Secondary cancer induction and fraction timing issues Flashcards
What 5 criteria must a cancer meet to be classified as a secondary cancer?
Occurs in locations irradiated by primary or secondary beams
Histology of second cancer is different from first - not a met
Latency period - typically a few years
Second tumour not present at RT
Patient does not have cancer prone syndrome
What is the radiation based cancer induction evidence?
Biolgical studies
A-bomb survivors
Patients expossed to diagnostic and therapeutic radiation
Occupationally exposed workers
What is the evidence for cancer induction by low doses of radiation?
ICRP 103 - assumes 5%/Sv
Biological effects of ionising radiation report VII - concludes linear no threshold model
UNSCEAR 2000 and 2006 reports
How is cancer induction risk expressed? What are the equations?
- Excess absolute risk per 10^4 person-years per Gy
EAR = Fraction of RT patients contracting cancer - Fraction of non-RT patients contracting cancer - Relative risk
RR = Fraction of RT patients contracting cancer / Fraction of non-RT patients contracting cancer - Excess relative risk
ERR = RR - 1
How should the linear no threshold approach be applied?
Sum dose distribution from different sources of radiation - apply organ specific coefficients - it is age and sex dependent
Apply a generalised risk coefficient of 5%/Sv
What does the linear exponential dose curve suggest?
Cell sterilisation can overtake cell cancer induction, reducing the response curve
Why might the linear exponential dose curve not be accurate?
Suggests the most likely location of secondary cancer is at the margins of treated areas and in IMRT low dose bath but this doesn’t correlate with RT patient data which suggests there is a plateau, potentially caused by cell repopulation
Why might A-bomb survivor data not be applicable for RT patients?
A-bomb data suggests only getting carcinoma whereas RT data suggests patients also get sarcomas
What is the organ equivalent dose?
For an inhomogeneous dose distribution the OED is the uniform dose with the same risk of radiation-induced cancer as the patient’s DVH
Why is OED good?
Accounts for dose response relationship for radiation-induced cancer in different organs - uses linear exponential dose risk model
What is the equation for OED?
OED = 1/N . sum(Di.e^(-alpha.Di))
How is the radiation induced cancer incidence rate at a uniform dose defined?
Iorg = Iorg,0 . OED
What 2 reasons contribute to IMRT treatments increasing the risk of second malignant neoplasms?
IMRT requires more fields so a larger volume is exposed to radiation
Out of field tissue is more exposed to leakage x-rays as IMRT requires 2 or 3 times as many MU
How is the integral dose for the IMRT dose bath?
Total energy deposited in the total irradiated volume of the patient: ID = m.D
For inhomogeneous dose distributions the total ID is the summed ID across all dose beams: ID = sum(Di.Vi)
What are concomitant doses?
All exposures within the course of RT other than treatment exposures. Include simulation, CT localisation, portal localisation, and verification images
They irradiate normal tissue outside the target volume or the intended path of the primary beam and therefore contribute to the potential detriment of the patient
What is the problem if there is incomplete repair between fractions?
A significant proportion of single strand breaks are not repaired so normal tissue tolerances are lower
What situations lead to incomplete repair?
Accelerated RT - reduce proliferation
Pulsed Brachytherapy - time between fractions = 1 hour
Continuous low dose Brachytherapy - ongoing repair during treatment
How long does it take for repairable damage to be repaired?
~6 hours
What is the correction that is made to the BED equation for fractionated RT?
beta.d^2 term in the survival fraction is modified as the relative effectiveness per unit dose is greater due to incomplete repair:
BED = nd(1 + (d(1+h)/(alpha/beta)))
What is the correction that is made to the BED equation for low doserate brachy?
BED = RT(1 + 2R/(mu(alpha/beta))) R = dose rate T = time
What are the possible causes of treatment gaps?
Patient non-attendance - too ill to attend, adverse weather, non-cooperation
Machine breakdown
How can both TCP and NCTP be kept constant after a treatment break?
Original number of #s and dose/#
Original treatment time - may need to treat on a weekend
Original repair between fractions
What are some issues with repair?
Have different repair half times between tissues - 1.5hrs for normal tissue, 0.5hrs for tumour tissue
Can have multiphasic repair - get quick initial repair followed by prolonged subsequent repair past 6 hours
What is the equation for BED considering tumour repopulation?
BED = D(1 + d/(alpha/beta)) - (ln2/alpha).((T - Tdelay)/Tp)
How should treatment gaps with time longer than T be handled?
Try to treat in time T by doubling up treatment days
If not then increase d and n to give same BED
What is the equation for the tumour potential doubling time?
Tpot = Tc/GF
Where Tc = cell cycle time
GF = Growth fraction - actively proliferating cells /all tumour cells
What is the equation for the maximum tumour growth rate with no cell loss?
1/Tpot
What is the equation for the actual tumour growth rate?
1/Tvol
What is the equation for the cell loss factor?
phi = 1-(Tpot/Tvol)
What are the cell loss factors for carcinomas and sarcomas? Why?
Carcinomas - high, >70%, due to origin as rapidly renewing epithelial cells -cell loss factor = 100%
Sarcomas - slow, <30%
What happens to the GF value of tumours before and during RT? Why?
Before GF slows down as the tumour is large
GF speeds up to maximum during RT as remaining cells get better nutrition as there are fewer of them
What factor should be used for radiobiology calculations during RT with proliferation?
Tpot
What are the 3 categories of patients? What do they mean?
1 - should not have their radical treatment prolonged
2 - every effort should be made to keep any prolongation of treatment to a minimum
3 - palliative care
How should unscheduled interuptions be prevented?
Transfer patient
Ensure schedule is properly managed
What compensation is recommended by the RCR for unavoidable and unscheduled gaps?
Acceleration (>6hr gap)
Weekend/bank holiday treatments
Adjust d,n to maintain T - sacrifice the therapeutic ratio a little
Add fractions if maintaining T is impossible - sacrifices therapeutic ratio more
What is the RCR equation for BED?
BED = nd(1 + (d/(alpha/beta))) - K(T-Tdelay)
K = ERD loss/day
= ln2/(alpha.Tpot)
