Rethinking the Soft Tissue Sarcoma Paradigm for the Local Management of Extraskeletal Ewing Sarcoma

Abstract

It remains an unsettled debated as to whether the optimal local therapy for patients with extraskeletal Ewing sarcoma (EES) is combined modality surgery and RT (CMT) versus single modality local therapy (SMT) as is done for Ewing sarcoma arising in bone. Given our comparatively large experience managing patients with EES, we sought to evaluate outcomes of this rare disease and better define optimal local management strategies. We conducted a retrospective review of 60 consecutive patients who received treatment for localized EES at our institution between 1994 and 2018. Kaplan-Meier curves were used to estimate oncologic outcomes, and a Cox proportional hazards regression was conducted to identify associated factors. The median follow-up time was 74 months (m) (interquartile range [IQR], 17-121), and the median age was 28 years (IQR, 21-39) with a 2:1 male:female distribution. Most patients had non-extremity tumors (60%: trunk, n = 32 of which 9 were visceral; H&N n = 4) and the median tumor size was 7cm (IQR, 4-11). Local treatment consisted of CMT in 50% of patients (n = 30), whereas the other 50% received SMT (surgery n = 26 or RT n = 4). The median RT doses were: preop 50 Gy (n = 16; IQR, 50-50), postop 56 Gy (n = 14; IQR, 45-60), and definitive 60 Gy (IQR, 52.8-60). All patients received chemo with 18 (30%) receiving only neoadjuvant, 17 (28%) only adjuvant, and 25 (41%) receiving both. The 5 year (y) overall survival was 76%. There were 13 (22%) deaths attributable to disease resulting in a median DSS of 57 m (IQR, 10-97) and a 5y DSS of 77%. Seventeen patients (28%) developed distant metastasis (DM), most commonly to the lung (n = 7) at a median time of 15 m (IQR, 4-42) resulting in a 5 y DM free survival of 70%. Eleven patients (18%) developed local recurrence at a median time of 14 m (IQR 2-19) for a 5-y local control (LC) of 77%. On univariate analysis, only tumor location was associated with worse LC: non-extremity (5y LC 65% vs extremity 95%, P = 0.03); use of CMT was not associated with improved LC (5y LC 83% vs. SMT 72%, P = 0.41). Ultimately, no factors emerged as significantly associated with LC on multivariate analysis. Of the 22 patients that relapsed, the median survival time after relapse was 16 m (IQR 6-56). At least 5 patients (local n = 3; distant n = 2) were ultimately salvaged; all received chemo followed by additional local therapy (surgery and/or RT). Patients with localized EES have favorable outcomes compared to Ewing sarcoma of bone but worse LC compared to that of other STS. In our series, CMT was not associated with a decreased rate of local relapse. These data suggest that SMT alone may be sufficient for LC in select patients, which has the added benefit of decreasing any delays of initiating systemic therapy. A multi-institutional collaborative effort should be considered to validate these findings.