Radiobiology Flashcards
What is the criteria for a radiation induced secondary tumour
Second tumour occurs in location irradiated by primary or secondary therapeutic beam
Histology of second tumour is different to first so cannot be a met
Latency period, typically of several years
Second tumour not present at time of radiation treatment
Patient does not have a cancer prone syndrome
Where is evidence for cancer induction from?
A Bomb survivors
Biological studies
Patients exposed to radiation
Occupationally exposed workers
What models should you assume for cancer induction risk for low and high doses
Low: linear no threshold model
High: non-linear model with parameters fitted from epidemiological evidence
What is ICRP 103 conclusion on cancer induction
Combined detriment to excess cancer and heritable effects is 5% per Sv
What is EAR?
Excess absolute risk
Fraction RT patients contracting Ca - Fraction non RT patients contracting cancer
What is RR?
Relative risk
Fraction RT patients contracting Ca/Fraction non-RT patients contracting Ca
Breast cancer RT patients have a RR of about 1.3 for secondary breast cancer
What is ERR?
Excess relative risk
ERR = RR - 1
Fraction or % per Gy
What has evidence from atomic bomb survivors shown?
ERR of secondary cancer induction depends on the age at exposure
Decreases with age up to 20
Increases slightly up to older age (60)
Decreases after 60
Due to initiation and promotion processes
How would you calculate risk with linear no threshold hypothesis?
Sum dose distributions from different sources of radiation dose
Apply organ specific coefficients
Age and sex dependent
Apply generalised risk coefficient (5% per Sv)
Does not account for individual factors such as smoking or diet
How does higher doses affect cancer induction
Cell sterilisation is thought to reduce response gradient and reduce the chance of cancer induction, as cell sterilisation rates overtake cell cancer induction
Linear exponential dose response curve
Where are we mostly likely to see secondary cancers according to the shape of linear exponential curves?
Near margins of RT TVs or in low dose bath volumes (not necessarily the case, it is likely that there is a plateau or slower fall off with large dose according to dose date from RT patients, may be caused by repopulation)
How does cancer induction in atomic bomb survivors differ to RT patients?
A bomb survivors suffer carcinoma ((in rapidly dividing epithelial cells) and little sarcoma
RT patients have significant induced sarcomas (MSK tissue)
Implies different response from fractionated treatment
What is OED and how is it calculated
Organ equivalent dose
For an inhomogeneous dose distribution, OED is the uniform dose with the same risk of radiation induced cancer as DVH
Uses linear exponential dose risk model
Break DVH into equal volume dose bins, lookup alpha beta values and sum over all dose bins to calculate
What is downside of IMRT in terms of radiobiology and why?
Risk of second malignant neoplasms can increase by almost twice as much, caused by:
IMRT requires more fields so larger volume is exposed to radiation
Exposure of out of field tissues form leakage x rays ig reater because IMRT requires more MUs
What is integral dose
Total energy deposited in total irradiated volume of patient in kg x Gy
ID = m.D
For inhomogeneous dose distribution, summed across dose bins
What are concomitant exposures
Exposures other than treatment exposures: imaging exposures alongside RT
What are the 5 Rs of radiotherapy
Repair (of sublethal damage)
Repopulation (following irradiation)
Redistribution (of cells within cell cycle)
Reoxygenation (of surviving cells)
Radiosensitivity (intrinsic)
What are the issues to consider with fraction timing?
Incomplete repair between fractions (repairable DNA strand breaks are not repairs, problem for normal tissue tolerance)
Treatment gaps (repopulation issue with unintentional prolongation of treatment)
When might incomplete repair occur
Accelerated radiotherapy (intervals < 24 hours, most repairable damage is repaired after 6 hours, debated evidence shows slow repair components in which case may be some unrepaired damage)
Pulsed brachytherapy (time between fractions 1 hour)
Continuous LDR BT (ongoing repair during irradiation - different BED formula)
What is an example of accelerated RT and was it effective?
CHART Trial
1.5Gy/fr 3fr/day every day instead of conventional 5fr/week
Local control/OS not improved in H&N
Significant benefit to lung patients (although more difficult for hospital to deliver)
What is expected impact of accelerated RT?
Late normal tissue reaction expected to decrease, but this happened less than expected
Acute normal tissue reaction increases with accelreated RT, more severe, peaks earlier
How is incomplete repair accounted for in equations?
Adjustment is derived from the fact that the beta d^2 term is modified such that the relative effectiveness per unit dose is greater due to incomplete repair
Fractionated radiotherapy, h term which is described by a number of functions depending on how repair is modelled
LDR, R and mu
Why are equivalent regimes used?
To compare regimes, may want to know how an existing OAR tolerance varies when # is moderated
What is Withers formula
Formula for calculating EQDX
EQDX = D (a/B + d) / (a/B + X)
Why are reirradiations more common?
Technical advances mean improved outcomes and increased survival
Higher probability that patients will experience recurrence or new primary tumour or need palliative care
How are OARs considered in reirradiation?
Often based on OAR BEDs, recovery taken into account where possible, in form of increased constraint for BED typically
What are the four types of reirradiation?
