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Radiation therapy | Understanding and definition of Radiation therapy | Side effects of Radiation therapy

Radiation therapy (in the USA), radiation oncology, or radiotherapy (in the UK, Canada and Australia), 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). Radiation therapy may be used for curative or adjuvant 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 radiation therapy technique used to prepare the body to receive a bone marrow transplant. Radiation therapy 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 radiation therapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers.

Radiation therapy is used for the treatment of malignant cancer, and may be used as a primary or adjuvant modality. It is also common to combine radiation therapy with surgery, chemotherapy, hormone therapy, Immunotherapy or some mixture of the four. Most common cancer types can be treated with radiation therapy in some way. The precise treatment intent (curative, adjuvant, neoadjuvant, therapeutic, or palliative) will depend on the tumor type, location, and stage, as well as the general health of the patient.

Radiation therapy is commonly applied to the cancerous tumor. The radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with tumor, 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 tumor 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 tumor position.

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.

Brachytherapy, in which a radiation source is placed inside or next to the area requiring treatment, is another form of radiation therapy that minimizes exposure to healthy tissue during procedures to treat cancers of the breast, prostate and other organs.

Radiation therapy works by damaging the DNA of cancerous cells. This DNA damage is caused by one of two types of energy, photon or charged particle. This damage is either direct or indirect 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. In the older, most common form of radiation therapy, Intensity-modulated radiation therapy (IMRT) (photons), most of the radiation effect is through free radicals. Because cells have mechanisms for repairing single-strand DNA damage, double-stranded DNA breaks prove to be the most significant technique to cause cell death. 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 healthy differentiated cells. This single-strand DNA damage is then passed on through cell division, accumulating damage to the cancer cell's DNA, causing them to die or reproduce more slowly.

One of the major limitations of photon radiation therapy is that the cells of solid tumors become deficient in oxygen. Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia. Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. 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. Much research has been devoted to overcoming hypoxia including 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.

Direct damage to cancer cell DNA occurs through high-LET (linear energy transfer) charged particles such as proton, boron, carbon or neon ions which have an antitumor effect which is independent of tumor oxygen supply because these particles act mostly via 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. They also more precisely target the tumor using the Bragg peak effect. See proton therapy for a good example, with photos, of the different effects of IMRT vs. charged particle therapy. The cyclotron's, dielectric wall accelerator (DWA), or Still River Systems's super conducting high field magnet (two new compact protron replacements) provide the energy source for charged particle therapy. These particles can be charged to different amounts to provide the desired tissue penetration. This procedure reduces damage to healthy tissue between the charged particle radiation source and the tumor and sets a finite range for tissue damage after the tumor has been reached. In contrast, with IMRT using uncharged particles (photons), its energy is deposited differently such that it is still damaging healthy cells when it exits the body. This exiting damage is not therapeutic, can increase treatment side effects, and increases the probability of secondary cancer induction. This difference is very important in cases where the close proximity of other organs makes any stray ionization very damaging (example: head and neck cancers). This x-ray exposure is especially bad for children, due to their growing bodies, and they have a 30% chance of a second malignancy after 5 years post initial RT.

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 too 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 intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) Tomotherapy. These advances allowed radiation oncologists to better see and target tumors, which have resulted in better treatment outcomes, more organ preservation and fewer side effects.

Historically, the three main divisions of radiation therapy are external beam radiation therapy (EBRT or XRT) or teletherapy, brachytherapy or sealed source radiation therapy, and systemic radioisotope therapy or unsealed source radiotherapy. The differences relate to the position of the radiation source; external is outside the body, brachytherapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion. Brachytherapy can use temporary or permanent placement of radioactive sources. The temporary sources are usually placed by a technique called afterloading. In afterloading a hollow tube or applicator is placed surgically in the organ to be treated, and the sources are loaded into the applicator after the applicator is implanted. This minimizes radiation exposure to health care personnel. Particle therapy is a special case of external beam radiation therapy where the particles are protons or heavier ions. Intraoperative radiation therapy or IORT is a special type of radiation therapy that is delivered immediately after surgical removal of the cancer. This method has been employed in breast cancer (TARGeted Introperative radiation therapy or TARGIT), brain tumors and rectal cancers.

Radiation therapy is in itself painless. Many low-dose palliative treatments (for example, radiation therapy to bony metastases) cause minimal or no side effects, although short-term pain flare up can be experienced in the days following treatment due to oedema compressing nerves in the treated area. Treatment to higher doses causes varying side effects during treatment (acute side effects), in the months or years following treatment (long-term side effects), or after re-treatment (cumulative side effects). The nature, severity, and longevity of side effects depends on the organs that receive the radiation, the treatment itself (type of radiation, dose, fractionation, concurrent chemotherapy), and the patient.

Most side effects are predictable and expected. Side effects from radiation are usually limited to the area of the patient's body that is under treatment. One of the aims of modern radiation therapy is to reduce side effects to a minimum, and to help the patient to understand and to deal with those side effects which are unavoidable.

The main side effects reported are fatigue and skin irritation, like a mild to moderate sun burn. The fatigue often sets in during the middle of a course of treatment and can last for weeks after treatment ends. The skin irritation will also go away, but it may not be as elastic as it was before.

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