Clinical Radiobiology Flashcards by Lozza Thompson

factors which influence radio sensitivity

RS is proportional to reproductive rate
inversely proportional to its degree of differentiation

increases with:
increased rate of cell division
low degree of specialisation (stem cells are very RS)
high metabolic rate
increased oxygenation
increased length of time they are actively proliferating
cell cycle stage
Rs is dependent on the cell stage

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what is radiosensitivity level

> 1

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first growth phase: cell performing normal function and growing

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DNA replication preparing to divide
LEAST RS - contains two DNA copies

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second growth phase: performs normal cell fcuntions, expanding and growing

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mitosis

cell divides to two cells
MOST RADIOSENSITIVE
sensitive to disruptions and is well oxygenated

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brain cells + spine cels are situated DONT REPLICATE
don’t have a cell cycle if they become damaged they will remain damaged

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what phases should we target

G2 and m phase

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where are the checkpoints

G1 & G2
if damaged will undergo cell apoptosis

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LQM

SSB = rate of damage and rate at which the sub lethal damage is repaired
if it can’t be repaired it can take weeks/months depending on the cell types, which is why there’s a delay with late effects

model for cell survival determines the efficacy of the fractionation scheme

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therapeutic ratio

ratio of normal tissue tolerance to lethal tumour dose

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tumour tolerance

lower than normal tissue tolerance due to tumours going through the cell cycle at a slower pace taking longer to repair, more cell kill is likely to occur as they are able to hit the tumour during sensitive stages

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TR =

normal tissue tol/ lethal tumour dose

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LQM assumptions

DNA hits are random
probability proportional to dose
DSB needed for cell death

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alpha =

DSB

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beta =

SSB

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what strand breaks are the most difficult at cell death

SSB, requires multiple hits

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how are DSB produced

single hit by a photon = alpha
two hits by a photon, in close proximity, each breaking a single strand, producing a DSB = beta

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clinical implications

early responding = high a:b
late responding = low a:b

prostate: radiation keeps causing damage, long time to respond to radiation

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high alpha beta ratio

cervical
40Gy in 20 in 4 weeks or 50Gy in 25 in 5 weeks

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low alpha beta ration

work best at hypo fractionated regime
60Gy in 20 fractions

what do high ratio benefit from

fractionation, as it reduces normal tissue toxicity without reducing tumour lethality significantly

what is biological effect determined by

total dose + treatment schedule

what is the cervical ratio

10 (low fraction sensitivity)

what is the prostate ratio

3/4 (slow proliferation, late reacting to radiation)

what is the optimum conditions for cervix

well oxygenated to maintain Hb levels

do SCC have fast or slow turnover

fast

4R's

repair: sublethal damage repopulation: CD and population growth reoxygenate: tumour cells often anoxic therefore radio resistant, fractionation allows for tumour cells to die, improves oxygenation for remaining cells increasing radiosensitvity redistribution's: each fraction the cell is in a different stage

higher ratio

more linear the cell survival curve is

lower ratio

the more curved the survival curve is

what does the ratio indicate

how resistant a cell is to damage

high alpha beta ratio

indicates that a single hit doesn't readily accumulate to lethal effects, little increase in cell kill per unit dose for higher total dose

low alpha beta ratio

that the accumulation os multiple single hits produces increased lethality for higher doses

give a tissue with high proliferation

mucosa

a tissue with slow proliferation

parenchyma

what are the RT cervix requirements

well oxygenated appropriate Hb RT must be delivered within 56 days normally SCC repopulate at a higher rate higher radiation dose = longer treatment CAT 1 = NO INTERRUPTIONS may have to hyper fractionate

late responding tissues

slow responding low alpha beta can tolerate low doses per fraction 2.7Gy - 4.9Gy good repair capability affected more than early responding with higher doses per fraction (hypofraction) dose per fraction is CRITICAL

acute responding

rapid proliferation alpha beta is high early effects seen but some recovery so cells can continue in high numbers

CAT 1

SCC lung SCC H&N SCC cervix

CAT 2

Ca endometrium Ca prostate sarcoma

CAT 3

whole brain spinal mets

what does EBRT and HDR brachytherapy permit

repair between fractions

biologically effective dose

allows for biological effects of a particular dose + fractionation scheme to be assessed

equivalent dose

looks at finding an equivalent fraction to a reference scheme

angiogenesis

development of blood supply occurs in tumours >1mm hypoxia has unfavourable clinical outcome

hypoxia causes

radioresistance

what is the iso-effective dose

the absorbed dose of a treatment under reference conditions providing the same biological effect in a given system as that of an actual treatment, all other conditions are the same

BED =

physical dose x relative efficiency

how can hypoxia be measured for ca cervix

functional MRI: provides biological information regarding the tumours physiology improves patient care DCA-MRI measures uptake patterns of a contrast agent GD - CPTA uptake depends on blood transfusion: can be analysed. patterns could demonstrate a particular gene profile (hypoxia gene sets), associated with poor outcomes advantages: MRI common, non invasive and visualises hypoxia

what chemo drug is a sensitiser

cis-platin synergistic with radiation- acute toxicity. It inhibits sublethal damage, synchronises cells to a radiosensitive phase in the cycle reducing tumour bulk enables reoxygenation

chemoradiation is designed for

patients with poor prognosis or bulky disease IB,IIB,III, IVA disease

pre treatment with cisplatin

doesn't affect the number of DSB with rad disrupts the repair of DSB low doses don't affect repair doesn't affect the repair of SSB