Comparison of Pathologic Tumor Necrosis of Conventional Versus Ultrahypofractionated Preoperative Radiation Therapy in Localized Extremity Soft Tissue Sarcoma and Its Correlation With Clinical Outcomes

Abstract

Purpose: We aimed to determine if ultrahypofractionated radiation therapy (UHYPO-RT) delivering 6 Gy x 5 fractions yields similar tumor necrosis compared with conventional radiation therapy (CONV-RT) with 2 Gy x 25 fractions in soft tissue sarcoma. The clinical significance of tumor necrosis on loco-regional recurrence-free survival (LRFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed.

Methods and materials: Patients with localized soft tissue sarcoma treated with CONV-RT or UHYPO-RT followed by surgery were included. Good response was defined as tumor necrosis ≥90%, and poor response as <90%. The Mann-Whitney U test compared median tumor necrosis. χ² analysis was used for categorical variables. The Kaplan-Meier function estimated LRFS, DDFS, and OS.

Results: A total of 64 patients received CONV-RT, and 45 received UHYPO-RT. The median tumor size was 7.0 cm, with the lower extremity being the most common site (55%). Myxofibrosarcoma (39%) and undifferentiated pleomorphic sarcoma (16%) were the most frequent histologies. The median time from radiation therapy to surgery was 35 days. There was a significant difference in median tumor necrosis between CONV-RT and UHYPO-RT, with rates of 40% and 60%, respectively (P = .022). Patients receiving UHYPO-RT had a higher percentage of tumor necrosis at the 90% cutoff, achieving 27% compared with 6% for CONV-RT (P = .003). At a median follow-up of 32 months, 12 patients (9%) experienced loco-regional recurrence, 24 patients (19%) faced distant failure, and 19 patients (15%) died of metastatic disease. Patients with <90% necrosis had higher rates of loco-regional (13% vs 0%, P = .207) and distant failure (25% vs 0%, P = .021). Three-year LRFS was 86% for <90% necrosis and 100% for ≥90% necrosis (P = .160). DDFS was 75% for <90% necrosis versus 100% for ≥90% (P = .036). OS rates were 79% and 93%, respectively (P = .290).

Conclusions: Preoperative RT with UHYPO-RT was associated with a higher rate of tumor necrosis ≥90% than CONV-RT. Our data suggest that more extensive necrosis is associated with better clinical outcomes.