What is radiation therapy?
An often used and successful modality in the 'local' treatment of cancers
What is the problem with radiation therapy?
There is a risk of inducing a variety of human cancers
What cancer treatments are used to achieve local control of the disease?
What cancer treatments are uesd to treat disseminated disease?
What cancer treatments are used for pallitation?
Is radiotherapy delivered as a monotherapy?
How is radiotherapy used in conjuction with surgery?
It can be used before or after surgery
Why might radiotherapy be used before surgery?
To shrink tumour so that it is more operable
What are the types of radiotherapy?
- External beam radiotherapy
- Unsealed sources
What happens in external beam radiotherapy?
X-rays are generated externally, and precisely targetted into the body
What happens in bracytherapy?
A sealed radiation source is inserted into the body
What kind of emitters are used in brachytherapy?
Short range, only a few cm
What kind of radiation is used in unsealed source radiotherapy?
High energy, short range
Give two examples of medications used in unsealed source radiotherapy
- Radioiodine in thyroid cancer
- Meta-iodobenzylG in neuroblastoma
What allows unsealed source radiotherapy to work?
Some drugs/chemicals have an affinity for certain organs
What are the rules for all forms of radiotherapy?
- Maximise dose to tumour
- Minimise dose to normal tissue
What % of cancer patients require RT at some stage of their illness?
What % of those treated with radiotherapy are treated with curative intent?
What % of those treated with curative intent have an >5 year survival?
How can radiotherapy improve in the future?
- Improvements in tumour control
- Reductions in toxicity
- Early detection
- Increases in tumour sensitivity
What can x-rays and gamma-rays be thought of as?
Waves (λv = cc) or as photons (E = hcv)
What does the equation λv = cc tell you about x-rays?
As the frequency goes up, the wavelength must go down to keep Cc constant
What are photons?
Packets of energy
What do electromagnetic radiations (x-rays or gamma-rays) interact with?
The electronic component of matter
What can absorption of energy from radiation lead to?
- Excitation - loss of an electron to a higher level
- Ionisation - actual ejection of the electron
What happens when an electron is ejected in ionisation?
The molecule has an unpaired electron, and so is a free radical
What is a free radical?
A chemically reactive entity that causes chemical changes to exposed atoms and molecules
What damage can be caused by free radicals?
Lethal damage or mutation
What kind of damage is good in terms of radiotherapy?
Lethal damage, as want to kill the tumour cells
Why it mutation bad in radiotherapy?
Because there is a change in function, which can be detrimental in a normal cell
What does the process, at an atomic level, by which x-rays are absorbed depend on?
The energy of photons, and the chemical composition of the absorbing material
What process of absorbtion dominates for high energy photons?
The Compton Process
What happens in the Compton process?
A photon interacts with loosely bound 'free' electrons, of low binding energy. Part of the photon energy is given to electron, knocking the electron out. The photon then proceeds with a reduced energy (longer wavelength)
What is the end result of the Compton process?
The production of fast electrons, many of which will go on and ionise other atoms of the absorbed. There is also a deflected/scattered photon of reduced energy
What process of absorption dominates for photons of low energy?
The photoelectric process
What happens in the photoelectric process?
The photon interacts with a tightly bound electron of higher binding energy, and gives up its energy entirely. The electron is ejected, and the photon is entirely absorbed
What is the end result of the photoelectric process?
The production of fast electrons but no photon
/Where are photons of lower energy used?
In diagnostic radiology
How do the Compton process and photoelectric process differ, in terms of the relevance of atomic number?
The Compton process is independent of the atomic number of the absorbing species, however the photoelectric process varies rapidly with atomic number
Where are the differences between the Compton process and the photoelectric process important?
In the application of x-rays to diagnosis and therapy
Which process is used for radiation therapy/
Why is the Compton process important for radiation therapy?
To avoid the problem of differential absorption in tissues, so bone doesn't shield the tumour
What process is used for diagnostic radiology?
The photoelectric process
Why is the photoelectric process good for diagnostic radiology?
Because bone differentially absorbs x-rays, resulting in the visualisation of bone structure
In what ways can ionising radiation at a molecular level?
Can be directly acting or indirectly acting
What is meant by directing acting ionising radiation?
If the atoms of the target molecule are ionised
Can directly acting ionising radiation be protected against?
Generally, can only be shielded, can't be modified by sensitisers and protectors
What is meant by indirectly acting ionising radiation?
If the radiation interacts with other molecules to produce free radicals that migrate into the DNA, this is an indirect effect
What % of the body is water?
What happens when ionising radiation hits a water molecule?
Produces an electron, which becomes solvated by water, and a H2O*+ radical
What happens to the H2O*+ radical?
