Q. A 78-year-old man is diagnosed with Gleason 4 + 4 adenocarcinoma of the prostate in 4/12 cores on TRUS biopsies. Imaging suggests organ-confined disease and after MDT discussion the patient opts to have radical radiotherapy. What is radiation? What is radiotherapy? How does it work?
A. Radiation is the emission of energy in the form of waves or particles. Ionising radiation is radiation that carries enough energy to remove electrons from an atom, causing the atom to become charged or ionised. X-rays and gamma rays are the two types of electromagnetic waves that can ionise atoms. Radiotherapy is the therapeutic use of ionising radiation to treat malignancy. The effects of radiation can be direct, whereby an electron interacts directly with DNA, or indirect, whereby an electron interacts with water molecules to produce a hydroxyl radical which in turn causes damage to DNA. The latter of these is the major process in therapeutic radiation.
Q. How is radiation delivered? What kind of machines do you know?
A. Radiation is most commonly delivered either from a linear accelerator or by the insertion of internal radiation sources (brachytherapy). Radiation that is delivered by a linear accelerator is often referred to as external beam radiotherapy. This can be delivered using an individual beam, which is often simple palliative radiotherapy, or from several directions at the target tissue. The ability to deliver high-dose radiation via this technique is limited by damage caused to healthy adjacent tissues. In three-dimensional conformal radiation therapy the profile of each radiation beam is shaped to the target tissue reducing damage to normal surrounding tissue and enabling delivery of higher doses of radiation. Intensity modulated radiation therapy (IMRT) enables delivery of highly conformal radiation doses to specific target tissues. This is achieved by regulating the intensity of the radiation beam and enables improved targeting of tumours with less side effects and better treatment outcomes. By better avoiding normal tissues, higher doses of radiation can be given to the target increasing the chance of cure.
Q. What is fractionation? What is the rationale behind it?
A. Fractionation is the process by which the total dose of radiation is divided into a number of fractions to optimise the desired effects to cancer cells, while sparing adjacent normal tissues. This confers a number of benefits:
1. Repair of sub-lethal damage between dose fractionations which is usually more effective in non-proliferating cells.
2. Repopulation of normal cells that divide rapidly, such as bowel.
3. Fractionation enables reoxygenation; hypoxic cells are relatively radioresistant and tumours may be acutely or chronically hypoxic.
4. Reassortment. The effects of radiotherapy are most effective in cells about to divide (G2 or M phases of the cell cycle). Cells in the S phase are relatively radioresistant.
With reapplication of radiotherapy at time intervals, cells redistribute themselves over all phases of the cell cycle.
Q. What other types of radiotherapy can be encountered in urology?
A. Other types of radiotherapy include brachytherapy and systemic radiotherapy.
Brachytherapy is a form of radiotherapy, used to treat organ-confined prostate cancer, although it is not recommended as monotherapy for high-risk prostate cancer. It involves the insertion of targeted radioactive pellets directly into the prostate gland via the perineum. In low-dose brachytherapy (LDR) permanent Iodine-125 or Palladium-103 seeds are inserted under ultrasound guidance, which deliver radiation over weeks or months. Patients should be counselled to avoid close contact with pregnant women or children for 3 months, and to use condoms for intercourse for the first few weeks after implantation.
In HDR brachytherapy iridium-192 seeds are temporarily inserted, delivering radiation in minutes. In contrast with LDR, there are no radiation protection issues. HDR brachytherapy may be given in combination with external beam radiation therapy for men with intermediate- and high-risk organ-confined prostate cancer.
Strontium-99 can be injected systemically to deliver systemic radiation. It is metabolised in a similar fashion to calcium and it There fore preferentially targets metabolically active areas of bone. In patients with metastatic prostate cancer this has been shown to have a benefit in the palliation of painful bony lesions.
References
1. Tolley D. Ureteric stents, far from ideal. The Lancet 2000; 356: 872-873.
2. Medtronic. http://www.valleylab.com/education/poes/index.html
3. Medicines and Healthcare products Regulatory Agency. http://webarchive.nationalarchives. gov.uk/20141204111618/http://www.mhra.gov.uk/home/groups/dts-bi/documents/ websiteresources/con2023451.pdf
4. The British Association of Urological Surgeons. https://www.baus.org.uk/patients/ information_leaflets/
5. National Patient Safety Agency and Royal College of Surgeons of England. National Patient Safety Alert 06. Joint Commission on Accreditation of Healthcare Organizations, April 2003; 2. www.npsa.nhs.uk