Techniques for Delivering Radiation Therapy

Radiation therapy may be delivered to the body:

• Externally
  
• Internally
  
• Systemically

External radiation therapy is delivered by a machine outside the body. The machine transmits high-energy rays through outer body tissues to the cancer.

Internal radiation therapy, called brachytherapy, is transmitted directly to the cancer by implants that are placed within the body. These implants, which may take the form of seeds, capsules, wires or other shapes, contain a small amount of radioactive material. They are placed in or near the cancer and can be permanent or temporary.

Systemic radiation therapy is administered by having the patient take a radioactive substance by mouth or by injecting a radioactive substance into a vein. Only radioactive materials that have been specifically formulated for this purpose may be used in this way. The radioactive material travels through the body until it reaches the target tissue.

Specific radiation therapy techniques are:

External Radiation Therapy

• External beam radiation therapy (EBRT)
  
• Three-dimensional conformal radiation therapy (3-D CRT)
  
• Intensity-modulated radiation therapy (IMRT)
  
• Image-guided radiation therapy (IGRT)
  
• Stereotactic surgery (SRS) and stereotactic radiotherapy (SRT)
  o Gamma Knife
  o Cyberknife
  o Extracranial radiosurgery
• Total body irradiation
  

Internal Radiation Therapy

• Brachytherapy
• Low dose rate (LDR) brachytherapy
• High dose rate (HDR) brachytherapy
• Breast brachytherapy
  

Systemic Radiation Therapy/Radioactive Nuclides

• Radioactive iodine for thyroid cancer
• Sumarium for bone metastasis
• Radioimmunotherapy
• Radioactive monoclonal antibody for non-Hodgkin's Lymphoma

EBRT is given by a machine known as a linear accelerator (also called a linac). These types of machines produce high-energy external radiation beams. The radiation beams penetrate outer body tissue and deliver the radiation dose deep into the areas where the cancer lies.

These modern machines and other state-of-the-art techniques, such as 3-D CRT, IMRT, and IGRT have enabled radiation oncologists to significantly reduce side effects while improving delivery of radiation to kill cancer cells. EBRT is typically given on an outpatient basis.

EBRT begins with a planning session (called a simulation). During simulation, marks are placed on your body and measurements are taken to line up the radiation beam in the correct position for each treatment. The actual area receiving radiation treatment may be large or small, depending on the cancer. Radiation may be delivered specifically to an organ or may include the surrounding area and lymph nodes.

During treatment, the patient lies on a table and is treated with radiation from the linear accelerator. The radiation beams can be aimed at the patient from multiple directions within a framework (gantry) that surrounds the patient. Both the gantry and the table that the patient is lying on can be moved, allowing radiation to be aimed at the tumor from the best possible angle.

Three-Dimensional Conformal Radiation Therapy (3-D CRT)

EBRT can be delivered more precisely using a technique called 3-D CRT. This technique represents an improved method for planning the delivery of radiation to the cancer. Planning with 3-D CRT takes into account the three-dimensional shape of the cancer (width, height, and depth) and any nearby vital body structures. The benefit of 3-D CRT is that it allows more radiation to be targeted at the cancer, to kill as much of it as possible, while resulting in less damage to nearby normal tissues.

3-D CRT is carried out using modern imaging techniques called computed tomography (CT) and/or magnetic resonance imaging (MRI). These techniques are used to create a three-dimensional computer model of your body and its structures. The model is very useful for understanding the exact volume of the cancer and its location with respect to your vital organs.

The radiation oncologist may also obtain images through functional imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and/or magnetic resonance spectroscopy (MRS). These images show the radiation oncologist how the cancer and surrounding tissues are functioning. For example, they may show very active cells within a cancer that need to be targeted by radiation, or active areas within normal organs that need to be protected from radiation.

The use of 3-D CRT results in radiation beams that more closely conform to the size, shape, and volume of the cancer. This spares nearby body structures and reduces the chance of injury. The risk of injuring normal tissues is one of the reasons why a radiation oncologist may lower the dose of radiation therapy. Since 3-D CRT can better target the area of cancer, radiation oncologists are evaluating whether higher doses of radiation can be given safely to achieve greater cancer cures.

