Version May 2024
INTRODUCTION — Radiation therapy (RT) was first used to treat cancer over a century ago [1,2]. Since then, enormous progress has been made to improve the effectiveness of this modality and minimize side effects.
Increasingly, RT has been used with surgery and systemic therapies in combined modality approaches for a wide range of malignancies to maximize tumor control and quality of life while minimizing toxicity and preserving the organs. The best outcomes are achieved when each patient is evaluated in a multidisciplinary setting and the team of clinicians, including surgeons, medical oncologists, radiation oncologists, and other specialists, jointly determine the best treatment.
In various settings, RT may be the sole treatment, can be given concurrently with systemic agents, or may precede or follow surgery to minimize the chance of microscopic disease left after treatment. In addition, RT may be used palliatively when disease is incurable. The duration of treatment can range from a single treatment up to eight weeks of daily irradiation. In each clinical scenario, the technique, dose, expected outcomes, and related toxicities vary depending upon the diagnosis and treatment site.
Organ preservation has become a very important component of clinical oncology patient management over the past 50 years. Randomized clinical trials have established equivalent outcomes between radical surgery and organ-preservation treatment with an RT backbone for appropriately selected patients with breast cancer, laryngeal cancer, extremity sarcoma, prostate cancer, and oropharyngeal cancer. Smaller trials have shown the appropriateness of organ preservation for patients with bladder cancer and early-stage lung cancer. Equivalent outcomes to surgery and better quality of life with organ preservation make definitive RT a very important option for managing carefully selected patients with potentially curable solid malignancies.
In this topic, the mechanism of action of radiation will be reviewed along with the key features of different RT modalities. The application of these treatment modalities in specific malignancies and its integration with other treatment modalities are discussed in the treatment topics for those diseases.
MECHANISM OF ACTION — RT is a treatment modality that delivers energy to kill malignant cells in the area specifically targeted by the clinician.
RT primarily damages the DNA of cancer cells by ionizing the atoms that make up the DNA chain. Ionizations result in broken atomic and molecular bonds; the generation of double-strand breaks in DNA is considered the dominant factor that causes cellular lethality [3].
Both malignant and normal cells in the treatment field are subject to the ionizing effects of radiation. Normal cells generally are better able to repair damage caused by radiation at the cellular level, using molecular machinery that detects DNA breaks and mutations and repairs them. In contrast, many malignant cells lack these molecular mechanisms and, therefore, are preferentially damaged by radiation. However, normal tissues have limits on the dose of radiation that they can safely withstand; these limits determine the maximum dose that can be safely administered during a course of treatment.
The most fundamental concept in radiation oncology is the therapeutic ratio, which provides a risk-benefit approach to planning RT. A careful balance must be achieved between what is an acceptable probability of a radiation-induced complication in a normal tissue and the probability of tumor control. The therapeutic ratio is optimized by minimizing the dose to normal tissues while maximizing the dose to the tumor target with special dose-shaping techniques. At the same time, the total dose of radiation is often divided (fractionated) into smaller daily doses to allow normal tissues to repair the radiation damage between treatments.
EXTERNAL BEAM RADIATION THERAPY — The most common RT approach is to deliver the radiation from a source outside the patient ("external beam radiation therapy" [EBRT]). EBRT machines produce ionizing radiation either by radioactive decay of a nuclide such as cobalt-60 or electronically by the acceleration of electrons or other charged particles, such as protons.
Linear accelerators — Linear accelerators have replaced most cobalt-60 machines in North America and Western Europe in recent decades. In a linear accelerator, electrons are accelerated to high energy and are allowed to either exit the machine as an electron beam or to strike a target that produces X-rays (also known as photons), which are directed at the tumor. Linear accelerators are relatively small devices, they can generate either photon or electron beams of various energies, and their output is managed with sophisticated computer controls.
Photons versus electrons — Photons are the most widely used radiation mode due to their ability to penetrate deeply and reach internal organs. Electrons are often used for superficial targets such as the skin and breast, where the goal is to minimize radiation to deeper tissues and organs. Clinicians exploit the advantages of electrons over photons when internal organs are not in the treatment target and better organ sparing can be achieved with this treatment modality. Often photons and electrons can be carefully mixed to deliver the best possible tumor and normal tissue dose distribution.
Treatment planning — Treatment planning includes careful patient immobilization and determination of the radiation field (the specific anatomic regions that will be irradiated) as well as the dose and schedule for treatment (image 1).
