Radiation Therapy for Ovarian Cancer
Radiation therapy or radiotherapy uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Radiation therapy, like surgery, is a local treatment used to eliminate or eradicate cancer that can be encompassed within a radiation field. Radiation therapy is not typically useful in 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, refers to the implantation of a small amount of radioactive material in or near the cancer.
Prior to the development of platinum-based chemotherapy, radiation therapy was frequently used in an effort to prevent ovarian cancer recurrences after surgery (adjuvant radiation therapy) or to treat recurrences. Currently, radiation therapy is sometimes used to treat a very localized recurrence, or as a treatment in women who cannot tolerate chemotherapy drugs. Radiation may also be used as palliative treatment (treatment of symptoms), when shrinking a tumor may provide symptom relief. In the vast majority of cases, however, the use of radiation therapy has been replaced by chemotherapy. Ongoing clinical trials are still trying to evaluate whether radiation therapy may have a place in the overall treatment of patients with advanced ovarian cancer.1
Delivery of Radiation Therapy for Ovarian Cancer
Modern radiation therapy for ovarian cancer is given via machines called linear accelerators that produce high-energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas 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 a curative radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue. For example, with modern radiation therapy, skin burns almost never occur, unless the skin is being deliberately targeted or because of unusual patient anatomy. For widespread ovarian cancer, the entire abdomen is often treated with radiation, with boosts to areas of large cancer growths in the pelvis.
After an initial consultation with a radiation oncologist, the next session is usually a planning session, which is called a “simulation.” This is a treatment planning session, during which the radiation treatment fields are determined. Of all of the visits to the radiation oncology facility, the simulation session may actually take the most time. During simulation, patients lie on a table somewhat similar to that used for a CT scan. The table can be raised and lowered and rotated around a central axis. The “simulator” machine is a machine whose dimensions and movements closely match that of an actual linear accelerator. 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, so that a patient’s internal anatomy can be observed (mainly the skeleton, but if contrast material is given, the kidneys, bowels, bladder or esophagus can be visualized as well). The room is periodically darkened while the treatment fields are being set, and temporary marks may be made on the patient’s skin with magic markers. The radiation oncologist is 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 15 minutes to an hour or more, depending on the complexity of what is being planned. Once the aspects of the treatment fields are satisfactorily set, x-rays representing the treatment fields are taken. In most centers, the patient is given multiple “tattoos” to mark the treatment fields and replace the marks previously made with magic markers. These tattoos are not elaborate and consist of no more than pinpricks followed by ink, appearing like a small freckle. Tattoos enable the radiation technologists 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, which contains a linear accelerator focused on a patient table similar to the one in the simulation 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.
A typical course of radiation therapy for ovarian cancer would entail daily radiation treatments, Monday through Friday, for 3 to 5 weeks. This may vary depending on individual circumstances. The actual treatment with radiation generally lasts no more than a few minutes, during which time the patient is unlikely to feel any discomfort. Anesthesia is not needed for radiation treatments and 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 to overexert themselves.
Side Effects and Complications
The majority of patients are able to complete radiation therapy for ovarian cancer without significant difficulty. Side effects and potential complications of radiation therapy are limited to the areas that are receiving treatment with radiation. The chance of a patient experiencing side effects, however, is highly variable. A dose that causes some discomfort in one patient may cause no side effects in other patients. In patients who undergo one or more surgical operations, bowel obstruction may occur. If side effects occur, the patient should inform the technologists and radiation oncologist, because treatment for these side effects is almost always available and effective.
Radiation therapy to the abdominal/pelvic area may cause diarrhea, abdominal cramping or increased frequency of bowel movements or urination. These symptoms are usually temporary and resolve once the radiation is completed. Occasionally, abdominal cramping may be accompanied by nausea. It is not unusual for some patients to note changes in sleep or rest patterns during the time they are receiving radiation therapy and some patients will describe a sense of tiredness and fatigue.
Blood counts can be affected by radiation therapy. In particular, the white blood cell and platelet counts may be decreased. This is dependent on how much bone marrow is in the treatment field and whether the patient has previously received or is currently receiving chemotherapy. These changes in cell counts are usually insignificant and resolve once the radiation is completed. However, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments.
Late complications are infrequent following radiation treatment of ovarian cancer. Potential complications do include bowel obstruction, ulcers, or cancers caused by the radiation. The probabilities of these late complications are also affected by previous extensive abdominal or pelvic surgery, radiation therapy and/or concurrent chemotherapy.
Adjuvant Radiation Therapy
It is important to understand that many patients with ovarian cancer already have small amounts of cancer that have spread into the lymph nodes and cannot be detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and the potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy and/or biologic therapy.
Adjuvant radiation therapy administered after surgery was frequently used before effective chemotherapy was developed. Adjuvant radiation has largely been replaced by adjuvant chemotherapy. However, the combination of chemotherapy and radiation therapy following surgical removal of the cancer may help prevent cancer recurrences.