Intensity-Modulated Radiation Therapy (IMRT)

IMRT, an external radiation therapy technique, is an advanced type of high-precision radiotherapy. The purpose of IMRT is to improve treatment success while minimizing side effects. It uses computer-controlled linear accelerators and three-dimensional imaging to deliver precise radiation doses to a malignant tumor or to specific areas within the tumor.

In IMRT, the radiation dose is designed to conform to the three-dimensional (3-D) shape of the tumor by modulating-or controlling-the intensity of the radiation beam. The radiation beam is controlled to focus a higher radiation dose to the tumor while minimizing radiation exposure to surrounding normal tissues.

IMRT differs from 3-D conformal radiation therapy (3-D CRT) in that it uses hundreds of pencil thin beams instead of a large radiation field. The angle and intensities of these beams are designed to conform as closely as possible to the size, shape, and volume of the cancer. Higher-intensity radiation is directed at the cancer, while lower-intensity radiation is directed at surrounding tissues.

The radiation beams are delivered to the body by a part of the linear accelerator that rotates and has many "leaves" (flat overlapping sections used to shape the radiation beams). The leaves are adjusted to either block or allow the passage of radiation. The ability to adjust the leaves and control rotation enable the radiation oncologist to control the angle, shape, and intensity of the radiation beams to target your cancer more precisely.

Image-Guided Radiation Therapy (IGRT)

IGRT is an external radiation therapy technique that enhances IMRT and 3-D CRT by using images that allow the radiation oncologist to take tumor motion into account. This allows more precise targeting of radiation therapy at the cancer. Surrounding normal tissues are spared as much as possible.

A cancer may shift its precise location day to day with small changes in patient position on the treatment table from one day to the next. In addition, cancers in some areas of the body move with normal body motion, such as breathing. Without IGRT, radiation oncologists must increase the volume of body tissue treated with high-energy radiation, so not to miss the cancer as it moves.

The problem with targeting an increased volume of body tissue to cope with tumor motion is that this exposes more normal surrounding tissues to radiation. When more normal tissues are exposed, side effects become more likely. It also becomes more likely that the dose of cancer-killing radiation may have to be limited.

Before IGRT, radiation oncologists tried to compensate for tumor motion during breathing by asking patients to hold their breath at regular intervals during radiation therapy, telling patients that they can only breathe at certain points during radiation therapy and using constraints to limit chest motion. As you can imagine, these techniques are not practical for many people.

IGRT helps radiation oncologists overcome these difficulties by using daily images to precisely locate the tumor and identify its motion. The positions of nearby normal tissues are also identified. When necessary, the motion of the tumor with breathing is tracked.

The type of imaging technique used for IGRT depends on the type of tumor. For certain types of tumors, ultrasound images are obtained. These images may be obtained after "markers" are implanted in the tumor to make it more visible on the image. For other types of tumors, computed tomography (CT) images are used. The information provided by these images is incorporated into the targeting of radiation therapy for that day.

Stereotactic Radiosurgery (SRS) and Stereotactic Radiotherapy (SRT)

Stereotactic radiosurgery (SRS) is an external radiation therapy technique that delivers a high dose of radiation to a precisely defined target. SRS does not involve actual surgery. It is called "radiosurgery" for two reasons:

• The high dose of radiation energy is so focused and involves such precisely targeted cell damage that it has been called "knifelike."
• The high dose of radiation therapy is designed to kill all the cells within the targeted volume of body tissue. This is done without planning for lower doses at an outer "margin" of normal tissue. For this reason, great care is taken to immobilize the body part being treated and to shield surrounding tissues.
  

SRS is performed for a number of reasons, but may be useful for controlling metastatic cancer. By delivering a single, very intense dose of radiation to a carefully defined volume of body tissue, SRS may help overcome the resistance of certain types of metastatic cancers to conventional radiation therapy.

