Local control and complications after radiation therapy for primary orbital lymphoma: a case for low-dose treatment.

Orbital involvement at the time of initial presentation is unusual in non-Hodgkin's lymphoma. In an effort to identify potential ways of improving the radiotherapeutic management of this disease, the records of 22 patients were reviewed retrospectively. All had biopsy-proven orbital non-Hodgkin's lymphoma, and the minimal, median, and maximal durations of follow-up in surviving patients were 4.8 years, 7.0 years, and 17.4 years, respectively. Permanent local control was achieved in 21 of the 22 patients (96%). Complications were scored according to a grading scheme in which grade 1 was the least significant complication and grade 4 was blindness as a result of radiation therapy. Of the 12 patients who received a radiation dose less than 35 Gy, 6 developed a grade 1 or grade 2 complication. Of the 10 patients treated with greater than or equal to 35 Gy, 6 experienced a complication, 1 of whom had a grade 4 complication resulting in blindness and another who developed a severe keratitis, which was scored as a grade 3 complication resulting in decreased visual acuity. At last follow-up, 10 patients were alive at 4.8 to 17.4 years after completion of radiation therapy, 4 had died of intercurrent disease at 3 months to 10.6 years, and 8 had died of disease at 3 months to 15.8 years. Actuarial survival for the entire group was 75% at 5 years and 48% at 10 years. Survival in patients with Stage I AE disease (lymphoma confined to orbit) at presentation was 87% at 5 years and 50% at 10 years, and survival in patients with Stage II A through Stage IV disease was 36% at 5 years and at 10 years. Primary orbital lymphoma is an indolent disease characterized by prolonged survival after radiation therapy. Excellent local control can be achieved with radiation doses of 20 Gy to 35 Gy. Higher doses may result in an increased risk of complications.

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis.

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years.

Spinal cord astrocytoma: pathological and treatment considerations.

Seventy-nine patients underwent surgery, with or without radiation therapy, for astrocytoma of the spinal cord. There were 43 tumors (54%) classified as pilocytic astrocytoma and 25 (32%) as diffuse fibrillary astrocytoma. Eleven tumors (14%) could not be classified other than as astrocytoma, "type not otherwise specified." The 10-year overall survival rate for all 79 patients was 50% but significantly differed by histological type: 81% for patients with pilocytic astrocytoma compared to 15% for those with diffuse fibrillary astrocytoma. Tumor grade by the Kernohan, et al., or St. Anne-Mayo methods was also a significant predictor of survival in patients with diffuse fibrillary astrocytoma. The extent of surgical resection (biopsy vs. subtotal resection vs. gross total resection) did not significantly impact survival among patients with pilocytic or nonpilocytic astrocytomas of the spinal cord, although there was a trend toward poorer survival in patients undergoing some degree of resection as opposed to biopsy. Postoperative radiation therapy improved survival but did so more for diffuse fibrillary astrocytoma than pilocytic astrocytoma. In this series, histological type was the most significant predictor of survival in patients with astrocytoma of the spinal cord. The survival rate was highest in patients who underwent biopsy followed by postoperative radiation therapy.

The interaction of etoposide with radiation: variation in cytotoxicity with the sequence of treatment.

Etoposide is commonly used in combination with radiation but the best method of integrating these two treatment modalities is not known. In this study, the interaction of etoposide and radiation was investigated using V79 hamster lung fibroblast cells. It was discovered that etoposide (0.25 microgram/ml) was a dramatic radiosensitizer if it was given for a 24 hour exposure after radiation. If the cells were exposed to the same concentration of etoposide for 24 hours prior to radiation, minimal or no radiosensitization occurred. Radiosensitization correlated with a prolongation of the radiation-induced G2 cell cycle arrest. These initial studies indicate that the sequence of radiation and etoposide treatments is important in order to maximize cytotoxicity in V79 cells. Further work using human cell lines will be required to determine the clinical applications of this discovery.