The Role of Irradiation in the Treatment of Metastatic Trophoblastic Disease

Abstract

Since li et al. (1) first reported the effect of methotrexate upon choriocarcinoma, chemotherapy has become the standard treatment for metastatic trophoblastic disease. Although the literature now contains a large number of references to the treatment of this disease, those relating to radiation therapy are very sparse. Ezes et al. (2) in 1956 reported a good response to irradiation in a single case of pulmonary metastasis, and Bromley (3) has subsequently reported 5 cases apparently cured with a combination of surgery and radiation therapy plus one case treated with radiation only. None of these patients received any chemotherapy. The purpose of this paper is to report further experience with radiation therapy as a part of the overall treatment of trophoblastic disease. The patients for this study were drawn from the group of 108 patients admitted to the Endocrinology Branch, National Cancer Institute, the Clinical Center, National Institutes of Health, for treatment of metastatic trophoblastic disease.3 Of these, a total of 29 were referred for radiation therapy of some aspect of their disease. Methods Earlier in the clinical study of these patients, several fatal cerebral hemorrhages were observed in patients who were showing a good response to the chemotherapeutic agents. Since few of the agents used penetrate the blood-brain barrier in the therapeutic concentrations (5), patients with neurological symptoms were referred for irradiation of brain metastasis. At the onset of this study, it was not clear how radiation-sensitive the trophoblastic tumor might be since Ezes used a prolonged treatment schedule and did not report a tumor dose. The fact that tumors sensitive to the chemotherapeutic agents are in general responsive to irradiation suggested that this tumor should be quite sensitive. For this reason, a tumor dose of 2,000 R was chosen and maintained throughout the course of this study. This permitted us to treat neural tissue a second time without incurring an excessive risk of radiation injury. All the treatments for this study were administered with a 2 Mev Van De Graaff machine, generating an x-ray beam with a half-value layer of 7.5 mm of lead. This machine has an output of about 100 R per minute at a distance of 80 cm. The treatments were delivered with large fields, using generous margins at a rate of 200 R per day in most instances. In the case of the brain, no effort was made to limit therapy to the individual metastases, and most if not all of the brain was included in the treatment field. The vast majority of these patients received methotrexate as the primary form of treatment, but some of the later ones received Actinomycin D and a few other agents. The relation between the radiation therapy and chemotherapy was random. The radiation required several weeks which may or may not have overlapped one of the courses of chemotherapy. Results