Clinical investigation: sarcoma
Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor

Presented at the 43nd Annual Meeting of the American Society for Therapeutic Radiology and Oncology, San Francisco, CA, November 6, 2001.
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Abstract

Purpose: Desmoplastic small round-cell tumor (DSRCT) is a rare, recently described intraperitoneal malignancy occurring predominantly in adolescent boys. Our objective was to evaluate the feasibility and outcome of whole abdominopelvic irradiation (WAPI) as part of a combined modality protocol for patients with DSRCT.

Methods and Materials: The records of all 21 patients treated with WAPI for DSRCT at our institution from 1992 to 2001 were retrospectively reviewed. Patients were treated on an institutional protocol with 7 cycles of an alkylator-based chemotherapy. After maximal surgical debulking, patients were treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 30 Gy.

Results: All 21 patients completed the prescribed treatment. The median follow-up was 28 months. The overall survival and relapse-free survival rate at 3 years was 48% and 19%, respectively. The median survival was 32 months, and the median time to relapse was 19 months. Most relapses were intraperitoneal and/or hepatic. Acute toxicities included Radiation Therapy Oncology Group Grade 2 upper and lower gastrointestinal toxicity in 81% and 71% of patients, respectively. All patients experienced acute hematologic toxicity, with Grade 4 thrombocytopenia, leukopenia, and anemia in 76%, 29%, and 33%, respectively. The major long-term toxicity was small bowel obstruction, which occurred in 7 patients (33%) after surgery and WAPI.

Conclusion: DSRCT is a rare and highly lethal disease, requiring aggressive multimodality therapy. WAPI is feasible in conjunction with intensive chemotherapy and surgery. Hematologic and gastrointestinal toxicities are expected but manageable with diligent supportive care. The long-term efficacy of this therapy remains disappointing, thus novel approaches are being investigated.

Introduction

Desmoplastic small round-cell tumor (DSRCT) is a rare, recently described, aggressive neoplasm with unique clinical, histologic, and biologic features 1, 2. It is primarily found in adolescent boys. Patients typically present with a bulky intraabdominal and/or pelvic, peritoneal-based mass (Fig. 1). More recently, extraserosal primary sites have also been reported 3, 4, 5, 6, 7. DSRCT belongs to the family of small, round, blue cell tumors of childhood, yet distinct characteristics distinguish it (8). The appearance of nests of tumor cells invested in a cellular desmoplastic stroma and polyphenotypic differentiation by immunohistochemistry is a classic finding for this entity (9). A novel reciprocal translocation, t(11:22)(p13:q12), has been identified in DSRCT that results in the fusion of the amino-terminus of the Ewing’s sarcoma gene (EWS) and the carboxy-terminus of the Wilms’ tumor gene (WT1) 10, 11, 12, 13, 14, 15. The EWS-WT1 chimeric transcript can be detected by cytogenetic analysis and polymerase chain reaction-based assays and is increasingly used to confirm the diagnosis 16, 17.

Clinically, these tumors are characterized by an extremely poor prognosis. Clinicopathologic studies and case reports have demonstrated rapid disease progression and a poor response to conventional chemotherapeutic regimens 8, 9, 18. Surgical debulking is limited by the diffuse nature of the peritoneal disease and direct visceral organ invasion 19, 20. The pattern of spread is similar to ovarian cancer, with dissemination throughout the serosal surfaces of the abdomen and pelvis. Because of this propensity for intraabdominal spread, whole abdominopelvic irradiation (WAPI) was introduced for consolidation after maximal surgical resection and to boost to areas of gross disease in the abdomen or pelvis.

The objective of this study was to retrospectively review our single institution experience with WAPI to evaluate its feasibility and role as part of a combined modality protocol for patients with DSRCT. This is the only known series to date reporting radiation techniques, toxicities, and outcomes of WAPI for this disease.

Section snippets

Methods and materials

Between 1992 and 2001, 21 patients were treated with WAPI for DSRCT at our institution. Four patients were included in a previous report 10, 21. Tissue diagnosis was determined by immunohistochemistry in all patients, and by polymerase chain reaction for the EWS-WT1 chimeric transcript in 15 patients. Pathologic specimens were centrally reviewed at our institution. All patients provided informed consent for treatment in accordance with institutional review board guidelines. The treatment plan

Patient characteristics

The patient age range was 8–34 years (median 16.5). The male/female ratio was 20:1. Of the 15 patients tested, polymerase chain reaction findings were positive for the EWS-WT1 chimeric transcript in 13 patients (87%). Fourteen patients were previously untreated and 7 had been referred to our institution for refractory or relapsed disease. All 21 patients were treated with at least 1 cycle of chemotherapy using the P6 regimen. Other chemotherapeutic agents, such as cisplatin, carboplatin,

Discussion

DSRCT remains a therapeutic challenge. Although it has gained recognition as a distinct entity among the small round-cell tumors of childhood on the basis of its unique clinical, histopathologic, immunophenotypic, and molecular genetic features, it is still a poorly understood neoplasm. The cell of origin in DSRCT is still unclear, although some investigators have proposed a “mesothelioblast” because of the serosal distribution and absence of a primary parenchymal site (23). The identification

Conclusion

The overall prognosis in DSRCT remains poor. Despite aggressive multimodality therapy, including intensive chemotherapy, surgical debulking, and EBRT, the treatment of patients with this rare and highly lethal disease is limited by its diffuse nature and chemoresistance. The results of this study demonstrate that WAPI is feasible in conjunction with intensive chemotherapy and surgery and, in exceptional cases, may contribute to a durable remission. Hematologic and GI toxicities are expected but

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