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

Abstract

IMPORTANCE Pediatric patients with high-grade gliomas have a poor prognosis. The association among the extent of resection, tumor location, and survival in these patients remains unclear.OBJECTIVE To ascertain whether gross total resection (GTR) in hemispheric, midline, or infratentorial pediatric high-grade gliomas (pHGGs) is independently associated with survival differences compared with subtotal resection (STR) and biopsy at 1 year and 2 years after tumor resection.DATA SOURCES PubMed, EBMR, Embase, and MEDLINE were systematically reviewed from inception to June 3, 2022, using the keywords high-grade glioma, pediatric, and surgery. No period or language restrictions were applied.STUDY SELECTION Randomized clinical trials and cohort studies of pHGGs that stratified patients by extent of resection and reported postoperative survival were included for study-level and individual patient data meta-analyses. DATA EXTRACTION AND SYNTHESISStudy characteristics and mortality rates were extracted from each article. Relative risk ratios (RRs) were pooled using random-effects models. Individual patient data were evaluated using multivariate mixed-effects Cox proportional hazards regression modeling. The PRISMA reporting guideline was followed, and the study was registered a priori. MAIN OUTCOMES AND MEASURESHazard ratios (HRs) and RRs were extracted to indicate associations among extent of resection, 1-year and 2-year postoperative mortality, and overall survival. RESULTSA total of 37 studies with 1387 unique patients with pHGGs were included. In study-level meta-analysis, GTR had a lower mortality risk than STR at 1 year (RR, 0.69; 95% CI, 0.56-0.83; P < .001) and 2 years (RR, 0.74; 95% CI, 0.67-0.83; P < .001) after tumor resection. Subtotal resection was not associated with differential survival compared with biopsy at 1 year (RR, 0.82; 95% CI, 0.66-1.01; P = .07) but had decreased mortality risk at 2 years (RR, 0.89; 95% CI, 0.82-0.97; P = .01). The individual patient data meta-analysis of 27 articles included 427 patients (mean [SD] age at diagnosis, 9.3 [5.9] years), most of whom were boys (169 of 317 [53.3%]), had grade IV tumors (246 of 427 [57.7%]), and/or had tumors that were localized to either the cerebral hemispheres (133 of 349 [38.1%]) or midline structures (132 of 349 [37.8%]). In the multivariate Cox proportional hazards regression model, STR (HR, 1.91; 95% CI, 1.34-2.74; P < .001) and biopsy (HR, 2.10; 95% CI, 1.43-3.07; P < .001) had shortened overall survival compared with GTR but no survival differences (continued) Key Points Question Is the extent of tumor resection associated with survival in pediatric patients with highgrade gliomas? Findings In this systematic review and meta-analysis of 37 studies involving 1387 unique pediatric patients with high-grade gliomas, gross total resection was independently associated with better overall survival compared with subtotal resection and biopsy, especially in patients with hemispheric and infratentorial tumors. Meaning Findings of this study suggest that m...

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“…Although the incidence of this tumor is relatively low (1.78 per 100,000 population) 2 , pHGG holds an exceptionally dismal prognosis, with a median overall survival of 14 to 20 months. 3 Despite decades of research and over 1,500 clinical trials, there remains no cure for pHGG. Standard therapy includes maximal safe resection, high-dose radiotherapy, and chemotherapy 4 , yet this multimodal therapy does little to change the course of the disease 5 .…”

“…Although the incidence of this tumor is relatively low (1.78 per 100,000 population) 2 , pHGG holds an exceptionally dismal prognosis, with a median overall survival of 14 to 20 months. 3 Despite decades of research and over 1,500 clinical trials, there remains no cure for pHGG. Standard therapy includes maximal safe resection, high-dose radiotherapy, and chemotherapy 4 , yet this multimodal therapy does little to change the course of the disease 5 .Although childhood and adult HGG, including glioblastoma multiforme (GBM), share many histopathological and clinical features, the advent of genomic, transcriptomic, and epigenomic profiling has led pHGG to be recognized as a distinct disease entity with substantial differences in its molecular characteristics 2,6-10 .…”