Lecture_2 Radiation effects.pptx

Biological Effects
IAEA Training Material on Radiation Protection in Radiotherapy

Radiation Protection in Radiotherapy Part 3, lecture 1: Radiation protection 2
Introduction
 What matters in the end is the biological
effect!
 Dose to the tumor determines probability of
cure (or likelihood of palliation)
 Dose to normal structures determines
probability of side effects and complications
 Dose to patient, staff and visitors determines
risk of radiation detriment to these groups

Introduction
 What matters in the end is the biological
effect!
 Dose to the tumor determines probability of
cure (or likelihood of palliation)
 Dose to normal structures determines
probability of side effects and complications
 Dose to patient, staff and visitors determines
risk of radiation detriment to these groups
High dose:
Deterministic effects
Low dose:
Stochastic effects

 Due to cell killing
 Have a dose
threshold - typically
several Gy
 Specific to
particular tissues
 Severity of harm is
dose dependent
dose
Severity of
effect
threshold

Stochastic effects
 Due to cell changes (DNA)
and proliferation towards a
malignant disease
 Severity (example cancer)
independent of the dose
 No dose threshold -
applicable also to very small
doses
 Probability of effect increases
with dose
dose
Probability
of effect

Contents:
1. Biological radiation effects
2. From Gray to Sievert
3. Epidemiological evidence
4. Risks and dose constraints

1. Radiation Effects
Ionizing radiation
interacts at the
cellular level:
• ionization
• chemical changes
• biological effect
cell
nucleus
chromosomes
incident
radiation

The target in the cell: DNA

Processes of Radiation Effects
Stage Process
Duration
Physical Energy absorption, ionization
10-15 s
Physico-chemical Interaction of ions with molecules,
10-6 s formation of free radicals
Chemical Interaction of free radicals with
seconds molecules, cells and DNA
Biological Cell death, change in genetic data
tens of minutes in cell, mutations
to tens of years

Early Observations of the
Effects of Ionizing Radiation
 1895 X Rays discovered by Roentgen
 1896 First skin burns reported
 1896 First use of X Rays in the treatment of cancer
 1896 Becquerel: Discovery of radioactivity
 1897 First cases of skin damage reported
 1902 First report of X Ray induced cancer
 1911 First report of leukaemia in humans and lung
cancer from occupational exposure
 1911 94 cases of tumour reported in Germany
(50 being radiologists)

Monument to radiation pioneers who
died due to their exposures

Radiation Effects
 Three basic types:
 Stochastic : probability of effect related to
dose, down to zero (?) dose
 Deterministic : threshold for effect - below,
no effect; above, certainty, and severity
increases with dose
 Hereditary: (genetic) - assumed
stochastic incidence, however, manifests
itself in future generations

 Due to cell killing
 Have a dose
threshold
 Specific to
particular tissues
 Severity of harm
is dose
dependent Radiation injury from an industrial source

Examples for deterministic
effects
 Skin breakdown
 Cataract of the lens of the eye
 Sterility
 Kidney failure
 Acute radiation syndrome (whole body)

Skin reactions
Injury
Threshold
Dose to
Skin (Sv)
Weeks to
Onset
Early transient erythema 2 <<1
Temporary epilation 3 3
Main erythema 6 1.5
Permanent epilation 7 3
Dry desquamation 10 4
Invasive fibrosis 10
Dermal atrophy 11 >14
Telangiectasis 12 >52
Moist desquamation 15 4
Late erythema 15 6-10
Dermal necrosis 18 >10
Secondary ulceration 20 >6
Skin damage
from prolonged
fluoroscopic
exposure

Threshold Doses for Deterministic
Effects
 Cataracts of the lens of the eye 2-10 Gy
 Permanent sterility
 males 3.5-6 Gy
 females 2.5-6 Gy
 Temporary sterility
 males 0.15 Gy
 females 0.6 Gy dose
Severity of
effect
threshold

Note on threshold values
 Depend on dose delivery mode:
 single high dose most effective
 fractionation increases threshold dose in
most cases significantly
 decreasing the dose rate increases
threshold in most cases
 Threshold may differ in different
persons

Stochastic effects
 Due to cell changes (DNA) and
proliferation towards a malignant
disease
 Severity (i.e. cancer) independent of the
dose
 No dose threshold (they are presumed
to occur at any dose however small)
 Probability of effect increases with dose

Biological Effects
 At low doses, damage to a cell is a
random effect - either there is energy
deposition or not.