SRS is an outpatient treatment. It is generally performed using devices such as the Gamma Knife or the Cyberknife. It may be prescribed to deliver the total dose of radiation in a single one-day treatment session. Alternatively, it may be given as a series of treatments. When performed in more than one session, SRS may be called "fractionated" or "staged" SRS.

Stereotactic radiotherapy (SRT) is very similar to SRS. Some medical centers differentiate the two as follows:

• If the stereotactic radiation involves only 1 day of treatment, then it is called SRS.
• If the stereotactic radiation involves multiple sessions, then it is called SRT.
  

Other medical centers define SRT as stereotactic radiation that is performed over multiple sessions and involves more than one dose of radiation (using lower doses to spare important body tissues).

Gamma Knife

The Gamma Knife was first developed for commercial use in 1968. It is an external radiation therapy technique and a form of stereotactic radiosurgery (SRS). For many years, it has been relied on as the standard of care for certain types of cancers that are difficult to treat or remove surgically. The Gamma Knife is not a knife, but a machine for delivering very precise, high-energy radiation therapy.

This device is called the "Gamma" Knife because it uses radioactive cobalt to generate gamma rays. These gamma rays are aimed precisely at the targeted area of cancer using a fixed frame. A boxlike frame is placed on the patient and attached to a frame on the machine as part of patient positioning for treatment. The patient must remain still within this rigid framework during treatment. The machine itself also does not move. The treatment generally takes place over one session.

SRS with the Gamma Knife is valuable because it provides physicians and patients with an alternative to surgery for certain inaccessible cancers. Treatment with the Gamma Knife allows the cancer to be damaged and "removed" without cutting through surrounding tissues.

The Gamma Knife can also be used as treatment following conventional surgery. Treatment with the Gamma Knife may remove areas of cancer that the surgeon was compelled to leave behind to prevent too much damage to surrounding normal tissue.

Additionally, the Gamma Knife can be used for certain patients who have not had good results with conventional radiation therapy. The Gamma Knife has a long track record of providing important benefits to patients needing radiation therapy.

Cyberknife

The Cyberknife is a relatively new form of stereotactic radiosurgery (SRS). It is not a knife, but a machine that delivers external radiation therapy to treat cancer. The Cyberknife uses a moveable robotic arm to aim radiation beams precisely at the cancer, taking into account patient movement and the slight movement of the cancer.

It is possible for the Cyberknife to compensate for movement because it continually obtains images during the treatment session. These images allow the Cyberknife to detect changes in cancer position, track movement, and correct the direction of the radiation beams to compensate. The goal is to use this precise tracking and correction to minimize damage to normal tissues.

The Cyberknife may be used for cancers in a variety of body systems. It can be used for one or several cancerous tumors during the same treatment session. It can also be used for tumors of complex sizes and shapes. During treatment with the Cyberknife, the patient is positioned without the use of a rigid frame. Instead, a mask or other nonrigid system is used to help the patient keep still. 

Extracranial Radiosurgery

Extracranial radiosurgery is stereotactic radiosurgery (SRS) performed to treat cancer in body systems outside the brain. Your cranium is your skull, and "extracranial" means "outside the skull." SRS is the precise delivery of high-dose external radiation therapy to a well-defined volume of body tissue to destroy cancer cells almost as if a surgeon had cut them out.

SRS was first developed to treat brain cancer. The use of extracranial radiosurgery has grown with the introduction of new imaging technologies that help radiation oncologists precisely characterize the location of cancers and target them with high-dose radiation therapy in other organs besides the brain.

New imaging techniques help radiation oncologists understand the three-dimensional shape, movement, and functional characteristics of cancers. Surrounding normal tissues are characterized in the same way. Finally, new technologies help radiation oncologists design and deliver high-dose radiation to these cancers while sparing normal tissues. The result is an almost surgical destruction of the targeted cancers. Cancers of the lungs, liver, pelvis, and other areas of the body may be treated in this way.

