Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer). Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology.
Radiation therapy is commonly applied to the cancerous tumor because of its ability to control cell growth. Ionizing radiation works by damaging the DNA of cancerous tissue leading to cellular death. To spare normal tissues (such as skin or organs which radiation must pass through 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. Besides the tumour itself, 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.
Radiation oncology is the medical specialty concerned with prescribing radiation, and is distinct from radiology, the use of radiation in medical imaging and diagnosis. Radiation may be prescribed by a radiation oncologist with intent to cure ("curative") or for adjuvant therapy. It may also be 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). 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. Total body irradiation (TBI) is a radiation therapy technique used to prepare the body to receive a bone marrow transplant. Brachytherapy, in which a radioactive 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 has several applications in non-malignant conditions, such as the treatment of trigeminal neuralgia, acoustic neuromas, severe thyroid eye disease, pterygium, pigmented villonodular synovitis, and prevention of keloid scar growth, vascular restenosis, and 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 of the pelvis, using a Varian Clinac iX linear accelerator. Lasers and a mould under the legs are used to determine exact position.
The response of a cancer to radiation is described by its radiosensitivity. Highly radiosensitive cancer cells are rapidly killed by modest doses of radiation. These include leukemias, most lymphomas and germ cell tumors. The majority of epithelial cancers are only moderately radiosensitive, and require a significantly higher dose of radiation (60-70 Gy) to achieve a radical cure. Some types of cancer are notably radioresistant, that is, much higher doses are required to produce a radical cure than may be safe in clinical practice. Renal cell cancer and melanoma are generally considered to be radioresistant but radiation therapy is still a palliative option for many patients with metastatic melanoma. Combining radiation therapy with immunotherapy is an active area of investigation and has shown some promise for melanoma and other cancers.
It is important to distinguish the radiosensitivity of a particular tumor, which to some extent is a laboratory measure, from the radiation "curability" of a cancer in actual clinical practice. For example, leukemias are not generally curable with radiation therapy, because they are disseminated through the body. Lymphoma may be radically curable if it is localised to one area of the body. Similarly, many of the common, moderately radioresponsive tumors are routinely treated with curative doses of radiation therapy if they are at an early stage. For example: non-melanoma skin cancer, head and neck cancer, breast cancer, non-small cell lung cancer, cervical cancer, anal cancer, and prostate cancer. Metastatic cancers are generally incurable with radiation therapy because it is not possible to treat the whole body.
Before treatment, a CT scan is often performed to identify the tumor and surrounding normal structures. The patient receives small skin marks to guide the placement of treatment fields. Patient positioning is crucial at this stage as the patient will have to be set-up in the identical position during treatment. Many patient positioning devices have been developed for this purpose, including masks and cushions which can be molded to the patient.
The response of a tumor to radiation therapy is also related to its size. Due to complex radiobiology, very large tumors respond less well to radiation than smaller tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection prior to radiation therapy. This is most commonly seen in the treatment of breast cancer with wide local excision or mastectomy followed by adjuvant radiation therapy. Another method is to shrink the tumor with neoadjuvant chemotherapy prior to radical radiation therapy. A third technique is to enhance the radiosensitivity of the cancer by giving certain drugs during a course of radiation therapy. Examples of radiosensitizing drugs include: Cisplatin, Nimorazole, and Cetuximab.
The impact of radiotherapy varies between different types of cancer and different groups. For example, for breast cancer after breast-conserving surgery, radiotherapy has been found to halve the rate at which the disease recurs.
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. Higher doses can cause 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. Side effects are dose- dependent; for example higher doses of head and neck radiation can be associated with cardiovascular complications, thyroid dysfunction, and pituitary axis dysfunction. Modern radiation therapy aims to reduce side effects to a minimum and to help the patient understand and deal with side effects that 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 irritated skin will heal, but may not be as elastic as it was before.
Late side effects occur months to years after treatment and are generally limited to the area that has been treated. They are often due to damage of blood vessels and connective tissue cells. Many late effects are reduced by fractionating treatment into smaller parts.
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.
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.
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. 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.
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.
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.
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 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 (TSC) 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 they have a 30% chance of a second malignancy after 5 years post initial RT.
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 tumor and minimizes dose to surrounding healthy tissues.
The total dose is fractionated (spread out over time) for several important reasons. 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.
