Radiation therapy - radiation therapy side effects for breast, prostate cancer

Radiation delivers energy to tissues, causing ionization and excitation of atoms and molecules. The biological effect is exerted through the generation of single- and double-strand DNA breaks, inducing apoptosis of cells as they progress through the cell cycle, and through the generation of short-lived free radicles, particularly from oxygen, which damage proteins and membranes.

The most commonly used form of radiotherapy is external beam or teletherapy from a linear accelerator source which provides X-rays, the energy of which is transmitted as photons. Cobalt-60 generators can also provide gamma rays and high-energy photons.

Brachytherapy is the use of radiation sources in close contact with the tissue to provide intense exposure over a short distance to a restricted volume.

Systemic radionuclides , e.g. iodine-131, or radioisotope-labelled monoclonal antibodies and hormones can be administered by intravenous or intracavitary routes to provide radiation targeted to particular tissue uptake via surface antigens or receptors.

The radiation dose is measured in grays (Gy), where 1 gray = 1 joule absorbed per kilogram of absorbing tissue and 1 centigray = 1 rad. The biological effect is dependent upon the dose rate, duration, volume irradiated, and the tissue sensitivity. Sensitivity to photon damage is greatest during the G 2 -M phase of the cell cycle and is also dependent upon the DNA repair capacity of the cell. Fractionation is the delivery of the radiation dose in increments separated by at least 4-6 hours to try to exploit any advantage in DNA repair between normal and malignant cells. Radiation dose is thus described by three factors:

total dose in cGy

number of fractions

time for completion.

Most treatments are delivered in 150-200 cGy fractions daily for 5 days per week, although a regimen of two fractions daily (hyperfractionation) has improved survival benefit in a recent lung cancer trial.

The radiation effect will also depend upon the intensity of the radiation source measured as the linear energy transfer or frequency of ionizing events per unit of path, which is subject to the inverse square law as the energy diminishes with the distance from the source.

The generation of free radicles depends upon the degree of oxygenation/hypoxia in the target tissues. This can affect the biological effect by up to threefold and is the subject of continuing research for hypoxic cell sensitizers.

The depth of penetration of biological tissues by the photons depends upon the energy of the beam. Low-energy photons from an 85 kV source are suitable for superficial treatments while high-energy 35 MeV sources produce a beam with deeper penetration, less scatter both at the initial skin boundary (skin sparing) and at the margins of the beam, and less absorption by bone. Superficial radiation may be also delivered by electron beams from a linear accelerator that has had the target electrode that generates the X-rays removed.

Radiotherapy treatment planning involves both detailed physics of the applied dose and knowledge of the biology of the cancer and whether the intention is to treat the tumour site alone, or include the likely loco-regional patterns of spread. Normal tissue tolerance will determine the extent of the side-effects and a balanced decision is made according to the curative or palliative intent of the treatment and the likely early or late side-effects.

Side-effects of radiotherapy

Radiotherapy side-effects may occur early within days to weeks of treatment when they are usually self-limiting but associated with general systemic disturbance. The side-effects will depend upon tissue sensitivity, fraction size and treatment volume and are managed with supportive measures until normal tissue repair occurs. The toxicity may also be enhanced by exposure to other radiation-sensitizing agents, especially some cytotoxics, e.g. bleomycin, actinomycin, anthracyclines, cisplatin and 5-fluorouracil.

Later side-effects occur from months to years later, unrelated to the severity of the acute effects because of their different mechanism. Late effects reflect both the loss of slowly proliferating cells and a local endarteritis which produces ischaemia and proliferative fibrosis.

Secondary malignancies following radiotherapy typically appear 10-20 years after the cure of the primary cancer. Haematological malignancies tend to occur sooner than the solid tumours from the irradiated tissues. The latter are very dependent upon the status of the tissue at the time of treatment, e.g. the pubertal breast is up to 300 times more sensitive to malignant transformation than the breast tissues of a woman in her thirties. Treatment of these secondary cancers can be successful providing there is normal bone marrow to reconstitute the haemopoietic system or the whole tissue at risk (e.g. thyroid after mantle radiotherapy for lymphoma) can be resected.

Cancer Tip

Are clinical trials right for you? There is no correct answer to that question. Clinical trials may be right for some people, and not for others. You may want to weigh the pros and cons of clinical trials in making a decision of which treatment to undergo.

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