Total Body Irradiation

Total body irradiation is the delivery of radiation therapy to the entire body. This treatment is only performed when it can be followed by bone marrow or peripheral stem cell transplantation. The treatment is only performed for certain types of cancers, when it appears to be the best option for survival and when the severity of the cancer justifies the risk of treatment.

The purpose of this treatment is to kill cancer cells that may be distributed throughout the body, for example, within the blood or lymphatic system. Another reason for performing the treatment is to suppress your immune system so that your body will be less likely to reject the transplanted bone marrow or stem cells.

Patients receiving total body irradiation may have certain types of cancers affecting the bone marrow. They would be expected to benefit from new bone marrow provided by a donor (an individual with cell markers that are as closely matched as possible to those of the patient). This is called a donor transplant.

Other patients may have functional bone marrow, but also have malignant cancers that have spread and cannot be eliminated any other way. These patients have their own bone marrow collected and stored. After total body irradiation is completed, the patients receive an infusion of their own bone marrow or stem cells. This is called an autologous transplant.

Sometimes other radiation therapy to parts of your body must be completed before total body irradiation is performed. Some patients have chemotherapy before total body irradiation.

Total body irradiation is generally given in more than one session. You may be positioned so that you are standing (with supports), sitting, or lying down for the procedure. You will need to be positioned carefully, with the placement of blocks to prevent more sensitive areas of your body from receiving too much radiation, and scatter screens to make sure your skin receives radiation without too high a dose.

After total body irradiation is completed, you are at high risk of infection. You will be protected against infection and receive an infusion of donor bone marrow or stem cells soon after the completion of therapy.

Brachytherapy

Brachytherapy is another name for internal radiation therapy. It is performed by placing a sealed radioactive source (implant) in or very near the cancerous tumor. The sealed implant contains a small amount of radioactive material. It is either:

• Implanted directly in the tumor (interstitial brachytherapy)
• Placed within an instrument that has been positioned in a nearby body cavity (intracavity brachytherapy)
  

The implant is allowed to remain in or near the cancerous tumor for a period of time. During this time, the cancer is exposed to radiation to damage and destroy the cancer cells. Sometimes implants are inserted and intended to remain permanently. Over time, the radiation in these types of implants becomes steadily weaker until it disappears. The implants remain with no further effect on the patient.

For example, prostate cancer is commonly treated by means of interstitial brachytherapy. Radioactive "seeds" (tiny, rod-shaped implants) are permanently implanted into the prostate gland through an operative procedure. The patient is anesthetized and specialized needles are used to insert the seeds into the prostate. An ultrasound probe is placed in the rectum to obtain clear images of the prostate. These images guide the placement of the seeds.

After the implantation, the patient may go home soon after the anesthesia wears off, assuming there are no problems, the patient does not drive, and a responsible adult accompanies the patient home. The patient may be able to return to work in about 2 days. The radiation that the patient is receiving does not pose a hazard to most other people, although the patient will be advised to avoid or limit contact with young children and pregnant women until the implants have had enough time to become nonradioactive.

Because implant radiation places the source of radiation within the cancer or just a few inches away, this form of radiation therapy may be used in patients with early-stage cancers. Alternatively, brachytherapy may be used after surgical removal of the tumor to treat microscopic traces of cancer that may remain. The advantage of using brachytherapy instead of surgically removing a wider margin of tissue is the preservation of a greater amount of normal tissue.

Brachytherapy also has the advantage of being able to deliver a higher dose of radiation to the tumor than external radiation therapy techniques. Ideally, as the radiation is emitted from the radioactive implant, it travels through the cancerous cells first. The radiation is absorbed by the cancerous cells and has little opportunity to penetrate to normal tissues. This benefits you by ensuring a lower dose of radiation to nearby normal tissues.

The implants used in brachytherapy take many different forms, depending on the body area and type of cancer being treated. Some implants look like tiny rods, while others look like wires, needles, capsules, plaques, or tubes. All are sealed with the radioactive material inside. Some brachytherapy implants are intended for permanent implantation, while others are implanted only temporarily.