Fractionation regimens are individualised between different radiation therapy centers and even between individual doctors. In North America, Australia, and Europe, the typical fractionation schedule for adults is 1.8 to 2 Gy per day, five days a week. In some cancer types, prolongation of the fraction schedule over too long can allow for the tumor to begin repopulating, and for these tumor types, including head-and-neck and cervical squamous cell cancers, radiation treatment is preferably completed within a certain amount of time. For children, a typical fraction size may be 1.5 to 1.8 Gy per day, as smaller fraction sizes are associated with reduced incidence and severity of late-onset side effects in normal tissues.
In some cases, two fractions per day are used near the end of a course of treatment. This schedule, known as a concomitant boost regimen or hyperfractionation, is used on tumors that regenerate more quickly when they are smaller. In particular, tumors in the head-and-neck demonstrate this behavior.
Patients receiving palliative radiation to treat uncomplicated painful bone metastasis should not receive more than a single fraction of radiation. A single treatment gives comparable pain relief and morbidity outcomes to multiple-fraction treatments, and for patients with limited life expectancy, a single treatment is best to improve patient comfort.
One fractionation schedule that is increasingly being used and continues to be studied is hypofractionation. This is a radiation treatment in which the total dose of radiation is divided into large doses. Typical doses vary significantly by cancer type, from 2.2 Gy/fraction to 20 Gy/fraction, the latter being typical of stereotactic treatments (stereotactic ablative body radiotherapy, or SABR – also known as SBRT, or stereotactic body radiotherapy) for subcranial lesions, or SRS (stereotactic radiosurgery) for intracranial lesions. The rationale of hypofractionation is to reduce the probability of local recurrence by denying clonogenic cells the time they require to reproduce and also to exploit the radiosensitivity of some tumors. In particular, stereotactic treatments are intended to destroy clonogenic cells by a process of ablation – i.e. the delivery of a dose intended to destroy clonogenic cells directly, rather than to interrupt the process of clonogenic cell division repeatedly (apoptosis), as in routine radiotherapy.
Different cancer types have different radiation sensitivity. However, predicting the sensitivity based on genomic or proteomic analyses of biopsy samples has proved difficult. An alternative approach to genomics and proteomics was offered by the discovery that radiation protection in microbes is offered by non-enzymatic complexes of manganese and small organic metabolites. The content and variation of manganese (measurable by electron paramagnetic resonance) were found to be good predictors of radiosensitivity, and this finding extends also to human cells. An association was confirmed between total cellular manganese contents and their variation, and clinically-inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients.
Historically, the three main divisions of radiation therapy are :
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.
The following three sections refer to treatment using x-rays.
Conventional external beam radiation therapy (2DXRT) is delivered via two-dimensional beams using kilovoltage therapy x-ray units or medical linear accelerators which generate high energy x-rays. 2DXRT mainly consists of a single beam of radiation delivered to the patient from several directions: often front or back, and both sides.
Conventional refers to the way the treatment is planned or simulated on a specially calibrated diagnostic x-ray machine known as a simulator because it recreates the linear accelerator actions (or sometimes by eye), and to the usually well-established arrangements of the radiation beams to achieve a desired plan. The aim of simulation is to accurately target or localize the volume which is to be treated. This technique is well established and is generally quick and reliable. The worry is that some high-dose treatments may be limited by the radiation toxicity capacity of healthy tissues which lie close to the target tumor volume.
An example of this problem is seen in radiation of the prostate gland, where the sensitivity of the adjacent rectum limited the dose which could be safely prescribed using 2DXRT planning to such an extent that tumor control may not be easily achievable. Prior to the invention of the CT, physicians and physicists had limited knowledge about the true radiation dosage delivered to both cancerous and healthy tissue. For this reason, 3-dimensional conformal radiation therapy is becoming the standard treatment for a number of tumor sites. More recently other forms of imaging are used including MRI, PET, SPECT and Ultrasound.
Stereotactic radiation is a specialized type of external beam radiation therapy. It uses focused radiation beams targeting a well-defined tumor using extremely detailed imaging scans. Radiation oncologists perform stereotactic treatments, often with the help of a neurosurgeon for tumors in the brain or spine.
There are two types of stereotactic radiation. Stereotactic radiosurgery (SRS) is when doctors use a single or several stereotactic radiation treatments of the brain or spine. Stereotactic body radiation therapy (SBRT) refers to one or several stereotactic radiation treatments with the body, such as the lungs.
