Radiotherapy

Definition

Radiotherapy is the use of high-energy penetrating radiation (x rays, gamma rays, proton rays, and neutron rays) to kill cancer cells.

Purpose

The primary purpose of radiotherapy is to eliminate or shrink localized cancers. It is also sometimes used to treat metastases—often brain metastases—in cases in which surgical treatment would be riskier. The aim of radiotherapy is to kill as many cancer cells as possible, while doing as little damage as possible to healthy tissue. In some cases, the purpose is to kill all cancer cells and effect a cure. In other cases, when cures are not possible, the purpose is to alleviate the patient's pain by reducing the size of the tumors that cause pain.

For some kinds of cancers (for example, Hodgkin's disease, non-Hodgkin's lymphoma, prostate cancer, and laryngeal cancer), radiotherapy alone is often the preferred treatment. Radiation is, however, also used in conjunction with surgery, chemotherapy, or both; and survival rates for combination therapy in these cases are often greater than survival rates for any single treatment modality used alone. Radiotherapy is especially useful when surgical procedures cannot remove an entire tumor without damaging the function of surrounding organs. In these cases, surgeons remove as much tumor mass as possible, and the remainder is treated with radiation (irradiated).

Precautions

Radiotherapy has serious side effects; therefore, anyone considering it should be sure that it is the best possible treatment option for their cancer. Cancer treatment research moves so rapidly that some doctors may not be aware of the latest advances in treatments outside their own specialties that might be safer and better. Accordingly, patients who have had radiotherapy recommended to them should consider getting a second opinion.

Description

Radiotherapy is also known as radiation therapy, radiation treatment, x-ray therapy, cobalt therapy, and electron beam or "gamma knife" therapy. Recent advances in medical technology have made it even more useful for patients and have reduced some of its unpleasant side effects. Radioactive implants allow delivery of radiation to localized areas, with less injury to surrounding tissues than radiation from an external source that must pass through those tissues. Proton radiation also causes less injury to surrounding tissues than traditional photon radiation, because proton rays can be tightly focused. Current research with radioimmunotherapy and neutron capture therapy may provide ways to direct radiation exclusively to cancer cells—and in the case of radioimmunotherapy, to cancer cells that have metastasized (spread to other sites throughout the body).

How radiotherapy works

High-energy radiation kills cells by damaging their DNA and thus blocking their ability to divide and proliferate. Other cytotoxic mechanisms include the production of poisonous OH⁻ free radicals in the cellular cytoplasm.

Radiation kills normal cells about as well as cancer cells, but cells that are undergoing rapid growth and division (such as cancer cells, skin cells, blood cells, immune system cells, and digestive system cells) are the most susceptible to radiation. Fortunately, most normal cells are better able to repair radiation damage than are cancer cells. Accordingly, radiation treatments are parceled into component treatments that are spaced over a given time interval (usually about seven weeks). The spacing of radiation treatments allows cells to repair themselves during the time between treatments. Since the repair rate of normal cells is greater than the repair rate of cancerous cells, a smaller fraction of the radiation-damaged cancerous cells will have been replaced by the time of the next treatment. This procedure is called fractionation because the total radiation dose is divided into fractions. Fractionation allows cancer cells to be killed more effectively with less ultimate damage to the surrounding normal cells. Ideally all the cancer cells will be gone after the last treatment session.

Types of radiation used to treat cancer

PHOTON RADIATION. Early radiotherapy made use of x rays and gamma rays. X rays and gamma rays are essentially high-energy, ionizing electromagnetic rays composed of massless particles of energy called photons. The distinction between the two is that gamma rays originate from the decay of radioactive substances (like radium and cobalt-60), while x rays are generated by devices that excite electrons (such as cathode ray tubes and linear accelerators). These ionizing rays are part of the electromagnetic spectrum, which also includes ultraviolet, visible, and infrared light; radio waves; and microwaves. Ionizing rays act on cells by disrupting the electrons of atoms within the molecules inside cells. These atomic changes disrupt molecules and hence disrupt cell functions, most importantly their ability to divide and make new cells.

PARTICLE RADIATION. Particle radiation is expected to become an increasingly important part of radiotherapy. Proton therapy has been available since the early 1990s on a limited scale. Proton rays consist of protons, which have mass and charge, in contrast to photons, which have neither mass nor charge. Like x rays and gamma rays, proton rays disrupt atomic electrons in target cells. The advantage of proton rays is that they can be directed to conform to the shape of the tumor more precisely than x rays and gamma rays. Consequently, proton rays cause less injury to surrounding tissue and fewer side effects. They allow physicians to deliver higher radiation doses to tumors without increasing damage to the surrounding tissue. Proton therapy is therefore more effective and requires fewer treatment sessions than conventional x-ray therapy.