Some implants are characterized by the release of relatively low levels of radiation over longer periods of time, while others are designed to release higher-energy radiation. If you are being treated with implants that release high-energy radiation, you may receive them only after being admitted to the hospital. Precautions may be needed to make sure that people caring for you or visiting you are not exposed to radiation.

Brachytherapy can be divided into two types, depending on the level of radiation energy used to treat the patient:

• High dose rate (HDR) brachytherapy
• Low dose rate (LDR) brachytherapy

Low Dose Rate (LDR) Brachytherapy

LDR brachytherapy uses implants that are intended to transmit lower levels of radiation over longer periods of time (days, weeks, or months). This type of brachytherapy was the first to be developed and represents the most conventional and well-known treatment. LDR brachytherapy remains a mainstay of treatment for many patients.

The exact duration of LDR brachytherapy and the types of implants and procedures used depend on the type of cancer being treated. When permanent implants are used, the patient may be kept within the hospital for a short time to recover from the implantation procedure and to allow radiation levels to decrease. However, after discharge, the patient may take part in most normal daily activities while receiving internal radiation therapy.

Patients who must receive temporary LDR brachytherapy implants, such as women with certain types of cervical cancer, stay in the hospital for the duration of their treatment session. They may return for other sessions. While in the hospital for treatment, the patient receives implants that are well-positioned for delivering radiation to the cancer, but are easy to dislodge. To prevent dislodgment, the patient must lie as still as possible in bed for about 2 days while receiving treatment. The patient is then discharged after the treatment session is over.

The low dose rate associated with LDR brachytherapy means that a longer period of treatment time is necessary to make sure the cancer receives a therapeutic dose of radiation. The low dose rate also means that even though the cancer is receiving enough radiation to be damaged, the surrounding normal tissues are less likely to be harmed.

LDR brachytherapy does not need as much training, technical expertise, and specialized equipment as the use of brachytherapy involving high levels of radiation. The technique allows for some flexibility since radiation levels are relatively low. However, radiation shielding is still needed for LDR brachytherapy, and hospital staff, visitors, and the patient must still take precautions to prevent unwanted radiation exposure.

High Dose Rate (HDR) Brachytherapy

HDR brachytherapy is performed with implants that are intended to transmit high levels of radiation over shorter periods of time (minutes). More treatment sessions may be needed with HDR brachytherapy than LDR brachytherapy. The advantage of HDR brachytherapy is that even though it may need to be performed over more treatment sessions, it is likely to result in less treatment time overall.

Because high levels of radiation are involved, HDR brachytherapy requires the use of specialized equipment and procedures. These are needed for storing the radioactive implants in a shielded safe, transporting them safely to the patient's body tissues for treatment and protecting against unwanted radiation exposure. Medical centers that provide HDR brachytherapy are responsible for carrying out these precautions with trained staff. As a result, there may be less risk of radiation exposure with HDR brachytherapy than with LDR brachytherapy.

HDR brachytherapy is often performed as an outpatient procedure. A patient is treated with HDR brachytherapy in a shielded room with health care staff monitoring from outside. The shielding prevents radiation from affecting those outside the room. Before treatment, applicators (for example, needles or "ribbons") are inserted in the body and placed in the tumor. The protruding ends of the applicators are attached to catheters (thin, hollow tubes). The other ends of the catheters are attached to a machine called an HDR afterloader.

The radioactive implants used in HDR brachytherapy are often in the form of little pellets, no larger than a pencil eraser. The pellets are contained within the HDR afterloader, which is designed with radiation shielding. The HDR afterloader is operated remotely with the help of a computer. When activated, the HDR afterloader extends wires or cables to "drive" the radioactive pellets through the catheters to a fixed point within the applicator (within the cancer) for a set amount of time. After a few minutes, the HDR afterloader retracts the pellet back inside the machine.

