Easy-to-use clinical tool for survival estimation in Ewing sarcoma at diagnosis and after surgery

S E Bosma,U Dirksen,M A J Van De Sande,H Gelderblom,C Lancia,M Fiocco,A J Rueten-Budde,P D S Dijkstra,A Ranft

doi:10.1038/s41598-019-46721-8

S E Bosma, U Dirksen + Show 7 more

Open Access

https://doi.org/10.1038/s41598-019-46721-8

Copy DOI

Abstract

Accurate survival estimations in Ewing sarcoma are necessary to develop risk- and response adaptive treatment strategies allowing for early decision-making. We aim to develop an easy-to-use survival estimation tool from diagnosis and surgery. A retrospective study of 1314 Ewing sarcoma patients was performed. Associations between prognostic variables at diagnosis/surgery and overall survival (OS), were investigated using Kaplan-Meier and multivariate Cox models. Predictive accuracy was evaluated by cross-validation and Harrell C-statistics. Median follow-up was 7.9 years (95%CI 7.6–8.3). Independent prognostic factors at diagnosis were age, volume, primary tumor localization and disease extent. 5 risk categories (A-E) were identified with 5-year OS of 88% (86–94), 69% (64–74), 57% (50–64), 51% (42–60) and 28% (22–34) respectively. Harrell C-statistic was 0.70. Independent prognostic factors from surgery were age, volume, disease extent and histological response. In categories A-B, 5y OS increased to 92% (87–97) and 79% (71–87) respectively for 100% necrosis and decreased to 76% (67–85) and 62% (55–69) respectively for <100% necrosis. In categories C-E, 5y OS increased to 65% (55–75), 65% (52–78) and 52% (38–66) respectively for ≥90% necrosis and decreased to 38% (22–54), 11% (0–26) and 7% (0–19) respectively for <90% necrosis. We present an easy-to-use survival estimation tool from diagnosis in Ewing sarcoma based on age, volume, primary tumor localization and disease extent. Histological response is a strong additional prognostic factor for OS.

Highlights

Ewing sarcoma (EwS) is an aggressive bone and soft-tissue tumor predominantly affecting children and young adults[1]
All patients were treated according to the protocol with the aim to administer six cycles of VIDE induction chemotherapy followed by local treatment of the primary tumor
Univariate and multivariate Cox proportional hazard models were estimated to investigate the effect of risk factors on overall survival (OS)

Summary

Introduction

Ewing sarcoma (EwS) is an aggressive bone and soft-tissue tumor predominantly affecting children and young adults[1]. Accurate estimations of survival according to the individual patient’s risk profile at different time points are necessary to offer EwS patients the most appropriate treatment, balancing survival and prognosis with toxicity and quality of life. In this young patient population, this balance is essential in our aim to provide the best possible care. Small homogeneous cohorts, that are either not validated or did not include all relevant variables in the model Keeping these shortcomings in mind, our aim was to develop an easy-to-use survival estimation tool for EwS. Objectives are to: (1) Identify prognostic factors for overall survival from diagnosis and surgery; (2) Develop an accurate baseline prognostic model; (3) Validate the models’ predictive accuracy; (4) Develop a second prognostic model from surgery

Objectives

Methods

Results

Conclusion