Radiation Therapy for Osteosarcoma
Radiation therapy uses high-energy x-rays to kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate cancer within the radiation field. Radiation therapy is not useful for eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the tumor site from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer.
Osteosarcoma is relatively resistant to radiation; therefore, conventional radiation therapy does not play a major role in its treatment. When patients with osteosarcoma are treated with radiation therapy, it is usually in combination with other therapies. For this reason, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving radiation oncologists, surgeons, medical oncologists, medical gastroenterologists, and nutritionists.
External Beam Radiation Therapy
Radiation is administered externally with machines called linear accelerators, which produce high-energy external radiation beams. This beam of radiation penetrates the tissues and delivers the radiation dose deep in the area of the body where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side effects while improving the ability to deliver radiation to areas of cancer.
Simulation: After an initial consultation with a radiation oncologist, a planning session, called a “simulation” is conducted. The purpose of the simulation is to determine the areas where the radiation will be delivered, called radiation treatment fields, and to plan the treatments. This session is conducted by the radiation oncologist, aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning. The simulation may last anywhere from fifteen minutes to an hour or more, depending on the complexity of the treatment.
During simulation, patients lay on a table similar to that used for a CT scan, and a machine called a “simulator” is used to establish the treatment fields. The dimensions and movements of the simulator closely match that of a linear accelerator. But rather than delivering radiation treatment, the simulator lets the radiation oncologist and technologists see the area to be treated. The simulation is usually guided by fluoroscopy in order to observe the patient’s internal anatomy. The radiologist can mainly see the skeleton with this technique, but the kidneys, bowels, bladder, or esophagus may also be visible. The table can be raised and lowered and rotated around a central axis. The lights are usually dimmed while the treatment fields are being set. Temporary marks may be made on the patient’s skin with magic markers.
Once the aspects of the treatment fields are satisfactorily set, x-rays representing the treatment fields are taken and the fields are marked with tattoos. These tattoos consist of only small pinpricks with a small amount of ink, appearing like a small freckle. The tattoos replace the marks previously made with magic markers. The use of tattoos enables the radiation technologist to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without worrying about obscuring the treatment fields.
Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room. The treatment plan is verified and treatment is started only after the radiation oncologist and technologists have rechecked the treatment field and calculations, and are thoroughly satisfied with the setup.
Treatment Schedules: A typical course of radiation for cancer of the head and neck lasts 3-5 weeks with daily treatments on Monday through Friday. The actual treatment with radiation generally lasts no more than a few minutes. Anesthesia is not needed for radiation treatments, since the patient is unlikely to feel any discomfort. Patients generally have few restrictions on activities during radiation therapy. Many patients continue to work during the weeks of treatment. Patients are encouraged, however, to carefully gauge how they feel and not overexert themselves.
Side Effects and Complications: The incidence of side effects from radiation therapy is highly variable. A dose which causes some discomfort in one patient may cause no side effects in other patients. Although patients do not feel anything while they are receiving radiation treatment, the effects of radiation gradually build up over time. It is not unusual for some patients to report tiredness, fatigue, and changes in sleep or rest patterns. Radiation may also cause skin damage in the areas receiving radiation. Large doses of radiation to patients with osteosarcoma can damage blood vessels and nerves. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment is almost always available and effective.
Strategies to Improve Treatment
Significant progress has been made in the treatment of osteosarcoma due to developments of adjuvant and neoadjuvant chemotherapy. The role of radiation therapy has been limited but there are areas of active research in specialized types of radiation delivery. Future progress in the treatment of osteosarcoma will result from continued participation in appropriate clinical trials. There are several areas of active exploration aimed at improving the treatment of osteosarcoma with radiation therapy.
Intraoperative Radiation Therapy (IORT): IORT consists of a single dose of radiation therapy that is delivered directly to the area of cancer during surgery. IORT is performed in specially-equipped operating rooms. Because of the advantage of being able to see the area being treated, the radiation doctor can protect sensitive structures, such as nerves and blood vessels, by moving them away from the radiation beam.
Results from one study evaluating IORT indicate that cancer may recur less often in the area of the surgery. In this study, very high-dose IORT was used in combination with chemotherapy with the aim of saving an affected limb. However, the cancer may still recur in surrounding tissue that is not radiated.
