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

Abstract

Background The role of surgery in the management of pediatric non-pilocytic infiltrative thalamic gliomas needs to be revisited specifically with regard to molecularly defined subtypes. Methods A 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. Results Forty-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). 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.

MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial

“…The role of tumor resection for midline pediatric HGG remains uncertain (20,21), with limited scope for maximal resection of thalamic tumors (22). In a recently published single-center retrospective analysis (49 children ,18 years of age with a thalamic tumor presenting between 1992 and 2018; 50% nonpilocytic infiltrative gliomas and 28% tumors with H3 K27 mutations) (23), EOR, ascertained on the basis of MRI, was stratified between major debulking (.50% tumor resection) in 16 of 25 patients (.90% resection in eight, 50%-90% resection in eight) and biopsy in the remaining nine patients. The authors found a survival benefit for patients undergoing major debulking.…”

Extent of Tumor Resection and Survival in Pediatric Patients With High-Grade Gliomas

“…Ultimately, 37 articles published between March 1984 and April 12, 2022, reporting on 1387 unique patients were included for data extraction. 15 , 16 , 18 , 19 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 Of the 37 articles, 8 (21.6%) were identified from screening the reference lists of the 29 (78.4%) initially found through the search strategy. 31 , 32 , 36 , 40 , 49 , 56 , 58 , 59 For the IPDMA, 27 articles (73.0%) provided IPD on 427 unique patients (mean [SD] age at diagnosis, 9.3 [5.9] years; 169 of 317 [53.3%] were boys, and 148 were girls [46.7%]).…”

“… 31 , 32 , 36 , 40 , 49 , 56 , 58 , 59 For the IPDMA, 27 articles (73.0%) provided IPD on 427 unique patients (mean [SD] age at diagnosis, 9.3 [5.9] years; 169 of 317 [53.3%] were boys, and 148 were girls [46.7%]). 18 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 45 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 62 Twenty-six articles (70.3%) were observational cohort studies, and 10 (27.0%) were prospective studies. Most of the 36 nonrandomized observational studies (33 [91.7%]) were graded as fair or good quality, and the only RCT was graded as poor quality (eTables 1 and 2 in the Supplement ).…”

“…After exclusion of 3120 duplicates, 8853 unique articles underwent title and abstract screening, of which 281 were full-text articles assessed for eligibility. Ultimately, 37 articles published between March 1984 and April 12, 2022, reporting on 1387 unique patients were included for data extraction . Of the 37 articles, 8 (21.6%) were identified from screening the reference lists of the 29 (78.4%) initially found through the search strategy .…”

Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle

“…The role of tumor resection for midline pediatric DMG remains uncertain, while, impressively, the HERBY trial showed no evidence of a different event-free survival (EFS) rate according to the surgical approach; meanwhile, patients who experience a (rare) near total resection (NTR) or debulking survived longer [ 74 ], as stated in other investigations [ 75 ].…”