The effect of delayed postoperative irradiation on local control of soft tissue sarcomas of the extremity and torso

Purpose: The impact of delayed adjuvant radiotherapy in patients treated by surgical resection for peripheral or torso soft tissue sarcoma has not been well characterized. We retrospectively examined this issue in an institutional patient cohort. Methods and Materials: One hundred two adult patients were treated at the University of Washington Medical Center between 1981 and 1998 with postoperative radiotherapy for cure of a newly diagnosed soft tissue sarcoma. Of this group, 58 patients had primary intermediate- or high-grade disease of the extremity or torso (50 extremity/8 torso). Tumor histology was predominantly malignant fibrohistiocytoma, synovial cell sarcoma, and leiomyosarcoma. The group was dichotomized according to time interval from definitive resection to the start of adjuvant radiation. Twenty-six patients had a short delay, defined as <4 months, and 32 patients had a long delay of ≥4 months. Both groups were balanced with regard to site, size, margin status, and tumor depth; however, the long-delay group had a larger proportion of high histologic grade lesions and was treated more frequently with chemotherapy (31/32 [97%] for long-delay patients vs. 14/26 [54%] for short-delay patients). Median follow-up was 49.5 months (range: 7-113 months). Median follow-up for patients still alive was 54 months (range: 9-113 months). Survival outcomes were estimated by the Kaplan-Meier method. Results: Overall local relapse-free survival at 5 years from the time of definitive resection was 74%. On univariate analysis, estimated 5-year local relapse-free survival was significantly improved in the short-delay group (88% vs. 62% for the long-delay group, p = 0.048 by log rank). Overall distant relapse-free survival, disease-free survival, and overall survival at 5 years were 77%, 68%, and 86%, respectively. These survival outcomes were statistically equivalent in both radiation delay groups. There was no evidence to suggest that delaying adjuvant systemic therapy for postoperative radiation negatively impacted distant relapse-free survival, disease-free survival, or overall survival. Patterns of failure analysis revealed that 11/12 disease failures in the long-delay group had a local component, with five patients presenting with solitary local recurrences. Severe chronic radiation-related soft tissue or peripheral nerve morbidity was infrequent (5/58 or 8.6%) and similar in both groups.Conclusions: Postoperative radiation delays of 4 months or greater were associated with inferior local disease control for intermediate- and high-grade soft tissue sarcomas of the extremity and torso. Our results suggest that timing postoperative radiation before postoperative chemotherapy may optimize local therapy for such patients without adversely affecting distant disease control, long-term morbidity, or overall survival. Prospective testing of this hypothesis is warranted.