During HDR treatment, the health care staff continually monitors the patient. A closed-circuit television monitor and an intercom are used to make sure that good communication and monitoring are maintained. Treatment must take place over a series of sessions. Since the radioactive implant is always removed after each session, the patient does not have to worry about being radioactive when not actively treated. After the last treatment session is completed, the applicators are removed from the patient's body.

Breast Brachytherapy

For women who have undergone breast-conserving surgery for cancer, breast brachytherapy may serve as an alternative to external beam radiation therapy (EBRT). Women undergoing breast-conserving surgery generally have only the cancerous tumor and a small amount of surrounding tissue removed (lumpectomy) instead of having all of the breast removed (mastectomy). After a lumpectomy, radiation therapy may be needed to reduce the risk that cancer could return.

Radiation therapy may be administered as EBRT or as breast brachytherapy.
Women treated with EBRT are generally scheduled for 6 weeks of radiation treatment, 5 days per week. Breast brachytherapy provides the advantage of shorter treatment duration. However, breast brachytherapy is not for everyone: women with larger tumors or more extensive tumor spread may be more effectively treated with EBRT. Women who are good candidates for breast brachytherapy may find it a reasonable alternative.

In high dose rate (HDR) breast brachytherapy, a high dose of radiation is administered to the targeted area of the breast for a few minutes during each treatment session. The treatment sessions generally take place over a 5-day period, with two sessions scheduled per day. One option for administering HDR breast brachytherapy is the balloon catheter technique. Another option is the multiple-catheter technique.

In the balloon catheter technique, a thin, flexible catheter with a deflated balloon at its tip is implanted into the breast. The balloon is placed in the cavity that remains after surgical tumor removal. If the decision to perform breast brachytherapy is made early enough, the implantation may be done at surgery. Otherwise, the balloon catheter may be implanted after the patient has recovered from surgery using ultrasound images to guide placement.

After implantation into the cavity, the balloon is inflated with saline solution (a watery fluid containing salt) and left in place with the catheter. During each treatment session, a radioactive pellet is pushed through the catheter and into the balloon by a remote-controlled machine called an HDR afterloader. This allows the target breast tissue surrounding the cavity to receive high-dose radiation for a specified time. The pellet is retrieved by the afterloader after the time elapses. The patient does not need to be concerned about being radioactive between treatment sessions.

Upon completion of the final treatment session, the pellet is removed as usual, the saline solution in the balloon is drained out, and the catheter and balloon are removed from the patient's body. The patient has no radioactivity in her body after the final treatment session and can go home once she is ready.

The balloon catheter technique is very commonly used for breast brachytherapy. However, women who do not have a defined, fluid-filled cavity within the breast after lumpectomy cannot be treated with this technique. Instead, they may be treated using the multiple-catheter technique. This is performed by inserting many thin, flexible catheters (without balloons) into the breast. The catheters are positioned in rows and at depths that allow them to surround the area of breast tissue needing treatment. Radioactive pellets are pushed through the catheters to deliver radiation to the breast by the HDR afterloader as before.

In the multiple-catheter technique, the rows of catheters are left in place after implantation for about the same amount of time as the balloon catheter (about 5 days). Other aspects of the treatment are also about the same.

Breast brachytherapy was originally developed as a low dose rate (LDR) brachytherapy procedure. Women had to stay in the hospital to receive LDR breast brachytherapy. After the low-intensity radioactive implant was inserted in the breast, a woman had to lie in bed over several days to receive treatment. Shielding and other radiation precautions were necessary to prevent radiation exposure to hospital staff and visitors.

A newer form of LDR breast brachytherapy has recently been introduced. This technique involves the implantation of a multichannel catheter designed to fit within the cavity left within the breast after surgical removal of the cancer. Radioactive strands associated with the catheter deliver low-intensity radiation to the patient. A shielded bra allows the patient to go home after implantation and, with the use of some precautions, safely interact with others. The patient returns for evaluation and removal of the catheter after a 4- or 5-day treatment period.

The same device (ClearPath) may be used to administer HDL breast brachytherapy. Patients receiving HDL breast brachytherapy with ClearPath are scheduled for treatment sessions twice per day, again over a 4- or 5-day treatment period.