Extreme care is required in treatment planning by the radiation oncology team. Failure to deliver the full planned dose of radiation to a tumor target can result in tumor undertreatment and a failure to control the tumor. Conversely, excessive irradiation (overtreatment) of normal tissue can result in serious toxicity. The treatment planning process involves several key steps:
●Definition of the tumor target – Prior to treatment, the precise anatomic location of the tumor and its relationship to adjacent structures must be determined.
●Patient immobilization – The administration of multiple doses of radiation to precisely the same region requires that the patient be reproducibly immobilized during the planning process and subsequent treatment. Immobilization requires special devices and body casts that allow for the best treatment geometry while maximizing the patient's comfort and the reproducibility of patient positioning.
●Imaging – After immobilization, a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the treatment area is obtained while the patient remains in the treatment position to allow for precise target delineation. Special ("fiducial") markers can be utilized to facilitate daily localization (image 2). These markers may be placed internally or superficially, and tattoo marks are often placed on the skin.
When breathing is known to affect the tumor location, four-dimensional imaging is obtained, which allows clinicians to target the tumor during all phases of the respiratory cycle or to use a gating technique in which patients are treated only in certain phases of the breathing cycle.
●Delineation of the target volumes – Clinicians use the imaging studies to delineate, or contour, the target volumes, as well as the normal structures, taking into account the knowledge, generated by previous studies, of areas of macroscopic and microscopic disease. The target volume will include some margin of seemingly normal tissue to ensure that no tumor is missed.
●Dose and schedule – Treatment planning requires consideration of the total dose of radiation needed to treat a specific tumor in a specific location and requires balancing this against the potential damage to normal tissues that may receive radiation.
Different tumors have different sensitivities to radiation. For example, highly radiosensitive tumors, such as seminoma and lymphoma, can often be eradicated with relatively low doses of radiation, whereas other tumor types (eg, melanoma, sarcoma) are considered relatively radioresistant and require much higher doses for tumor eradication.
Similarly, normal tissues differ substantially in their sensitivity to radiation damage. Normal tissue tolerances have been defined in numerous clinical trials over the past several decades. This collective experience has been summarized in the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review [4] and is used to improve treatment effectiveness by allowing treatment dose escalation and to improve quality of life outcomes by minimizing toxicity.
Conformal therapy — Conformal therapy is a term that describes a strategy for matching ("conforming") the high-dose radiation region to the target volume while minimizing the radiation dose to normal tissues. This term is typically used when the target volumes are defined on a CT or other high-definition imaging study used during the treatment planning. Therefore, three-dimensional conformal radiation therapy (3D-CRT) usually implies a CT- or MRI-based treatment plan. These plans allow radiation oncologists to calculate and optimize the radiation dose received by the tumor, as well as the adjacent normal tissues.
Refinements of 3D-CRT include intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Conformal therapy has not been demonstrated to improve survival for the majority of clinical situations. However, conformal therapy is generally accepted as a way to reduce toxicity [5-7]. With reduced toxicity, dose escalation trials have become possible in an effort to improve long-term tumor control. Furthermore, use of 3D-CRT has made retreatment of a previously irradiated area feasible in more situations than were previously possible.
Intensity-modulated radiation therapy — IMRT is an advanced form of 3D-CRT that changes the intensity of radiation in different parts of a single radiation beam while the treatment is delivered.
Varying the dose of radiation administered within each beam enables IMRT to simultaneously treat multiple areas within the target to different dose levels, thus providing a simultaneous integrated boost [8]. However, IMRT results in a larger volume of normal tissue receiving lower doses of radiation compared with older techniques. This drawback may be particularly important in children and other patients with a prolonged anticipated survival, where a heterogeneous low-dose volume may result in a higher incidence of secondary malignancies or unintended developmental consequences [9-11]. Nevertheless, at least in the short to intermediate term, toxicities appear to be less with IMRT. In a randomized trial in 279 patients with endometrial or cervical cancer receiving pelvic radiation and followed for a median of 38 months, those in the IMRT therapy arm experienced less high-level diarrhea compared with those in the conventional radiation arm (6 versus 15 percent) [12]. Moreover, at three years, women in the conventional radiation arm reported a decline in urinary function, while those receiving IMRT experienced improvements.
A possible disadvantage of IMRT is the prolonged time for each treatment compared with other treatment techniques, with its unknown biological impact [13-15].
