Historically, the three main divisions of radiation therapy are: •
external beam radiation therapy (EBRT or XRT) or teletherapy; •
brachytherapy or sealed source radiation therapy; and • systemic radioisotope therapy or
unsealed source radiotherapy. The differences relate to the position of the radiation source; external is outside the body, brachytherapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion. Brachytherapy can use temporary or permanent placement of radioactive sources. The temporary sources are usually placed by a technique called afterloading. In afterloading a hollow tube or applicator is placed surgically in the organ to be treated, and the sources are loaded into the applicator after the applicator is implanted. This minimizes radiation exposure to health care personnel.
Particle therapy is a special case of external beam radiation therapy where the particles are
protons or heavier
ions. A review of radiation therapy randomised clinical trials from 2018 to 2021 found many practice-changing data and new concepts that emerge from RCTs, identifying techniques that improve the therapeutic ratio, techniques that lead to more tailored treatments, stressing the importance of patient satisfaction, and identifying areas that require further study.
External beam radiation therapy The following three sections refer to treatment using X-rays.
Conventional external beam radiation therapy Historically conventional external beam radiation therapy (2DXRT) was delivered via two-dimensional beams using kilovoltage therapy X-ray units, medical linear accelerators that generate high-energy X-rays, or with machines that were similar to a linear accelerator in appearance, but used a sealed radioactive source like the one shown above. 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 has become the standard treatment for almost all tumor sites. More recently other forms of imaging are used including MRI, PET, SPECT and Ultrasound.
Stereotactic radiation 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.
Virtual simulation, and 3-dimensional conformal radiation therapy 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. IMRT also improves the ability to conform the treatment volume to concave tumor shapes, 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 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. A well-studied issue with IMRT is the "tongue and groove effect" which results in unwanted underdosing, due to irradiating through extended tongues and grooves of overlapping MLC (multileaf collimator) leaves. While solutions to this issue have been developed, which either reduce the TG effect to negligible amounts or remove it completely, they depend upon the method of IMRT being used and some of them carry costs of their own.
Volumetric modulated arc therapy (VMAT) 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 protection of the organ at risk (OAR).
Temporally feathered radiation therapy (TFRT) Temporally feathered radiation therapy (TFRT) is a radiation technique introduced in 2018 which aims to use the inherent non-linearities in normal tissue repair to allow for sparing of these tissues without affecting the dose delivered to the tumor. The application of this technique, which has yet to be automated, has been described carefully to enhance the ability of departments to perform it, and in 2021 it was reported as feasible in a small clinical trial, though its efficacy has yet to be formally studied.
Automated planning Automated treatment planning has become an integrated part of radiotherapy treatment planning. There are in general two approaches of automated planning. 1) Knowledge based planning where the treatment planning system has a library of high quality plans, from which it can predict the target and dose-volume histogram of the organ at risk. 2) The other approach is commonly called protocol based planning, where the treatment planning system tried to mimic an experienced treatment planner and through an iterative process evaluates the plan quality from on the basis of the protocol.
Particle therapy 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 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.
Motion compensation In many types of external beam radiotherapy, motion can negatively impact the treatment delivery by moving target tissue out of, or other healthy tissue into, the intended beam path. Some form of patient immobilisation is common, to prevent the large movements of the body during treatment, however this cannot prevent all motion, for example as a result of
breathing. Several techniques have been developed to account for motion like this.
Deep inspiration breath-hold (DIBH) is commonly used for breast treatments where it is important to avoid irradiating the heart. In DIBH the patient holds their breath after
breathing in to provide a stable position for the treatment beam to be turned on. This can be done automatically using an external monitoring system such as a
spirometer or a camera and markers. The same monitoring techniques, as well as
4DCT imaging, can also be for respiratory gated treatment, where the patient breathes freely and the beam is only engaged at certain points in the breathing cycle. Other techniques include using 4DCT imaging to plan treatments with margins that account for motion, and active movement of the treatment couch, or beam, to follow motion.
Contact X-ray brachytherapy Contact X-ray brachytherapy (also called "CXB", "electronic brachytherapy" or the "Papillon Technique") is a type of radiation therapy using low energy (50 kVp) kilovoltage
X-rays applied directly to the tumor to treat
rectal cancer. The process involves endoscopic examination first to identify the tumor in the rectum and then inserting treatment applicator on the tumor through the
anus into the rectum and placing it against the cancerous tissue. Finally, treatment tube is inserted into the applicator to deliver high doses of X-rays (30Gy) emitted directly onto the
tumor at two weekly intervals for three times over four weeks period. 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. prostate, breast, and skin cancer and can also be used to treat tumors in many other body sites. In brachytherapy, radiation sources are precisely placed directly at the site of the cancerous tumor. 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 tumor 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.
Radionuclide therapy Radionuclide therapy (also known as systemic radioisotope therapy, radiopharmaceutical therapy, molecular radiotherapy, or targeted radionuclide therapy), 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, for example an 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, of peptide-bound
lutetium-177 (
Lutathera) and
yttrium-90 to treat
neuroendocrine tumors (
peptide receptor radionuclide therapy), and of peptide-bound
lutetium-177 (
Pluvicto) to treat
prostate cancer. In April 2024 the
United States Food and Drug Administration (FDA) approved
Lutathera, invented by
Novartis, for pediatric patients aged 12 or older with somastotatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs). For the same indication in adults, approval was received in 2018.
Pluvicto, also invented by
Novartis, was approved for metastatic castration-resistant prostate cancer in March 2022. 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-Hodgkin's lymphoma.
Intraoperative radiotherapy Intraoperative radiation therapy (IORT) is applying therapeutic levels of radiation to a target area, such as a
cancer tumor, while the area is exposed during
surgery.
Rationale 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. ==History==