Radiation Protection in Radiotherapy

1
Radiation Protection inRadiotherapy
IAEA Training Material on Radiation Protection in
Radiotherapy

• Part 3
• Biological Effects

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

3
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
4
Deterministic effects

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

5
Stochastic effects
Probability of effect

• 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
6
Two objectives

• Radiotherapy deliberately uses radiation on
  patients to produce deterministic effects (tumour
  cell kill) - in this context some deterministic
  effects and stochastic effects are accepted (
  side effects)
• Radiation protection aims to minimize the risk of
  unacceptable radiation effects to the patient
  ( complications) due to mistakes or suboptimal
  irradiation practice and minimize risk of
  detrimental effect to others.

7
some room for interpretation in practice

• Some complications are events which have not been
  predictable for an individual patient because
  of biological variations between patients - they
  appear with low frequency (compare ICRP report
  86)
• Radiation protection must be concerned with
  unintended irradiation (e.g. wrong dose, wrong
  patient) and optimization of delivery to minimize
  the risk of complications

8
Contents of Part 3

• Lecture 1 Radiobiology of radiation protection
• Deterministic, stochastic and genetic effects
• Relevant radiation quantities
• Risks
• Lecture 2 Radiobiology of radiotherapy
• Deterministic effects cell kill
• Radiobiological models time effects

9
Objectives of Part 3

• To understand the various effects of radiation on
  human tissues
• To appreciate the difference between high and low
  dose deterministic and stochastic effects
• To gain a feel for the order of magnitude of dose
  and effects
• To appreciate the risks involved in the use of
  ionizing radiation as a starting point for a
  system of radiation protection

10
Radiation Protection inRadiotherapy
IAEA Training Material on Radiation Protection in
Radiotherapy

• Part 3
• Biological Effects
• Lecture 1 Radiation Protection

11
Contents

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

12
1. Radiation Effects

• Ionizing radiation
• interacts at the cellular level
• ionization
• chemical changes
• biological effect

cell
nucleus
incident radiation
chromosomes
13
A note of caution Energy deposition in matter is
a random event and the definition of dose breaks
down for small volumes (e.g. a single cell).
The discipline of Micro- dosimetry aims
to address this issue.
Adapted from Zaider 2000
14
The target in the cell DNA
15
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

16
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)

17
Monument to radiation pioneers who died due to
their exposures
18
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

19
Deterministic effects

• Due to cell killing
• Have a dose threshold
• Specific to particular tissues
• Severity of harm is dose dependent

Radiation injury from an industrial source
20
Examples for deterministic effects

• Skin breakdown
• Cataract of the lens of the eye
• Sterility
• Kidney failure
• Acute radiation syndrome (whole body)

21
Skin reactions
Skin damage from prolonged fluoroscopic exposure
22
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

23
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

24
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

25
Biological Effects

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

26
order of magnitudes

• 1cm3 of tissue 109 cells
• 1 mGy --gt 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)

27
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...

28
2. From Gy to Sv Quantities and Units for
Radiation
Exposure Absorbed Dose Equivalent
Dose Effective Dose
29
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

30
Radiation Quantities

• 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

31
Radiation Weighting Factors (ICRP report 60)
32
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.

33
Radiation Quantities

• 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)

34
Tissue Weighting Factors (ICRP 60)
35
Tissue Weighting Factors (ICRP 60)
Genetic risks are considered about 4 times less
important than cancer induction
36
Radiation Quantities

• 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

37
Radiation Quantities

• 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)

38
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

39
How do we know all this?

• Epidemiology (observations of humans)
• Experimental radiobiology (studies on animals)
• Cellular and molecular radiation biology

40
3. Epidemiological Evidence
41
Scale of Radiation Exposures
CT scan
Chest X-ray
Typical Radiotherapy Fraction
Annual Background
42
Sources of Background radiation
43
Contributions to Radiation Exposure in the UK
Total 2-3mSv/year
44
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

45
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
46
Epidemiological Evidence
Data from Hiroshima Nagasaki and 131-I Thyroid
studies
?
47
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)

48
What happens at the low-dose end of the graph,
below 100 mSv?
49
Epidemiological Evidence
Linear No-Threshold (LNT) Hypothesis reduced at
low dose and dose rate by a factor of 2 - in
general agreement with data
50
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

51
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 lt 200 mGy or the dose rate is below 0.1
  mGy/min.

52
Risk estimates

• ICRP 60 summary of lifetime risks of cancer
  mortality
• High Dose Low Dose (0.2 Gy)
• High Dose Rate Low Dose Rate
• (lt0.1 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

53
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
54
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

55
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

56
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
57
TYPES OF EFFECTS FOLLOWING IRRADIATION IN UTERO
58
Incidence of Prenatal Neonatal Death and
Abnormalities

• Hall, Radiobiology for the Radiologist pg 365

59
Genetic Risks

• Ionizing radiation is known to cause heritable
  mutations in many plants and animals
• BUT
• intensive studies of 70,000 offspring of the
  atomic bomb survivors have failed to identify an
  increase in congenital anomalies, cancer,
  chromosome aberrations in circulating lymphocytes
  or mutational blood protein changes.

Neel et al. Am. J. Hum. Genet. 1990, 461053-1072
60
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
152374-389
61
Average Annual Risk of Death in the UK from
Industrial Accidents and from Cancers due to
Radiation Work
From L Collins 2000
62
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

63
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

64
Summary (3)

• 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

65
Where to Get More Information

• From parts 2 and 4 of the course
• International Commission on Radiological
  Protection (ICRP) Reports.
• In particular The 1990 recommendations if the
  International Commission on Radiological
  Protection, ICRP report 60. Oxford Pergamon
  Press 1991.
• International Commission on Radiation Units and
  Measurements (ICRU) Reports

66
Any questions?
67
Question

• Why is our information of radiation effects of
  low radiation doses(e.g. lt 20mSv) limited?

68
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.