Impact of Pathological Response to Preoperative Radiotherapy in Soft Tissue Sarcoma

Abstract

<h3>Purpose/Objective(s)</h3> The therapeutic response of soft tissue sarcoma (STS) to neoadjuvant treatment has been associated with improved margin status, disease control, and survival. Given the rarity of this disease and the confounding effects of chemotherapy, this study analyzes whether the pathological necrosis rate (PN) of preoperative radiation (RT) alone is associated with improved clinical outcomes for STS. <h3>Materials/Methods</h3> An IRB retrospective review was conducted on a database of 315 patents treated at our institution between 1987 and 2015 who received neoadjuvant RT alone followed by surgical resection, of which 203 had documented PN. Time to event outcomes estimated via Kaplan-Meier included overall survival (OS), progression-free survival (PFS), time to loco-regional failure (TTLRF), and time to distant failure (TTDF). Cox regression analyses were performed to determine prognostic variables associated with clinical outcomes. <h3>Results</h3> With a median follow up of 87 months, 157 patients (77%) obtained a clear resection margin (R0). The average PN rate was 56% and 37 patients (18%) achieved a PN≥95%. PN was significantly higher for R0 (vs. R1) resection (70% vs. 45%, <i>P</i> = 0.014) and achieving a PN≥95% was associated with an R0 resection (<i>P</i> = 0.057). PN≥95% was associated with a 5-year non-significant benefit in TTLRF (94% vs 86%, <i>P</i> = 0.274) and TTDF (70% vs 45%, <i>P</i> = 0.130), which translated to a significant 5-year PFS benefit (65% vs. 45%, <i>P</i> = 0.036). R0 margin status was associated with a 5-year TTLRF improvement (91% vs 80%, <i>P</i> = 0.046). On multivariate analysis, PN ≥95% independently associated with PFS (HR 0.4, 95% CI 0.2-0.8, <i>P</i> = 0.015), and achieving an R0 resection was independently associated with improved PFS (HR 0.5, 95% CI 0.30-0.83, <i>P</i> = 0.007) and OS (HR 0.52, 95% CI 0.29-0.91, <i>P</i> = 0.027). <h3>Conclusion</h3> Therapeutic response to preoperative radiation alone is associated with improved surgical margin status and clinical outcomes in STS. Achieving PN ≥95% independently predicts for a higher PFS and contributes to improved negative margin resection rate which was associated with improved local control, PFS, and OS. Future prospective studies are required to validate the relationship between pathologic response to radiation and outcome, and to elucidate the potential mechanisms for distant control and PFS benefit.