Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis

Abstract

Background Neoadjuvant radiotherapy (RT) is increasingly advocated in the management of soft tissue sarcoma (STS). Therefore, we sought to characterize the impact of neoadjuvant RT on rates of R0 resection and overall survival (OS) in extremity STS patients undergoing surgery. Methods From January 2003 to December 2012, we identified patients with a diagnosis of extremity STS from the National Cancer Database. After excluding patients with age < 18 years, not undergoing surgery, metastases at diagnosis, intraoperative RT, and missing/unknown data, we identified 27,969 patients. Using logistic regression and Cox-proportional hazard analysis, we compared rates of R0 resection among preoperative, postoperative and no RT cohorts and determined predictors of R0 resection and OS. Results The mean age was 59.5 (±17.1) years, and 45.9% were female. Median tumor size was 10.5cm. 51% of patients did not receive RT, 11.8% received pre-operative RT and 37.2% received post-operative RT. Rates of R0 resection for preoperative RT, postoperative RT, and no RT cohorts were 90.1%, 74.9%, and 79.9%, respectively (P<0.001). Independent predictors of achieving R0 resection included academic facility type (OR 1.36, 95% CI 1.20-1.55), histologic subtype, tumor size (OR 0.99, 95% CI 0.99-0.99), Charlson score (OR 0.92, 95% CI 0.84 – 0.99), and preoperative RT (OR 1.83, 95% CI 1.61-2.07). R0 resection as well as RT (pre-operative or post-operative) was associated with increased OS. Conclusions Pre-operative RT independently predicts higher rates of R0 resection in patients with extremity STS undergoing surgical resection. Negative surgical margins and pre-operative or post-operative RT are associated with improved OS.

Extremity soft tissue sarcoma in the elderly: Are we overtreating or undertreating this potentially vulnerable patient population?

“…Variables examined included sex, race, facility type, facility location, year of diagnosis, primary payor, income, urban/rural, distance to treatment, Charlson‐Deyo score, histology, grade, tumor size, surgical treatment, reason for no surgical treatment, surgical margins, inpatient length of stay, readmission rate, radiation therapy, radiation‐surgery sequence, chemotherapy, and 90‐day mortality. We grouped histologies into 22 separate subtypes based on ICD‐O3 codes . Overall survival (OS) was measured as the time from diagnosis to last contact or death, in months.…”

Limb‐sparing surgery plus radiotherapy results in superior survival: an analysis of patients with high‐grade, extremity soft‐tissue sarcoma from the NCDB and SEER

“…Of note, this study did not distinguish between preoperative and postoperative RT; furthermore, unlike the current study, this prior NCDB study could not assess SM due to lack of information on this endpoint in the NCDB . Another NCDB study also showed a benefit to either preoperative or postoperative RT combined with resection although type of surgery (LSS or amputation) was not analyzed . Several other studies have shown a survival benefit to combine surgery and RT compared to surgery alone; however, they did not distinguish between LSS and amputation and also included patients with truncal sarcomas …”

“…No significant difference in OS was seen between pre‐RT vs post‐RT in two SEER studies . An NCDB study showed improved rates of negative surgical margins in patients receiving preoperative RT compared to postoperative RT; however, survival between these two treatment strategies was not directly compared . In contrast, a study of the National Oncology Database showed a significant OS and cause‐specific survival benefit to preoperative RT compared to postoperative RT.…”

“…In contrast, three other SEER studies showed either no survival benefit for RT or a benefit only in patients with tumors >5 cm . Importantly, most of these studies did not contain data from the last decade, and all except two excluded patients treated with amputation or did not specify type of resection . Several SEER or smaller retrospective studies found no difference in survival or LC between preoperative and postoperative RT.…”

Adjuvant radiation for positive margins in adult head and neck sarcomas is associated with improved survival: Analysis of the National Cancer Database

“…Treatment recommendations for head and neck sarcomas tend to emerge from data collected from trials involving sarcomas of the extremities, despite the anatomical differences . One analysis of the National Cancer Database by Mahmoud found a reduction in hazard ratio by 37% with adjuvant radiation therapy for extremity and trunk soft tissue sarcoma; another by Gingrich found that both neoadjuvant and adjuvant radiation therapy for extremity soft tissue sarcoma increased overall survival . Ideally, these tumors would be managed with complete surgical resection .…”