Radiobiology Flashcards
what are the three phases within the body
physical, chemical, biological
describe the physical phase
- CS
- x-rays/ gamma rays remove an atom due to an interaction with an orbital electron, this vacancy is then filled by an inner electron via CR. The scattered photon continues interacting as well as releasing an electron
10^-18 cross DNA
10^-14 sec to cross cell - leads to chemical change
describe chemical change
- H2O causes indirect DNA damage
- change within the body
- occurs before the patient leaves the room
describe the biological phase
- won’t see a change for a few days
- direct damage, partial interactions, within DNA + indirect damage (cell kill)
- cell cycle damage
what happens with SSB
the backbone is broken affecting only one strand
what happens with DSB
there is a break at either side, damaging the nitrogenous base, which affects both stands
- only a small proportion of damage
why is DSB vital
in order for cell kill
what does 1-2 Gy result in
1000 SSB = 40 DSB
describe direct DNA damage
- x-rays only slightly damage the DNA
- higher doses are needed
- direct ionisation occurs at the critical target of DNA
- DNA damage, breaks the crosslinks between DNA and protein
- chromosome aberrations - breaking and rejoining of chromosomes, sticky ends join with sticky ends creating a distortion
describe indirect damage
- chemical change
- X-rays / photons by products of water
- secondary electrons ad protons (interact with tissue)
name highly sensitive tissue
- epithelial lining of the alimentary canal
- haemapoetic tissue
- reproductive cells
these demonstrate damage in 3-4 days
epithelial skin damage is within 7-10 days
where are SSB repairable
checkpoints
what is the irradiated volume
it is the normal tissue which receives a significant dose
what is the therapeutic ratio
ratio between normal and tumour cell damage. Effects of tumour response and normal tissue damage
what happens to the tumour response as dose increases
it increases
how does tissues differ within the SI
both tumour and normal cells are responsive within the SI which causes more damage causing a greater effect
do tumours and normal cells differ in affected by radiation
they act in the same way but tumour cells become damaged at a lower dose
what happens with radio-sensitivity and radioresistant
if the tumour is radio resistant (T shifts right) or if normal cells are radiosensitive (C shifts right), lowering the tumour response.
why are radio-resistant tumours less likely to be treated with RT
more normal tissue would be irradiated as higher doses are needed
considerations
- early effects = skin erythema
- late effects = telangectasia
- initial x-ray deposition occurs rapidly
- eye lens is radiosensitive
- the latent period after irradiation is inversely related to the dose administered and ranges from minutes to years
what is radio-sensitivity
- relative vulnerability of cells which are damaged by IR
- number of cells killed by the dose
- dependent on cell type (malignant or normal), histology
which structures have intermediate sensitivity
- lung
-kidney - eye lens
- supportive nervous tissue
- demonstrated within a week or so
low sensitivity structures
- muscle
-bone - connective tissue
- nervous tissue
- slow reproduction rate
what is the standard regime involve fraction wise
2 Gy
what are the four R’s
Reoxygenation
Reassortment
Recovery
Repopulation
Describe re-oxygenation
- applies to the tumour cells
- hypoxic cells gain access to oxygen which causes DNA fixation damage
- low O2 = tumour reaper, indirect damage causing SSB
- increased susceptibility to radiation damage
- occurs within 24 hours
- daily treatment gives a better response
- links with angiogenesis
describe re-assortment
- occurs over a few hours
- M phase is twice as sensitive as the late S cells
- single fractions kills cells preferentially
- RT is cell specific
- increases chances of hitting cell in a sensitive stage
- single exposure damages fewer cells
- radiation introduces a block in G2
- checkpoint ensure successful replication otherwise cell apoptosis
describe recovery
- all cells repair radiation damage
- can recover from SSB
- occurs over a few hours
- normal cells have a higher capacity at recovering after a fractionation
describe repopulation
- allows for proliferation of tumour cels
- shorter RT has less repopulation, resulting in higher doses in order for cell kill
- everyday of fractionated RT over 3-4 weeks results in a loss of 0.6 Gy so an additional 0.6 Gy must be given at each fraction
