A Phase 2 Trial of Five-Day Neoadjuvant Radiation Therapy for Patients with High-Risk Primary Soft Tissue Sarcoma

Purpose: In a single-institution phase II study, we evaluated the safety of a five-day dose-equivalent neoadjuvant radiation therapy (RT) regimen for high-risk primary soft tissue sarcoma (STS). Methods: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late radiation toxicity. Major wound complications, local recurrences and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization. Results: Over two years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline single nucleotide polymorphisms in miRNA binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared to the preceding two-year period, the number of patients treated with neoadjuvant RT alone at our institution increased three-fold, with a concomitant increase in the catchment area. Conclusions: A shorter five-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after two years follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.