M. H. Squires1, L. Suarez-Kelly1, P. Y. Yu1, T. M. Hughes1, R. Shelby1, C. G. Ethun2, T. B. Tran3, G. Poultsides3, J. Charlson4, T. Gamblin4, J. Tseng5, K. K. Roggin5, K. Chouliaras6, K. Votanopoulos6, B. A. Krasnick7, R. C. Fields7, R. E. Pollock1, V. Grignol1, K. Cardona2, J. Howard1 1Ohio State University,Division Of Surgical Oncology,Columbus, OH, USA 2Emory University School Of Medicine,Division Of Surgical Oncology,Atlanta, GA, USA 3Stanford University,Department Of Surgery,Palo Alto, CA, USA 4Medical College Of Wisconsin,Division Of Surgical Oncology,Milwaukee, WI, USA 5University Of Chicago,Department Of Surgery,Chicago, IL, USA 6Wake Forest University School Of Medicine,Department Of Surgery,Winston-Salem, NC, USA 7Washington University,Department Of Surgery,St. Louis, MO, USA
Introduction: In the randomized controlled trial (RCT) EORTC-62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We sought to evaluate whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at 7 academic referral centers.
Methods: The US Sarcoma Collaborative (USSC) database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000-2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded.
Patients were divided by treatment era into early (2000-2011, pre-EORTC trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy delivery, standard demographics, and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses (MVA) were used to determine factors associated with OS and RFS.
Results: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% vs 14.6%; p=0.73). Patients within the early and late cohorts demonstrated similar median OS (128 mos vs median not reached [MNR], p=0.84) and RFS (107 mos vs MNR, p=0.94).
Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 vs 8.9cm, p<0.001), younger age (53.3 vs 63.7 yrs, p<0.001), margin-positive resection (p=0.04), and receipt of adjuvant radiation (p<0.001).
On MVA, risk factors associated with decreased OS (Table 1) were increasing ASA class (p=0.02), increasing tumor size (p<0.001), and margin-positive resection (p=0.01). Adjuvant chemotherapy was not associated with OS (p=0.88). Risk factors associated with decreased RFS included increasing tumor size (p<0.001) and margin-positive resection (p=0.04); adjuvant chemotherapy was not associated with RFS (p=0.22).
Conclusion: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the USSC, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC-62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts, but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age, than by prospective, randomized data.