1 - overlap of irradiated volumes with or without concern for toxicity
2 - no overlap of irradiated volumes with concern for toxicity from cumulative doses
Repeat organ irradiation - no overlap of irradiated volumes or concern for toxicity but TVs in same organ
Repeat irradiation - no overlap of irradiated volumes, no concern for toxicity, TVs in different organs
What is often issue with reirradiation data?
Poor quality, heterogeneous evidence, lack of QoL data, lack of clinical data, or lots of clinical data but no doses, no a/b values
Usually small cohorts, poorly reported, not correlated with clinical follow up
Recovery poorly modelled and poor assumptions made
Ambiguous dose stats (lung, right +left? lungs - targets? lungs - old vs new target?)
What does amount of recovery depend on?
Amount of recovery depends on OAR, time between treatments, initial dose (consider distribution, max, mean?)
What are the primary sources of evidence about radiobiology?
Emami data
Data from clinical trials
QUANTEC
PENTEC
What is one approach for re irradiations of complex dose distributions
Deformable registration and dose propagation
Summing EQD2 maps
How can you deal with a treatment gap?
Treat on weekends
Treat twice a day
Accelerated treatment
What are time factor considerations of missing treatments?
Repopulation of tumours and normal tissues can take part in treatments, although this is less an issue for normal tissues
Extending course of RT means cells repopulate and increase the number of cells to kill
How do we account for repopulation and proliferation
Use proliferation correction to account for BED loss due to tumour proliferation
No PC for normal tissue - won’t respond in timescale of treatment
When does repopulation begin and how do we compensate for it?
Repopulation in rapidly growing human cancer accelerates at about 28 days after initiation of RT
Higher doses must be delivered to compensate
Where is guidance on gaps?
RCR has published guidance on gaps
Timely delivery of radical radiotherapy: guidelines for the management of unscheduled treatment interuptions
What do we consider for lungs in reirradiation
Want Dmean below 20Gy EQD2
If higher, check areas of overlap and whether new course of RT adds to Dmean by previously unirradiated tissue or not (if same area, risk of pneumonotis lower than new are; area of 25-30Gy can help judge loss of total lung function)
Keep volume comparable to one remaining lung below 25-30 Gy
What do we consider for parallel organs for re irradiation?
Clinical judgement along with risk patient is willing to accept
No real answers, large uncertainties without good evidence
DIR and register previous plans to current CT, if uncertainty in match then use caution in critical areas of OARs and use PRVs
Why would we want to use TCP NTCP models?
Generate hypotheses for new clinical trials
To understand effects in uncertainty in dose
For relative plan evaluation
For plan optimisation
What is worse, cold or hot spots on a DVH?
Cold spots quickly drive TCP to zero
Overdose does not compensate for similarly sized underdose
How does tumour size impact DVH?
Greater probability of controlling smaller tumours, TCP higher in same DVH with smaller TV
What are added complexities for TCP?
Spread of alpha across patients (including radiosensitivity)
TCP across a cohort is shallower than TCP with a unique alpha value
Proliferation and repopulation requires longer TT
What are grading systems?
Systems grading toxicity, generally 1 - 5, mild to lethal.
Different ones, some grade patient reported, physician reported, subjectivity
Often grouped (1-2) due to low numbers
What are serial and parallel organs sensitive to?
Serial - hot spots
Parallel - mean dose
although often more complicateed, rectum bleeding, fistula based on high dose to small volume
Intermediate dose also important for late effects
What are the properties of acute effects?
Usually within 90 days
Tend to be in cells with low sensitivity to fractionation
Shorter overall treatment time increases acute effects
Transient, usually resolve
Can be serious if they will cause treatment gap
Eg dermatitis, mucositis
What are the properties of late effects?
Occur after months or years
Occur in cells with high sensitivity to fractionation
Greater damage may lead to shorter latent period
Little variation with treatment time
Irreversible
What are some patient factors of normal tissue effects
Age
Smoking
Diet
Genetic factors
Co morbidities
What are some sources of NTCP data
QUANTEC, HyTEC
What is method most often used for NTCP - DVH reduction
Lyman Kutcher Burman (LKB) model
Transform DVH into equivalent uniform dose and work out Veff (effective volume of uniform radiation) - uniform partial organ irradiation which is radiobiologically equivalent to true inhomogeneous dose distribution
Use empirical formula to determine NTCP, with TD50, m, n relevant to tissue
What are precautions to consider of TCP NTCP models
They are only models
Model patient cohort should match dataset
Volume definition should be checked
Consider dose grid, algorithm
What are some examples of TCP NTCP applications
Covid reduced fractionation
Cyber attack, natural disaster
Clinical trials: isotoxic lung escalation
CT: oesophagus dose escalation for improved TC
Investigating dose algorithm effects
What is BED equation taking into account proliferation?
BED = D(1+d/(a/B)) - K(T-T_delay)
K is daily BED equivalent of repopulation
T_delay is time from onset ot treatment to beginning of repopulation
What factors would impact how you decided to compensate for missed fractions?
How many fractions are left
Magnitude of tumour proliferation
Delay time before onset of proliferation
What datasets have replaced EMAMI?
QUANTEC - Quantitative Analysis of Normal Tissue Effects in the Clinic and Emami Update 2013
What cohorts are initiation and promotion associated with?
Initiation: younger patients
Promotion: increases with age
Which tissues are spared more by fractionation?
Lower a/B tissues
