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Radiation therapy (or radiotherapy) is the use of ionizing radiation to control tumor growth. Radiotherapy may be curative or be used as an adjuvant therapy. It may also be employed for palliation (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where the therapy has survival benefit but is not curative). The use of radiotherapy is limited by concerns of radiation-associated toxicity.
To spare normal tissues (such as skin or organs which radiation must pass through in order to treat the tumor), 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.
Mechanism of action
Radiation therapy works by causing DNA damage. The damage is caused by a photon, proton or electron beam directly or indirectly ionizing the atoms that make up the DNA chain. Indirect DNA damage happens as a result of the ionization of water, forming free reactive oxygen species (free radicals), which then damage DNA. In the most common forms of radiation therapy, most of the radiation effect is through free radicals. Because cells have mechanisms for repairing DNA damage, breaking the DNA on both strands proves to be the most significant technique in modifying cell characteristics. Because cancer cells generally are undifferentiated and stem cell-like, they reproduce more, and have a diminished ability to repair sub-lethal damage compared to most more differentiated cells. The DNA damage is inherited through cell division, accumulating damage to the cancer cells, leading to apoptosis or slowed cell division. Proton radiotherapy works by causing direct cell damage by delivery of protons with varying kinetic energy to the tumor.
The amount of radiation used in radiation therapy is measured in gray (Gy), and varies depending on the type and stage of cancer being treated. For curative (radical) cases, the typical dose for a solid epithelial tumor ranges from 60 to 80 Gy. In whole brain radiotherapy given for metastatic disease, the typical dose is 3000 cGy broken up into 300 cGy delivered daily for 10 days, although variations on this regimen are commonly employed depending on a number of patient factors. For Glioblastoma, the typical dose is 5400-6000cGy delivered to the tumor-plus volume in 180 to 200 cGy fractions daily for 6 weeks with a reduced dose to the remainder of the brain tissue.
The total dose is fractionated (spread out over time) in order to allow normal cells to recover and increase the number of tumor cells in a radiation-vulnerable state.
Modes of delivery
Radiotherapy may consist of photon-based, electron-based or proton-based radiation. Most commonly, photon- or electron-based therapies are used, with delivery based upon a conventional external beam radiotherapy or conformal or intensity-modulated radiotherapy paradigm.