Austrian researchers treated 64 women with advanced ovarian cancer who underwent surgery and chemotherapy treatment with Paraplatin®, Ellence®, and prednimustine. After this initial treatment, 32 women who had no remaining detectable cancer were assigned to receive either no further treatment or radiation therapy. The radiation therapy regimen consisted of the delivery of high-energy rays to the whole abdominal area, with additional treatment to the pelvis and para-aortic areas, over a period of 4 weeks. After 2 years, 31% of the women who had received radiation therapy and 44% of those who had not received radiation therapy had experienced a recurrence. After 5 years, 51% of those who had received radiation therapy and 74% of those who did not experienced a recurrence. The 2-year survival rates were 87% in women who received radiation therapy and 61% in those who had not. The 5-year survival rates were 59% for the radiation therapy group and 33% for the group having chemotherapy only. This clinical trial suggests that the additional use of radiation therapy following surgery and platinum-based chemotherapy may reduce the risk of cancer recurrence and prolong survival compared to chemotherapy alone.
Palliative Radiation Therapy
The goal of palliative therapy is to decrease cancer symptoms, such as pain , in order to improve a patient’s quality of life. Prior to the development of effective chemotherapy regimens for patients with ovarian cancer, whole abdominal radiation was frequently used to control ovarian cancer growth. In order to treat the entire abdomen, lower than normal total doses of radiation therapy were used.
When chemotherapy-resistant ovarian cancers are relatively localized, they can be palliatively treated with large doses of radiation. In other instances, cancer may have invaded critical areas such as the spinal cord and can cause considerable symptoms such as pain or weakness. Radiation therapy in these instances is usually effective in “palliating” the symptoms. The radiation oncologist usually selects a dose that is expected to be effective, but is also under the tolerance of the nearby normal tissues and organs. The radiation oncologist will also take into account whether chemotherapy is being administered.
Researchers in Pittsburgh recently treated 16 women who had recurrent, platinum-resistant ovarian cancer. All patients received high-dose (or high-fraction) radiation therapy, which was delivered once or twice per day, to the entire abdominal area. This regimen was relatively convenient for the patients, and the high doses allowed more cancer cells to be destroyed. All women experienced relief from their symptoms, including 5 who had complete pain relief and 7 who had partial pain relief. Thirty-one percent also experienced shrinkage of the cancer and most patients reported an improvement in their quality of life. The average duration of the response to treatment was 22 weeks, and the average survival time was 3 months. The main side effects of the treatment were nausea and vomiting, which lasted for 1 to 2 days.
These results indicate that short courses of high-dose radiation therapy to the entire abdominal area may help relieve pain and other symptoms and improve quality of life for women with recurrent platinum-resistant ovarian cancer.
Strategies to Improve Treatment
The progress that has been made in the treatment of ovarian cancer has resulted from improved development of adjuvant chemotherapy treatments and from participation in clinical studies. Future progress in the treatment of ovarian cancer will result from continued participation in appropriate studies. There are several areas of active exploration utilizing radiation therapy to improve the treatment of ovarian cancer.
Consolidative Adjuvant Radiation Therapy: Some clinical centers continue to evaluate whether the addition of radiation therapy to chemotherapy can improve the cure rates achieved with primary chemotherapy alone. Some clinical trials have suggested that the additional use of radiation therapy following surgery and platinum-based chemotherapy may reduce the risk of cancer recurrence and prolong survival compared to chemotherapy alone; therefore, additional trials are ongoing to determine the optimal method of combining chemotherapy and radiation and to confirm the benefits of adjuvant radiation chemotherapy.
Intraperitoneal Radioactive Isotopes: Radiation therapy can also be administered by placing an isotope into the area of the cancer or in the area where micrometastasis (unseen cancer) is suspected. This is also called intracavitary radiation treatment. Isotope therapy does not penetrate very deeply and can only be used for treatment of cancer cells on the surface of the lining of the abdomen and pelvis. Researchers are evaluating radioactive isotopes linked to monoclonal antibodies that “home” to ovarian cancer cells when injected into the abdomen. This is a promising new approach for treatment of ovarian cancer that grows predominantly around the cells lining the abdomen and on the surface of the large and small bowels.
Palliative Radiation: Doctors are evaluating shortened courses of radiation therapy to provide optimal relief from symptoms of recurrent cancer with minimal inconvenience. For example, a single radiation dose of 700 cGy or 4 doses given of 300 c/Gy given twice a day have been utilized. This mode of radiation therapy is convenient and the larger doses increase the number of cancer cells killed. Symptomatic improvement occurred in all 16 patients treated with this program. Thirty-one percent of patients experienced shrinkage of cancer. The average duration of improvement was 22 weeks. The main side effects were nausea and vomiting for 1-2 days. There was improvement in the quality of life in most patients but not in those who were the most incapacitated by their cancer. These doctors concluded that a short, intense course of radiation therapy to the entire abdomen provided palliation for some patients with chemotherapy resistant ovarian cancer.
Ethyol®: Because radiation therapy produces significant side effects, there is great interest in developing compounds that protect normal cells from radiation damage. Ethyol® is a compound that protects some organs from side effects of radiation and chemotherapy and has been approved by the Food and Drug Administration for use in selected situations where radiation or Platinol® chemotherapy is administered. Clinical trials continue to evaluate the use of Ethyol® with radiation and other chemotherapy agents in patients with advanced ovarian cancer.
1 Armstrong, D. “Ovaries and fallopian tubes.” In: Abeloff MD ed. Abeloff’s Clinical Oncology, 4th ed. Philadelphia: Churchill Livingstone; 2008: 1827-50.