Neutron therapy is a second type of particle radiation. Neutron rays are very high-energy rays composed of neutrons, which are particles with mass but no charge. Unlike x rays, gamma rays, and proton rays, they disrupt atomic nuclei rather than electrons; thus the likelihood of cells repairing this kind of intensive damage is very small. Neutron therapy can be more effective at treating larger tumors than conventional radiotherapy. The central part of large tumors lack sufficient oxygen to be susceptible to damage from conventional radiation, which is dependent upon oxygen. Neutron radiation, however, can do its damage in the absence of oxygen, so it can kill cells in the centers of large tumors. Neutron therapy has been shown to be especially effective for the treatment of inoperable salivary gland tumors, bone cancers, and some advanced cancers of the pancreas, bladder, lung, prostate, and uterus.

Another promising type of neutron therapy, neutron capture therapy, is still in the experimental stage. It has, however, the advantage of being able to deliver high doses of radiation to a very limited area. Neutron capture therapy begins with a medication that binds to tumor cells but not to other cells. The medication is chemically combined with boron and given to the patient. The tumor is then irradiated with neutrons. When the neutrons interact with the boron atoms, the boron nuclei split, creating tiny nuclear fission events just big enough to kill one cell. If the drug does not bind to neighboring noncancerous cells, then only cancer cells will be damaged, and the damage to these cells should be irreversible.

Phototherapy is the newest approach to radiotherapy. In phototherapy, a porphyrin derivative is used to attach to and illuminate the tumor. The tumor can then be targeted for selective uptake of radiation.

Modes of delivery

EXTERNAL BEAM THERAPY. Traditionally, radiotherapy has been delivered from a beam of radiation originating outside the body. This modality is called "external beam therapy." The external beam passes through the body before and after it irradiates the tumor; thus it can injure tissue in its path.

BRACHYTHERAPY. In brachytherapy, the radiation remains inside the body. Brachytherapy uses gamma ray-generating radioactive isotopes such as cesium-137 or iodine-125. The isotope is placed in small tubes and implanted close to or inside the tumor. The patient stays in the hospital for a few days; after that time, the radioactive isotope has either decayed to a low level, or the implant is removed. This form of therapy is especially useful in treating tumors for which surgery or external beam therapy radiation would cause critical damage to tissues surrounding the tumor. Brachytherapy has been effective against prostate cancer and cervical cancer.

RADIOIMMUNOTHERAPY. Until the mid-1990s, the only way to treat cancer that has spread (metastasized) to multiple locations throughout the body has been with traditional chemotherapy, which uses drugs that kill cells that divide and reproduce quickly (proliferate) in a nonspecific way. Recently, cancer vaccines have been used successfully to extinguish metastatic melanoma. Vaccine treatment is a form of immunotherapy; it specifically kills melanoma cells and not other cells, even though they may also be proliferating.

Radioimmunotherapy is another form of immunotherapy that is still experimental. Researchers expect that radioimmunotherapy will be able to kill metastatic cancer cells almost anywhere in the body. Antibodies are immune system molecules that specifically recognize and bind to only one molecular structure, and they can be designed to bind specifically to a certain type of cancer cell. To carry out radioimmunotherapy, antibodies with the ability to bind specifically to a patient's cancer cells will be attached to an isotope that emits gamma rays when it is injected into the patient's bloodstream. These special antibody molecules will travel around the body until they encounter a cancer cell, and then they will bind to it. Then the gamma rays will kill the cancer cell. It will be difficult, however, for researchers to calculate the correct dose of antibody and isotope that will kill an unknown number of cancer cells and at the same time use isotope levels that won't destroy the antibody molecules before they encounter cancer cells.

Preparation

Before radiotherapy, the size and location of the patient's tumor, as well as the nature of the surrounding tissue in the path of the radiation beam, must be determined as accurately as possible so that the radiation treatment will be maximally effective. Magnetic resonance imaging (MRI) and computed tomography (CT) are used to provide detailed images of the tumor. The correct radiation dose, the number of sessions (fractions), the interval between sessions, and whether to give each fraction from the same direction or from different directions to lower the total dose imparted to a given surrounding area, are calculated on the basis of the tumor type, its size, and the sensitivity of the nearby tissues.

