Radiation and Radioimmunotherapy

Radiation therapy (also called radiotherapy) uses high-energy X-rays or other types of radiation to kill cancer cells and shrink tumors. The term is generally used to describe external-beam radiotherapy, in which a radiation beam is delivered from a machine; however, certain drugs can also deliver radioactive molecules directly to tumor cells (see “Radioimmunotherapy” below).

Radiation therapy is part of the treatment for most people with Hodgkin lymphoma (HL), especially when cancer is limited to one part of the body. Radiation might be used to treat non-Hodgkin lymphoma (NHL) in the following settings:

• As main treatment in some types of early-stage NHL.
• In combination with chemotherapy (drugs that stop the growth of or kill cancer cells) for some advanced and aggressive forms of NHL.
• In combination with high-dose chemotherapy in people who are getting a stem cell transplant.
• As palliative treatment (pain relief) in cases where NHL has spread to internal organs (like the brain or spinal cord) or to ease pain when a tumor is pressing on nerves.

A radiation oncologist (a doctor who has training in using radiation to treat cancer) directs radiation therapy. The part of the body that will be the target of radiation therapy is called the radiation field. Doctors usually limit the radiation field to the affected lymph nodes (small bean-shaped structures that help the body fight disease), the areas immediately surrounding lymph nodes, or other areas where lymphoma is present. Doctors determine the type of radiation used and the size of the radiation field depending on the type of lymphoma and the extent of disease (if the lymphoma is only in one part of the body or if it has spread to other parts).

To prepare for radiation therapy, the healthcare team marks the patient’s body with tiny ink dots to make sure that only the targeted areas receive radiation. On the day of treatment, lead shields are used to protect the normal tissues around the radiation field. The radiation team also uses plastic forms, pillows, and rolled blankets to make patients comfortable and keep them in the proper position.

Patients lie still on a table beneath a large machine that delivers the radiation painlessly. Once the preparations have been made, it takes only a few minutes to deliver the prescribed dose. The total dose of radiation is usually divided and given over one to six weeks. During and after the radiation treatment, patients need to carefully protect the radiation site from exposure to sunlight. It is most important to avoid becoming sunburnt. Some of the more common types of radiation therapy and delivery methods used in lymphoma are shown in the table on the following page.

Radiation therapy itself is painless, but it can cause short-term and long-term side effects that vary depending on the type of radiation, the dosage, and the area of the body treated. Side effects are usually worse when radiation therapy and chemotherapy are given at the same time. Short-term side effects caused by radiation therapy used to treat patients with lymphoma include dry mouth, fatigue, loss of appetite and taste, nausea, skin reactions and throat irritation. Other side effects develop during treatment and last for months or longer (called “long-term side effects”) and others appear long after the treatment has ended (called “late side effects”) and include cardiovascular (heart and blood vessels) damage and secondary cancers.

External-beam radiation does not cause a patient’s tissue to become radioactive. However, some types of internal radiation techniques that leave radioactive particles in the body may result in low levels of radiation being emitted from the patient. In some cases, the patient remains in the hospital and is shielded from others during short exposures to internal radiation therapy. With permanent internal radiation and systemic radiation treatment, patients are sent home emitting low levels of radiation, especially through bodily fluids. In these cases, patients should temporarily avoid contact with pregnant women and young children. The healthcare team can provide more information to patients, family members, and caregivers about special precautions that should be taken. The radioactivity breaks down over time to the point where no radiation can be measured outside the patient’s body.

Radioimmunotherapy (RIT) is a type of cancer therapy that combines a radioactive substance with a monoclonal antibody (a protein made in the laboratory that binds to cancer cells and helps the immune system destroy them) to kill cancer cells.

Antibodies are normal components of the body’s immune system that can recognize and destroy foreign invaders such as bacteria and viruses. Scientists can now create monoclonal antibodies designed to recognize specific antigens (targets) that are present on the surface of certain cancer cells. Monoclonal antibody therapy can be administered by intravenous (IV; into a vein) or subcutaneous (under the skin) infusion, generally on an outpatient basis. Once in the bloodstream, monoclonal antibodies travel throughout the body and attach themselves to the target antigens on cancer cells. This helps the body’s immune system identify and destroy the cancer cells. Sometimes normal cells that have the same target antigen on their surface may be affected as well, but the body can usually replace these cells following treatment.

In RIT treatment, radioisotopes (radioactive particles) are attached to monoclonal antibodies and then infused into the body. Each time an antibody comes into contact with a cancer cell, the attached radioisotope delivers radiation directly to that cell. The major advantage of this approach is that it substantially reduces the exposure of healthy cells to radiation. Nuclear medicine physicians or radiation oncologists, as well as other healthcare professionals such as oncologists or medical physicists, may be involved in the administration of RIT. Treatment is commonly administered by IV infusion, similar to monoclonal antibody therapy.

Ibritumomab tiuxetan (Zevalin) was the first RIT approved by the U.S. Food and Drug Administration (FDA). This RIT contains a radioisotope called yttrium-90 (Y90) that kills cancer cells. Ibritumomab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of malignant (cancer) B cells. Tiuxetan is a chelator (connector) that links the Y90 molecule to the ibritumomab molecule. Ibritumomab tiuxetan has been approved for the treatment of adult patients with relapsed (disease returns after treatment) or refractory (disease does not respond to treatment) low-grade or follicular B-cell NHL. It is also approved for use in previously untreated adult patients with follicular NHL who achieve partial or complete responses to first-line chemotherapy.