Some doctors say an advantage to stereotactic treatments is that they deliver the right amount of radiation to the cancer in a shorter amount of time than traditional treatments, which can often take 6 to 11 weeks. Plus treatments are given with extreme accuracy, which should limit the effect of the radiation on healthy tissues. One problem with stereotactic treatments is that they are only suitable for certain small tumors.
Stereotactic treatments can be confusing because many hospitals call the treatments by the name of the manufacturer rather than calling it SRS or SBRT. Brand names for these treatments include Axesse, Cyberknife, Gamma Knife, Novalis, Primatom, Synergy, X-Knife, TomoTherapy, Trilogy and Truebeam. This list changes as equipment manufacturers continue to develop new, specialized technologies to treat cancers.
The planning of radiation therapy treatment has been revolutionized by the ability to delineate tumors and adjacent normal structures in three dimensions using specialized CT and/or MRI scanners and planning software.
Virtual simulation, the most basic form of planning, allows more accurate placement of radiation beams than is possible using conventional X-rays, where soft-tissue structures are often difficult to assess and normal tissues difficult to protect.
An enhancement of virtual simulation is 3-dimensional conformal radiation therapy (3DCRT), in which the profile of each radiation beam is shaped to fit the profile of the target from a beam's eye view (BEV) using a multileaf collimator (MLC) and a variable number of beams. When the treatment volume conforms to the shape of the tumor, the relative toxicity of radiation to the surrounding normal tissues is reduced, allowing a higher dose of radiation to be delivered to the tumor than conventional techniques would allow.
Intensity-modulated radiation therapy (IMRT) is an advanced type of high-precision radiation that is the next generation of 3DCRT. IMRT also improves the ability to conform the treatment volume to concave tumor shapes, for example when the tumor is wrapped around a vulnerable structure such as the spinal cord or a major organ or blood vessel. Computer-controlled x-ray accelerators distribute precise radiation doses to malignant tumors or specific areas within the tumor. The pattern of radiation delivery is determined using highly tailored computing applications to perform optimization and treatment simulation (Treatment Planning). The radiation dose is consistent with the 3-D shape of the tumor by controlling, or modulating, the radiation beam's intensity. The radiation dose intensity is elevated near the gross tumor volume while radiation among the neighboring normal tissues is decreased or avoided completely. This results in better tumor targeting, lessened side effects, and improved treatment outcomes than even 3DCRT.
3DCRT is still used extensively for many body sites but the use of IMRT is growing in more complicated body sites such as CNS, head and neck, prostate, breast, and lung. Unfortunately, IMRT is limited by its need for additional time from experienced medical personnel. This is because physicians must manually delineate the tumors one CT image at a time through the entire disease site which can take much longer than 3DCRT preparation. Then, medical physicists and dosimetrists must be engaged to create a viable treatment plan. Also, the IMRT technology has only been used commercially since the late 1990s even at the most advanced cancer centers, so radiation oncologists who did not learn it as part of their residency programs must find additional sources of education before implementing IMRT.
Proof of improved survival benefit from either of these two techniques over conventional radiation therapy (2DXRT) is growing for many tumor sites, but the ability to reduce toxicity is generally accepted. This is particularly the case for head and neck cancers in a series of pivotal trials performed by Professor Christopher Nutting of the Royal Marsden Hospital. Both techniques enable dose escalation, potentially increasing usefulness. There has been some concern, particularly with IMRT, about increased exposure of normal tissue to radiation and the consequent potential for secondary malignancy. Overconfidence in the accuracy of imaging may increase the chance of missing lesions that are invisible on the planning scans (and therefore not included in the treatment plan) or that move between or during a treatment (for example, due to respiration or inadequate patient immobilization). New techniques are being developed to better control this uncertainty—for example, real-time imaging combined with real-time adjustment of the therapeutic beams. This new technology is called image-guided radiation therapy (IGRT) or four-dimensional radiation therapy.
Another technique is the real-time tracking and localization of one or more small implantable electric devices implanted inside or close to the tumor. There are various types of medical implantable devices that are used for this purpose. It can be a magnetic transponder which senses the magnetic field generated by several transmitting coils, and then transmits the measurements back to the positioning system to determine the location. The implantable device can also be a small wireless transmitter sending out an RF signal which then will be received by a sensor array and used for localization and real-time tracking of the tumor position.
