Prognostic Implication of Patient Age in H3K27M-Mutant Midline Gliomas

Abstract

IntroductionPediatric and adult H3K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups.MethodsPubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of H3K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS).ResultsWe included 43 studies comprising 272 adults and 657 pediatric midline gliomas with H3K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of H3.1 K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric H3K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, ACVR1 mutations were more common whereas MGMT methylation, FGFR1, and NF1 mutations were less prevalent in the pediatric cohort.ConclusionPediatric H3K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.

Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma

“…A systematic review including 43 studies showed more aggressive features, including higher rates of pathologic features of high-grade tumors and a higher Ki-67 proliferation index, occurred in pediatric H3K27M-mutant DMG when compared to adults, which resulted in a worse prognosis in the children subgroup. 25 Moreover, there are differences in the molecular characteristics of H3K27M-mutant DMG between pediatric and adult patients. Several studies demonstrated that ACVR1 mutation frequently occurred in children, whereas FGFR1, neurofibromatosis type 1 (NF1), and ATRX mutations were more common in adults.…”

“…The distinct mechanisms accounting for the different prognosis between children and adults have not been fully explored. A systematic review including 43 studies showed more aggressive features, including higher rates of pathologic features of high‐grade tumors and a higher Ki‐67 proliferation index, occurred in pediatric H3K27M‐mutant DMG when compared to adults, which resulted in a worse prognosis in the children subgroup 25 . Moreover, there are differences in the molecular characteristics of H3K27M‐mutant DMG between pediatric and adult patients.…”

“…Comparative survival data between adults and children within the same study are limited and show inconsistent results. Some retrospective studies have reported significantly longer OS in adults compared to the pediatric group, [25][26][27] while others have found similar prognoses between adults and children. 28,29 There is also a scarcity of studies examining prognostic factors between pediatric and adult subgroups.…”

H3 K27M-Altered Diffuse Midline Gliomas: A Review

“…2 ). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 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 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82…”

“…DMG H3 K27-altered may also occur in the adult population. 3 We review the features of DMG H3 K27-altered in the adult and pediatric populations and compare their genetic, epidemiological, clinical, radiological, histopathological, treatment, and prognostic characteristics.…”