Patients being treated with ibritumomab tiuxetan (Zevalin) first receive two infusions of rituximab (Rituxan), another monoclonal antibody that also targets CD20 but does not carry any radioisotope, followed by a one-time infusion of ibritumomab tiuxetan (Zevalin). On day one, the patient receives premedication with acetaminophen (Tylenol) and diphenhydramine (Benadryl) followed by an IV infusion of rituximab (Rituxan). Seven to nine days later, the patient returns for a second infusion of rituximab followed by ibritumomab tiuxetan (Zevalin) four hours later. Dosing is based on the patient’s weight and platelet count.

Ibritumomab tiuxetan (Zevalin) is generally well tolerated, without the hair loss and nausea that often accompany chemotherapy. The most common side effect is a temporary decrease in blood cell counts, which start to occur two to three weeks after treatment. Blood cell counts typically return to near-normal levels within 10 weeks after receiving treatment. Platelet counts usually drop the most and can cause a patient to bruise more easily; in some cases, patients may bleed more easily. The most serious side effects are low blood counts that don’t improve and having an allergic reactions to the infusion. The side effects of rituximab (Rituxan) can include headache, nausea, flushing (involuntary, temporary reddening of the skin), indigestion, light-headedness, and mild fever and chills, especially after the first dose. This is not a complete list of side effects. Physicians will check for these and other effects during follow-up visits.

Radiation from ibritumomab tiuxetan (Zevalin) does not escape outside the body, but a small amount may be present in body fluids such as blood and urine. Because of this, patients should wash their hands thoroughly after urination and use a condom during sexual intercourse. It is not necessary to avoid contact with friends or family during this time, and patients can typically return to work and their usual activities following treatment. Patients should speak with their physician regarding safety precautions.

Lutetium (177Lu) lilotomab satetraxetan (Betalutin) is an RIT agent under investigation for relapsed and refractory follicular lymphoma. This drug combines the anti-CD37 murine antibody lilotomab with a small molecule called p-SCN-Bn-DOTA, which binds to the beta-emitting isotope lutetium-177 (177Lu). r

Questions to Ask Before Starting Radiation Therapy or Radioimmunotherapy

• What is the goal of my radiation therapy/radioimmunotherapy?
• How will the radiation be given?
• How long will the treatment last, and how often will it be given?
• How will I feel during the therapy?
• What are the side effects? Is there anything that can be done to prevent them?
• Are there any lasting side effects?
• What can I do to take care of myself during and after the therapy?
• How will we know if the radiation therapy/radioimmunotherapy is working?
• How will the radiation treatment affect my normal activities (work, school, childcare, driving, sexual activity, and exercise)?

Clinical trials are crucial in identifying effective drugs and determining optimal doses for patients with lymphoma. Patients interested in participating in a clinical trial should view the Understanding Clinical Trials fact sheet on the Lymphoma Research Foundation’s (LRF’s) website at www.lymphoma.org/publications, talk to their physician, or contact the Lymphoma Resource Center for an individualized clinical trial search by calling (800) 500-9976 or emailing [email protected].

Patients with lymphoma should have regular visits with a physician who is familiar with their medical history and the treatments they have received. During these visits, medical tests (like computed tomography [CT] or positron emission tomography [PET] scans) may be required to evaluate the need for additional treatment.

Some treatments can cause long-term side effects (occur during treatment and continue for months or years) or late side effects (appear only months, years or decades after treatment has ended). These can vary depending on the following factors:

• Duration of treatment (how long the treatment has lasted)
• Frequency of treatment (how often the treatment was administered)
• Type of treatment given
• Patient’s age and gender
• Patient’s overall health of at the time of treatment.

A physician will check for these effects during follow-up care. Visits may become less frequent the longer the patient stays in remission (lack of signs and symptoms of disease).

Patients and their caregivers are encouraged to keep copies of all medical records. This includes test results as well as information on the types, amounts, and duration of all treatments received. Medical records are important for keeping track of any side effects resulting from treatment or potential disease recurrences. The Foundation’s Lymphoma Care Plan (lymphoma.org/publications) can help patients manage this documentation.

Keeping your information in one location can help you feel more organized and in control. This also makes it easier to find information pertaining to your care and saves valuable time. The Foundation’s Lymphoma Care Plan document organizes information on your health care team, treatment regimen, and follow-up care. You can also keep track of health screenings and any symptoms you experience to discuss with your health care provider during future appointments. The Lymphoma Care Plan document can be accessed by visiting lymphoma.org/publications.

The Foundation also offers a variety of educational activities, including live meetings and webinars for individuals looking to learn directly from lymphoma experts. These programs provide the lymphoma community with important information about the diagnosis and treatment of lymphoma, as well as information about clinical trials, research advances and how to manage/cope with the disease. These programs are designed to meet the needs of a lymphoma patient from the point of diagnosis through long-term survivorship. To view our schedule of upcoming programs, please visit lymphoma.org/programs.

The Foundation’s Lymphoma Resource Center staff are available to answer your general questions about lymphoma and treatment information, as well as provide individual support and referrals to you and your loved ones. Callers may request the services of a language interpreter. The Foundation also offers a one-to-one peer support program called the Lymphoma Support Network and clinical trials information through our Clinical Trials Information Service. For more information about any of these resources, visit our website at lymphoma.org, or contact the Lymphoma Resource Center at (800) 500-9976 or [email protected].

Para información en Español, por favor visite lymphoma.org/es. (For Information in Spanish please visit lymphoma.org/es).