Volumetric modulated arc therapy (VMAT) is a radiation technique introduced in 2007 which can achieve highly conformal dose distributions on target volume coverage and sparing of normal tissues. The specificity of this technique is to modify three parameters during the treatment. VMAT delivers radiation by rotating gantry (usually 360° rotating fields with one or more arcs), changing speed and shape of the beam with a multileaf collimator (MLC) ("sliding window" system of moving) and fluence output rate (dose rate) of the medical linear accelerator. VMAT has an advantage in patient treatment, compared with conventional static field intensity modulated radiotherapy (IMRT), of reduced radiation delivery times. Comparisons between VMAT and conventional IMRT for their sparing of healthy tissues and Organs at Risk (OAR) depends upon the cancer type. In the treatment of nasopharyngeal, oropharyngeal and hypopharyngeal carcinomas VMAT provides equivalent or better OAR protection. In the treatment of prostate cancer the OAR protection result is mixed with some studies favoring VMAT, others favoring IMRT.
In particle therapy (proton therapy being one example), energetic ionizing particles (protons or carbon ions) are directed at the target tumor. The dose increases while the particle penetrates the tissue, up to a maximum (the Bragg peak) that occurs near the end of the particle's range, and it then drops to (almost) zero. The advantage of this energy deposition profile is that less energy is deposited into the healthy tissue surrounding the target tissue.
Auger therapy (AT) makes use of a very high dose of ionizing radiation in situ that provides molecular modifications at an atomic scale. AT differs from conventional radiation therapy in several aspects; it neither relies upon radioactive nuclei to cause cellular radiation damage at a cellular dimension, nor engages multiple external pencil-beams from different directions to zero-in to deliver a dose to the targeted area with reduced dose outside the targeted tissue/organ locations. Instead, the in situ delivery of a very high dose at the molecular level using AT aims for in situ molecular modifications involving molecular breakages and molecular re-arrangements such as a change of stacking structures as well as cellular metabolic functions related to the said molecule structures.
Contact x-ray brachytherapy (also called "CXB", "electronic brachytherapy" or the "Papillon Technique") is a type of radiation therapy using kilovoltage X-rays applied close to the tumour to treat rectal cancer. The process involves inserting the x-ray tube through the anus into the rectum and placing it against the cancerous tissue, then high doses of X-rays are emitted directly into the tumor at two weekly intervals. It is typically used for treating early rectal cancer in patients who may not be candidates for surgery. A 2015 NICE review found the main side effect to be bleeding that occurred in about 38% of cases, and radiation-induced ulcer which occurred in 27% of cases.
Brachytherapy is delivered by placing radiation source(s) inside or next to the area requiring treatment. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, and skin cancer and can also be used to treat tumours in many other body sites.
In brachytherapy, radiation sources are precisely placed directly at the site of the cancerous tumour. This means that the irradiation only affects a very localized area – exposure to radiation of healthy tissues further away from the sources is reduced. These characteristics of brachytherapy provide advantages over external beam radiation therapy – the tumour can be treated with very high doses of localized radiation, whilst reducing the probability of unnecessary damage to surrounding healthy tissues. A course of brachytherapy can often be completed in less time than other radiation therapy techniques. This can help reduce the chance of surviving cancer cells dividing and growing in the intervals between each radiation therapy dose.
As one example of the localized nature of breast brachytherapy, the SAVI device delivers the radiation dose through multiple catheters, each of which can be individually controlled. This approach decreases the exposure of healthy tissue and resulting side effects, compared both to external beam radiation therapy and older methods of breast brachytherapy.
Systemic radioisotope therapy (RIT) is a form of targeted therapy. Targeting can be due to the chemical properties of the isotope such as radioiodine which is specifically absorbed by the thyroid gland a thousandfold better than other bodily organs. Targeting can also be achieved by attaching the radioisotope to another molecule or antibody to guide it to the target tissue. The radioisotopes are delivered through infusion (into the bloodstream) or ingestion. Examples are the infusion of metaiodobenzylguanidine (MIBG) to treat neuroblastoma, of oral iodine-131 to treat thyroid cancer or thyrotoxicosis, and of hormone-bound lutetium-177 and yttrium-90 to treat neuroendocrine tumors (peptide receptor radionuclide therapy).
