Molecular Landscape in Infant High-Grade Gliomas: A Single Center Experience

Abstract

High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10–12% of pediatric HGGs (pHGG) occur in children younger than five years of age at diagnosis, specifically infants (iHGG), with an unexpected overall survival rate (OS) in 60–70% of cases. In the literature, iHGGs include a large variety of heterogeneous lesions with different molecular profiles that likely explain their different outcomes. We report our single-institution experience of iHGG including 11 children under five years of age with newly diagnosed HGG between 2011 and 2021. All patients received surgery and adjuvant chemotherapy; only two patients received radiotherapy because their age at diagnosis was more than four years-old. Molecular investigations, including next generation sequencing (NGS) and DNA methylation, detected three NTRK-fusions, one ROS1-fusions, one MN1-rearrangement, and two PATZ1-fusions. According to the molecular results, when chemotherapy failed to control the disease, two patients benefited from target therapy with a NTRK-Inhibitor larotrectinib, achieving a complete remission and a very good partial response, respectively, and no severe side-effects. In conclusion, molecular investigations play a fundamental role in the diagnostic work-up and also in the therapeutic decision. Their routine use in clinical practice could help to replace highly toxic chemotherapy regimens with a target therapy that has moderate adverse effects, even in long-term follow-up.

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 ).…”

Paediatric-type diffuse high-grade gliomas in the 5th CNS WHO Classification

“…However, spinal examples are also reported ( Fig. 6P - Q ) 55 raising the question of whether the inclusion of tumour location within the WHO definition of this entity may be too restrictive.…”

How Genetics and Genomics Advances Are Rewriting Pediatric Cancer Research and Clinical Care

“…Di Ruscio et al [ 173 ] reported on a study of iHGG patients who received surgery and adjuvant chemotherapy; only two patients received the radiotherapy because their age at their diagnosis was over four-years-old. Molecular investigations, including next-generation sequencing (NGS) and DNA methylation, identified three gene fusions that involve NTRK , one ROS1 fusion, one MN1 rearrangement, and two PATZ1 fusions.…”

“…Molecular investigations, including next-generation sequencing (NGS) and DNA methylation, identified three gene fusions that involve NTRK , one ROS1 fusion, one MN1 rearrangement, and two PATZ1 fusions. According to the molecular results, when the chemotherapy failed to control the disease, the two patients benefited from a target therapy with the NTRK inhibitor larotrectinib, thereby achieving complete remission, an excellent partial response, and no serious side effects [ 173 ].…”