TREATMENT BY RADIATION THERAPY

1. What is radiation therapy?
   Radiation therapy uses high-energy radiation to shrink tumors and kill cancer cells (1). X-rays, gamma rays, and charged particles are types of radiation used for cancer treatment.
   The radiation may be delivered by a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy, also called brachytherapy).
   Systemic radiation therapy uses radioactive substances, such as radioactive iodine, that travel in the blood to kill cancer cells.
   About half of all cancer patients receive some type of radiation therapy sometime during the course of their treatment.
2. How does radiation therapy kill cancer cells? Radiation therapy kills cancer cells by damaging their DNA (the molecules inside cells that carry genetic information and pass it from one generation to the next) (1). Radiation therapy can either damage DNA directly or create charged particles (free radicals) within the cells that can in turn damage the DNA.
   Cancer cells whose DNA is damaged beyond repair stop dividing or die. When the damaged cells die, they are broken down and eliminated by the body’s natural processes.
3. Does radiation therapy kill only cancer cells? No, radiation therapy can also damage normal cells, leading to side effects.
   Doctors take potential damage to normal cells into account when planning a course of radiation therapy. The amount of radiation that normal tissue can safely receive is known for all parts of the body. Doctors use this information to help them decide where to aim radiation during treatment.

1. Why do patients receive radiation therapy?
2. Radiation therapy is sometimes given with curative intent (that is, with the hope that the treatment will cure a cancer, either by eliminating a tumor, preventing cancer recurrence, or both) (1). In such cases, radiation therapy may be used alone or in combination with surgery, chemotherapy, or both.
3. Radiation therapy may also be given with palliative intent. Palliative treatments are not intended to cure. Instead, they relieve symptoms and reduce the suffering caused by cancer.
4. Some examples of palliative radiation therapy are:
5. Radiation given to the brain to shrink tumors formed from cancer cells that have spread to the brain from another part of the body (metastases).

• Radiation given to shrink a tumor that is pressing on the spine or growing within a bone, which can cause pain.
• Radiation given to shrink a tumor near the esophagus, which can interfere with a patient’s ability to eat and drink.

1. How is radiation therapy planned for an individual patient?
2. A radiation oncologist develops a patient’s treatment plan through a process called treatment planning, which begins with simulation.
3. During simulation, detailed imaging scans show the location of a patient’s tumor and the normal areas around it. These scans are usually computed tomography (CT) scans, but they can also include magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasound scans.

Computed Tomography Scanner

CT scans are often used in treatment planning for radiation therapy. During CT scanning, pictures of the inside of the body are created by a computer linked to an x-ray machine.

1. During simulation and daily treatments, it is necessary to ensure that the patient will be in exactly the same position every day relative to the machine delivering the treatment or doing the imaging. Body molds, head masks, or other devices may be constructed for an individual patient to make it easier for a patient to stay still. Temporary skin marks and even tattoos are used to help with precise patient positioning.

Radiation Therapy Head Mask

Patients getting radiation to the head may need a mask. The mask helps keep the head from moving so that the patient is in the exact same position for each treatment.

1. After simulation, the radiation oncologist then determines the exact area that will be treated, the total radiation dose that will be delivered to the tumor, how much dose will be allowed for the normal tissues around the tumor, and the safest angles (paths) for radiation delivery.
2. The staff working with the radiation oncologist (including physicists and dosimetrists) use sophisticated computers to design the details of the exact radiation plan that will be used. After approving the plan, the radiation oncologist authorizes the start of treatment. On the first day of treatment, and usually at least weekly after that, many checks are made to ensure that the treatments are being delivered exactly the way they were planned.
3. Radiation doses for cancer treatment are measured in a unit called a gray (Gy), which is a measure of the amount of radiation energy absorbed by 1 kilogram of human tissue. Different doses of radiation are needed to kill different types of cancer cells.
4. Radiation can damage some types of normal tissue more easily than others. For example, the reproductive organs (testicles and ovaries) are more sensitive to radiation than bones. The radiation oncologist takes all of this information into account during treatment planning.
5. If an area of the body has previously been treated with radiation therapy, a patient may not be able to have radiation therapy to that area a second time, depending on how much radiation was given during the initial treatment. If one area of the body has already received the maximum safe lifetime dose of radiation, another area might still be treated with radiation therapy if the distance between the two areas is large enough.
6. The area selected for treatment usually includes the whole tumor plus a small amount of normal tissue surrounding the tumor. The normal tissue is treated for two main reasons:
7. To take into account body movement from breathing and normal movement of the organs within the body, which can change the location of a tumor between treatments.

