Radiation therapy • Since the discovery of

x-rays radiation therapy for the treatment of various types of cancers

• Radiotherapy involves nuclear medicine which is employing radioactive materials for diagnosis and treatment of cases.

• It is a well known fact that ionizing radiation kills cells

• Radio sensitivity refers to the susceptibility of the cells or tissue to the killing effect of absorbed radiation.

• Radio responsive is the degree to which a normal or neoplastic tissue visibility changes during or after radiotherapy.

• Radio curability in veterinary medicine is a two year patient survival after radiotherapy without further progress of the neoplasm and subsequent metastases.

• The nuclides which have the same atomic number but different mass number are the radioisotopes i.e. isotopes of a given atom have same number of protons but differ in number of neutrons.

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• Naturally occurring or artificially produced by irradiation of stable nuclides by subatomic particles such as neutrons in a nuclear reactor.

• The unstable nuclides of heavy elements such as cobalt, cesium etc are unstable and undergo the process of spontaneous decay to form stable nuclides by the process of radioactive decay and emit radiations which include alpha or beta rays or gamma rays also sometimes.

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Mechanism of action of Radiation

• These are explained by direct or target theory and indirect theory

• Direct: Radiant energy acts by a direct hit on the target molecules within the cell causes ionization and ejection of the orbital electrons. This causes damage to the cell.

• DNA molecule is the most important target of radiation in the cell, especially its linkages and bonds.

The main effects on the DNA molecule is

• Genetic damage: Occurs in the germ cells, response is observed in the next generation.

• Production of Cancer: the derangement of Nucleic acid result in abnormal metabolic activity producing a malignant disease.

• Cell death: Due to radiation damage to the DNA the multiplication of cells is affected causing cell death and it very well explains the theory behind death of cancerous cells by ionizing radiation.

Indirect theory

• Production of free hot radicals such as peroxides within the cell occurs that damage the specific target.

• Water molecule is split into H+ and OH- and other unstable particles such as HO2 and H2O2.

These radicals are very unstable and produce a crucial biological change in the cell which leads to cell death.

Tissue tolerance to radiotherapy• Amount of energy transferred: The rate at which energy is

transferred from ionizing radiations to the expose tissue is called as linear energy transfer (LET)

• Oxygenation of tissues: Due to high proliferation potential of a tumor, tissue amount is unable to receive required circulation. Thus many cells are hypoxic and also radio resistant.

• Radiation therapy is more effective in oxygenated cells. So it is always attempted to increase the oxygenation of tissues which is attempted by the use of high pressure oxygen tanks, blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs such as misonidazole and metronidazole, and hypoxic cytotoxins (tissue poisons), such as tirapazamine.

• Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals.

• The radio sensitivity is directly proportional to the mitotic activity of the cell and indirectly proportional to their level of specialization.

Normal tissue response

• Normal tissue response to radiations is the main limiting factor of radiation therapy.

• Tumoricidal doses of radiation to treat any neoplasm should be done with minimal normal tissue complication.

• Different types of neoplasm require different lethal dose i.e. the dose of radiation at which in vivo lethal effects of radiation can bring about 80- 90% of regression.

• The therapeutic ratio i.e. the ratio of normal tissue tolerance dose to the neoplasm lethal dose.

• The sensitive neoplasm have therapeutic ratio higher for e.g. squamous cell carcinoma. The resistant neoplasms like fibrosarcoma only 34% regression occur. Mast cell neoplasm is an e.g. of moderately sensitive neoplasm where the therapeutic ratio is 1 and only about 54% regression is brought about in the neoplasm.

Indications:• Localized solid neoplasm that can not be excised

completely. It is usually not indicated in met static neoplasm.

• When surgery has failed to treat neoplasm or is expected to fail

• When regional or distant metastases has not occurred.

• When radical surgery is unable to remove whole of the lesion.

• To reduce the bulk of the neoplasm destined to be removed after surgery

Multiple treatments are given over a period of time called fractioned

therapy•Fractionation allows normal cells time to recover, while tumor cells are generally less efficient in repair between fractions.•Fractionation also allows tumor cells that were in a relatively radio-resistant phase of the cell cycle during one treatment to cycle into a sensitive phase of the cycle before the next fraction is given. •Similarly, tumor cells that were chronically or acutely hypoxic (and therefore more radioresistant) may reoxygenate between fractions, improving the tumor cell kill.

•Radiotherapy is synergistic with chemotherapy. Radiation therapy is combined often with surgery, chemotherapy, hormone therapy, immunotherapy to decrease the dose of radiation.•To encourage more and more normal cell formation 4 R’s of the radiotherapy is followed i.e. re oxygenation, repopulation, redistribution and repair.

Shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing a much larger absorbed dose there than in the surrounding, healthy tissue. Include a margin of normal tissue around the tumor to allow for uncertainties in daily set-up and internal tumor motion.

In animals it is usually 10 – 12 fractions of a radiation dose of 4-5 Gy each time usually three times per week. In man it is usually 1.8 – 2.0 Gy with a total dose of 60- 70 Gy over a period of 6- 7 weeks.

• Techniques • Teletherapy: source of radiation is at a distance from the

lesion. Superficial x- ray therapy works in the energy range of 60- 100 KeV. For eg in small superficial lesion of skin.

• Deep x-ray therapy: energy range of 200- 300 KeV for eg small shallow lesion,

• Supervoltage therapy: linear accelerator (1 MeV to 20 MeV) or cyclotron and through isotopic x-ray machine with cobalt or cesium in a sealed form eg. small deep lesions or substantial lesions

• Total body irradiation (TBI) is a radiation therapy technique used to prepare the body to receive a bone marrow transplant. .

Particulate beam therapy: • Electro, neutron or proton :• Antitumor effect independent of

tumor oxygen supply • Direct energy transfer usually

causing double-stranded DNA breaks.

• Due to their relatively large mass, protons and other charged particles have little lateral side scatter in the tissue; the beam does not broaden much, stays focused on the tumor shape, and delivers small dose side-effects to surrounding tissue.

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Brachytherapy

• The therapeutic use of radioisotopes either

• Within the interstitium (Interstitial Brachy therapy: 198Au, 60CO etc) or

• On the surface of a neoplasm (Pliesotherapy: 90Sr) or

rice-sized transponder used in treating prostate cancer

Systemically administered (systemic brachytherapy ; 131 I and 32P). Extensive lesions and specific malignant conditions (leukaemia, thyroid cancer etc is treated with systemic fluid isotope therapy)

Complications of Radiotherapy: •The immediate complications are seen within minutes or days after irradiation e.g., epilation , moist desquamation of skin, skin erythema , chromosome aberration, haematological depression etc, and in human beings it is Damage to the epithelial surfaces, Mouth and throat sores, Intestinal discomfort, Infertility, Swelling

Radiation can cause a sunburn-like damage to the skin

Permanent xerostomiaEven though the dry mouth

(xerostomia) improves in most people with time, it can be long lasting.

• latent complications which are seen after a long time like over years e.g. leukemia, cancer, life span shortening and lethal genes in coming generations’ .

• While treating a particular case for eg ophthalmic neoplasm irradiation leads to conjunctivitis, keratitis, cataract etc.

• In case of radiotherapy to the bone complications may include fracture, septic osteoradionecrosis and sarcoma formation.