Radioactive Iodine for Thyroid Cancer

Patients with thyroid cancer may receive systemic radiation therapy with a radioactive form of iodine (iodine 131) as part of their treatment. Not all patients with thyroid cancer need iodine 131 treatment. However, for appropriate patients, iodine 131 is a standard and well-known treatment for thyroid cancer.

Iodine 131 is taken by mouth in liquid or capsule form. Only preparations of iodine 131 that have been specifically prepared for administration by mouth are given to patients. A controlled dose is given as prescribed by your physician. Always cooperate with health care staff as they verify that you are the correct patient receiving the correct dose. Because health care staff will also be making sure that it is safe to give you a radioactive compound, answer their questions fully and honestly even if you have heard them before. Be sure to question anything that you do not understand or that contradicts what your physician has told you before taking the radioactive preparation.

The treatment works because thyroid tissue normally takes up and traps iodine. As the radioactive iodine circulates through your body, it is either taken up by the thyroid cancer cells that need treatment, or it is eliminated through normal body processes.

Radioactive iodine is given to patients only after surgery for thyroid cancer. The purpose of treatment is to:

• Eliminate thyroid tissue or cancer that may remain at the surgical site after surgery to remove the thyroid, and/or
• To eliminate thyroid cancer that has already spread to other parts of the body.
  

Patients treated with radioactive iodine are radioactive and eliminate radioactive wastes for a period of time after treatment. Precautions must be taken to prevent vulnerable individuals (young children, unborn babies, pregnant women) from being exposed to radiation during this time. The radiation may be detected by security screening.

If you are going to receive radioactive iodine, you need to fully understand what precautions to take with respect to household activities and interactions with others. You should plan with your physician and employer when it is appropriate for you to return to work and/or resume travel, and you should obtain documentation of your treatment from your physician if you must enter any areas involving security screening.

Radioimmunotherapy

Radioimmunotherapy is the combination of both radiation and the immune system to treat cancer. Most commonly, it means the use of radioactive immune proteins to carry damaging radiation directly to cancer cells. The goal is to combine the ability of the immune system to recognize and target cancer cells with the ability of radiation to destroy tumors. 

For the treatment to work, it is necessary to understand what antigens (foreign proteins) are present in cancer cells that the immune system can recognize. Monoclonal antibodies are developed to act specifically against a cancer antigen. The monoclonal antibodies are attached to radioactive elements, then administered to the patient. 

Currently approved forms of radioimmunotherapy include monoclonal antibodies for treating non-Hodgkin’s lymphoma. Other potential treatments are being explored through research. Potential strategies that offer promise for the future include combining radioimmunotherapy with other methods for selectively destroying cancer cells; with techniques for boosting the immune system response; and with advanced methods for identifying cancer cell type. 

Radioactive Monoclonal Antibody for Non-Hodgkin's Lymphoma

Radioactive molecules attached to a monoclonal antibody may be used as systemic therapy for certain patients with non-Hodgkin's lymphoma, a cancer of the immune system. Treatment with radioactive monoclonal antibodies is a relatively recent development. It does not work for all types of non-Hodgkin's lymphoma, and may be associated with severe side effects. Only patients with very specific types and stages of disease are likely to benefit from this kind of treatment.

An antibody is a protein normally produced by the human immune system. Antibodies recognize and bind strongly to very specific types of proteins, depending on the exact type of antibody. The purpose of this protein binding is to help the body fight infection. People normally produce many different types of antibodies as part of the immune response. A monoclonal antibody is a highly purified preparation of one specific type of antibody; this antibody is not mixed with the large variety of other antibodies that exist.

Two types of treatment for non-Hodgkin's lymphoma involving radioactive monoclonal antibodies have been approved by the United States Food and Drug Administration:

• Zevalin® (ibritumomab tiuxetan), and
• Bexxar® (tositumomab and iodine [I 131] tositumomab)
  

Each treatment is associated with serious risks and is not suitable for all patients. Careful consultation with your physician is needed to determine whether either treatment would help you overcome non-Hodgkin's lymphoma.