… order of magnitudes
 1cm3 of tissue = 109 cells
 1 mGy --> 1 in 1000 or 106 cells hit
 999 of 1000 lesions are repaired - leaving
103 cells damaged
 999 of 1000 damaged cells die (not a major
problem as millions of cells die every day in
every person)
 1 cell may live with damage (could be
mutated)

Cancer induction
 The most important stochastic effect for
radiation safety considerations
 Is a multistage process - typically three
steps: each of them requires an event…
 Is a complicated process involving cells,
communication between cells and the
immune system...

2. From Gy to Sv: Quantities and
Units for Radiation
Exposure
Absorbed Dose
Equivalent Dose
Effective Dose

Radiation Quantities
Absorbed dose D
 the amount of energy deposited per unit
mass in any target material
 applies to any radiation
 measured in gray (Gy) = 1 joule/kg
 old unit the rad = 0.01 Gy

Equivalent Dose H
 takes into account the effect of the
radiation on tissue by using a radiation
weighting factor WR
 measured in sievert (Sv)
 old unit the rem = 0.01 Sv
 H = D x wR

Radiation Weighting Factors
(ICRP report 60)
Type of Radiation WR
beta 1
alpha 20
X Rays 1
gamma rays 1
neutrons <10 keV 5
neutrons (10 keV – 100 keV) 10
neutrons (100 keV – 2 MeV) 20
neutrons (2 meV – 20 MeV) 10
neutrons >2 MeV 5

Note:
 The ‘radiobiological effectiveness’ for
different radiation types depends on the
endpoint looked at. The ICRP figures
given on the previous slide apply only
for stochastic effects.

Effective Dose E
 Takes into account the varying sensitivity of
different tissues to radiation using the Tissue
Weighting Factors wT
 Measured in sievert (Sv)
 Used when multiple organs are irradiated to
different dose, or sometimes when one organ
is irradiated alone
 E = Sumall organs (wT H) = Sumall organs (wT wR D)

Tissue Weighting Factors (ICRP 60)
Tissue WT
Gonads 0.2
Red bone marrow 0.12
Colon 0.12
Lung 0.12
Stomach 0.12
Bladder 0.05
Breast 0.05
Liver 0.05
Oesophagus 0.05
Thyroid 0.05
Skin 0.01
Bone surfaces 0.01
Remainder 0.05
TOTAL 1

Tissue Weighting Factors (ICRP 60)
Tissue WT
Gonads 0.2
Red bone marrow 0.12
Colon 0.12
Lung 0.12
Stomach 0.12
Bladder 0.05
Breast 0.05
Liver 0.05
Oesophagus 0.05
Thyroid 0.05
Skin 0.01
Bone surfaces 0.01
Remainder 0.05
TOTAL 1
Genetic risks are considered
about 4 times less important
than cancer induction

 Effective dose is used to describe the
biological relevance of a radiation exposure
where different tissues/organs receive
varying absorbed dose potentially from
different radiation sources
 The concept of effective dose and the tissue
weighting factors given are only applicable to
stochastic effects
 Effective dose is a quantification of risk

Collective Dose
 this is used to measure the total impact
of a radiation practice or source on all
the exposed persons
 for example diagnostic radiology
 measured in man-sievert (man-Sv)

Quantification of Stochastic Effects
 Total lifetime risk of fatal cancer for
general population = 5% / Sv
 Lifetime fatal cancer risk for cancer of :
 bone marrow 0.5 % / Sv
 bone surface 0.05
 breast 0.2 %
 lung 0.85
 thyroid 0.08

