doi:10.1016/j.ijrobp.2004.09.010 CLINICAL INVESTIGATION Ovary CONSOLIDATIVE ABDOMINOPELVIC RADIOTHERAPY AFTER SURGERY AND CARBOPLATIN/PACLITAXEL CHEMOTHERAPY FOR EPITHELIAL OVARIAN CANCER ROBERT DINNIWELL, M.D.,* MICHAEL LOCK, M.D.,* MELANIA PINTILIE, M.SC., † ANTHONY FYLES, M.D.,* STEPHANE LAFRAMBOISE, M.D., § DENNY DEPETRILLO, M.D., § WILFRED LEVIN, M.D.,* LEE MANCHUL, M.D.,* JOAN MURPHY, M.D., § AMIT OZA, M.D., ‡ BARRY ROSEN, M.D., § JEREMY STURGEON, M.D., ‡ AND MICHAEL MILOSEVIC, M.D.* *Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, and Departments of † Clinical Study Coordination and Biostatistics, ‡ Medical Oncology, and § Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada Purpose: To assess the feasibility and morbidity of sequential cytoreductive surgery, carboplatin/paclitaxel chemotherapy, and consolidative abdominopelvic radiotherapy (APRT) in ovarian cancer. Methods and Materials: Between 1998 and 2000, 29 patients with optimally cytoreduced epithelial ovarian cancer were treated with carboplatin (135 mg/m 2 ) and paclitaxel (area under the curve [AUC] of 6) followed by APRT in a prospective protocol. All patients were clinically, radiographically, and biochemically (CA-125) free of disease at the completion of chemotherapy. Abdominopelvic radiotherapy was delivered using 6 MV anterior- posterior photon fields to encompass the peritoneal cavity. Median follow-up was 4 years. Results: Two patients experienced Radiation Therapy Oncology Group Grade 3 gastrointestinal toxicity during APRT; 6 patients, Grade 3 or 4 neutropenia; and 3 patients, Grade 3 or 4 thrombocytopenia. Overall, 10 patients had Grade 3 or 4 acute toxicity. All of the acute side effects resolved after treatment was completed, and there were no serious consequences such as sepsis or hemorrhage. Abdominopelvic radiotherapy was abandoned prematurely in 3 patients. Late side effects were seen in 5 patients, including 1 small bowel obstruction, 2 symptomatic sacral insufficiency fractures, 1 case of severe dyspareunia, and 1 case of prolonged fatigue. All resolved with supportive management. The 4-year actuarial disease-free survival was 57%, and the overall survival was 92%. Eleven of 12 patients who relapsed received salvage chemotherapy, which was well tolerated. Conclusions: Abdominopelvic radiotherapy after optimal surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late side effects and does not limit subsequent salvage chemo- therapy. Consolidative APRT warrants further investigation as a means of improving the outcome of patients with ovarian cancer. © 2005 Elsevier Inc. Ovarian cancer, Chemotherapy, Radiotherapy. INTRODUCTION Ovarian cancer is the fifth leading cause of cancer death among U.S. women and has the highest mortality rate of all gynecologic cancers (1). The majority of patients present with Stage III or IV disease and have a poor prognosis. Chemotherapy with platinum and paclitaxel is the standard of treatment after laparotomy, surgical staging, and resec- tion of abdominal and pelvic disease (2, 3). Unfortunately, despite advances in initial surgery and chemotherapy, many patients will have recurrence in the abdomen or pelvis that frequently is not responsive to further chemotherapy and carries an ominous prognosis (4). Therefore, treatments that improve initial disease control in the abdomen and pelvis have the potential to extend the progression-free interval and possibly also survival. Abdominopelvic radiotherapy (APRT) has long been rec- ognized as an effective adjuvant treatment for women with early-stage optimally debulked ovarian cancer (5) that spe- cifically targets the anatomic sites at highest risk. A ran- domized study of APRT in the pre– chemotherapy era dem- onstrated improved survival relative to pelvic radiotherapy and chlorambucil (6). In general, APRT has not been advo- cated as postoperative treatment for patients with residual disease in the upper abdomen, because the radiation dose that can safely be delivered to this region is limited by the radiation tolerance of the small bowel, kidneys, and liver. Reprint requests to: Michael Milosevic, M.D., Radiation Med- icine Program, Princess Margaret Hospital, 610 University Ave- nue, Toronto, ON M5G 2M9, Canada. Tel: (416) 946-2124; Fax: (416) 946-6566; E-mail: mike.milosevic@rmp.uhn.on.ca Presented as an oral presentation at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, November 2002, in New Orleans, LA. Received Nov 25, 2003, and in revised form July 13, 2004. Accepted for publication Sep 7, 2004. Int. J. Radiation Oncology Biol. Phys., Vol. 62, No. 1, pp. 104 –110, 2005 Copyright © 2005 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/05/$–see front matter 104