It breaks down to produce *OH- and H+
What is the problem with the hydroxyl radical (*OH-)?
It is very reactive, and generates more free radicals from water molecules
What proportion of cellular damage is caused by indirectly acting radication?
How can indirectly acting radiation be modified?
Sensitisers and protectors
What is an important characteristic of ionising radiation, regarding its release?
The energy is not uniformly released, but deposited unevenly in discrete nm-localised events of concentrated energy
How much energy is released by ionising radiation?
About 33eV - enough energy to do considerable amount of damage to biological molecules
What is the biological effect of ionising radiation determined by?
The photon energy size, not the amount of energy absorbed
What is the principle target for the bio-effects of ionising radiation?
What lesions can be caused by the interaction of ionising radiation with DNA?
- Base damage
- Sugar damage
- Strand breaks
Give two examples of base damage that can occur as a result of the interaction of ionising radiation with DNA?
- Thymine glycols
GIve two examples of sugar damage that can occur due to the interaction of ionising radiation with DNA
- Abasic sites
- Strand break lesions
Why are double strand breaks so important?
- Unrepaired DSBs are thought to be critical cell killing lesions
- DBS repair is problematic and error-prone in mammalian systems
Why is DBS repair problematic?
Because you may loose genetic material, causing a sequence change and therefore protein change
What is the significance of misrepaired double strand breaks?
They are the principle lesions of radiation mutation and visible chromosomal aberration formation
How much radiation is given in radiotherapy?
Typically, 30 fractions of 2Gy each, given Monday-Friday for 6 weeks
What is fractionation of the radiation dose?
The splitting of the total dose into many single fractions
What is the advantage of fractionation of the radiation dose?
- Produces better tumour control for a given level of normal tissue toxicity than the administration of a large dose
- Spares normal tissue by allowing for damage repair between doses
How does fractionations spare normal tissue?
Normal tissue has its full complement of DNA repair, whereas tumour tissue has compromised repair. This means that only the normal tissue can repair its DNA in the interval
What happens as solid tumours rapidly grow?
They start to exceed their supply of oxygen and nutrients, and tend to become hypoxic
What % of solid tumour cells are hypoxic?
What is the problem with hypoxic tumour cells?
- They are radioresistant, but still viable
- They are more aggressive
What is the difference in dose needed to kill hypoxic cells known as?
The OER - oxygen enhancement ratio
What is the OER at low doses?
What can be done to overcome the problem of tumour hypoxia?
How dose dose fractionation overcome the problem of tumour hypoxia?
It allows for reoxygenation
What does multiple beam radiotherapy allow?
The radiologist to superimpose the X-ray dose over the tumour bearing region, to allow high doses to the tumour volume with sparing of adjacent tissue
What needs to be done regarding the positioning in mulitiple beam radiotherapy?
- Have to position the patient accurately and reproducibly
- Have to adjust to take into account tumour shrinkage using image guided ultrasound
What is used to shape the beam to the tumour volume?
What does the use of multiple beam techniques combined with multi-lead collimators allow the radiologist to do?
Shape the x-ray beam to the tumour shape to allow a high dose region to fit the tumour volume, with greater sparing of adjacent tissue
How is multiple beam radiotherapy developing?
Now using an increasing number of beams
What is the problem with multiple beam radiotherapy?
No region is left unexposed
What is it hoped will be achieved with fractionation and multi-beam conformal radiotherapy?
The situation of positive therapeutic gain occurs, whereby the dose required to control the tumour is achieved, with an accetable level of normal tissue damage
What is a proton?
A subatomic particle with a positive electric charge of 1 elementary charge, and a mass of slightly less than a neutron
What is the Bragg peak?
A pronounced peak on the Bragg curve which plots the energy loss of ionising radiation during its travel through matter. For protons this occurs immediately before the particles come to rest - the Bragg peak
What does the depth to which the protons penerate into the patient depend on?
The energy of the proton beam
What is the result of the precise control of the energy of the proton beam?
It means the proton beam stops at the target, and so the target gets more of a radiation dose than the overlying tissue, and the underlying tissue receives no radiation dose.
How do x-rays compare to protons in term of penetration?
X-rays are more penetrating than protons, and so cannot be stopped at the target so higher doses of radiation are delivered to surrounding tissues
What have large scale animal studies and epidemiological studies of human populations shown about radiation?
It is a universal carcinogen
What is meant by a universal carcinogen?
Induces cancer in most tissues, of most species, of all ages
What does the universal nature of radiation as a carcinogen relate to?
The all-penetrating character of ionising radiation
How does the carcinogenic potential and mutagenic potential of radiation compare to other chemical agents/
It is a weak carcinogen and mutagen
Why is radiation only a weak carciongen and mutagen?
Because it is such a good cell killing agent