Image-guided radiation therapy — Uncertainty about patient positioning requires that clinicians add extra margins to the target volumes beyond that based upon the original imaging of the tumor. This uncertainty may be due to imprecision in patient positioning on a daily basis, despite immobilization, or to inherent organ motion (eg, respiration).
Real-time imaging of the treatment target and normal organs during each treatment allows for minimization of such additional margins and the reduction of irradiated volumes, as it decreases the chance of missing a target. This technology is collectively referred to as IGRT, and it employs various methods for real-time imaging and treatment adjustment.
Particle therapy — Particle therapy is a special form of EBRT, with protons being the most widely used [16]. Special equipment is used to generate high-energy particles, and these devices are large and costly to build and operate.
Proton beam — Proton radiation reduces the dose to normal tissues by allowing for more precise dose delivery because of the unique physical properties of heavy particles. Protons penetrate tissue to a variable depth, depending upon their energy, and then deposit that energy in the tissue in a sharp peak, known as a Bragg peak (figure 1). This rapid dose falloff at a depth that can be controlled by the initial energy of the protons allows for decreased radiation to adjoining normal tissue by a factor of 2 to 3 [17].
At the present time, the clinical superiority of protons compared with photons is clearly established in some pediatric populations [18,19] and in rare situations when normal structures in close proximity to the treatment target limit the ability to deliver conventional photon beam therapy, such as uveal melanoma [20-22] and sarcomas of the skull base [23,24] and spine [25]. In other situations, such as prostate cancer, proton beams are being increasingly used, but the available data have not demonstrated an advantage compared with other 3D-CRT techniques [26,27]. Although they have been evaluated in a single-arm study in breast cancer [28], as well as randomized trials in esophageal cancer [29], brain glioblastoma [30], and locally advanced non-small cell lung cancer [31], protons have not yet been established as clinically superior through randomized clinical trials in any adult solid tumor. Additional trials are underway to determine the role of protons. (See "External beam radiation therapy for localized prostate cancer", section on 'Proton beam'.)
Proton beam treatment generates neutrons as a byproduct, which can be scattered into adjacent normal tissues. These neutrons have a greater biologic effect and, thus, theoretically might increase the risk of second malignancies [10,32]. Despite these theoretical concerns, large retrospective studies have not found increased rates of secondary malignancies in patients treated with protons compared with photons. [33,34].
Other heavy particles — Other heavy particles have also been used for RT. Neutrons have a very limited clinical application, and experience with carbon ions is limited to only a few countries, such as Japan and Germany.
Neutron RT is believed to have an advantage in the treatment of certain tumors that exhibit a resistance to conventional photon beam RT, such as inoperable or recurrent salivary gland malignancies [35,36] or incompletely resected sarcomas of bone, cartilage, and soft tissue [37]. Increased risk of secondary malignancy with neutron exposure remains a major concern [38].
Further studies are required to determine the magnitude of clinical benefit for various diagnoses as the number of centers offering these modalities is limited, as is clinical experience with these special forms of EBRT.
Stereotactic radiation therapy techniques — Stereotactic RT techniques administer the full calculated dose of radiation in one or a very limited number of treatment fractions (figure 2). Stereotactic techniques typically utilize photons that are generated by a linear accelerator or by a cobalt-60 source. (See 'Linear accelerators' above and "Stereotactic cranial radiosurgery", section on 'Gamma Knife'.)
Stereotactic radiosurgery (SRS) refers to a single-fraction treatment of intracranial and spinal targets, whereas stereotactic body radiation therapy (SBRT) refers to multifractional (typically two to five fractions) treatment of intracranial, spinal, or extracranial sites, such as the lung, head and neck, liver, pancreas, and prostate. (See "Stereotactic cranial radiosurgery".)
High-resolution imaging is required for stereotactic radiation techniques to accurately delineate the tumor and its relationship to normal structures. These advances led to the use of a single or limited number of fractions when a well-delineated small tumor can easily be visualized and targeted while minimizing exposure of normal tissues to high doses of radiation.
This is in contrast to conventional EBRT, which utilizes dose fractionation, where the total dose is administered over a period of many days to allow normal cells to recover between the daily fractions. Although these stereotactic techniques lack the theoretical biologic advantages associated with fractionation, clinical efficacy has been demonstrated in a variety of settings (eg, brain and liver metastases, lung tumors). (See "Stereotactic body radiation therapy for lung tumors" and "Overview of the treatment of brain metastases", section on 'Efficacy of SRS alone'.)
