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net Radiation therapy (in North America), or radiotherapy (in the UK and Australia) also called radiation oncology, and sometimes abbreviated to XRT, is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). Radiotherapy may be used for curative or adjuvant cancer treatment. It is used as palliative treatment (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 and it can be curative). Total body irradiation (TBI) is a radiotherapy technique used to prepare the body to receive a bone marrow transplant. Radiotherapy has several applications in non-malignant conditions, such as the treatment of trigeminal neuralgia, severe thyroid eye disease, pterygium, pigmented villonodular synovitis, prevention of keloid scar growth, and prevention of heterotopic ossification. The use of radiotherapy in non-malignant conditions is limited partly by

worries about the risk of radiationinduced cancers. Radiotherapy is used for the treatment of malignant tumors (cancer), and may be used as the primary therapy. It is also common to combine radiotherapy with surgery,chemotherapy, hormone t herapy or some mixture of the three. Most common cancer types can be treated with radiotherapy in some way. The precise treatment intent (curative, adjuvant, neoadjuvant, therapeutic, or palliative) will depend on the tumour type, location, and stage, as well as the general health of the patient. Radiation therapy is commonly applied to the cancerous tumour. The radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with tumour, or if there is thought to be a risk of subclinical malignant spread. It is necessary to include a margin of normal tissue around the tumour to allow for uncertainties in daily set-up and internal tumor motion. These uncertainties can be caused by internal movement (for example, respiration and bladder filling) and movement of external skin marks relative to the tumour position.

To spare normal tissues (such as skin or organs which radiation must pass through in order to treat the tumour), shaped radiation beams are aimed from several angles of exposure to intersect at the tumour, providing a much larger absorbed dose there than in the surrounding, healthy tissue. Radiation therapy has been in use as a cancer treatment for more than 100 years, with its earliest roots traced from the discovery of x-rays in 1895 by Wilhelm Röntgen. The field of radiation therapy began to grow in the early 1900s largely due to the groundbreaking work of Nobel Prize-winning scientist Marie Curie, who discovered the radioactive elements polonium and radium. This began a new era in medical treatment and research. Radium was used in various forms until the mid-1900s when cobalt and caesium units came into use. Medical linear accelerators have been used to as sources of radiation since the late 1940s. With Godfrey Hounsfield’s invention of computed tomography (CT) in 1971, three-dimensional planning became a possibility and created a shift from 2-D to 3-D radiation delivery; CT-based

planning allows physicians to more accurately determine the dose distribution using axial tomographic images of the patient's anatomy. Orthovoltage and cobalt units have largely been replaced by megavoltage linear accelerators, useful for their penetrating energies and lack of physical radiation source. The advent of new imaging technologies, including magnetic resonance imaging (MRI) in the 1970s and positron emission tomography (PET) in the 1980s, has moved radiation therapy from 3-D conformal to intensitymodulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). These advances have resulted in better treatment outcomes and fewer side effects.

Radiation therapy works by damaging the DNA of cells. The damage is caused by a photon, electron, proton, neutron, or ion beam directly or indirectly ionizing the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming free radicals, notably hydroxyl radicals, which then damage the DNA.

damage is most commonly indirectly ionizing via free-radical intermediaries formed from the radiolysis of cellular water. which in turn ionizes the atom present in the DNA molecule. The DNA damage is inherited through cell division. causing a lowoxygen state known as hypoxia. This breakage leads to irreversible loss of the reproductive integrity of the cell and eventual cell death. breaking the DNA on both strands proves to be the most significant technique in modifying cell characteristics. Cell survival. Solid tumors can outgrow their blood supply. cell senescence. and apoptosis (programmed cell death). Many of these processes are only now beginning to be elucidated and manipulated in order to make radiation therapy more effective. Radiation damage can be directly ionizing. hypoxic cell radiosensitizers such as misonidazole and metronidazole. general principles. in clinical therapy. The photons and the electrons present in the radiation source ionizes the water molecules producing free radicals (OH radicals). is thought to cause the initial shoulder. increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. single fraction. will either die or reproduce slowly. One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen.In the most common forms of radiation therapy. most of the radiation effect is through free radicals. Repeated small doses of radiation are less damaging to a sensitive cell than a single fraction containing an equivalent total dose (see the image below). Read more: Radiotherapy Mechanism | Medindia http://www. The therapeutic mechanism for radiation is based on the intrinsic ability of cells to repair damage and the ability of the radiation oncologist to take advantage of any geometric separation between malignant and nonmalignant tissues. Cell survival after exposure can be expressed in terms of a logarithmic curve of survival versus dose. which varies with the dose (see the image below). such as tirapazamine. Oxygen is a potent radiosensitizer. The curve forms an initial shoulder followed by a logarithmic decline in survival. Because cells have mechanisms for repairing DNA damage. Radiation can also affect the processes of the cell cycle necessary for cell growth. Radiation therapy. and hypoxic cytotoxins. blood substitutes that carry increased oxygen. Much research has been devoted to overcoming this problem including the use of high pressure oxygen patients/patientinfo/Radiotherapy_ Mechanism. Sublethal damage. and have a diminished ability to repair sublethal damage compared to most healthy differentiated cells. A large body of evidence supports doublestranded breaks of nuclear DNA as the most important cellular effect of radiation. Generally normal cells have excellent repair mechanisms but cancer cells are have diminished ability to repair the damages and hence continue to produce cells with the damage. they reproduce more. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment. Manipulation of the cellular environment can alter the shape of the survival curve. accumulating damage to the cancer cells. These cells.htm#ixzz2Xo4g8ZT1 Biologic Basis The exact mechanism of cell death due to radiation is still an area of active investigation. Because cancer cells generally are undifferentiated and stem cell-like. There is also interest in the fact that high-LET (linear energy transfer) particles such as carbon or neon ions may have an antitumor effect which is less dependent of tumor oxygen because these particles act mostly via direct damage. which must be overcome with each fraction of radiation therapy. however.medindia. which have the damaged DNA. . causing them to die or reproduce more slowly.