Another example is the injection of radioactive yttrium-90 or holmium-166 microspheres into the hepatic artery to radioembolize liver tumors or liver metastases. These microspheres are used for the treatment approach known as selective internal radiation therapy. The microspheres are approximately 30 µm in diameter (about one-third of a human hair) and are delivered directly into the artery supplying blood to the tumors. These treatments begin by guiding a catheter up through the femoral artery in the leg, navigating to the desired target site and administering treatment. The blood feeding the tumor will carry the microspheres directly to the tumor enabling a more selective approach than traditional systemic chemotherapy. There are currently three different kinds of microspheres: SIR-Spheres,TheraSphere and QuiremSpheres.
A major use of systemic radioisotope therapy is in the treatment of bone metastasis from cancer. The radioisotopes travel selectively to areas of damaged bone, and spare normal undamaged bone. Isotopes commonly used in the treatment of bone metastasis are radium-223, strontium-89 and samarium (153Sm) lexidronam.
In 2002, the United States Food and Drug Administration (FDA) approved ibritumomab tiuxetan (Zevalin), which is an anti-CD20 monoclonal antibody conjugated to yttrium-90. In 2003, the FDA approved the tositumomab/iodine (131I) tositumomab regimen (Bexxar), which is a combination of an iodine-131 labelled and an unlabelled anti-CD20 monoclonal antibody. These medications were the first agents of what is known as radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkins lymphoma.
The rationale for IORT is to deliver a high dose of radiation precisely to the targeted area with minimal exposure of surrounding tissues which are displaced or shielded during the IORT. Conventional radiation techniques such as external beam radiotherapy (EBRT) following surgical removal of the tumor have several drawbacks: The tumor bed where the highest dose should be applied is frequently missed due to the complex localization of the wound cavity even when modern radiotherapy planning is used. Additionally, the usual delay between the surgical removal of the tumor and EBRT may allow a repopulation of the tumor cells. These potentially harmful effects can be avoided by delivering the radiation more precisely to the targeted tissues leading to immediate sterilization of residual tumor cells. Another aspect is that wound fluid has a stimulating effect on tumor cells. IORT was found to inhibit the stimulating effects of wound fluid.
Deep inspiration breath-hold (DIBH) is a method of delivering radiotherapy while limiting radiation exposure to the heart and lungs. It is used primarily for treating left-sided breast cancer. The technique involves a patient holding their breath during treatment. There are two basic methods of performing DIBH: free-breathing breath-hold and spirometry-monitored deep inspiration breath hold.
Medicine has used radiation therapy as a treatment for cancer for more than 100 years, with its earliest roots traced from the discovery of x-rays in 1895 by Wilhelm Röntgen. Emil Grubbe of Chicago was possibly the first American physician to use x-rays to treat cancer, beginning in 1896.
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 (1867–1934), who discovered the radioactive elements polonium and radium in 1898. This began a new era in medical treatment and research. Through the 1920s the hazards of radiation exposure were not understood, and little protection was used. Radium was believed to have wide curative powers and radiotherapy was applied to many diseases.
Prior to World War 2, the only practical sources of radiation for radiotherapy were radium, its "emanation", radon gas, and the x-ray tube. External beam radiotherapy (teletherapy) began at the turn of the century with relatively low voltage (<150 kV) x-ray machines. It was found that while superficial tumors could be treated with low voltage x-rays, more penetrating, higher energy beams were required to reach tumors inside the body, requiring higher voltages. Orthovoltage X-rays, which used tube voltages of 200-500 kV, began to be used during the 1920s. To reach the most deeply buried tumors without exposing intervening skin and tissue to dangerous radiation doses required rays with energies of 1 MV or above, called "megavolt" radiation. Producing megavolt x-rays required voltages on the x-ray tube of 3 to 5 million volts, which required huge expensive installations. Megavoltage x-ray units were first built in the late 1930s but because of cost were limited to a few institutions. One of the first, installed at St. Bartholomew's hospital, London in 1937 and used until 1960, used a 30 foot long x-ray tube and weighed 10 tons. Radium produced megavolt gamma rays, but was extremely rare and expensive due to its low occurrence in ores. In 1937 the entire world supply of radium for radiotherapy was 50 grams, valued at £800,000, or $50 million in 2005 dollars.
The invention of the nuclear reactor in the Manhattan Project during World War 2 made possible the production of artificial radioisotopes for radiotherapy. Cobalt therapy, teletherapy machines using megavolt gamma rays emitted by cobalt-60, a radioisotope produced by irradiating ordinary cobalt metal in a reactor, revolutionized the field between the 1950s and the early 1980s. Cobalt machines were relatively cheap, robust and simple to use, although due to its 5.27 year half-life the cobalt had to be replaced about every 5 years.
