Hypofractionated Preoperative Radiation Therapy for Extremity and Superficial Trunk Soft Tissue Sarcomas: Results of a Prospective, Phase 2 Trial

Abstract

Purpose: Preoperative radiation therapy (RT) for resectable extremity soft tissue sarcomas has historically been delivered over 5 weeks and associated with a 35% major wound complication (WC) rate. We investigated the rate of WC in a cohort of soft tissue sarcoma patients treated with a moderately hypofractionated course of preoperative RT.

Methods and materials: MC1973 was a single-arm, prospective, phase 2, noninferiority trial completed at Mayo Clinic in Minnesota and Arizona. We administered preoperative RT to 42.75 Gy in 15 fractions. Patients underwent standard of care tumor resection afterward. The primary endpoint was a major WC occurring within 120 days of surgery. Wilcoxon Rank Sum tests, Fisher Exact tests, and Conchran-Armitage Trend tests were used to evaluate associations with WC. Kaplan-Meier analysis was used to report early survival-associated outcomes.

Results: Between November 24, 2020 and January 30, 2024, 120 patients enrolled on trial. One patient withdrew before receiving treatment. Most common tumor location was proximal lower extremity (48.7%). After RT, 117 patients (97.5%) underwent tumor resection. Two patients treated with RT came off study before surgery because of death. A major WC developed in 27 of 117 patients (23.1%). Median time to WC resolution was 17.4 weeks. The rate of persistent WC at 6 months was 26%. On univariate analysis, leiomyosarcoma histology (n = 5) correlated with a higher WC rate (60%). Median follow-up was 21.1 months. Fourteen patients experienced acute grade 3 adverse events. One year disease-free survival was 86.0% (95% CI, 79.7%-92.9%). Two patients developed local recurrence. One fracture was observed.

Conclusions: The major WC rate was 23.1% with a preoperative regimen of 42.75 Gy in 15 fractions. This suggests moderate hypofractionation is not inferior compared with historical standards of major WC rate. Additional follow-up will allow evaluation of oncologic outcomes, long-term treatment-associated adverse events, and patient-reported outcomes.