Radiotherapy Flashcards
What is the primary treatment for breast cancer?
Surgery
What is the primary treatment for oral pharynx cancer?
Radiotherapy
What is the primary treatment for small cell lung cancer?
Chemotherapy
How many patients in the UK at treated with radiotherapy at some point during their disease?
~50%
How many patients in the UK are hugely impacted by radiotherapy?
~20%
What are the 3 phases of a cell and tissues response to radiation?
The physical
The chemical
The biological
Describe the physical phase
Deposition of energy: isolation and production of fast electrons
Direct action of radiation - electrons damage DNA
Describe the chemical phase
Electrons interact with molecules to produce chemical changes: Free radical damage biological targets - indirect action
Describe the biological phase
The chemical damage has biological effects
The whole system
In terms of organic radicals, how does hypoxic conditions effect the cell?
The damage can be repaired and therefore the tissues are resistant to damage via radiation
What is the effect if the cells are well-oxygenated?
Organic peroxide is formed and the tissues cannot repair the damage since the organic peroxide fixes the damage
What is physical dose?
A measure of the energy deposited in the medium or the kinetic energy transferred
What does the biological effect of a physical dose dependent on?
The type of radiation
Number of fractions into which dose has been divided
Interval between fractions
The time the radiation is received
Dose rate of each individual fraction
Biological tissue/ endpoint under consideration
What are the two types of radiation?
Alpha particles
500NEB X-rays
What is the difference between the types of radiation?
Alpha particles produce more ionisation per dose than x-rays, therefore, alpha particles have a greater biological effect
How many Grey are fatal?
10 Grey
How many joules is 10 Grey equivalent too?
700J
Why does 700J kill you?
Due to the quantisation
What is quantisation?
It is put into a small package rather than a large distribution
Why is personalised medicine needed for radiotherapy?
We normally give the wrong dose of the drug
What are acute effects?
Occur at or around the time of radiation
Effects on the tumour appear to be parallel with the effects on normal cells
What are late effects?
Develop after 6 months of irradiation
Name a late effect of radiotherapy in breast cancer patients
They can develop cardiovascular disease
How long can the late effects of radiation occur for?
Can still occur 20 years later
What is the main issue with radiotherapy?
It targets well oxygenated cells
Normal cells are well oxygenated
Cancer cells tend to be hypoxic
What are the 5 R’s of radiobiology?
Repair Repopulation Reoxygenation Redistribution Radiosensitivity
What is reoxygenation?
during therapy, tumours reoxygenate - may be how some cells are responsive to therapy
What is redistribution?
During the cell cycle, the tumours have high levels of oxygenation
What is radiosensitivity?
Why some cells resist therapy and others don’t
What types of damage can radiotherapy and chemotherapy induce?
Missing base Single-strand break Bulky adduct Replication error (wrong base) Double-strand break
What repair mechanisms counteract the damage induced by radiotherapy and chemotherapy?
Base excision repair
Nucleotide excision repair
Mismatch repair
Homologous recombination end joining
What are the clinical advantages of radiotherapy?
Elimination of adjacent pre-malignant cells
Increased killing of tumour stem cells
Differentiation of undifferentiated tumour cells
Increased proliferation of normal cells
Increased radioresistance in adapted normal cells
Rapid relief of symptoms
What are the clinical disadvantages of radiotherapy?
Second malignancies Increased acute toxicity Increased proliferation of tumour cells Increased radioresistance in adapted tumour cells Increased systemic effects Late organ damage
What is radiogenomics?
The study of the link between germ line genotypic variations and the large clinical variability in response to radiotherapy
How can radiation effect genes?
It can upregulate and downregulate them
How can you use proteomics to see if a patient will respond to radiotherapy?
Look for hypoxic gene signatures in the tumour
How much does nimorazole cost per patient?
25 dollars
What is the function of nimorazole?
Sensitises hypoxic cells
What cancer responds well to nimorazole?
Head and neck cancer
How could you improve nimorazole distribution?
Use gene signatures to see if a patients tumour is hypoxic
It is more effective in more hypoxic cells
Describe the concept of self-vaccinating
Radiation produces massive cell death -> releases a lot of antigens into the blood -> encounters the immune system -> immune system produces anti- tumour antibodies
What is the issue with combining radiotherapy with immune modulation?
You could overwhelm the immune system and paralyse it
What is cyberknife?
a multidimensional planning couch and treatment head moves
Patients lay on the coach, the machine goes around and it irradiates the bits you want to irradiate
What is the novalis system?
A radiotherapy machine which rotates 360 degrees without moving a mm
What is tomotherapy?
CT scanner in reverse
the patients move through the tunnel and there is an array of x-rays targetting the tumour
you know you are targetting the tumour since it takes pictures throughout
What can go wrong with modernised machines?
They are all controlled by algorithms so if the algorithm is wrong it’ll target the wrong thing
