Radiotherapy Flashcards
5 Rs of radiobiology
Repair Repopulation Redistribution Reoxygenation Radiosensitivity
Repair
Radiation induce DSB and SSB which can induce repair of the cancer cell
Repopulation
Cancer cells die and repopulate
The cell death induces inflammation which can can cause more cell death of the cancer cells
Redistribution
The cells in certain parts of the cell cycle are more responsive to radiation that other
G2 phase more responsive than G1 not enough time to repair all the chromosomes
So when it divides not sustainable with life so those cells die and leads to a redistribution of cell ages
Reoxygenation
Cells that are hypoxic in the middle of the tumour are less susceptible to radiation than the normoxic ones on the outside
So the ones on the outside are killed and the other ones on the inside become normoxic again so more susceptible until the tumour has disappeared
Radiosensivity
Some tumours and some cells in the tumour are more responsive than others this could be due to the receptor pathways of those cells
Example RTK mapkinase vs PI3K
Mapkinase susceptible as main output is proliferation
So can be affected by radiation in repopulation and redistribution
PI3K concerned with cell survival so not susceptible as others, this is radiosensivity
Proliferation causes stress and stress causes weakness that radiation can attack
Damage -> 2 repair pathways A and B
Cancer cell -> A pathway knocked out
Normal both okay
Find a way to knock out repair pathway B cancer cell can be killed by radiation whereas normal cell still has A to repair itself
Radiation dies something to induces angiogenesis
Don’t know what he didn’t go into it no notes on lecture
One of cancer hallmarks is resisting cell death what is important about the type of cell death radiotherapy induces
If it induces cellular senescence then the cell is immunologically silent immune system can’t see it
Necrosed immune system can and can remove it
Need a way to make all cell death by radiotherapy necrotic
What dies radiation cause
DNA damage
What makes cancer sensitive to radiation
Hallmarks of cancer
What is dose measured in
Gray
Physical quantity describing the amount of energy absorbed from the radiation beam at a given point
1Gy = 1J/1kg
What is the tumour lethal dose
Dose of radiation that eradicates the tumour within the treated time
Total number of surviving cells is proportional to the initial number present and the number killed after each dose
What limits the dose
Normal tissue tolerance to the radiation
SE
How dies normal tissue tolerance vary between tissues
Vascularity Immune effects Age Serial vs parallel organs Radiogenomics
What is the therapeutic index
Between dose having an effect to where it becomes too lethal 85% tumour 5% SE - worthwhile 85% tumour 70% SE - not worth while
What is the total dose dependent on ?
Intent of the treatment - palliative vs radical
Diagnosis - lymphoma vs HNSCC
Size of treatment volume - T1 larynx or T4N2c Tonsil
What determine the treatment time
Time taken to deliver the prescribed dose
General rule- the longer the treatment time, the great the dose required
The greater the dose required the longer the treatment time should be
What is fractionation
Splitting up the dose
Dose delivered per day I.e. Function of total dose and treatment time
Why fractionate - repair
Small dose a day allows the normal tissue to repair and recover
Differential dsDNA repair between cancer and normal tissue leads to gradual tumour death with preservation of normal tissue
What fractionate - redistribution
Proliferating tumour cells progress into more radiosensitive part of the cell cycle at each session
Why fractionate - repopulation
Both normal and cancer cells repopulate
Repopulation is the basis for tissue repair
Repopulation can lead to loss of cure
- accelerated repopulation
Cancer cells respond to cell death by proliferating more quickly for about 4 weeks
Tumour control drops if treatment is prolonged
Basis of twice daily fractionation
Why fractionate - reoxygenation
Gradual tumour death during treatment normalises vasculature
Hypoxia falls and radiosensivity rises
Types of fractionation regimes
Conventional
Hyper fractionation
Hypo fractionation
What does GTV stand for and what is it
Gross tumour volume - the visible tumour assessed by imaging and clinical assessment
What does CTV stand for and what does it do
Clinical target volume - includes the GTV and the area at risk macroscopic and microscopic disease
What does PTV stand for and what is it
Planning target volume and it is volume of tissue that should be irradiated to ensure that the CTV is targeted adequately during each fraction
Accounts for any movement, set up error, tumour response during treatment - margin for error
Acute SE of radiotherapy
Fatigue
Nausea
Dermatitis
Mucositis - eating drinking, communicating, pain and mucus
Long term side effects
Dry mouth/ taste changes
Skin fibrosis
Dental caries
Rare-
Osteoradionecrosis of the jaw
Stroke
Second malignancy