Medical linear particle accelerators, developed since the 1940s, began replacing x-ray and cobalt units in the 1980s and these older therapies are now declining. The first medical linear accelerator was used at the Hammersmith Hospital in London in 1953. Linear accelerators can produce higher energies, have more collimated beams, and do not produce radioactive waste with its attendant disposal problems like radioisotope therapies.
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. 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 to 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.
Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.Acromegaly is typically due to the pituitary gland producing too much growth hormone. In more than 95% of cases the excess production is due to a benign tumor, known as a pituitary adenoma. The condition is not inherited from a person's parents. Rarely acromegaly is due to tumors in other parts of the body. Diagnosis is by measuring growth hormone after a person has drunk glucose or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to look for an adenoma. If excess growth hormone is produced during childhood the result is gigantism.Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the preferred treatment and is most effective when the tumor is smaller. In those in whom surgery is not effective, medications of the somatostatin analogue or GH receptor antagonist type may be used. The effects of radiation therapy are more gradual than that of surgery or medication. Without treatment those affected live on average 10 years less; with treatment, however, life expectancy is typically normal.Acromegaly affects about 6 per 100,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. The first medical description of the disorder occurred in 1772 by Nicolas Saucerotte. The term is from Greek ἄκρον akron meaning "extremity" and μέγα mega meaning "large".Cyberknife
The CyberKnife System is a radiation therapy device manufactured by Accuray Incorporated. The system is used to deliver radiosurgery for the treatment of benign tumors, malignant tumors and other medical conditions.External beam radiotherapy
External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachytherapy (sealed source radiotherapy) and unsealed source radiotherapy, in which the radiation source is inside the body, external beam radiotherapy directs the radiation at the tumour from outside the body. Orthovoltage ("superficial") X-rays are used for treating skin cancer and superficial structures. Megavoltage X-rays are used to treat deep-seated tumours (e.g. bladder, bowel, prostate, lung, or brain), whereas megavoltage electron beams are typically used to treat superficial lesions extending to a depth of approximately 5 cm (increasing beam energy corresponds to greater penetration). X-rays and electron beams are by far the most widely used sources for external beam radiotherapy. A small number of centers operate experimental and pilot programs employing beams of heavier particles, particularly protons, owing to the rapid dropoff in absorbed dose beneath the depth of the target.Hodgkin's lymphoma
Hodgkin's lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cells called lymphocytes. Symptoms may include fever, night sweats, and weight loss. Often there will be non-painful enlarged lymph nodes in the neck, under the arm, or in the groin. Those affected may feel tired or be itchy.About half of cases of Hodgkin's lymphoma are due to Epstein–Barr virus (EBV). Other risk factors include a family history of the condition and having HIV/AIDS. There are two major types of Hodgkin lymphoma: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Diagnosis is by finding Hodgkin's cells such as multinucleated Reed–Sternberg cells (RS cells) in lymph nodes. The virus-positive cases are classified as a form of the Epstein-Barr virus-associated lymphoproliferative diseases.Hodgkin lymphoma may be treated with chemotherapy, radiation therapy, and stem cell transplant. The choice of treatment often depends on how advanced the cancer has become and whether or not it has favorable features. In early disease, a cure is often possible. The percentage of people who survive five years in the United States is 86%. For those under the age of 20, rates of survival are 97%. Radiation and some chemotherapy drugs, however, increase the risk of other cancers, heart disease, or lung disease over the subsequent decades.In 2015, about 574,000 people had Hodgkin's lymphoma, and 23,900 died. In the United States, 0.2% of people are affected at some point in their life. The most common age of diagnosis is between 20 and 40 years old. It was named after the English physician Thomas Hodgkin, who first described the condition in 1832.Intraoperative electron radiation therapy
Intraoperative electron radiation therapy is the application of electron radiation directly to the residual tumor or tumor bed during cancer surgery. Electron beams are useful for intraoperative radiation treatment because, depending on the electron energy, the dose falls off rapidly behind the target site, therefore sparing underlying healthy tissue. IOERT has been called "precision radiotherapy," because the physician has direct visualization of the tumor and can exclude normal tissue from the field while protecting critical structures within the field and underlying the target volume. One advantage of IOERT is that it can be given at the time of surgery when microscopic residual tumor cells are most vulnerable to destruction. Also, IOERT is often used in combination with external beam radiotherapy (EBR) because it results in less integral doses and shorter treatment times.Intraoperative radiation therapy
Intraoperative radiation therapy, is the application of therapeutic levels of radiation to the tumor bed while the area is exposed during surgery. IORT is typically a component in the multidisciplinary treatment of locally advanced and recurrent cancer, in combination with external beam radiation, surgery and chemotherapy. As a growing trend in recent years, IORT can also be used in earlier stage cancers such as prostate and breast cancer.Monitor unit
A monitor unit (MU) is a measure of machine output from a clinical accelerator for radiation therapy such as a linear accelerator or an orthovoltage unit. Monitor units are measured by monitor chambers, which are ionization chambers that measure the dose delivered by a beam and are built into the treatment head of radiotherapy linear accelerators.Particle therapy
Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions for cancer treatment. The most common type of particle therapy as of 2012 is proton therapy. Although a photon, used in x-ray or gamma ray therapy, can also be considered a particle, photon therapy is not considered here. Additionally, electron therapy is generally put into its own category. Because of this, particle therapy is sometimes referred to, more correctly, as hadron therapy (that is, therapy with particles that are made of quarks).