How do we know all this?
 Epidemiology (observations
of humans)
 Experimental radiobiology
(studies on animals)
 Cellular and molecular
radiation biology

3. Epidemiological Evidence
1
10
100
1000
10000
0.1 1 10 100 1000 10000
Dose (mGy)
Cancer
deaths
/year/1M
people
natural cancer
mortality
additional cancer
deaths due to radiation

Scale of Radiation Exposures
1
10
100
1000
10000
0.1 1 10 100 1000 10000
Dose (mGy)
Cancer
deaths
/year/1M
people
natural cancer
mortality
additional cancer
Annual
Background
CT scan
Chest
X-ray Typical
Radiotherapy
Fraction

Sources of Background
radiation

Contributions to Radiation Exposure in the UK
Total: 2-3mSv/year

Epidemiology of Cancer Risks
 LIFE SPAN STUDY
(Hiroshima and
Nagasaki): Only ~5%
of 7,800 deaths from
cancer or leukaemia
due to radiation
 Other evidence
(examples)
 131-I thyroid
exposures in
Scandinavia
 Radium dial painters
 Chernobyl
 Air plane crews
 many other studies

Example of Radiation Exposure
to Aircrew to Cosmic Radiation
Exposure of New Zealand aircrew
International Routes
 1000 hours per year, with 90% of the time at an altitude of
12 km
 6.5 mSv annual dose from cosmic radiation
Domestic Routes
 1000 hours per year, with 70% of the time at an altitude of
11 km
 3.5 mSv annual dose from cosmic radiation
Adapted from L Collins 2000

Epidemiological Evidence
1
10
100
1000
10000
0.1 1 10 100 1000 10000
Dose (mGy)
Cancer
deaths
/year/1M
people
natural cancer
mortality
additional cancer
Data from Hiroshima
Nagasaki and 131-I
Thyroid studies
?

Problems with Data at Low Doses
 Cell culture and animal data difficult to
extrapolate to humans
 Human experience
 Not randomized controlled
 would be highly unethical
 Many assumptions in Life time study
 Poor dose information (to part or whole body)
 Unknown co-existing conditions
 Poor statistics (small numbers)

What happens at the low-dose end of
the graph, below 100 mSv?

Epidemiological Evidence
1
10
100
1000
10000
0.1 1 10 100 1000 10000
Dose (mGy)
Cancer
deaths
/year/1M
people
natural cancer
mortality
additional cancer
Linear No-Threshold (LNT)
Hypothesis reduced at low
dose and dose rate by a
factor of 2 - in general
agreement with data

4. Risk Estimates
 Risk = probability of effect
 Different effects can be looked at - one needs
to carefully look at what effect is considered:
e.g. thyroid cancer mortality is NOT identical
to thyroid cancer incidence!!!!
 Risk estimates usually obtained from high
dose and extrapolated to low dose

The Influence of Dose Rate on
Stochastic Effects
 Studies on mice comparing acute radiation with
continuous exposure demonstrates a dose-rate
reduction factor of between 2 and 5 for life-
shortening, and between 1 and 10 for tumour
induction.
 In humans, the atomic bomb survivor data suggests
a Dose Dose Rate Effectiveness Factor (DDREF) of
2.0 for leukaemia and 1.4 for all other cancers.
 A DDREF should be applied either if the total dose
is < 200 mGy or the dose rate is below 0.1
mGy/min.

Risk estimates
 ICRP 60 summary of lifetime risks of cancer mortality
High Dose Low Dose (0.2 Gy)
High Dose RateLow Dose Rate
(<0.1 Gy/h)
Working population 0.08 per Sv 0.04 per Sv
Whole population 0.10 per Sv 0.05 per Sv
(Includes younger people)
 Studies of many RT patients show a risk of second
malignancy of 5%
 Genetic risk (ICRP 60): 0.006 per Sv

Comparison of Radiation Worker
Risks to Other Workers
Mean death rate 1989
(10-6/y)
Trade 40
Manufacture 60
Service 40
Government 90
Transport/utilities 240
Construction 320  max permissible exposure
Mines/quarries 430 over a lifetime
Agriculture 400
Safe industries
 2 mSv/y