what are the factors of biological radiation doses
number of fractions
total dose
TT
what are tissue tolerances
the degree of risk which is independent on the seriousness of the resultant disease
- < or equal to 2cm included in the tangential fields
- 5% risk of bowel damage is acceptable for CA cervix
- < or equal !% spinal cord damage is acceptable
- cataract formation occurs 100% patients who receive 7 Gy to the lens
what are low tolerances equal to
radiosensitive tissue
when are low doses given
whole organ irradiation
when are high doses given
partial organ irradiation
what are oxic cells
fully oxygenated cells
what are anoxic cells
cells which lack oxygen
what are hypoxic cells
poorly oxygenated cells
what happens beyond the anoxic region
necrosis, so some tissue will die
what is acute hypoxia
hypoxia which is temporary when capillaries open and close, this occurs randomly
describe chronic hypoxia
- angiogenesis is not well developed
- cells may proliferate well, dead
- responses vary
- cells won’t reoxygenate
what determines the amount of radiation given
normal tissue tolerance
what is classed as category 1
- radical intent, with prolongation likely to adversely affect the outcome
- NO unscheduled interruptions
- SCC H&N, SCC cervix, medulloblastoma
what is classed as category 2
- radical intent, no clear evidence that prolongation will adversely affect the outcome
- should be kept to a minimum
- IF there’s a break it needs to absolutely necessary
what is classed as category 3
- palliative intent
- no evidence that it will cause affect
- hypo fractionated
- less impactful
what is the tolerance dose
max amount of radiation a tissue can receive before becoming permanently damaged
what is tolerance dose dependent on
- radiation type
- tissue type
- fractionated
what is angiogenesis
- formation of new blood vessels
any tumours over 400um
background info on oxygen effect
- broad beans were irradiated in a surplus supply of oxygen as well as a deficit
why is being in an oxygenated environment beneficial
- allows for more DSB
- capillaries supply oxygen to toxic tissue
- cells irradiated in an absence of oxygen tend to be more radioresistent, so more susceptible to damage
- tumours are capable of VEGF, (vascular epithelial growth factor), enoucrgaing capillary growth
give the radiolysis process
O2 + OH. -> free radical preventing sublethal damage
R. + O2 -> RO2.
(RO2. causes permanent DNA damage)
what is oxygen classed as?
a fixer, it fixed damage in place making it permanent
hypoxic cells are less reactive
what is the gold standard for breast cancer
40 gray, 15 fractions
what mmHg is most beneficial
20
what is the oxygen enhancement ratio
how sensitive cells are when fully oxygenated
typical = 2.5-3
equation for OER
OER = hypoxia/ oxia
what is the max ppO2 in well vascularised tissue
40 mmHg
what is the bystander effect
cell survival is reduced when communicating with adjacent irradiated cells. Bystander 1: cells receiving a low dose during RT exhibit increased survival when neighbouring cells receive a lethal dose
conventional RT
- 2 gy per fraction
- 20-25 fractions
- 35-40 fractions
hyPOfractionated
- under fractionated, high doses
- less frequent RT
- single exposure = 8 Gy per fraction, once weekly, twice for NSCLC
- bone metastases = 15 gy single exposure
- 3.3-3.6 Gy per daily fraction, total 15 fractions
- radioresistent tumours
- not used in head and neck
HyPERfractionated
- more than one fraction per day
- 6 hour gap due to serious tissue damage/ late morbidity, allows reoxygenation
- no more than 3 a day
- head and neck
CHART Wel
- CHART weekend less
- 1.5 Gu, 40 fractions
- 3 fractions per day over 17-19 days, total of 60 Gy
- head and neck and NSCLC
continuous
- no weekend breaks
- hyperfractionated or conventional
- reoxygenation can occur
- addresses repopulation
- management issues, lack of staff
CHART
- for short doubling time tumours
- hyPERfractionated
- 1.5 Gy/ 36 fractions
- 3 fractions per day over 12 days = 54 Gy
Accelerated
- 5+ fractions per week
- addresses recovery from sub-lethal damage in low LET
- addresses repopulation: can’t repopulate
- fractionation over 4 weeks must have higher doses
- normal tissues can’t repair, increasing side effects
- recurrence of tumour is hard to treat
how is unscheduled gaps compensated
- twice daily fractions min 6 hour gap
- weekend treatment
- BED, fewer fractions to achieve planned overall, dose is higher
- additional fractions to compensate within the original TT, treatments are added
- category 1 patients must be treated first twice daily
