Twenty-five year outcome of sequential abdominal radiotherapy and melphalan:implications for future management of epithelial carcinoma of the ovary

Abstract

Objective: The purpose of the present study is evaluation of the long-term efficacy of sequential abdominopelvic radiotherapy and melphalan in the management of ovarian carcinoma.

Methods: From 1970 to 1976, 94 women with stages I-III epithelial ovarian carcinoma enrolled in a prospective nonrandomized clinical trial were prescribed 20 Gy to the upper abdomen and 50 Gy to the pelvis followed by courses of melphalan (1 mg/kg/course). Primary endpoints were survival, recurrence, and toxicity.

Results: There were 19 stage I, 25 stage II, and 50 stage III patients. For all stages, overall survival was 42% at 5 years, 30% at 10 years, and 17% at 25 years. Median follow-up of the survivors was 24 years. Disease-free survival was 48% at 5 years and remained at 45% from 10 to 25 years. All but two recurrences occurred within the first 27 months. No recurrence or treatment-related death occurred after 8 years. No recurrence was salvaged. All but one initial recurrence was within the peritoneal cavity. Of the 31 patients undergoing a second-look surgical procedure, 84% were free of tumor. Only 8% of patients recurred after a negative second look. Stage and the presence of palpable postoperative disease were significant prognostic factors. Disease-free survivals were 95% from 5 to 25 years for stage I, 70% at 5 years and 60% at 25 years for stage II, and 20% from 5 to 25 years for stage III (P < 0.0001). Although no patient with postoperative palpable tumor was cured, 25% lived beyond 2 years. Stage III patients without postoperative palpable tumor achieved a 47% 25-year disease-free survival. Acute toxicity was acceptable, and 98% of patients completed radiation therapy. Chronic toxicity included a 12% small bowel obstruction rate and a 3% fatal second malignancy/hematological toxicity rate (two cases of acute myelocytic leukemia, one case of thrombocytopenia).

Conclusions: The long-term disease-free survival obtained with abdominopelvic radiotherapy followed by single alkylating agent chemotherapy has not been exceeded by three subsequent decades of multiagent chemotherapy trials. Abdominal radiotherapy may be useful to consolidate complete responses following therapy multiagent chemotherapy, particularly with the upper abdominal dose escalation provided by intensity modulated radiation therapy and possibly in conjunction with chemotherapy.