Shields are sometimes constructed for the patient to protect certain areas of the body. The patient's skin may be marked with ink or tattoos to help achieve correct positioning for each treatment, or molds may be built to hold tissues in exactly the right place each time.

Three-dimensional conformal external beam therapy

For some types of tumors, including prostate cancer, a beam-shaping technique known as three-dimensional conformal therapy is used to deliver higher doses of radiation to the tumor site while sparing surrounding tissue to a greater extent than is possible with the nonconformal approach. Three-dimensional conformal therapy requires CT scans that allow the radiologist and physicist to accurately plan field shapes and prepare shields appropriately shaped for the treatment plan.

Intensity-modulated radiotherapy (IMRT)

As with three-dimensional conformal therapy, intensity-modulated radiotherapy requires a CT scan prior to dose planning. The information from the CT scan is used to plan the delivery of the radiation. The key difference between three-dimensional conformal therapy and IMRT is that IMRT produces a plan that can be transferred to a floppy or optical disk. The diskette is then used to control a dynamic beam-shaping device called a collimator that is attached to the linear accelerator. The collimator has multiple small fingers about three millimeters wide that move in and out of the radiation field during treatment. The information on the floppy or optical disk controls the movement of the beam-shaping fingers. The beam rotates around the patient in some treatment regimens. The ability of IMRT to precisely shape the beam in very small increments even while it's moving allows the therapist to deliver even higher doses to the tumor and spare even more of the healthy surrounding tissues than three-dimensional conformal therapy does. For some tumors, like prostate cancer, even greater precision can be attained by using a special ultrasound machine. Prior to each treatment, the ultrasound machine is used to pinpoint the location of the prostate gland relative to the radiation source. The information from the ultrasound scan allows the therapist to position the patient with a degree of precision measured in millimeters before the therapy begins.

Aftercare

Follow-up is important for patients who have received radiotherapy. They should go to their radiation oncologist at least once within the first several weeks after their final treatment to see if their treatment was successful. They should also see an oncologist every six to twelve months for the rest of their lives so they can be checked to see if the tumor has reappeared or spread.

Treatment of symptoms following radiotherapy depends on which part of the body is being treated and the type of radiation. Nevertheless, many patients experience skin burn, hair loss, fatigue, nausea, and vomiting regardless of the treatment area.

Affected skin should be kept clean and can be treated like a sunburn, with skin lotion or vitamin A and D ointment. Patients should avoid perfume or scented skin products, and protect affected areas from the sun.

Nausea and vomiting are expected when the dose is high or if the abdomen or another part of the digestive tract is irradiated. Sometimes nausea and vomiting occur after radiation to other regions, but in these cases the symptoms usually disappear within a few hours after treatment. Nausea and vomiting can be treated with antacids or with such antiemetics as Compazine, Tigan, or Zofran.

Fatigue frequently sets in after the second week of therapy and may continue until about two weeks after the therapy is finished. Patients may want to limit their activities, cut back their work hours, or take time off from work. They also may need to take naps and get extra sleep at night.

Patients who receive external beam therapy do not become radioactive and should be assured that they do not pose a danger to others. Some patients who receive brachytherapy, however, do go home with low levels of radioactivity inside their bodies. These patients should be given instructions about any dangers they might pose to children and people of childbearing age, and how long these dangers will last.

Emotional support is an important part of the care for patients undergoing any treatment for cancer. Radiotherapy can cause significant changes in a patient's appearance—particularly hair loss—and many patients fear that their spouses or partners will no longer find them attractive. There are many support groups available for radiotherapy patients and their families, as well as resources to help them cope with the external side effects of radiation treatment.

Complications

Radiotherapy can be highly toxic to patients because it kills normal cells as well as cancerous ones. There are risks of anemia, nausea, vomiting, diarrhea, hair loss, skin burn, sterility, and death. The benefits of radiation therapy, however, almost always exceed the risks involved.

Results

The probable outcome of radiation treatment is highly variable depending on the disease. For some diseases like Hodgkin's disease, about 75% of the patients are cured. Moreover, up to 86% of prostate cancer victims treated with both external and internal radiation are symptom-free five years after radiotherapy. On the other hand, radiation therapy is less successful in treating lung cancer; only about 9% of lung cancer patients are cured.