Ibritumomab consists of a monoclonal antibody attached to either of two radioactive elements: indium-111 (In-111) or yttrium-90 (Y-90). It is given as an infusion (IV drip) through a vein. Patients first receive an infusion with another monoclonal antibody, Rituxan® (rituximab), then an infusion of In-111 ibritumomab. Patients then receive another infusion with rituximab and finally an infusion of Y-90 ibritumomab.

Because ibritumomab may be associated with very serious reactions, including death, patients are monitored very closely during treatment and regularly after treatment. After you receive ibritumomab, the radiation that stays within your body does not penetrate through body tissues and does not make the outside of your body radioactive. However, your body fluids or eliminated solids (such as saliva, blood, urine, stool, and semen) are radioactive. Precautions must be taken to safely contain, wash, and dispose of these fluids to protect yourself and others from unnecessary radiation exposure.

Bexxar consists of both the monoclonal antibody tositumomab and tositumomab attached to the radioactive element iodine 131. Patients receive Bexxar as an infusion through a vein. Potassium iodide in tablet form is first given to the patient to prevent the iodine 131 from being taken up by the thyroid gland, since this would damage thyroid tissue.

The treatment regimen with Bexxar involves four infusions: an initial infusion of tositumomab followed by enough I-131 tositumomab to measure its distribution within the body. If the distribution is found to be acceptable, an initial infusion of tositumomab is given again, followed by a therapeutic dose of I-131 tositumomab. Bexxar has been associated with severe reactions, including death. Patients are closely monitored during infusions and between treatments, and need regular monitoring after treatment.

The full treatment regimen with Bexxar is given only once. Patients must take precautions for a number of days after treatment to prevent radiation exposure to other individuals. Patients should receive lifelong monitoring of thyroid gland function after receiving treatment.

Samarium-153 and Strontium-89 for Metastatic Bone Cancer

Another type of systemic radiation therapy is the injection of radioactive compounds to treat metastatic bone cancer, a condition in which cancer has spread to bone. After injection, the compound is taken up by bone tissue, carrying radioactivity directly to the cancer cells within bone. The treatments are specific for this purpose: they are not used to treat other organs besides bone, and are not used to treat cancer before it has spread. 

Although not offering a cure, effective treatments for metastatic bone cancer are important because they relieve pain and help prevent bones from becoming weakened and at risk for breaking. This helps people coping with cancer maintain or improve their quality of life. For example, it may make it possible to reduce or stop taking powerful painkilling drugs (and therefore reduce side effects from these drugs). 

The advantage of using systemic radiation therapy instead of external radiation is that the individual does not need to undergo repeated targeting of multiple tumors by a radiation beam. The radioactive compounds are selected to be those that bone tissue will readily take up from the blood. It may take time (weeks) to achieve pain relief through this treatment, but once achieved, the relief may last for months. 

Metastron^® (strontium-89 chloride injection) is commonly used for the systemic radiation treatment of bone metastases. Quadramet^® (samarium SM 153 lexidronam injection) is another treatment. Repeated dosing of samarium SM 153 was recently found to be effective for patients who had been treated earlier for pain but had experienced a return of symptoms. Researchers are also studying the effectiveness of other compounds, including rhenium-186, rhenium-188, and tin-17.

After receiving a strontium-89 or samarium SM 153 injection, you should be careful to observe precautions against exposing others to radioactivity, since your body fluids will be radioactive for a period of time. Be sure you understand the precautions explained to you by your doctor or nurse, or ask about them if they aren’t mentioned. 

Treatment with strontium-89 or samarium SM 153 may be associated with a temporary increase in bone pain soon after receiving the injection. This is called a flare reaction and is usually treatable with pain medication until it goes away. The treatments may also result in temporary bone marrow suppression, making you more susceptible to infection and other problems. Be sure to take precautions against infection as explained to you by the medical staff, and promptly report any physical problems to them.