Radiobio part 5 Flashcards
Gaps in RT
Why do gaps matter?
- initially after first 1-3 weeks there is little or no repopulation.
- After approx 3 weeks there is steady repopulation - therefore there is need for additional dose to achieve the same effect (level of tumour control).
- if there is a gap in treatment adding this on at the end of the regimen will NOT have an adequete effect on tumour control as there is a need for additional dose.
If overall treamtent time increases BED decreases. Repopulation means that the same dose provides less control.
Impact of gaps depends on
- Tumour type and treatment type ie. radical vs palliative
- Duration of the gap
- Timing of the gap - early or late in the course - early gaps are better as they are less likely to be in the repopulation phase and also this leaves more time within the prescribed regime to compensate for the gap.
- Method of compensation.
Prioritisation of patient (categories)
Cat 1 : 95% should complete within +2 days of prescribed regime (e.g H&N, Cervix SCC, NSCLC). Compensate if delays >2 days.
Cat 2: aim to complete within 2 days but up to 5 days acceptable (will not cause adverse outcome)
= all other radical treatments. Consider compensation if delay >5 days.
Cat 3: palliative - overall time is less critical. Consider compensation of delay is > 7 days.
Errors
if made early in treatment and to keep overall treatment as planned:
- if higher dose given (hypofractionation error) caused by hyperfractionating rest of treatment
- If lower dose given (hyperfractionation error) - correct by hypofractioning rest of treatment.
Different dose rates
LDR - ultimate form of fractionation, equivalent to multiple infinitely small fractions being given without radiation free intervals - therefore damage induction and repair occurs simultaneously.
Continuous LDR - brachytherapy with temporary or permanent source implantation.
If DR is lowered - time taken to deliver a particular dose increases. It then becomes possible for other biological processes to take place & modify the observed radiation response.
- Intracellular repair is the fastest - T1/2 is about 1 hour, therefore if dose exposure is increased more repair will take place and will therefore modify radiation effects. DR range from around 0.1-1Gy/min
In time orer:
Recovery
Reassortment
Reoxygenation
Repopulation
In contrast - repopulation is much slower with doubling time >1 day.
As DR decreases, effect per unit dose decreases, there is more time for SLD repair.
Continuous LDR exposure is the most efficient way of allowing maximum tissue recovery in the shortest overall time. It minimises the effect of cell proliferation - advantageous in terms of tumour cell damage but disadvantageous for tolerance of early responding tissues that rely more on repopulation than intracellular repair.
Brachytherapy dose rates
LDR
Medium DR
High DR
Pulsed DR
LDR - 0.4-2Gy/hr
MDR 2-12 Gy/hr
HDR >12Gy/hr
Pulsed dose rate - LDR delivered as HDR - tx delivered once per hour.
Very LDR - permanent implant, delivery over weeks or months
Brachytherapy Advantages
- Rapid fall off in dose
- High dose directly to tumour with relative sparing of normal tissues
- No need for margins to account for motion
- Can be used when limited by normal tissue tolerance
- Re-treatment
- Short treatment time - reduced repopulation
Moving From LDR to HDR
Advantages - short treatment times (HDR only takes minutes). Stepping source allows optimisation of dose distributions by varying dwell times at each position
Disadvantages - short treatment times do not allow for repair of SLFR or redistribution of cells within the cell cycle or reoxygenation. Additional radiation protection procedures are needed
= relative increase in NT effects.
Pulsed Brachy
dose delivered in a large no. of small fractions with short intervals. Provides same radiobiological advantage as continous LDR with added benefit of optimised dose distribution & patient logistics.
RBE
= the ratio of dos between a standard radiation and a test radiation for a given effect (to produce same biological response)
Standard radiation = 250 KeV xrays (photons)
Correlation with LET:
- Radiation is more effective at causing damage as LET approaches 100 kEV/um, before falling off again.
- it is thought that over 100kEV/um so much energy is deposited in a cell that some of the energy is ‘wasted’ - also known as overkill.
- radiation is wasted on the already dead cell rather than travelling on to another cell to cause more damage.
- RBE depends on - LET, dose, no. fractions, dose-rate, biological system/end point
- The let at which RBE reaches a peak is much the same (about 100 kev/um) for a wide range of mammalian cells.
- As LET increases, the RBE increases slowly at first and then more rapidly as the LET increases beyond 10 kev/um.
- Between 10 and 100 kev/um the RBE increases rapidly with increasing LET and reaches the maximum at about 100 kev/um.
- Beyond this value for the LET the RBE again falls to lower values.
Oxygen as a radiosensitiser
Oxygenation is a radiosensitisor - shifts curve to hte left.
Hypoxic modification = improved local control.
- if higher conc of o2 more chance of oxygen fixation -> free radical induced DNA damage.
- increasing o2 delivery to tumour during RT improved effect of DNA damage both directly and indirectly.
- To produce its effect oxygen must be present during the radiation exposure or at least during the lifetime of the free radicals generated.
OER
OER = ratio of doses with or without oxygen to produce the same biological effect.
Cells typically 3 x more sensitive to radiation in the presence of oxygen.
- only small amounts required for sensitisation
OER ~ 3 x the dose to hypoxic vs oxygenated tissues to have the same amount of cell kill.
OER xrays = 3
protons = 3
neutrons = 1.6
charged particles i.e electrons = 1 (work by direct damage).
Hypoxic fraction = surviving cells in oxygenated conditions/surviving cells in hypoxic conditions.
Role of reoxygenation
Hypoxic areas of tumour (those furthest from blood vessels) have less DNA damage.
- Tumour hypoxia is independent of tumour size and is prognostic indicator of poor outcome
- Chronic hypoxia = increased C02, therefore acidic and low pH
Fractionating radiotherapy counteracts this:
oxygenated tumour cells die more quickly with a low dose of RT.
- This allows hypoxic cells to migrate towards blood vessels (reoxygenation) -> oxygenation of tumour cells improves
- These cells die more easily with the next fraction.
- Also in differnent areas of the tumour, blood vessels will be contracting/dilating at different times (hypoxia is dynamic) - more fractions = more chance of targeting a tumour when vessels are dilated.
OER & LET
With sparsely ionising radiation eg. xrays - as ionisation density (LET) increases the OER is reduce.
- this is because high LET radiations are much more heavily reliant on direct ionisation to cause DNA damage and therefore o2 level is less important.