"Association of Reactive Oxygen Species Levels and Radioresistance in Cancer Stem Cells. Antioxidants. desquamation. the position of the cell in the mitotic cycle. In the linear-quadratic model. S. The quadratic beta component represents irreparable damage. September 2011. comes in two major types: photons (the most common source and comes from cobalt.3 Cartilage – Fibrosis. The linear component is proportional to the dose. 3. 4th Ed (McGraw-Hill. Radiation therapy. Onkol. Schneider et al. Wu.5 [1] "Radiation Therapy Principles.5 Values for α/β in late responding normal tissue are as follows: Skin – Telangiectasia. Genetics: Analysis and Principles. The ionizing radiation. proton beams are a newer application that causes little damage to tissues they pass through but kill cells at the end of their path. 1. 2.R edistribution." Nutrition 18. 30 Jan 12. neutrons. and β particles). Besides being related to intrinsic cellular radiosensitivity. "The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence. or through the use of radioactive drugs (systemic). [1] How does the ionizing radiation kills cells and damage DNA? Radiation therapy. This difference between tumor and lateresponding tissues is useful in designing therapeutic schemes that use multiple daily fractions rather than the conventional oncedaily treatments." American Cancer Society. Yang and G. [2] Y. 11. Composition of cell survival curve. [6] U.13 Tonsil . respectively (see the image below).16 Oropharynx . "Free Radicals. Diehn et al.6.2  Oral mucosa – Mucositis. [3] R. J. general principles. protons. general principles. α particles. The linear alpha component is responsible for the initial shoulder on the cell survival curve and is caused by repairable damage to the target. Z. Brooker.16 Vocal cord . cell survival is also related to oxygen tension. whereas the quadratic component is proportional to the dose squared.Skin – Erythema. R epopulating. according to which the surviving fraction is equivalent toe(αD .7 Skin (squamous or carcinoma) 8. which forms ions in the cells of the tissues it passes through thereby killing the cells or altering their DNA. R epair. [4] M.8 Values for α/β in early-responding tumor tissue are as follows:  [5] "Second Cancers Caused by Cancer Treatment...7 Spinal cord – Myelitis. late-responding tissues have smaller α/β ratios." American Cancer Society. 4. 780 (2009).βD2).    . 10. possibly resulting in fewer side effects. 2011). Electron and most particle beams are used for tumors close to the body surface because they do not go deeply into tissues. Values for α/β in early-responding normal tissue are as follows:      Nasopharynx . 872 (2002). 10. or a linear accelerator) and particles (electrons." Nature 458. cesium. fibrosis. and R eoxygenation. Early-responding tissues and tumors have a relatively larger alpha component and a larger α/β ratio. The cell survival curve can be interpreted to follow a linear-quadratic model. 2 components of cell injury are present. These features are responsible for the 4 Rs of radiobiology— namely. Fang. 182 647 (2006) Radiation therapy involves administration of ionizing radiation from an external source. and Nutrition.7. Effect of fractionation. from a source placed inside the body (brachytherapy). and dose rate. where α and β represent the alpha and beta components. Several models have been used to conceptualize radiation-induced cell death and to explain the cell survival curve." Strahlenther. On the other hand.

These agents are very chemically reactive due to their free electron. if enough DNA is damaged. or programmed cell death. [3] . the cells will be unable to replicate. free radicals and reactive oxygen species (ROS) form. free radicals and ROS are likely to attack the covalent bonds of the DNA and other cells they encounter. At the same time. and ROS is a subset of free radicals that involve oxygen. Free radicals are simply atoms. when the radiation targets the tumor cells. [2] Due to this high reactivity. or ions with unpaired electrons. Thus. and these reactions typically occur in chains. Enough injury in the cell will result in apoptosis. effectively reducing or eliminating the cancer. the affected cells will die or be unable to proliferate.When the cells are ionized. molecules.