Towards a new era in the treatment of Ewing sarcoma

Although international consensus exists that dose intensification improves outcomes for patients with radiographically localised Ewing sarcoma, treatment strategies to achieve this intensification, and how to translate this improvement to patients with metastatic disease, has remained controversial and enigmatic. 1 Juergens C Weston C Lewis I et al. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-EWING 99 clinical trial. Pediatr Blood Cancer. 2006; 47: 22-29 Crossref PubMed Scopus (207) Google Scholar , 2 Luksch R Tienghi A Hall KS et al. Primary metastatic Ewing's family tumors: results of the Italian Sarcoma Group and Scandinavian Sarcoma Group ISG/SSG IV Study including myeloablative chemotherapy and total-lung irradiation. Ann Oncol. 2012; 23: 2970-2976 Summary Full Text Full Text PDF PubMed Scopus (70) Google Scholar , 3 Whelan J Le Deley MC Dirksen U et al. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of EURO-EWING 99 and Ewing-2008. J Clin Oncol. 2018; 36 (JCO2018782516) Crossref Scopus (84) Google Scholar , 4 Womer RB West DC Krailo MD et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2012; 30: 4148-4154 Crossref PubMed Scopus (442) Google Scholar An intercontinental divide for the upfront treatment of Ewing sarcoma has persisted: patients in Europe are most often offered induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), and consolidation with vincristine, actinomycin D, and ifosfamide or cyclophosphamide (VAI or VAC), or busulfan and melphalan (BuMel), whereas in the USA the standard of care consists of interval-compressed cycles of cyclophosphamide, doxorubicin, and vincristine (VDC) plus ifosfamide and etoposide (IE). 2 Luksch R Tienghi A Hall KS et al. Primary metastatic Ewing's family tumors: results of the Italian Sarcoma Group and Scandinavian Sarcoma Group ISG/SSG IV Study including myeloablative chemotherapy and total-lung irradiation. Ann Oncol. 2012; 23: 2970-2976 Summary Full Text Full Text PDF PubMed Scopus (70) Google Scholar In The Lancet, Bernadette Brennan and colleagues 5 Brennan BKL Marec-Bérard P et al. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial. Lancet. 2022; 400: 1513-1521 Google Scholar report the results of EURO EWING 2012 (EE2012), a phase 3, randomised controlled trial done in ten European countries that compared these approaches to establish the regimen of choice in patients with Ewing sarcoma. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trialDose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma. Full-Text PDF