADIATION

in this room?


Radiation from Natural SourcesRadiation from Natural Sources

• Normally 1-3 mSv/year

• In areas of high background, 3-13 mSv/year


Interventional Cardiology

CT

Radiography



NucleusDouble 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


Induction of DNA changesInduction of DNA changes


radiation hits a cell nucleus!

No change

DNA mutation


DNA Mutation p a D

Cell survives but mutated

Stoch.eff.

Mutation repaired

Unviable Cell

Viable Cell

Cell death


Deterministic effects caused by cell Deterministic effects caused by cell death: burns, organ failure, death death: burns, organ failure, death


Normal Normal processprocess Altered process due to mutated Altered process due to mutated

genesgenes


Stochastic effects Stochastic effects

Cancerogenesis

Hereditary effects

Effects in the embryo/foetus


CarcinogenesisCarcinogenesis



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.


OK, Agree that Radiation can cause cancer, But how do I know if I will get cancer!!!


Life Insurance Agent

Malpractice Insurance

Probability



RadiosensitivityRadiosensitivity

• Probability of a cell, tissue, or organ suffering an effect per unit dose

• Will be greater if the cell:

• Is highly mitotic

• Is undifferentiated


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 86,500 14109 2573 10834 95217 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 40 0-15 years 18-64 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 Features of somesome epidemiological studies of radiation-induced cancer risks epidemiological studies of radiation-induced cancer risks


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 WorkersParameter (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, Allorgans mainly those bone marrow, irradiated in proximity thyroid, skin to spine and breast

Availability Organ doses: Mean organ Organ doses: Brain, thyroid & Individual whole-bodyof dose individual basis doses: indiv. Individual basis skin doses: external doses estimates only for red individual basis bone marrow at presentRange dose Mainly 0-4 Gy Mainly 0-20 Gy Mainly 0-3 Gy Brain: 0-6 Gy Mainly 0-0.5 Sv (mean 1.5 Gy) (mean 0.034 Sv) Thyroid:0-0.5 Gy (mean 0.09 Gy)Dose rate High High High, but highly High Low fractionatedRadiation Mainly low-LET Low-LET Low-LET Low-LET Mainly low-LET Quality

Features of some epidemiological studies of radiation-induced cancer risksFeatures of some epidemiological studies of radiation-induced cancer risks


LIFE SPAN STUDYLIFE SPAN STUDYExcess absolute risk for solid cancer mortality

30 40 50 60 70 80 900

10

20

30

40

50

A G E (years)

EX

CE

SS

CA

SES

PER

10,

000

PY A

T 1

Sv

A ge a t exposure: 10 , 30 , 50 ye arsM ales

5030

10

F em ales


LIFE SPAN STUDYLIFE SPAN STUDYAtomic Bomb SurvivorsAtomic 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


Hereditary EffectsHereditary Effects


Heritable effectsHeritable effects

• Effects to be observed in offspring born after one or both parents had been irradiated prior to conception.


Hereditary effectsHereditary effects

Descendents of Hiroshima and Nagasaki

survivors were studied

but no statistical but no statistical abnormalities were detected.abnormalities were detected.



A cohort of A cohort of 31,150 children born to parents who31,150 children born to parents who were were

within 2 km of the hypocenter at the time of the bombing within 2 km of the hypocenter at the time of the bombing

was compared was compared with a control cohort of 41,066 childrenwith a control cohort of 41,066 children..

No indicator was significantly modified by parental radiation exposure.


In the absence of human data the estimation of hereditary effects is based on animal studies.


UNSCEAR 2001 ReportUNSCEAR 2001 ReportHEREDITARY EFFECTS OF RADIATIONHEREDITARY EFFECTS OF RADIATION

Risks to offspring following prenatal exposure:

•Total risk = 0.0003 - 0.0005% per mGyto the first generation(3000 to 4700 cases per grayper one million progeny)

•Includes multifactorial diseases

•1/10 the risk of fatal carcinogenesis•Constitutes 0.4-0.6% of baseline frequency


……aboveabove the prevalent the prevalent background dosebackground dose, ,

an an increment in doseincrement in dose

results in a results in a proportional proportional

incrementincrement in the probability of in the probability of hereditary hereditary

effectseffects of of

0.0005% per mSv of 0.0005% per mSv of

dosedose..


OK, Understood that these radiation effects have a probability

But, I want to know about ME, if I will get these


Do you worry about?

Not reallyYes

Yes, Very much


Do you worry about?


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 1000.

Note: The probability calculations are for a group of people and not for individual case


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



Are there reports of increased cancer incidence among Cardiologists ?

One, Last Question!!!


Let us look into the data for other professional groups like radiologists…

(Because cardiologists have traditionally not interacted with safety and radiation effects professionals)


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


UK RadiologistsUK Radiologists

Around 2700 male radiologists, registered from 1897- 1979.Standardized mortality ratio (SMR)Annual exposure, 0.1 Sv before 1950, 0.05 Sv in early 1950’sCompared mortality rates and death from Circulatory disease: Observed number of deaths were generally close to or lower than expected.


US Radiological TechnologistsUS 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]


US Radiologists StudyUS Radiologists Study

1920-1939: Cohort with highest exposure, 15% higher mortality from cardiovascular disease than other physicians., after age 55. No information about smoking and other risk factors.




May involve small children, young females and pregnant patients


Radiosensitivity In Children Radiosensitivity In Children and Young Patientsand 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


Z Kardiol. 2003 Aug;92(8):682-5.

Radiation-induced coronary artery disease.

Mert M, Arat-Ozkan A, Ozkara A, Aydemir NA, Babalik E.

Istanbul University, Institute of Cardiology, Istanbul, Turkey. [email protected]

• 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


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)




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): 235-9 [contd.]


674 children who underwent cardiac catheterization due to congenital anomalies, between the years 1950-1970 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 : 1.7-16.2). 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 : 1.0-14.2).


may potentially cause a small increase in the lifetime risk of fatal malignancy, with lung malignancy being most likely


Non-neoplastic effectsNon-neoplastic effectsof Radiationof Radiation

Risk of Cardiovascular

Diseases

following Radiation

Exposures


Does radiation exposure…Does radiation exposure…

• …induce cardiovascular system damage?, e.g.

• congestive heart failure,

• arrhythmia,

• angina pectoris, or

• myocardial infarction…or

• …does it accelerate arteriosclerosis?


• Chernobyl workers,

• atomic bomb

survivors, and

• radiotherapy

patients…


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 1960-1990 at Stanford University Medical Centre JAMA 270 (16), 1949-55, 1993.

• Increased relative risk (RR) of cardiovascular disease demonstrated




Who is at risk?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.


PregnancyPregnancy


Circulation 2001 Aug 21; 104(8): 893-7

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.


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.


Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years = 1.4, 95% confidence interval (CI) = 1.2-1.8), This increased risk was observed only among women with a history of benign breast disease.



Re-CapRe-Cap

1. What can radiation do?2. Effect that have threshold3. No threshold effect- cancer, genetic4. Effects at the level of Cell, DNA..5. Probability of Cancer, genetic effects6. Individual risk7. Radiologists, Technologists8. Patients- Children, young & pregnant female

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