1. Eyad Alsaeed MD, FRCPC. Consultant Radiation Oncologist Acting Head of Radiation Oncology Prince Sultan Hematology @ Oncology center KFMC

2. define survival curve (2), draw survival curve for 250kvp and neutrons, and label Do, Dq, n (4), draw the survival curve as per linear quadratic model, label e  d, e  d2 and the dose at which  /  occurs (4) 10/27/20152 semi loghrythmic plot of the dose (linear scale) to the cell survival (log. Scale)

3. D° D1 Dq N in survival curve D ° (final slope) the dose required to reduce the survival from 0.1 to 0.037 &0.01 to 0.0037 and so on. D1:(the initial slope) :the dose required to reduce the survival to 0.37on the initial straight portion of the survival curve. N (the extrapolation no.) measure the width of the shoulder (large for the large shoulder)  radio resistance and small for the small shoulder  radiosensitive). Dq (quasi threshold dose) the dose which below it there is no effect or minimal. 10/27/20153

4. Linear quadratic model Alpha-α :represent the linear non-repairable component of the CSC. Beta-β : represent the cell kill at dose level which have exceeded the capacity of some repair processes to repair radiation damage. i.e represent the repairable component of cell killing. α\ β ratio: the dose where the α component (linear) equal the quadratic component β 10/27/20154

5. linear-quadratic (  /  ) system considers  /  ratio for the dose-limiting effect (i.e., transverse myelitis), number of fractions, and dose per fraction to derive a biologically equivalent dose in units of cGy biologically equivalent dose = (total dose ). (relative effectiveness) BED = (nd). ( 1 + [d /  /  ] ) when performing  /  calculations for determining biologically equivalent doses, certain assumptions are made each dose in a fractionated regimen produces the same biologic effect full repair of sublethal damage takes place between fractions no cell proliferation takes place between fractions either both schedules involve the same overall time or the isoeffect endpoint is not time-dependent (as with most late reactions) All tumor have same  /  ratio =10 Each organ have different  /  LQ is good model 10/27/20155

6. α\ β ratio 10/27/20156

7. Relative Biological Effectiveness RBE ratio of D250/Dr, where D250 and Dr are dose of test radiation required to produce an equal biological effect factors that determine RBE 1. radiation quality (i.e., LET): RBE is a function of LET 2. number of fractions 3. dose rate ( ↓ dose rate ↑ RBE) 4. biological system or endpoint : higher for late NTR than Early@2Gy/# 10/27/20157

8. define RBE (2), what are the 4 factors that affect RBE (4) RBE= dose of standard XRT/dose of new modality(neutrone) to give the same biological effect. Affected by : 1. LET 2. No.of fractions 3. Dose rate 4. endpoint 10/27/20158

9. LET Energy deposited per unit of track length measured in kev/  m 10/27/20159

10. OER Ratio of Anoxic dose to Oxic dose to achieve same biological effect. Rapidly change from 0 - ½% (3mmHg) O 2 saturation and after 2% (12mmHg) indistinguishable from aerated cells 10/27/201510

11. OER X-Ray Low LET 2.5 -3.5 α-particle1 Proton1 Neutron1.6 10/27/201511

12. 10/27/201512 OER

13. radiation weighting factor (WR) definition: factor with which to multiply absorbed dose for a given radiation to provide an equivalent dose when compared to a standard radiation units of equivalent dose for Gray: sieverts for rad: rem range of values for low-LET radiation =1 10/27/201513

14. radiation weighting factor (WR) 10/27/201514 Equivelant Dose: Average dose x WR (unit Sv )

15. Effective Dose definition: sum of the products of the equivalent dose in a tissue and the appropriate tissue weighting factor for that tissue for all exposed tissues unit of measure: Sv (rem) this is the most suitable quantity for relating exposure to cancer risk  (absorbed dose. WR. WT) 10/27/201515

16. Tissue weighting factor (WT) definition: factor used for radiation protection purposes to account for differences in relative contribution of each tissue to the total detriment resulting from uniform irradiation of the whole body unit of measurement: Sv 10/27/201516

17. Theraputic ratio, 4 approaches to improve it Ratio of the probability of local tumor control to the probability of producing serious normal tissue effect Approaches: Fractionation Hypoxic cell radisensetisers Concurrent chemorad. Bioreductive agents ARCON 10/27/201517

18. Stochastic Risk The effect is all-or-non in the exposed individual Any dose (theoretically) have probability of producing effect May occur after the passage of single particle through the cell e.g α-particle The frequency of effect occurring increases with POPULATION dose Effects usually have long latent period leukemia 2 - 4y solid tumors 15 – 30y. Poorly understood 10/27/201518

19. Deterministic Risks The effect increases in severity with dose to exposed individual 150 msv or more is required to produce an effect. i.e DOSE THRESHOLD PRESENT The threshold varies from tissue to tissue,dose rate,no. of exposures. Short latent period Relatively well understood 10/27/201519

20. Stochastic & Deterministic effect Stochastic effect no dose threshold probability of the effect increases with dose and dose rate. severity of the effect is not dose related associated mainly with low-dose exposures dose-response curve has linear-quadratic shape examples: all heritable genetic effects and cancer Deterministic effect dose threshold probability of the effect increases with dose severity of the effect is dose related The higher the dose the sooner the effect associated mainly with intermediate and high-dose exposures dose-response curve has sigmoid shape examples: all non-cancer somatic effects (i.e., radiation cataractogenesis) 10/27/201520

21. Normal tissue tolerance 10/27/201521

22. Cerebrovascular syndrome Fatal doses > 100Gy death within 24 – 48 hours from neurological and cardiovascular breakdown symptoms: severe nausea and emesis within minutes  disorientation, loss of coordination, respiratory distress, seizures, coma,  death mechanism: unknown, but ? due to intracranial fluid leakage due blood vessel permeability. 10/27/201522

23. Gastrointestinal syndrome fatal doses > 10Gy death follows 3 – 10 days symptoms: nausea, emesis, and prolonged bloody diarrhea mechanism: depletion of gastrointestinal tract stem cells, ultimately leading to water, electrolyte, and protein loss 10/27/201523

24. Hematopoietic syndrome some survivors are reported doses of 3 – 8Gy death follow within weeks symptoms: typical prodromal syndrome  symptom-free latent period  onset of chills, fatigue, petechiae, ulceration, and epilation by 3 weeks mechanism: depletion of blood element precursors, ultimately leading to infection 10/27/201524

25. Management of accedental WBXRT for doses < 500 cGy patient is treated expectantly prophylactic blood transfusions are not given in order to permit regeneration of blood-forming organs for doses 500 – 800 cGy patient is bathed repeatedly in antiseptic solutions and given large doses of antibiotics (antibiotics can raise LD50 by a factor of 2) then, patient is placed in an airtight plastic unit and fed sterilized food for doses 800 – 1000 cGy: same antibiotic precautions as above are recommended plus bone marrow transplant for doses > 1000 cGy: death from gastrointestinal syndrome is inevitable, and supportive care only is recommended long-term survivors have not been observed to have a higher incidence of malignancy or shorter lifespan than expected 10/27/201525

26. THANK YOU