Infiltrative gliomas of the thalamus in children: the role of surgery in the era of H3 K27M mutant midline gliomas

Christian Dorfer,Thomas Czech,Karl Roessler,Amedeo A Azizi,Andreas Peyrl,Karin Dieckmann,Arthur Hosmann,Mariella G Filbin,Irene Slavc,Johannes Gojo,Gregor Kasprian,Christine Haberler

doi:10.1007/s00701-020-04589-y

Abstract

BackgroundThe role of surgery in the management of pediatric non-pilocytic infiltrative thalamic gliomas needs to be revisited specifically with regard to molecularly defined subtypes.MethodsA retrospective review of a consecutive series of children operated on a thalamic tumor between 1992 and May 2018 was performed. Neuroimaging data were reviewed for localization and extent of resection; pathology was re-reviewed according to the current WHO classification, including assessment of histone H3 K27 mutational status.ResultsForty-nine patients with a thalamic tumor aged < 18 years at diagnosis were identified. Twenty-five patients (51%) had a non-pilocytic infiltrative glioma, of which the H3 K27M status was available in 22. Fourteen patients were diagnosed as diffuse midline glioma (DMG) H3 K27M mutant. There was no statistically significant difference in survival between patients harboring the H3 K27M mutation and wildtype. Resection (“any resection > 50%” vs “biopsy”) and histological tumor grade (“°II” vs “°III+°IV”) were statistically significant predictors of survival (univariate: p = 0.044 and p = 0.013, respectively). These results remained significant on multivariate analysis (HR 0.371/p = 0.048, HR 9.433/p = 0.035).ConclusionWe advocate to still consider an attempt at maximal safe resection in the multidisciplinary treatment of unilateral thalamic non-pilocytic gliomas irrespective of their H3 K27-mutational status.

Highlights

Thalamic tumors are rare neoplastic lesions representing about 2–5% of all pediatric brain tumors [12, 31, 37]
Twenty-two patients (45%) had a pilocytic astrocytoma (WHO °I) and a World Health Organization (WHO) grade II–IV tumor was diagnosed in 27 children (55%)
All 22 patients with a pilocytic astrocytoma are alive after a median follow-up time of 10.9 years

Summary

Introduction

Thalamic tumors are rare neoplastic lesions representing about 2–5% of all pediatric brain tumors [12, 31, 37]. The updated WHO classification thereby combines all infiltrating gliomas harboring the same canonical mutation at the Lysine 27 of the histones H3 tail and arising in the pons, thalamus, and spinal cord into one entity [24, 26]. This mutation was identified as the most important predictor of worse outcome in thalamic tumors regardless of histology [32]. Resection (“any resection > 50%” vs “biopsy”) and histological tumor grade (“°II” vs “°III+°IV”) were statistically significant predictors of survival (univariate: p = 0.044 and p = 0.013, respectively) These results remained significant on multivariate analysis (HR 0.371/p = 0.048, HR 9.433/p = 0.035). Conclusion We advocate to still consider an attempt at maximal safe resection in the multidisciplinary treatment of unilateral thalamic non-pilocytic gliomas irrespective of their H3 K27-mutational status

Results

Discussion

Conclusion