Basis for Exposure Limits
 Limits have changed with time
 Biological information
 Genetic risks are smaller, carcinogenic risks
are larger than thought in 1950s
 Social philosophy
 Ability to control exposures

Comment on Fetus/Embryo
 Fetus/embryo is more sensitive to ionizing radiation
than the adult human
 Increased incidence of spontaneous abortion a few
days after conception
 Increased incidence
 Mental retardation
 Microcephaly (small head size) especially 8-15 weeks after
conception
 Malformations: skeletal, stunted growth, genital
 Higher risk of cancer (esp. leukemia)
 Both in childhood and later life

Comment on Fetus/Embryo
 Fetus/embryo is more sensitive to ionizing radiation
than the adult human
 Increased incidence of spontaneous abortion a few
days after conception
 Increased incidence
 Mental retardation
 Microcephaly (small head size) especially 8-15 weeks after
conception
 Malformations: skeletal, stunted growth, genital
 Higher risk of cancer (esp. leukemia)
 Both in childhood and later life
Deterministic effect
Stochastic effect

Time after Effect Normal incidence
conception in live-born
First three weeks No deterministic or stochastic -
effects in live-born child
3rd through 8th Potential for malformation of 0.06
weeks organsa (1 in 17)
8th through 25th Potential for severe mental 5 x 10-3
weeks retardationb (1 in 200)
4th week throughout Cancer in childhood or in adult 1 x 10-3
pregnancy lifec (1 in 1000)
a Deterministic effect. Threshold ~ 0.1 Gy
b 30 IQ units shift: 8-15th week; <30 IQ units shift: 16 - 25th week
c Risk in utero ~ risk < 10 years of age
TYPES OF EFFECTS FOLLOWING
IRRADIATION IN UTERO

Non-cancer Stochastic Effects
of Radiation
 The LSS data has been analysed to
determine the non-cancer mortality for
those who died between 1950 - 1990.
 A statistically significant increase with
radiation dose has been shown for:
 Stroke
 Heart Disease
 Respiratory Diseases
 Digestive Diseases
Shimizu T et al, Radiation Research, 1999; 152:374-389

Average Annual Risk of Death in the UK
from Industrial Accidents and from
Cancers due to Radiation Work
Coal mining 1 in 7,000
Oil and gas extraction 1 in 8,000
Construction 1 in 16,000
Radiation work (1.5 mSv/y) 1 in 17,000
Metal manufacture 1 in 34,000
All manufacture 1 in 90,000
Chemical production 1 in 100,000
All services 1 in 220,000
From L Collins 2000

Summary
 Cancer induction is the most significant
risk from exposure to ionizing radiation
at low doses
 Cancer induction is a stochastic effect
 At high radiation doses also
deterministic effects play a role

Summary: Dose Quantities
Absorbed dose (Gy “gray”)
Energy deposited in tissue
Equivalent dose (Sv “sievert”)
Absorbed dose modified by a radiation
weighting factor
Effective Dose (Sv “sievert”)
Whole-body radiation dose - a measure for risk

Summary
 Risks can be calculated
 However:
 the numbers are typically small and may not be
meaningful for everyone
 The action taken to avoid or minimize risks
depends on interpretation and the perceived
benefits - this can vary significantly from one
person to the next and amongst societies
 Dose constraints can be chosen to
match risks in other professions

Question:
Why is our information of radiation
effects of low radiation doses
(e.g. < 20mSv) limited?

The answer should include but
not be limited to:
 Close to background radiation - dosimetry
difficult
 Limited epidemiological evidence
 Research and experiments with humans are
ethically impossible
 The effects are very small (if any)
 It is likely that there is a dose and dose rate
effect - at lower doses and dose rate
radiation effects are likely to be smaller than
at high doses.

Lecture_2 Radiation effects.pptx

More Related Content

What's hot

Similar to Lecture_2 Radiation effects.pptx

Recently uploaded

Lecture_2 Radiation effects.pptx

Editor's Notes