Background Outcome and toxicity data in adolescent-adult Ewing’s Sarcoma (AA-ES) patients is sparse and merits exploration. Methods Histopathologically confirmed, non-metastatic AA- ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) comprising of ifosfamide plus etoposide and vincristine, doxorubicin, plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 (15-61) years; 159(67.7%) were males, 155 (65.9%) had skeletal primary and 114(48.5%) had extremity tumors. 196(83.4%) were treatment naïve (primary efficacy cohort, PEC) and of these 119 (60.7%) had surgery. In PEC, at a median follow up of 36.4 (IQR 20 – 55) months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%) respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow up of 39 (IQR 26- 57) months had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariable analysis good prognostic factors included, longer symptom(s) duration (HR=0.93, 95% CI 0.86-0.994), ≥ 99% necrosis (HR=0.30, 95% CI 0.11-0.77) and treatment completion (HR=0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile-neutropenia (119, 50.6%), anemia (130,55.3%), peripheral neuropathy (37,15.7%), with 3(1.3%) chemo-toxic deaths . Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen could be considered a standard-of-care in AA-ES.

Introduction: Vascular endothelial growth factor (VEGF)is an angiogenic marker and implicated in carcinogenesis and prognostication of cancers. However its prognostic potential in a rare cancer-Ewing’s sarcoma merits exploration. Methods: Histopathologically confirmed consecutive ES cases registered at our institute from 2014 to 2018 were analysed. Immunohistochemical staining for VEGF was performed on tumour tissues and they were further classified based on VEGF intensity. Results: There were 105 patients including 53 non-metastatic and 52 metastatic. VEGF immunostaining in non-metastatic and metastatic cohort was negative in 20 (37.7%) and 21 (40.4%), mildly positive in 13 (24.5%) and 9 (17.3%) cases, moderately positive in 14 (26.4%) and 16 (30.8%), and was intensely positive in 6 (11.3%) and 7 (13.5%) patients, respectively. VEGF immunoexpression up to 25% was seen in 14 (13.3%) and 10 (9.5%) patients within the non-metastatic and metastatic cohort, respectively. The median EFS and OS for the entire cohort were 26.4 (95% CI 17.6-NA) and 32.5 (21.3-NA) months, respectively. Metaststatic ES patients having either VEGF immunostaining in >25% tumor cells or moderate /strong immunostaining were found to inferior EFS and OS [p= 0.017, HR-0.153; p=0.013, HR-0.109 respectively].Additionally, treatment-naïve, compliant and non-metastatic patients had superior EFS (p=0.000, 0.000, 0.020, 0.022 respectively) and OS (p=0.000, 0.000, 0.006, 0.041 respectively). Conclusion: VEGF expression and intensity were found as independent negative prognostic marker in Ewing sarcoma .This may translate to therapeutic relevance but needs validation in the subsequent, larger prospective studies.

Background Outcomes of Ewing sarcoma (ES) in low and middle income countries lags behind the rest of the world owing to multiple tumoral, logistical and socio-economic factors. The data of outcomes and toxicity in these countries is sparse, especially in the adolescent and adult (AA) population and merits exploration Procedure This was a retrospective analysis of prospectively collected data of non-metastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) along with surgery or definitive radiotherapy. Various cohorts were analyzed for treatment-related toxicities, event- free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 years. One hundred and ninety six were treatment naïve (primary efficacy cohort, PEC) and of these 119 had surgery. In PEC, at a median follow up of 36.4 months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%), respectively. Of these, 158 complying with intended treatment, had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariate analysis, good prognostic factors included longer symptom duration, ≥ 99% necrosis and treatment completion. Among PSC, grade 3-4 toxicities were febrile-neutropenia (50.6%), anemia (55.3%), peripheral neuropathy (15.7%), with 3 (1.3%) chemo-toxic deaths. Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity and can be considered as standard-of-care, especially in LMICs.