Neutron capture therapy might be considered a type of particle therapy, but it is not discussed here, as the damage it does to tumors is mostly from energetic ions produced by the secondary nuclear reaction after the neutrons in the external beam are absorbed into boron-10 (or occasionally some other nuclide), and not due primarily to the neutrons themselves. It is therefore a type of secondary particle therapy.
Muon therapy, a rare type of particle therapy not within the categories above, has occasionally been attempted.Pencil (optics)
In optics, a pencil or pencil of rays is a geometric construct used to describe a beam or portion of a beam of electromagnetic radiation or charged particles, typically in the form of a narrow cone or cylinder.
Antennas which strongly bundle in azimuth and elevation are often described as "pencil-beam" antennas. For example, a phased array antenna can send out a beam that is extremely thin. Such antennas are used for tracking radar. See Beamforming for further details.
In optics, the focusing action of a lens is often described in terms of pencils of rays. In addition to conical and cylindrical pencils, optics deals with astigmatic pencils as well.In electron optics, scanning electron microscopes use narrow pencil beams to achieve a deep depth of field.Ionizing radiation used in radiation therapy, whether photons or charged particles, such as proton therapy and electron therapy machines, is sometimes delivered through the use of pencil beam scanning.In Backscatter X-ray imaging a pencil beam of x-ray radiation is used the scan over an object to create an intensity image of the Compton-scattered radiation.Plaque radiotherapy
Plaque radiotherapy is a type of radiation therapy used to treat eye tumors. A thin piece of metal (usually gold) with radioactive seeds placed on one side is sewn onto the outside wall of the eye with the seeds aimed at the tumor. It is removed at the end of treatment, which usually lasts for several days.
Iodine-125 is among the isotopes used.Pneumonitis
Pneumonitis is an inflammation of lung tissue due to factors other than microorganisms. Those can be radiation therapy of the chest , exposure to medications used during chemo-therapy, the inhalation of debris (e.g., animal dander), of food particles during vomiting, herbicides or fluorocarbons and some systemic diseases.
It is distinguished from pneumonia on the basis of causation as well as its manifestation since pneumonia can be described as pneumonitis combined with consolidation and exudation of lung tissue due to infection with microorganism.Proton therapy
In the field of medical procedures, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often in the treatment of cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that as a charged particle the dose is deposited over a narrow range of depth, and there is minimal entry, exit, or scattered radiation dose.Radiation proctitis
Radiation proctitis (and the related radiation colitis) is inflammation and damage to the lower parts of the colon after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctitis most commonly occurs after treatment for cancers such as cervical cancer, prostate cancer, and colon cancer. Radiation proctitis involves the lower intestine, primarily the sigmoid colon and the rectum, and is part of the conditions known as pelvic radiation disease and radiation enteropathy.Radiosurgery
Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy (also called radiotherapy), it is usually used to treat cancer. Radiosurgery was originally defined by the Swedish neurosurgeon Lars Leksell as "a single high dose fraction of radiation, stereotactically directed to an intracranial region of interest".In stereotactic radiosurgery (SRS), the word "stereotactic" refers to a three-dimensional coordinate system that enables accurate correlation of a virtual target seen in the patient's diagnostic images with the actual target position in the patient. Stereotactic radiosurgery may also be called stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) when used outside the central nervous system (CNS).Stereotactic radiation therapy
Stereotactic radiation therapy, also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy, is a type of external radiation therapy that uses special equipment to position the patient and precisely deliver radiation to a tumor. The total dose of radiation is divided into several smaller doses given over several days. Stereotactic radiation therapy is used to treat brain tumors and other brain disorders. It is also being studied in the treatment of other types of cancer, such as lung cancer.
