Risk of recurrence and survival after relapse in patients with Ewing sarcoma

Abstract

BackgroundThe prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.ProcedureWe analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow‐up or death.ResultsMedian follow‐up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2–24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five‐year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5‐year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five‐year OSr was 0.07 (SE = 0.01) in patients who relapsed 0–2 years after the diagnosis of primary disease, as compared to a 5‐year OSr of 0.29 (SE = 0.03) when relapse occurred later.Conclusions5‐year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse. Pediatr Blood Cancer 2011; 57: 549–553. © 2011 Wiley‐Liss, Inc.

High-Throughput Tyrosine Kinase Activity Profiling Identifies FAK as a Candidate Therapeutic Target in Ewing Sarcoma

“…Although progress has been made in treating this disease with conventional chemotherapy combined with surgery or radiation for local control, outcomes for relapsed and metastatic disease are notably poor (9,10,22). Furthermore, an emerging literature on the long-term side effects of these conventional treatment modalities in pediatric cancer survivors leaves us unsatisfied with the current standard of care (23).…”

“…Therefore, we leveraged a recently described, bead-based tyrosine kinase activity assay that profiles the phosphorylation of a large panel of tyrosine kinases, many of which have available inhibitors (8). We focused on Ewing sarcoma, the second most common bone tumor diagnosed in children, where survival remains poor for patients with metastatic and recurrent disease despite intensive regimens (9,10). New therapeutic approaches are needed to improve the survival of patients with this disease.…”

NCCN Guidelines Insights: Bone Cancer, Version 2.2017

“…The probability of 5-year postrelapse survival was also significantly higher for patients with late versus early relapse. 6,57,58 Ifosfamide in combination with etoposide with or without carboplatin has been shown to be active in clinical trials for the treatment of patients with relapsed or refractory sarcoma. 59,60 A recent review of 239 patients with Ewing sarcoma suggested a potential risk-reduction benefit of high-dose versus conventional chemotherapy for treating first relapse.…”

Deep Sequencing in Conjunction with Expression and Functional Analyses Reveals Activation of FGFR1 in Ewing Sarcoma

“…Ewing sarcoma has been reported to contain a low number of mutations in coding regions (20). Given the still dismal prognosis of advanced Ewing sarcoma (27,28), we performed whole genome sequencing (WGS) of diagnosis and relapse samples to identify potential drivers and relapse-associated genes. Furthermore, we performed exome sequencing to expand the findings and to identify novel therapeutic targets.…”