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Radiation Protection in Radiotherapy

Radiation Protection in Radiotherapy. IAEA Training Material on Radiation Protection in Radiotherapy. Part 3 Biological Effects. Introduction. What matters in the end is the biological effect! Dose to the tumor determines probability of cure (or likelihood of palliation)

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Radiation Protection in Radiotherapy

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  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 Part 3, lecture 1: Radiation protection

  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 Low dose: Stochastic effects High dose: Deterministic effects Part 3, lecture 1: Radiation protection

  4. Severity of effect dose threshold Deterministic effects • Due to cell killing • Have a dose threshold - typically several Gy • Specific to particular tissues • Severity of harm is dose dependent Part 3, lecture 1: Radiation protection

  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 Part 3, lecture 1: Radiation protection

  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. Part 3, lecture 1: Radiation protection

  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 Part 3, lecture 1: Radiation protection

  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 Part 3, lecture 1: Radiation protection

  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 Part 3, lecture 1: 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 Part 3, lecture 1: Radiation protection

  12. 1. Radiation Effects • Ionizing radiation • interacts at the cellular level: • ionization • chemical changes • biological effect cell nucleus incident radiation chromosomes Part 3, lecture 1: Radiation protection

  13. The target in the cell: DNA Part 3, lecture 1: Radiation protection

  14. 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 Part 3, lecture 1: Radiation protection

  15. 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) Part 3, lecture 1: Radiation protection

  16. Monument to radiation pioneers who died due to their exposures Part 3, lecture 1: Radiation protection

  17. 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 Part 3, lecture 1: Radiation protection

  18. 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 Part 3, lecture 1: Radiation protection

  19. Examples for deterministic effects • Skin breakdown • Cataract of the lens of the eye • Sterility • Kidney failure • Acute radiation syndrome (whole body) Part 3, lecture 1: Radiation protection

  20. Skin reactions Skin damage from prolonged fluoroscopic exposure Part 3, lecture 1: Radiation protection

  21. Severity of effect dose threshold 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 Part 3, lecture 1: Radiation protection

  22. 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 Part 3, lecture 1: Radiation protection

  23. 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 Part 3, lecture 1: Radiation protection

  24. Biological Effects • At low doses, damage to a cell is a random effect - either there is energy deposition or not. Part 3, lecture 1: Radiation protection

  25. … 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) Part 3, lecture 1: Radiation protection

  26. 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... Part 3, lecture 1: Radiation protection

  27. 2. From Gy to Sv: Quantities and Units for Radiation Exposure Absorbed Dose Equivalent Dose Effective Dose Part 3, lecture 1: Radiation protection

  28. 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 Part 3, lecture 1: Radiation protection

  29. 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 Part 3, lecture 1: Radiation protection

  30. Radiation Weighting Factors (ICRP report 60) Part 3, lecture 1: Radiation protection

  31. 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. Part 3, lecture 1: Radiation protection

  32. 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) Part 3, lecture 1: Radiation protection

  33. Tissue Weighting Factors (ICRP 60) Part 3, lecture 1: Radiation protection

  34. Tissue Weighting Factors (ICRP 60) Genetic risks are considered about 4 times less important than cancer induction Part 3, lecture 1: Radiation protection

  35. 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 Part 3, lecture 1: Radiation protection

  36. 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) Part 3, lecture 1: Radiation protection

  37. 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 Part 3, lecture 1: Radiation protection

  38. How do we know all this? • Epidemiology (observations of humans) • Experimental radiobiology (studies on animals) • Cellular and molecular radiation biology Part 3, lecture 1: Radiation protection

  39. 3. Epidemiological Evidence Part 3, lecture 1: Radiation protection

  40. Scale of Radiation Exposures CT scan Chest X-ray Typical Radiotherapy Fraction Annual Background Part 3, lecture 1: Radiation protection

  41. Sources of Background radiation Part 3, lecture 1: Radiation protection

  42. Contributions to Radiation Exposure in the UK Total: 2-3mSv/year Part 3, lecture 1: Radiation protection

  43. 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 Epidemiology of Cancer Risks Part 3, lecture 1: Radiation protection

  44. 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 Part 3, lecture 1: Radiation protection

  45. Epidemiological Evidence Data from Hiroshima Nagasaki and 131-I Thyroid studies ? Part 3, lecture 1: Radiation protection

  46. 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) Part 3, lecture 1: Radiation protection

  47. What happens at the low-dose end of the graph, below 100 mSv? Part 3, lecture 1: Radiation protection

  48. Epidemiological Evidence Linear No-Threshold (LNT) Hypothesis reduced at low dose and dose rate by a factor of 2 - in general agreement with data Part 3, lecture 1: Radiation protection

  49. 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 Part 3, lecture 1: Radiation protection

  50. 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. Part 3, lecture 1: Radiation protection

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