Immobilization is even more critical for SRS or SBRT than for EBRT in order to achieve high reproducibility and precision. As an example, a custom body cast with radiopaque markers is used to establish a coordinate system in the three-dimensional space for treatment of thoracic, spine, and abdominal tumors. Single-fraction SRS treatments may utilize rigid head frames, which are fixed to the head using pins or screws, or a frameless system with a head mask and a bite-block system similar to a dental mold (figure 3).
Timing relative to systemic therapy — Although metastases-directed SBRT is generally well tolerated, there are limited data regarding potential interactions between SBRT and systemic therapy. Our general practice is to hold most systemic therapies on the days of SBRT, and resume anywhere between one week and one cycle later, depending on the patient's tolerance of SBRT, the type of systemic treatment and urgency to restart systemic treatment to control patient's disease, and proximity of radiation therapy treatment target to critical structures (spinal cord, internal organs). Systemic therapy after SBRT to bone metastases in upper and lower extremities can be reinitiated after SBRT without delay. Hormonal therapies do not need to be held for SBRT.
In the United Kingdom, SBRT is approved for oligometastatic disease based on a prospective registry-based study, which mandated discontinuation of chemotherapy for four weeks and targeted drugs for two weeks before SBRT, and allowed continuation of hormone therapy during SBRT [39]. Expert guidelines based on a systematic review suggest holding most immunotherapy and targeted agents on the day of SBRT, but pertuzumab and trastuzumab may be administered on the day of SBRT [40]. Further data are needed to clarify the optimal strategy.
Total body irradiation — Total body irradiation (TBI) with conventional photons is widely used as a component of preparative cytoreductive regimens for hematopoietic cell transplantation.
There are two main purposes of TBI: immunosuppression to allow engraftment of donor stem cells and eradication of malignant cells. TBI has several advantages over systemic chemotherapy agents, such as the ability to penetrate sanctuary sites, independence of blood supply, and no cross-resistance with other agents.
Hematopoietic cell transplantation for leukemias and lymphomas is the most common situation where TBI is used.
BRACHYTHERAPY — Brachytherapy is a form of RT in which a radiation source is placed inside or next to the area requiring treatment. The radiation emitted is generally active over only a relatively short distance. Thus, the advantage of brachytherapy is the ability to deliver high doses of radiation to the tumor while reducing the dose to the surrounding normal tissues.
Brachytherapy can be delivered with either a low dose rate (LDR) or high dose rate (HDR) system. The International Commission on Radiation Units (ICRU) defines LDR brachytherapy as 0.4 to 2 Gy per hour, whereas HDR brachytherapy is delivered at >12 Gy per hour.
Brachytherapy has defined roles in a number of malignancies. The potential role of brachytherapy is illustrated by its use in prostate cancer, gynecologic malignancies, and breast cancer:
●Prostate cancer – For appropriately selected men with localized prostate cancer, LDR brachytherapy is well established as a way to provide treatment in a single outpatient session. LDR brachytherapy involves the placement of radioactive seeds that are permanently implanted into the prostate gland. The planned RT dose is emitted over several months, depending upon the specific isotope. Both iodine-125 and palladium-103 are widely used. (See "Brachytherapy for low-risk or favorable intermediate-risk, clinically localized prostate cancer".)
HDR brachytherapy is frequently used in conjunction with EBRT to provide a boost to prostate tumor. With HDR brachytherapy, transperineal catheters are inserted into the prostate through a template that is fixed to the perineum. The hollow guides are then loaded with an isotope, such as iridium-192. The HDR brachytherapy dose is administered in two or more large-dose fractions, with each treatment typically taking 24 to 40 hours. Patients must be admitted to the hospital for treatment and retain the perineal catheters in place for the entire period.
●Gynecologic malignancies – Brachytherapy represents an integral component of treatment for cervical, endometrial, and vaginal carcinoma, either as monotherapy or in conjunction with EBRT depending upon the situation. The instruments to position the radioactive source are placed into the uterus and vagina with the patient under sedation, which can range from conscious sedation to general anesthesia. (See "Management of locally advanced cervical cancer" and "Overview of resectable endometrial carcinoma", section on 'Role of adjuvant therapy'.)