What differentiates Stereotactic from conventional radiotherapy is the precision with which it is delivered. There are multiple systems available, some of which use specially designed frames which physically attach to the patient's skull while newer more advanced techniques use thermoplastic masks and highly accurate imaging systems to locate the patient. The end result is the delivery of high doses of radiation with sub-millimetre accuracy.Testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility.Risk factors include an undescended testis, family history of the disease, and previous history of testicular cancer. The most common type is germ cell tumors which are divided into seminomas and nonseminomas. Other types include sex-cord stromal tumors and lymphomas. Diagnosis is typically based on a physical exam, ultrasound, and blood tests. Surgical removal of the testicle with examination under a microscope is then done to determine the type.Testicular cancer is highly treatable and usually curable. Treatment options may include surgery, radiation therapy, chemotherapy, or stem cell transplantation. Even in cases in which cancer has spread widely, chemotherapy offers a cure rate greater than 80%.Globally testicular cancer affected about 686,000 people in 2015. That year it resulted in 9,400 deaths up from 7,000 deaths in 1990. Rates are lower in the developing than the developed world. Onset most commonly occurs in males 20 to 34 years old, rarely before 15 years old. The five-year survival rate in the United States is about 95%. Outcomes are better when the disease remains localized.Tomotherapy
Tomotherapy is a type of radiation therapy in which the radiation is delivered slice-by-slice (hence the use of the Greek prefix tomo-, which means "slice"). HT is a form of computed tomography (CT) guided intensity modulated radiation therapy (IMRT). HT machines are purpose built for IMRT and differ from IMRT delivered by conventional medical linear accelerators (LINACs) in a number of ways. The main difference is that in HT a narrow intensity modulated pencil beam is delivered from a rotating gantry while the patient is simultaneously moved through the bore, compared to the much wider intensity modulated beam and static patient in conventional IMRT. HT units are therefore better able to target treatment sites throughout the body without a pause for the patient to be moved and set-up differently.Treatment of cancer
Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development. Under current estimates, two in five people will have cancer at some point in their lifetime.Complete removal of the cancer without damage to the rest of the body (that is, achieving cure with near-zero adverse effects) is the ideal goal of treatment and is often the goal in practice. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness; and chemotherapy and radiotherapy can have a negative effect on normal cells. Therefore, cure with nonnegligible adverse effects may be accepted as a practical goal in some cases; and besides curative intent, practical goals of therapy can also include (1) suppressing the cancer to a subclinical state and maintaining that state for years of good quality of life (that is, treating the cancer as a chronic disease), and (2) palliative care without curative intent (for advanced-stage metastatic cancers).
Because "cancer" refers to a class of diseases,
it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases. Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.Uterine cancer
Uterine cancer, also known as womb cancer, are two types of cancer that develops from the tissues of the uterus. Endometrial cancer forms from the lining of the uterus and uterine sarcoma forms from the muscles or support tissue of the uterus. Symptoms of endometrial cancer include unusual vaginal bleeding or pain in the pelvis. Symptoms of uterine sarcoma include unusual vaginal bleeding or a mass in the vagina.Risk factors for endometrial cancer include obesity, metabolic syndrome, type 2 diabetes, and a family history of the condition. Risk factors for uterine sarcoma include prior radiation therapy to the pelvis. Diagnosis of endometrial cancer is typically based on an endometrial biopsy. A diagnosis of uterine sarcoma may be suspected based on symptoms, a pelvic exam, and medical imaging.Endometrial cancer can often be cured while uterine sarcoma typically is harder to treat. Treatment may include a combination of surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy. Just over 80% of people survive more than 5 years following diagnosis.In 2015 about 3.8 million people were affected globally and it resulted in 90,000 deaths. Endometrial cancer is relatively common while uterine sarcoma is rare. In the United States they represent 3.6% of new cancer cases. They most commonly occur in women between the ages of 55 and 74.
Radiation (physics and health)