BACKGROUND: Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd). METHODS: Thirty-seven patients with large sarcomas of the head and neck, mediastinum, retroperitoneum, or extremity received three or five cycles of sequential IdUrd infusion (1000-1600 mg/m2/d x 5 d) alternating weekly with twice daily radiation (125-150 cGy per dose) and were then evaluated for resection. The delivered preoperative radiation dose was up to 6250 to 7500 cGy. RESULTS: Five patients (14%) had a partial response to preoperative therapy, and 28 of 37 patients underwent successful resection. There were no intra- or postoperative deaths. Local control was achieved in 19 of 28 resected patients, but in only 1 of 6 patients who remained unresectable despite therapy. With a median follow-up of 5.8 years, 28% of patients are alive with no evidence of disease, 17% are alive with disease, and 53% have died of their disease. CONCLUSIONS: Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy.
BACKGROUND: Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd). METHODS: Thirty-seven patients with large sarcomas of the head and neck, mediastinum, retroperitoneum, or extremity received three or five cycles of sequential IdUrd infusion (1000-1600 mg/m2/d x 5 d) alternating weekly with twice daily radiation (125-150 cGy per dose) and were then evaluated for resection. The delivered preoperative radiation dose was up to 6250 to 7500 cGy. RESULTS: Five patients (14%) had a partial response to preoperative therapy, and 28 of 37 patients underwent successful resection. There were no intra- or postoperative deaths. Local control was achieved in 19 of 28 resected patients, but in only 1 of 6 patients who remained unresectable despite therapy. With a median follow-up of 5.8 years, 28% of patients are alive with no evidence of disease, 17% are alive with disease, and 53% have died of their disease. CONCLUSIONS: Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy.
Authors: Shivaani Kummar; Larry Anderson; Kimberly Hill; Eva Majerova; Deborah Allen; Yvonne Horneffer; S Percy Ivy; Larry Rubinstein; Pamela Harris; James H Doroshow; Jerry M Collins Journal: Clin Cancer Res Date: 2013-02-12 Impact factor: 12.531