Pre-Operative Radiotherapy in STS: Does Downsizing Matter?

Abstract

Soft tissue sarcomas (STS) are a rare but insidious tumor that arises from mesenchymal tissue. Preoperative RT, followed by resection, is routinely used in extremity and truncal STS. The impact of RT on tumor volume and implications for prognosis is a great concern for patients, as changes in volume is often perceived as a reflection of treatment response. To date, data between tumor volume changes after RT and overall survival (OS) and distant metastasis-free survival (DMFS) in STS is sparse. In this study, we investigate changes in tumor volume after preoperative RT and its impact on OS and DMFS. Between 2000 and 2022, patients with stage I-III primary sarcoma of the extremity or trunk treated with pre-operative RT and wide resection were retrospectively reviewed from a prospective repository. Tumors were contoured using T2 sequences on MRIs within 2 weeks of initiation of RT and within 4 weeks post-RT. Tumor volume was determined using the medical image merge software. Univariate analysis (UVA) was performed using the log-rank test. Multivariate analysis (MVA) was performed using the Cox proportional hazards model. One hundred thirty-two patients had both pre- and post-RT MRIs available for contours. Median follow-up was 6 years. Median age at diagnosis was 56 years (range = 19-92). Most patients had stage III (73%) disease in the lower extremity (75%). The most common histology was undifferentiated sarcoma (30%). Median dose was 50 Gy in 25 fractions. Chemotherapy was administered in 44 (33%) patients. Median tumor volume prior to and after RT was 198 cc (range = 7.49 - 3899.87) and 225.21 cc (range = 0-9879.2), respectively. A decrease in tumor volume was seen in 90 patients (68%) from pre- to post-RT. In these patients, the mean percent change was -35%. Forty-two patients had an increase in tumor volume post-RT with a mean percent change of 56%. Overall local control was 98%. The 2- and 5-year OS were 89% and 76%, respectively. The 2- and 5-year DMFS was 76% and 70%, respectively. On UVA, increased age (p < 0.001), KPS ≤80 (p = 0.002), and smokers (p = 0.009) were associated with decreased OS. No variables were associated with DMFS. On MVA, age (p = 0.01) was associated with decreased OS and female gender (p = 0.03) and high-grade disease was associated with decreased DMFS (p = 0.04) Change in tumor volume did not impact OS (p = 0.15) or DMFS (p = 0.75). The 2- and 5-year DMFS for patients with a decrease in tumor volume was 79% and 71%, respectively. The 2 and 5-year DMFS for patients with an increase in tumor volume was 77% and 70%, respectively. The 2- and 5-year OS for patients with a decrease in tumor volume was 92% and 80%, respectively. The 2 and 5-year OS for patients with an increase in tumor volume was 83% and 69%, respectively. Change in tumor volume did not significantly impact OS and DMFS. Further studies with an increased sample size are warranted to corroborate these findings, however these results may assuage patient anxieties about the perceived tumor response to RT.