In osteosarcoma, IORT is often used in an attempt to save an affected limb. IORT combined with chemotherapy appears to improve quality of life of some patients with osteosarcomas in the extremities. When 39 patients with osteosarcoma of the extremity were treated with very high doses of IORT, local recurrences occurred in 19 of these patients and 23 had distant metastases. After a median follow-up of 10 years, 43% of the patients lived 5 years without a cancer recurrence. 1
Three-dimensional conformal radiation: Three-dimensional conformal radiation therapy can precisely target cancer cells decreasing the amount of healthy cells exposed to radiation. Using computerized tomography (CT) scans and other scans, radiation oncologists have developed methods for determining the 3-dimensional size and shape of the cancer. This allows high-dose external beam radiation therapy to be delivered primarily to the cancer with less damage to normal tissues, such as the liver, stomach, and kidneys.
Intensity Modulated Radiation Therapy (Tomotherapy): Tomotherapy delivers varying intensity of radiation with a rotating device. The intensity is varied by the placement of “leaves” which either block or allow the passage of radiation. The rotating component of this technique allows for more specific targeting of the cancer. In conventional radiation therapy, the beam is usually delivered from several different directions, possibly 5-10. The greater the number of beam directions, the more the dose will be confined to the target cancer cells, sparing normal cells from exposure. Tomotherapy delivers radiation from every point on a helix, or spiral, instead of from just a few points.
Tomotherapy is similar to CT scanning. In CT, a beam rotates about the patient, creating a sequence of cross-sectional images. Tomotherapy also uses a rotating beam, except the beam delivers radiation. Tomography also delivers treatment one cross-section at a time.
Brachytherapy: Internal delivery of radiation by the use of implants is called brachytherapy. With brachytherapy, high radiation doses may be delivered to specific cancer cells, without damaging adjacent normal tissues. The radioactive implants are needles or tubes containing a radioactive substance. Such implantations, if carefully performed, are effective, safe, and have a low risk of complications. Brachytherapy can be a useful addition to external beam irradiation in the treatment of patients with head and neck cancer.
Removeable implants are especially important in the treatment of cancers of the mouth, tongue, throat, and nasopharynx where they are given as intracavitary boosts following external beam radiation therapy. The implants are placed in the area of the cancer and removed when the appropriate dose is administered. The most commonly used radioactive substance in removable implants is iridium 192.
In some cases, permanent placement of radioactive sources may be necessary. Instances in which permanent implants are effective include recurrent nasophayngeal malignancies, for palliation of accessible recurrences of primary sites in the mouth and throat, or for cervical lymph node metastases. Iodine 125 and palladium 103 are the radioactive substances used for permanent implants.
Brachytherapy has not been systematically studied in patients with osteosarcoma. However, the principle was proven in one report by Japanese researchers who treated 14 patients with bone and soft tissue sarcomas with high dose rate brachytherapy. After 1 year, local control of the cancer was evident in 75% of patients. After 2 years, 48% still showed local control of cancer. The treatment was considered safe and well-tolerated. 2
Bone Seeking Isotopes: Sumarium-153 is an isotope that localizes to bone and emits primarily beta particles to the surrounding areas. The main toxicity of samarium-153 is hematologic toxicity with resultant low blood counts. Sumarium has been used in one patient to treat osteosarcoma who had a dramatic but transient response. 3 Preliminary results from another study indicate that treatment of osteosarcoma with samarium-153 with autologous stem cell transplant is feasible and warrants further evaluation. In this study, 6 patients with osteosarcoma were treated with samarium-153-EDTMP, followed two weeks later with autologous stem cell infusion. 4 All patients in this study had recurrent and unresectable osteosarcoma. One patient was a long-term survivor and the rest achieved significant palliation.
Oya N, Kokubo M, Mizowaki T. Definitive Intraoperative Very High-Dose Radiotherapy for Localized Osteosarcoma. International Journal of Radiation Oncology, Biology, and Physics 2001;51:87-83.
Koizumi M, Inoue T, Yamazaki H, et al. Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors. Int J Radiat Oncol Biol Phys 1999 Mar 15;43(5):989-932.
Bruland OS, Skretting A, Solheim OP. Targeted radiotherapy of osteosarcoma using 153 Sm-EDTMP. A new promising approach. Acta Oncol 1996;35(3):381-4.
Franzius C, Bielack S, Flege S, et al. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma. Nuklearmedizin 2001;40:215-20.