fractionated permanent hair loss may not occur until dose exceeds 45 gy. dryness the salivary glands and tear glands have a radiation tolerance of about 30 gy in 2 gy fractions, a dose which is exceeded by most radical head and neck cancer treatments. dry mouth (xerostomia) and dry eyes (xerophthalmia) can become irritating long-term problems and severely reduce the patient's quality of life. similarly, sweat glands in treated skin (such as the armpit) tend to stop working, and the naturally moist vaginal mucosa is often dry following pelvic irradiation. lymphedema lymphedema, a condition of localized fluid retention and tissue swelling, can result from damage to the lymphatic system sustained during radiation therapy. it is the most commonly reported complication in breast radiation therapy patients who receive adjuvant axillary radiotherapy following surgery to clear the axillary lymph nodes . cancer radiation is a potential cause of cancer, and secondary malignancies are seen in some patients. cancer survivors are already more likely than the general population to develop malignancies due to a number of factors including lifestyle choices, genetics, and previous radiation treatment. it is difficult to directly quantify the rates of these secondary cancers from any single cause. studies have found radiation therapy as the cause of secondary malignancies for only a small minority of patients. new techniques such as proton beam therapy and carbon ion radiotherapy which aim to reduce dose to healthy tissues will lower these risks. it starts to occur 4–6 years following treatment, although some haematological malignancies may develop within 3 years. in the vast majority of cases, this risk is greatly outweighed by the reduction in risk conferred by treating the primary cancer even in pediatric malignancies which carry a higher burden of secondary malignancies. cardiovascular disease radiation can increase the risk of heart disease and death as observed in previous breast cancer rt regimens. therapeutic radiation increases the risk of a subsequent cardiovascular event (i.e., heart attack or stroke) by 1.5 to 4 times a person's normal rate, aggravating factors included. the increase is dose dependent, related to the rt's dose strength, volume and location. cardiovascular late side effects have been termed radiation-induced heart disease (rihd) and radiation-induced vascular disease (rivd). symptoms are dose dependent and include cardiomyopathy, myocardial fibrosis, valvular heart disease, coronary artery disease, heart arrhythmia and peripheral artery disease. radiation-induced fibrosis, vascular cell damage and oxidative stress can lead to these and other late side effect symptoms. most radiation-induced cardiovascular diseases occur 10 or more years post treatment, making causality determinations more difficult. cognitive decline in cases of radiation applied to the head radiation therapy may cause cognitive decline. cognitive decline was especially apparent in young children, between the ages of 5 to 11. studies found, for example, that the iq of 5-year-old children declined each year after treatment by several iq points. radiation enteropathy histopathology of radiation cystitis, including atypical stromal cells ("radiation fibroblasts") the gastrointestinal tract can be damaged following abdominal and pelvic radiotherapy. atrophy, fibrosis and vascular changes produce malabsorption, diarrhea, steatorrhea and bleeding with bile acid diarrhea and vitamin b12 malabsorption commonly found due to ileal involvement. pelvic radiation disease includes radiation proctitis, producing bleeding, diarrhoea and urgency, and can also cause radiation cystitis when the bladder is affected. radiation-induced polyneuropathy radiation treatments may damage nerves near the target area or within the delivery path as nerve tissue is also radiosensitive. nerve damage from ionizing radiation occurs in phases, the initial phase from microvascular injury, capillary damage and nerve demyelination. subsequent damage occurs from vascular constriction and nerve compression due to uncontrolled fibrous tissue growth caused by radiation. radiation-induced polyneuropathy, icd-10-cm code g62.82, occurs in approximately 1–5% of those receiving radiation therapy. depending upon the irradiated zone, late effect neuropathy may occur in either the central nervous system (cns) or the peripheral nervous system (pns). in the cns for example, cranial nerve injury typically presents as a visual acuity loss 1–14 years post treatment. in the pns, injury to the plexus nerves presents as radiation-induced brachial plexopathy or radiation-induced lumbosacral plexopathy appearing up to 3 decades post treatment. radiation necrosis radiation necrosis is the death of healthy tissue near the irradiated site. it is a type of coagulative necrosis that occurs because the radiation directly or indirectly damages blood vessels in the area, which reduces the blood supply to the remaining healthy tissue, causing it to die by ischemia, similar to what happens in an ischemic stroke. because it is an indirect effect of the treatment, it occurs months to decades after radiation exposure. cumulative side effects cumulative effects from this process should not be confused with long-term effects – when short-term effects have disappeared and long-term effects are subclinical, reirradiation can still be problematic. these doses are calculated by the radiation oncologist and many factors are taken into account before the subsequent radiation takes place. effects on reproduction during the first two weeks after fertilization, radiation therapy is lethal but not teratogenic. high doses of radiation during pregnancy induce anomalies, impaired growth and intellectual disability, and there may be an increased risk of childhood leukemia and other tumours in the offspring. in males previously having undergone radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. however, the use of assisted reproductive technologies and micromanipulation techniques might increase this risk. effects on pituitary system hypopituitarism commonly develops after radiation therapy for sellar and parasellar neoplasms, extrasellar brain tumours, head and neck tumours, and following whole body irradiation for systemic malignancies. 