Primary and Metastatic Intracranial Ewing Sarcoma at Diagnosis: Retrospective International Study and Systematic Review.

Lianne M Haveman,Michael Paulussen,Stephanie Klco-Brosius,Andreas Ranft,Henk Van Den Berg,Ruth Ladenstein,Johannes H.M Merks,Uta Dirksen,Heribert Juergens

doi:10.3390/cancers12061675

Abstract

Intracranial Ewing sarcoma (EwS) is rare and publications on primary or metastatic intracranial EwS are minimal. The aim of this study was to describe incidence, clinical behavior, treatment, and factors associated with outcome in patients with primary intracranial EwS or patients with a primary extracranial EwS and cerebral metastases at diagnosis. We reviewed all patients with primary or with metastatic intracranial EwS at diagnosis registered in the International Clinical Trial Euro-E.W.I.N.G.99 (EE99). In total, 17 of 1435 patients (1.2%) presented with primary intracranial EwS; 3 of them had metastatic disease. Four patients (0.3%) with primary extracranial EwS presented with intracranial metastatic lesions. The 3-year event-free survival (EFS) was 64% and overall survival (OS) was 70% in patients with a primary intracranial EwS. Local control in patients with primary intracranial EwS consisted of surgery (6%), radiotherapy (RT) (18%), or both modalities (76%). Univariate analysis showed that patients < 15 years of age had significantly better outcome (EFS: 72%; OS: 76%) compared to those aged above 15 years (EFS: 13%; OS: 25%). In conclusion, primary intracranial EwS and extracranial EwS with cerebral metastases at diagnosis is rare, yet survival is comparable with local and metastatic EwS elsewhere in the body. Age and stage of disease are important prognostic factors. Besides chemotherapeutic treatment, local control with surgical resection combined with RT is recommended whenever feasible.

Highlights

According to the World Health Organization, the peripheral primitive neuroectodermal tumors, classic Ewing Sarcoma (EwS) and extraskeletal Ewing sarcomas (EwSs), constitute the Ewing sarcoma family of tumors.Cancers 2020, 12, 1675; doi:10.3390/cancers12061675 www.mdpi.com/journal/cancersPrimitive neuroectodermal tumors (PNETs) are composed of small undifferentiated embryonal-type round cells
For intracranial PNETs, a distinction is made between primitive neuroectodermal tumors of the central nervous system which includes medulloblastoma, supratentorial PNETs, and pineoblastoma, versus primitive neuroectodermal tumors of the peripheral nervous system, which encompasses Ewing sarcomas (EwSs), mainly arising from bone and soft tissue
We reviewed all patients with primary intracranial EwS and patients with extracranial EwS and intracranial metastatic disease at diagnosis treated according to the International Clinical Trial Euro-E.W.I.N.G. 99 (EE99) protocol and included in the GPOH-EE99 registry [10]

Summary

Introduction

According to the World Health Organization, the peripheral primitive neuroectodermal tumors, classic Ewing Sarcoma (EwS) and extraskeletal EwS, constitute the Ewing sarcoma family of tumors.Cancers 2020, 12, 1675; doi:10.3390/cancers12061675 www.mdpi.com/journal/cancersPrimitive neuroectodermal tumors (PNETs) are composed of small undifferentiated embryonal-type round cells. For intracranial PNETs, a distinction is made between primitive neuroectodermal tumors of the central nervous system which includes medulloblastoma, supratentorial PNETs, and pineoblastoma, versus primitive neuroectodermal tumors of the peripheral nervous system, which encompasses Ewing sarcomas (EwSs), mainly arising from bone and soft tissue. EwSs of the central nervous system may histologically appear quite similar to primitive neuroectodermal tumors of the central nervous system, EwSs show the characteristic chromosomal translocation t(11;22)(q24;12) in 85–90% of patients. This translocation results in fusion of the gene

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