• To reduce the likelihood of tumor recurrence from cancer cells that have spread to the normal tissue next to the tumor (called microscopic local spread).

1. How is radiation therapy given to patients?
2. Radiation can come from a machine outside the body (external-beam radiation therapy) or from radioactive material placed in the body near cancer cells (internal radiation therapy, more commonly called brachytherapy). Systemic radiation therapy uses a radioactive substance, given by mouth or into a vein, that travels in the blood to tissues throughout the body.
3. The type of radiation therapy prescribed by a radiation oncologist depends on many factors, including:
4. The type of cancer.

• The size of the cancer.
• The cancer’s location in the body.
• How close the cancer is to normal tissues that are sensitive to radiation.
• How far into the body the radiation needs to travel.
• The patient’s general health and medical history.
• Whether the patient will have other types of cancer treatment.
• Other factors, such as the patient’s age and other medical conditions.

1. External-beam radiation therapy
2. External-beam radiation therapy is most often delivered in the form of photon beams (either x-rays or gamma rays) (1). A photon is the basic unit of light and other forms of electromagnetic radiation. It can be thought of as a bundle of energy. The amount of energy in a photon can vary. For example, the photons in gamma rays have the highest energy, followed by the photons in x-rays.

Linear Accelerator Used for External-beam Radiation Therapy

Many types of external-beam radiation therapy are delivered using a machine called a linear accelerator (also called a LINAC). A LINAC uses electricity to form a stream of fast-moving subatomic particles. This creates high-energy radiation that may be used to treat cancer.

1. Patients usually receive external-beam radiation therapy in daily treatment sessions over the course of several weeks . The number of treatment sessions depends on many factors, including the total radiation dose that will be given.
2. One of the most common types of external-beam radiation therapy is called 3-dimensional conformal radiation therapy (3D-CRT). 3D-CRT uses very sophisticated computer software and advanced treatment machines to deliver radiation to very precisely shaped target areas.
3. Many other methods of external-beam radiation therapy are currently being tested and used in cancer treatment. These methods include:

• 1. Intensity-modulated radiation therapy (IMRT): IMRT uses hundreds of tiny radiation beam-shaping devices, called collimators, to deliver a single dose of radiation (2). The collimators can be stationary or can move during treatment, allowing the intensity of the radiation beams to change during treatment sessions. This kind of dose modulation allows different areas of a tumor or nearby tissues to receive different doses of radiation.
  Unlike other types of radiation therapy, IMRT is planned in reverse (called inverse treatment planning). In inverse treatment planning, the radiation oncologist chooses the radiation doses to different areas of the tumor and surrounding tissue, and then a high-powered computer program calculates the required number of beams and angles of the radiation treatment (3). In contrast, during traditional (forward) treatment planning, the radiation oncologist chooses the number and angles of the radiation beams in advance and computers calculate how much dose will be delivered from each of the planned beams.
  The goal of IMRT is to increase the radiation dose to the areas that need it and reduce radiation exposure to specific sensitive areas of surrounding normal tissue. Compared with 3D-CRT, IMRT can reduce the risk of some side effects, such as damage to the salivary glands (which can cause dry mouth, or xerostomia), when the head and neck are treated with radiation therapy (4). However, with IMRT, a larger volume of normal tissue overall is exposed to radiation. Whether IMRT leads to improved control of tumor growth and better survival compared with 3D-CRT is not yet known (4).
• Image-guided radiation therapy (IGRT): In IGRT, repeated imaging scans (CT, MRI, or PET) are performed during treatment. These imaging scans are processed by computers to identify changes in a tumor’s size and location due to treatment and to allow the position of the patient or the planned radiation dose to be adjusted during treatment as needed. Repeated imaging can increase the accuracy of radiation treatment and may allow reductions in the planned volume of tissue to be treated, thereby decreasing the total radiation dose to normal tissue (5).
• Tomotherapy: Tomotherapy is a type of image-guided IMRT. A tomotherapy machine is a hybrid between a CT imaging scanner and an external-beam radiation therapy machine (6). The part of the tomotherapy machine that delivers radiation for both imaging and treatment can rotate completely around the patient in the same manner as a normal CT scanner.
  Tomotherapy machines can capture CT images of the patient’s tumor immediately before treatment sessions, to allow for very precise tumor targeting and sparing of normal tissue.
  Like standard IMRT, tomotherapy may be better than 3D-CRT at sparing normal tissue from high radiation doses (7). However, clinical trials comparing 3D-CRT with tomotherapy have not been conducted.
• Stereotactic radiosurgery: Stereotactic radiosurgery (SRS) can deliver one or more high doses of radiation to a small tumor. SRS uses extremely accurate image-guided tumor targeting and patient positioning. Therefore, a high dose of radiation can be given without excess damage to normal tissue.
  SRS can be used to treat only small tumors with well-defined edges. It is most commonly used in the treatment of brain or spinal tumors and brain metastases from other cancer types. For the treatment of some brain metastases, patients may receive radiation therapy to the entire brain (called whole-brain radiation therapy) in addition to SRS.
  SRS requires the use of a head frame or other device to immobilize the patient during treatment to ensure that the high dose of radiation is delivered accurately.
• Stereotactic body radiation therapy: Stereotactic body radiation therapy (SBRT) delivers radiation therapy in fewer sessions, using smaller radiation fields and higher doses than 3D-CRT in most cases. By definition, SBRT treats tumors that lie outside the brain and spinal cord. Because these tumors are more likely to move with the normal motion of the body, and therefore cannot be targeted as accurately as tumors within the brain or spine, SBRT is usually given in more than one dose . SBRT can be used to treat only small, isolated tumors, including cancers in the lung and liver .
  Many doctors refer to SBRT systems by their brand names, such as the CyberKnife®.
• Proton therapy: External-beam radiation therapy can be delivered by proton beams as well as the photon beams described above. Protons are a type of charged particle.
  Proton beams differ from photon beams mainly in the way they deposit energy in living tissue. Whereas photons deposit energy in small packets all along their path through tissue, protons deposit much of their energy at the end of their path (called the Bragg peak) and deposit less energy along the way.
  In theory, use of protons should reduce the exposure of normal tissue to radiation, possibly allowing the delivery of higher doses of radiation to a tumor. Proton therapy has not yet been compared with standard external-beam radiation therapy in clinical trials.
• Other charged particle beams: Electron beams are used to irradiate superficial tumors, such as skin cancer or tumors near the surface of the body, but they cannot travel very far through tissue. Therefore, they cannot treat tumors deep within the body.

