Eyad Alsaeed MD, FRCPC.

Consultant Radiation Oncologist Acting Head of Radiation Oncology

Prince Sultan Hematology @ Oncology centerKFMC

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 ed, ed2 and the dose at which / occurs (4)

04/20/23 2semi loghrythmic plot of the dose (linear scale) to the cell survival (log. Scale)

D° D1 Dq N in survival curveD ° (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.

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Linear quadratic modelAlpha-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

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linear-quadratic (/) systemconsiders / 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 madeeach dose in a fractionated regimen produces the same biologic

effect full repair of sublethal damage takes place between fractionsno cell proliferation takes place between fractionseither 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 =10Each organ have different / LQ is good model04/20/23 5

α\ β ratio

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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 RBE1. radiation quality (i.e., LET): RBE is a function of

LET2. number of fractions3. dose rate (↓dose rate ↑RBE)4. biological system or endpoint : higher for late

NTR than Early@2Gy/#

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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. LET2. No.of fractions3. Dose rate4. endpoint

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LETEnergy deposited

per unit of track length

measured in kev/m

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OER

Ratio of Anoxic dose to Oxic dose to achieve same biological effect.

Rapidly change from 0 - ½% (3mmHg) O2 saturation and after 2% (12mmHg) indistinguishable from aerated cells

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OERX-Ray

Low LET

2.5 -3.5

α-particle1

Proton1

Neutron1.6

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OER

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 dosefor Gray: sievertsfor rad: remrange of valuesfor low-LET radiation =1

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radiation weighting factor (WR)

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Equivelant Dose: Average dose x WR (unit Sv )

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)

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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: Sv04/20/23 16

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:FractionationHypoxic cell

radisensetisers Concurrent chemorad.Bioreductive agentsARCON

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Stochastic RiskThe effect is all-or-non in the exposed

individualAny 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 understood04/20/23 18

Deterministic RisksThe effect increases in severity with dose to

exposed individual150 msv or more is required to produce an

effect. i.e DOSE THRESHOLD PRESENTThe threshold varies from tissue to

tissue ,dose rate ,no. of exposures.Short latent periodRelatively well understood

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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)

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Normal tissue tolerance

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Cerebrovascular syndromeFatal doses > 100Gy death within 24 – 48 hours from

neurological and cardiovascular breakdownsymptoms: 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.

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Gastrointestinal syndromefataldoses > 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

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Hematopoietic syndromesome survivors are reporteddoses of 3 – 8Gy death follow within weeks symptoms: typical prodromal syndrome

symptom-free latent periodonset of chills, fatigue, petechiae, ulceration, and epilation

by 3 weeksmechanism: depletion of blood element

precursors, ultimately leading to infection

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Management of accedental WBXRTfor doses < 500 cGy

patient is treated expectantlyprophylactic blood transfusions are not given in order to permit

regeneration of blood-forming organsfor 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 transplantfor 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 expected04/20/23 25

THANK YOU