High Response Rates and Promising Outcomes of Patients with Relapsed Ewing Sarcoma, Especially in Adolescents and Young Adults Treated on a Novel Hybrid Salvage Chemotherapy Regimen

Purpose:About 30%-35% of nonmetastatic and 60%-80% of metastatic Ewing Sarcoma (ES) will relapse post-treatment and outcomes after relapse continue to be poor over last several decades. Prognostic factors affecting survival after relapse of ES are also not robustly known. We present outcomes using a novel hybrid salvage protocol of four active chemotherapeutic agents in our cohort of patients after relapse of ES. Methods:This is a retrospective analysis of all consecutive relapsed ES patients treated with curative intent over 4 years (January 2012 to December 2015). All received 12-cycles of hybrid chemotherapy regimen with surgery/radiotherapy done after first 4 cycles. Event-free survival (EFS)/overall survival (OS) estimates were analyzed by Kaplan-Meier product-limit estimator. Cox regression analysis was performed to identify prognostic factors predicting outcome in relapsed ES. Results:Salvage regimen was given to 53/108 relapsed ES patients with the rest having opted for palliation upfront. Median age of the treated patients was 19 years (range: 4-40); male:female ratio was 2.7:1. Median time to first relapse was 18.8 months (range: 2.2-91). While 41/53 patients (77%) completed salvage therapy, 6 (11.3%) progressed and 6 (11.3%) abandoned treatment. Median follow-up of the study cohort is 31 months (range: 4-81). Of the analyzable cohort (n = 47), 30 (64%) had a second relapse or progression on salvage treatment. At last follow-up, 31 patients had died (including one due to toxicity and rest due to disease) and 16 patients were alive (14 with no active disease and 2 with disease). The 4-year EFS and OS are 28% and 37%, respectively, for the entire cohort. While adolescents and young adult patients (AYA) had a better survival (p-0.041), relapsed ES patients with shorter disease-free interval (DFI) (<24 months) had a poorer survival (p-0.004). The type of relapse (local or metastatic or combined) after primary treatment did not affect outcome after salvage therapy. Conclusions:We have used a novel hybrid chemotherapy protocol using four active agents in relapsed ES, which is well tolerated and shows promising results. Older age (>= 15 years) and longer DFI (>24 months) portend better survival post-relapse. In our cohort of relapsed ES, AYAs fared better than others and type of relapse after primary treatment did not affect outcome after salvage therapy.

Automated summary

This study presented outcomes of a novel hybrid salvage protocol using four active chemotherapeutic agents in relapsed ES patients. While some patients showed promising results, overall prognosis remains poor. Adolescents and young adults, as well as patients with longer disease-free intervals, had better survival post-relapse.