1. Patients can discuss these different methods of radiation therapy with their doctors to see if any is appropriate for their type of cancer and if it is available in their community or through a clinical trial .
2. Internal radiation therapy
3. Internal radiation therapy (brachytherapy) is radiation delivered from radiation sources (radioactive materials) placed inside or on the body. Several brachytherapy techniques are used in cancer treatment. Interstitial brachytherapy uses a radiation source placed within tumor tissue, such as within a prostate tumor. Intracavitary brachytherapy uses a source placed within a surgical cavity or a body cavity, such as the chest cavity, near a tumor. Episcleral brachytherapy, which is used to treat melanoma inside the eye, uses a source that is attached to the eye.
4. In brachytherapy, radioactive isotopes are sealed in tiny pellets or “seeds.” These seeds are placed in patients using delivery devices, such as needles, catheters, or some other type of carrier. As the isotopes decay naturally, they give off radiation that damages nearby cancer cells.
5. If left in place, after a few weeks or months, the isotopes decay completely and no longer give off radiation. The seeds will not cause harm if they are left in the body (see permanent brachytherapy, described below).
6. Brachytherapy may be able to deliver higher doses of radiation to some cancers than external-beam radiation therapy while causing less damage to normal tissue .
7. Brachytherapy can be given as a low-dose-rate or a high-dose-rate treatment:
8. In low-dose-rate treatment, cancer cells receive continuous low-dose radiation from the source over a period of several days.

• In high-dose-rate treatment, a robotic machine attached to delivery tubes placed inside the body guides one or more radioactive sources into or near a tumor, and then removes the sources at the end of each treatment session. High-dose-rate treatment can be given in one or more treatment sessions.
  An example of a high-dose-rate treatment is the MammoSite® system, which is being studied to treat patients with breast cancer who have undergone breast-conserving surgery.

1. The placement of brachytherapy sources can be temporary or permanent:
2. For permament brachytherapy, the sources are surgically sealed within the body and left there, even after all of the radiation has been given off. The remaining material (in which the radioactive isotopes were sealed) does not cause any discomfort or harm to the patient. Permanent brachytherapy is a type of low-dose-rate brachytherapy.

• For temporary brachytherapy, tubes (catheters) or other carriers are used to deliver the radiation sources, and both the carriers and the radiation sources are removed after treatment. Temporary brachytherapy can be either low-dose-rate or high-dose-rate treatment.

1. Doctors can use brachytherapy alone or in addition to external-beam radiation therapy to provide a “boost” of radiation to a tumor while sparing surrounding normal tissue