Radiation is the emission of energy, in the forms of waves or particles.
Ionising radiation is radiation that has enough energy to remove electrons from an atom, causing the atom to become charged or ionised.
- Ionising radiation can be x-rays or gamma-rays.
- Photons are minute energy packets of radiation.
Radiotherapy = using ionising radiation therapeutically to treat malignancy.
Radiation therapy generally works by inducing double-strand breaks in DNA
Can be direct damage (direct ionisation effects on DNA) or more predominantly indirect damage (production of free radicals which damage DNA). SBRT may also cause direct cell apoptosis and cell membrane disruption with higher doses per fraction.
How is radiation delivered?
It can be delivered externally from a linear accelerator (external beam radiotherapy) or from internal radiation sources (brachytherapy).
- Linac uses electricity to power an electron gun, generating electrons which are accelerated down a waveguide to a high energy, striking tungsten and generating photons.
EBRT can be delivered from a single beam (often in palliative radiation) or more often from several directions.
Modern 3D conformal radiotherapy uses a 3D recreation of the target tissue and surrounding organs at risk using axial images.
Intensity modulated radiation therapy (IMRT) is an advanced form of conformal radiotherapy which uses a multi-leaf collimator to vary the intensity/number of photons across the radiotherapy beams in multiple dimensions – tightly conforming to target tissue and sparing organs at risk.
- Combination of advanced software for planning and hardware (collimator).
Volumetric modulated arc therapy (VMAT) is a form of IMRT where the Linac rotates continuously around the patient and delivers the IMRT dose quicker.
Image guided radiotherapy – used to target better and account for motion (of both target and OAR).
- Fiducial markers
- Tattoos
- Daily cone beam CT
Radiotherapy is typically delivered in fractions. The total dose of radiation delivered is divided into fractions to optimise the oncological effect whilst reducing toxicity to normal tissue.
The rationale for fractionation is:
- Radiation causes cell damage by damaging DNA – the effect of radiation on cells is only seen during M phase or G2 – cells in S phase generally resistant – delivering doses at different times (“reassortment/re-organisation”) also increased efficacy.
- Normal cells have the ability to repair DNA damage – malignant cells do not – fractionation allows time for normal cells to repair sub-lethal DNA damage
- It also allows rapidly dividing cells like bowel and bladder to recover (“repopulate”)
- More oxygenated cells are more radiosensitive (presumably related to free radicals) – as these cells are killed, other cells become less relatively hypoxic and more oxygenated and therefore more sensitive (“reoxygenation”)
Conventional fractionation generally refers to daily dose of 1.8 – 2.0 Gy.
Accelerated hyperfractionation refers to more than one treatment per day, with at least 6 hours between treatments.
Hypofractionation is the use of larger fraction doses over a shorter period of time
Stereotactic ablative radiotherapy (SABR) is a more extreme form of hypofractionation – relatively very high doses of radiation (up to 8 Gy / fraction) in a small number of fractions with precise image guided aim – associated with direct apoptosis.
The optimal fractionation and dose for different tissue is based on the duration of tissue’s cell cycle and ability to repair sublethal damage.
- ‘Early responding’ – skin, mucosa, bone marrow, cancer
- ‘Late responding’ – heart, spinal cord
- Can be estimated with a/b ratio and ‘linear quadratic model’
Proton therapy is a novel technique using protons instead of photons (x-rays) – proposed to deliver more precise therapy sparing surrounding tissue. It is not currently used in urological cancers but is being studied.
“The abscopal effect is the ability of localized radiation to induce an antitumor response throughout the body at sites that were not subjected to targeted RT”