Traditionally, LDR brachytherapy used sources such as cesium-137 and iridium-192 given in one to two insertions over a 48 to 72 hour period during an inpatient hospitalization in a shielded room. Technological advances have made HDR brachytherapy feasible, which resulted in outpatient treatment convenience, decreased radiation exposure for health care workers, and better dosimetric treatment of tumors.
●Breast cancer – Brachytherapy has been historically used as a technique to deliver a boost dose to the surgical cavity in addition to whole-breast irradiation. However, most clinicians use external beam electron or photon boosts in this setting. At the same time, accelerated partial-breast irradiation (APBI) has gained considerable popularity and has seen a 10-fold increase in its use between 2002 and 2007 [41]. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'Accelerated partial-breast irradiation'.)
For appropriately selected women with early-stage breast cancer, APBI allows for the delivery of adjuvant therapy after breast-conserving surgery in one week or less. Intracavitary balloons and interstitial multicatheter implants are currently the most widely used brachytherapy-based APBI treatment modalities.
The advantages of brachytherapy come at the expense of requiring an invasive procedure to be carried out, and the benefits of brachytherapy must be balanced against possible complications.
Outcomes are often dependent on the experience of a particular clinician. Accurate source placement is needed to avoid worse tumor control [42,43]. There has been a move to increase the quality assurance and radiation safety in conjunction with brachytherapy administration. This has resulted in even greater quality of treatments delivered at high-volume centers with specialized expertise, while brachytherapy has been abandoned by other centers.
INTRAOPERATIVE RADIATION THERAPY — Intraoperative radiation therapy (IORT) is the delivery of radiation at the time of surgery. Whereas the dose delivered by external beam radiation therapy (EBRT) is limited by the tolerance of surrounding normal tissues, IORT allows exclusion of part or all of the dose-limiting sensitive structures by operative mobilization and/or direct shielding of these structures. A single-fraction treatment is used, and dose is limited by structures (nerves, fixed organs) that cannot be displaced.
The decision to deliver IORT is often made intraoperatively, based upon clinical and frozen-section pathology evaluation. Areas at high risk of local recurrence (positive margins, incompletely resected tumors) can be visualized and targeted while the patient is under anesthesia.
The use of IORT was initiated in the 1960s in Japan [44], and currently, a linear accelerator-based electron treatment approach is used in approximately 90 centers in at least 16 countries worldwide. IORT is most useful for pelvic and abdominal malignancies where normal bowel limits the dose that can be delivered with EBRT. However, the dose delivered in a single fraction with IORT is rarely sufficient for tumor control, and therefore, IORT is usually preceded or followed by additional EBRT.
TARGETED RADIONUCLIDE THERAPY — Highly specific targeting of radiation can also be achieved using radionuclides that decay within the body in very specific locations. These forms of radiation can be based upon the specific tissue properties or on targeting the radionuclide based upon its chemical composition or structure.
Examples of these approaches include the following:
●Thyroid cells selectively accumulate iodine-131. The release of radiation as the iodine-131 decays can be used to destroy thyroid tissue and, thus, treat thyroid cancer. (See "Differentiated thyroid cancer: Radioiodine treatment".)
●Radioisotopes that are accumulated in bone may be particularly valuable for the treatment of bone metastases. In particular, radium-223 emits alpha particles, which release their energy over a very short distance, thus sparing other organs. Radium-223 has been developed as an important alternative for patients with extensive bone metastases from prostate cancer. (See "Bone metastases in advanced prostate cancer: Management", section on 'Bone-targeted radioisotopes'.)
●Radionuclides have been chemically linked to monoclonal antibodies that can selectively target a specific antigen and, thus, deliver radiation to that target. The most successful clinical application of this form of treatment has been for the treatment of lymphoma and leukemia with anti-CD20 monoclonal antibodies. (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Radioimmunotherapy'.)
●Radionuclides can be imbedded into glass or resin microspheres and administered intraarterially for direct radioembolization of tumors [45]. This approach is suitable in the absence of known tumor markers and with target tissues appropriate for radioembolization, such as the liver. (See "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for local thermal ablation", section on 'Radioembolization'.)
A novel treatment modality for metastatic prostate cancer is a beta particle emitter lutetium-177 (177-Lu), linked to prostate-specific membrane antigen (PSMA), also known as folate hydrolase I and glutamate carboxypeptidase II, which is a cell membrane protein that is highly expressed on the surface of prostate cancer cells. This therapy has been evaluated in a phase III randomized clinical trial [46]. (See "Overview of the treatment of castration-resistant prostate cancer (CRPC)", section on 'Radioligand therapy for PSMA-positive tumors'.)
