Dose Response Relationships in Radiotherapy

1. Dose Response Relationships in Radiotherapy

3. Concepts End-point: A specific event that may or may not have occurred at a given time after irradiation Severity: grade of radiation effect Incidence and dose response curve: A dose response curve is an incidence or a probability of response as a function of dose

4. Radiation generates clusters of ionisations, and this produces discrete double strand breaks in DNA. Various stages like physical , physiochemical and biochemical and biological stages need to be treated to deal this problem. This will involve dealing with hydrated DNA, production of radicals, diffusion and reaction of radicals, chromatin structure, enzyme kinetics etc. It is a very complex area requiring vast computer power and reliable interaction data. This modern theoretical approach is beyond the scope of this talk.Radiation generates clusters of ionisations, and this produces discrete double strand breaks in DNA. Various stages like physical , physiochemical and biochemical and biological stages need to be treated to deal this problem. This will involve dealing with hydrated DNA, production of radicals, diffusion and reaction of radicals, chromatin structure, enzyme kinetics etc. It is a very complex area requiring vast computer power and reliable interaction data. This modern theoretical approach is beyond the scope of this talk.

5. The main difference between biophysical models and repair models given here is the way in which they interpret the bending of the survival curves. Biophysical models postulate the existance of theoritically repairable damage whose accumulation of an interaction lead to irreparable damage Repair models emphasise the role of cellular repair in survival; the bending of the survival curve is thus explained in terms of repair interaction, repair saturation and repair pool depletion. However, there is no complete agreement on the interpretation of the shoulder of the survival curve. All the above models are mechanistic models based on Poisson statistics and target theory. Target theory is briefly described in the next slide.The main difference between biophysical models and repair models given here is the way in which they interpret the bending of the survival curves. Biophysical models postulate the existance of theoritically repairable damage whose accumulation of an interaction lead to irreparable damage Repair models emphasise the role of cellular repair in survival; the bending of the survival curve is thus explained in terms of repair interaction, repair saturation and repair pool depletion. However, there is no complete agreement on the interpretation of the shoulder of the survival curve. All the above models are mechanistic models based on Poisson statistics and target theory. Target theory is briefly described in the next slide.

6. Radiation dose-curves have a sigmoid (S) shape, with the incidence of radiation effects tending to zero as dose tending to 100% at very large doses. Models (like Poisson, logistic or probit) do not fit clinical data very well due to statistical noise.Radiation dose-curves have a sigmoid (S) shape, with the incidence of radiation effects tending to zero as dose tending to 100% at very large doses. Models (like Poisson, logistic or probit) do not fit clinical data very well due to statistical noise.

7. Tumor Control Probability (TCP)

8. Tumor Control Probability (TCP)

9. TCP

10. TCP

13. Normal Tissue Complication Probability (NTCP) models

14. NTCP models

17. Tolerance doses

18. NTCP models

19. uncomplicated tumour control