Importance of Radiotherapy Timing and Resection Margin Status for Postoperative Radiotherapy in Extremity STS

Abstract

It is well known that adjuvant radiotherapy (RT) improves local control in extremity STS (STS) patients because it is difficult to obtain adequate surgical margin while conserving function. However, the treatment options are still debatable due to some practical problem such as lack of multi-disciplinary approach. The aim of this study was to analyze whether the treatment outcome of extremity STS differs by resection margin status and RT timing who received conserving surgery and postoperative RT. A total of 260 extremity STS patients who treated with conserving surgery and postoperative RT between January 1981 and June 2017 were included in this study. Patients who received amputation or palliative RT were excluded. We classified the surgical resection margin status into three groups using the R classification; R0, R1, R2 margin. We also categorized the timing of RT into two; Immediate and delayed RT. Immediate RT was defined as planned RT after the first conserving operation of STS. We defined delayed RT as RT performed after re-operations for several times due to local recurrence. The primary end point was local control (LC). Progression free survival (PFS) was also evaluated. In addition, propensity score matching was performed to balance the characteristics between the two groups; immediate RT group, delayed RT group. The LC rate and PFS were evaluated using Kaplan-Meier curves, and log-rank test for statistical significance. P values less than 0.05 were considered statistically significant. The LC and DFS were significantly worse for patients with R2 resected tumor comparing with R0 or R1 resected group (5-year LC R0: 84.8%, R1: 80.3%, R2: 62.0%, p < 0.001; 5-year DFS R0: 68.9%, R1: 60.8%, R2: 43.1%, p = 0.001). In regard to timing of RT, the adjuvant RT group (81.9%) showed better LC than salvage RT group (66.8%, p = 0.002). Through the subgroup analysis, the R1 resection group showed the biggest difference of LC between adjuvant RT group (85.6%) and salvage RT group (49.1%, p < 0.001). Among the patients received adjuvant RT, the LC of R1 group (85.6%) was comparable to R0 group (89.5%, p = 0.738). Concordant with LC results, adjuvant RT (64.8%) showed better DFS than salvage RT (44.7%, p= 0.007) The difference of 5-year DFS was significant between adjuvant RT (65.2%) and salvage RT (20.7%) for R1 resected group (p < 0.001) and among adjuvant RT group, R0 (66.2%) and R1 (65.2%) group showed comparable results (p = 0.844). The resection margin status was well correlated with LC and DFS. For timing of RT, the adjuvant RT showed better LC and DFS than salvage RT group. Following these results, R0 resection group and R1 resection group showed comparable LC and DFS when adjuvant was performed.