Download RADIOBIOLOGY

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 ed,
ed2 and the dose at which / occurs (4)
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semi loghrythmic plot of the dose (linear scale) to the cell survival (log.
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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-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 (/) 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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α\ β ratio
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Relative Biological Effectiveness RBE
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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.
2.
3.
4.
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radiation quality (i.e., LET): RBE is a function of LET
number of fractions
dose rate (↓dose rate ↑RBE)
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)
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1.
2.
3.
4.
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RBE= dose of standard XRT/dose of new
modality(neutrone) to give the same biological
effect.
Affected by :
LET
No.of fractions
Dose rate
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 - ½% (3mmHg) O2
saturation and after 2% (12mmHg)
indistinguishable from aerated cells
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OER
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X-Ray
Low LET
α-particle
2.5 -3.5
Proton
1
Neutron
1.6
1
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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 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
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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
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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
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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
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.
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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 periodonset 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