40-50% of children treated for childhood cancer develop some endocrine side effect. radiation-induced hypopituitarism mainly affects growth hormone and gonadal hormones. in contrast, adrenocorticotrophic hormone (acth) and thyroid stimulating hormone (tsh) deficiencies are the least common among people with radiation-induced hypopituitarism. changes in prolactin-secretion is usually mild, and vasopressin deficiency appears to be very rare as a consequence of radiation. radiation therapy accidents there are rigorous procedures in place to minimise the risk of accidental overexposure of radiation therapy to patients. however, mistakes do occasionally occur; for example, the radiation therapy machine therac-25 was responsible for at least six accidents between 1985 and 1987, where patients were given up to one hundred times the intended dose; two people were killed directly by the radiation overdoses. from 2005 to 2010, a hospital in missouri overexposed 76 patients (most with brain cancer) during a five-year period because new radiation equipment had been set up incorrectly. although medical errors are exceptionally rare, radiation oncologists, medical physicists and other members of the radiation therapy treatment team are working to eliminate them. astro has launched a safety initiative called target safely that, among other things, aims to record errors nationwide so that doctors can learn from each and every mistake and prevent them from happening. astro also publishes a list of questions for patients to ask their doctors about radiation safety to ensure every treatment is as safe as possible. use in non-cancerous diseases the beam's eye view of the radiotherapy portal on the hand's surface with the lead shield cut-out placed in the machine's gantry radiation therapy is used to treat early stage dupuytren's disease and ledderhose disease. when dupuytren's disease is at the nodules and cords stage or fingers are at a minimal deformation stage of less than 10 degrees, then radiation therapy is used to prevent further progress of the disease. radiation therapy is also used post surgery in some cases to prevent the disease continuing to progress. low doses of radiation are used typically three gray of radiation for five days, with a break of three months followed by another phase of three gray of radiation for five days. technique mechanism of action radiation therapy works by damaging the dna of cancerous cells and can cause them to undergo mitotic catastrophe. this dna damage is caused by one of two types of energy, photon or charged particle. this damage is either direct or indirect ionization of 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 photon therapy, most of the radiation effect is through free radicals. cells have mechanisms for repairing single-strand dna damage and double-stranded dna damage. however, double-stranded dna breaks are much more difficult to repair, and can lead to dramatic chromosomal abnormalities and genetic deletions. targeting double-stranded breaks increases the probability that cells will undergo cell death. cancer cells are generally less differentiated and more stem cell-like; they reproduce more than most healthy differentiated cells, and have a diminished ability to repair sub-lethal damage. single-strand dna damage is then passed on through cell division; damage to the cancer cells' dna accumulates, 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, hyperthermia therapy (heat therapy which dilates blood vessels to the tumor site), blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs such as misonidazole and metronidazole, and hypoxic cytotoxins (tissue poisons), such as tirapazamine. newer research approaches are currently being studied, including preclinical and clinical investigations into the use of an oxygen diffusion-enhancing compound such as trans sodium crocetinate as a radiosensitizer. charged particles such as protons and boron, carbon, and neon ions can cause direct damage to cancer cell dna through high-let (linear energy transfer) and have an antitumor effect 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 of the different effects of intensity-modulated radiation therapy (imrt) vs. charged particle therapy. 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, imrt's use of uncharged particles causes its energy to damage 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 while depending on a multitude of factors, they are around 10 times more sensitive to developing secondary malignancies after radiotherapy as compared to adults. dose the amount of radiation used in photon radiation therapy is measured in grays (gy), and varies depending on the type and stage of cancer being treated. for curative cases, the typical dose for a solid epithelial tumor ranges from 60 to 80 gy, while lymphomas are treated with 20 to 40 gy. preventive (adjuvant) doses are typically around 45–60 gy in 1.8–2 gy fractions (for breast, head, and neck cancers.) many other factors are considered by radiation oncologists when selecting a dose, including whether the patient is receiving chemotherapy, patient comorbidities, whether radiation therapy is being administered before or after surgery, and the degree of success of surgery. delivery parameters of a prescribed dose are determined during treatment planning (part of dosimetry). treatment planning is generally performed on dedicated computers using specialized treatment planning software. depending on the radiation delivery method, several angles or sources may be used to sum to the total necessary dose. the planner will try to design a plan that delivers a uniform prescription dose to the