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Eyad Alsaeed MD, FRCPC.

Consultant Radiation Oncologist


Acting Head of Radiation Oncology
Prince Sultan Hematology @ Oncology center
KFMC
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)

10/12/2017 semi loghrythmic plot of the dose (linear scale) to the cell survival (log. 2
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.

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Linear quadratic model
Alpha- :represent the linear non-repairable
component of the CSC.
Beta- : 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 .
\ ratio: the dose where the component (linear)
equal the quadratic component

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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
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\ 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 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/#

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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. LET
2. No.of fractions
3. Dose rate
4. endpoint

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LET
Energy deposited per
unit of track length
measured in kev/mm

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OER

Ratio of Anoxic dose to Oxic dose to achieve same


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

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OER
X-Ray 2.5 -3.5
Low LET
-particle 1

Proton 1

Neutron 1.6

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OER

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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

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radiation weighting factor (WR)

Equivelant Dose: Average dose x WR (unit Sv )


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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: Sv

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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

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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 -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
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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

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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
Fatal
syndrome
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.

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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

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Hematopoietic syndrome
some survivors are reported
doses of 3 8Gy death follow within weeks
symptoms: typical prodromal syndrome
symptom-free latent periodonset of chills, fatigue,
petechiae, ulceration, and epilation by 3 weeks
mechanism: depletion of blood element precursors,
ultimately leading to infection

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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
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THANK YOU