RADIATION SIDE EFFECTS — The side effects experienced by patients during or after a course of RT largely depend upon the anatomic area of treatment and are related to treatment factors such as the cumulative dose, dose per fraction, proximity of sensitive tissues and organs, and effect of other cancer treatments, such as surgery and chemotherapy.
As a general rule, tissues swell during the RT, leading to acute side effects related to this swelling, or edema, in the target tissue. Most acute side effects are predictable and are limited to the area of the patient's body that is under treatment. Abdominal radiation leads to development of nausea and vomiting. Head and neck irradiation causes mouth and throat sores, whereas thoracic irradiation causes esophagitis. These symptoms in turn can lead to dysphagia, poor oral intake, and dehydration. Pelvic radiation can lead to urinary symptoms and bowel changes. As swelling and tissue irritation decrease after the treatment, the acute side effects largely resolve.
Long-term sequelae of RT are largely related to the irradiated tissue fibrosis. These side effects must be balanced against the potential benefits of treatment. (See "Clinical manifestations, prevention, and treatment of radiation-induced fibrosis".)
Specific late toxicities are related to the organs exposed to irradiation and the dose of radiation. Examples include:
●Infertility is a serious issue for pediatric and young adult cancer patients, as ovaries and testicles are highly sensitive to the effects of radiation. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery", section on 'Mechanism of injury' and "Effects of cytotoxic agents on gonadal function in adult men".)
●Cardiac toxicity can be a late complication of treatment of a number of malignancies, including breast cancer, Hodgkin lymphoma, and other cancers in which the heart receives some irradiation. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies" and "Cardiotoxicity of radiation therapy for Hodgkin lymphoma and pediatric malignancies".)
●Second cancers have an established relationship with prior RT [47]. As an example, a large population-based analysis noted an 8 percent risk of second malignancies among cancer survivors treated with radiation between 1973 and 2002 [48]. However, this analysis was not controlled for the development of cancer in a population not exposed to radiation, and many of these malignancies are likely to be unrelated to the radiation exposure. Nevertheless, this concern is real and is especially critical in pediatric and young adult patients, as it may take 10 to 15 years or more before a secondary malignancy becomes apparent.
SUMMARY
●Mechanism of action of radiation therapy – Radiation therapy (RT) is an effective modality to treat cancer. RT is applicable in a wide range of tumors and can be used alone or in conjunction with surgery and/or systemic therapy. RT works by causing double-stranded breaks in DNA, which are repaired more slowly in tumor compared with normal tissues. (See 'Mechanism of action' above.)
●Treatment planning – Treatment with RT requires precise planning, incorporating both the area to be irradiated (the "field") and the dose and schedule of irradiation. (See 'Treatment planning' above.)
●Techniques – A variety of radiation techniques have been developed. The most widely used of these include:
•External beam radiation therapy (EBRT), which now primarily uses three-dimensional conformal radiation therapy (3D-CRT) techniques to maximize the dose of radiation to the tumor and minimize exposure of normal tissue to radiation. Important variants on three-dimensional techniques include intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). (See 'Conformal therapy' above.)
•Stereotactic techniques (stereotactic radiosurgery [SRS] and stereotactic body radiation therapy [SBRT]), which use a single fraction or a limited number of fractions of radiation to ablate tumors. Stereotactic techniques rely upon very accurate tumor localization, using magnetic resonance imaging or computed tomography, combined with precise patient immobilization. (See 'Stereotactic radiation therapy techniques' above.)
•Brachytherapy, in which a radiation source is placed inside or next to the area requiring treatment. Brachytherapy has a particularly important role in the management of men with prostate cancer and of women with gynecologic malignancies. (See 'Brachytherapy' above.)
●Radiation side effects – Side effects of radiation include both acute effects, which are generally due to swelling in and around the tissues being irradiated, and late effects, which may not appear until years or decades after treatment. The risks of these side effects must be weighed against the potential benefits. (See 'Radiation side effects' above.)
ACKNOWLEDGMENT — We are saddened by the death of Jay Loeffler, MD, who passed away in June 2023. UpToDate acknowledges Dr. Loeffler's past work as a section editor for this topic.
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