Prognostic factors for survival in Ewing sarcoma: A systematic review

Development of a prognostic model for survival can assist in stratifying treatment according to the individual patients' risk, leading to risk- and response adaptive treatment strategies which allow for early decision making. The aim of this systematic review is to provide an overview of prognostic factors for overall survival (OS) and event-free survival (EFS) in Ewing sarcoma to be used in the development of prediction models and clinical trial design. A literature search was performed using Pubmed, Embase, Web of Science, Academic search premier and Cochrane databases. Studies were eligible if: 1) Sample size ≥100; 2) Follow-up ≥2 years or dead within 2 years; 3) Recruitment after 1975; 4) Outcome measure OS or EFS; 5) Multivariate analysis to assess the effect of prognostic factors on survival outcomes; 6) Study published in English. In case studies were derived from the same database the most all-embracing was selected. Study selection and quality assessment was performed by two reviewers independently. For each risk factor a level of evidence synthesis was performed. Kappa-statistic was used to determine inter-observer agreement. A total of 149 full-text articles were found, 21 eligible for inclusion. 24 prognostic factors were investigated, 14 relevant for this review. Prognostic factors associated with survival include metastasis at diagnosis, large tumors (volume ≥ 200 ml or largest diameter ≥ 8 cm), primary tumors located in the axial skeleton, especially pelvic and a histological response of less than 100%. These factors should be included as risk factors in the development of prediction models for ES.