Novel Pharmacological Treatment Options in Pediatric Glioblastoma—A Systematic Review

Abstract

Background: Pediatric glioblastoma (GBM) is an aggressive central nervous system tumor in children that has dismal prognosis. Standard of care is surgery with subsequent irradiation and temozolomide. We aimed to outline currently available data on novel pharmacological treatments for pediatric GBM. Methods: We conducted a systematic literature search in PubMed and Embase, including reports published in English from 2010 to 2021. We included randomized trials, cohort studies and case series. Phase I trials were not analyzed. We followed PRISMA guidelines, assessed the quality of the eligible reports using the Newcastle-Ottawa scale (NOS) and the RoB-2 tool and registered the protocol on PROSPERO. Results: We included 6 out of 1122 screened reports. All six selected reports were prospective, multicenter phase II trials (five single-arm and one randomized controlled trial). None of the investigated novel treatment modalities showed any benefit regarding overall or progression free survival. Conclusions: To date, the role of pharmacological approaches regarding pediatric GBM remains unclear, since no novel treatment approach could provide a significant impact on overall or progression free survival. Further research should aim to combine different treatment strategies in large international multicenter trials with central comprehensive diagnostics regarding subgrouping. These novel treatment approaches should include targeted and immunotherapeutic treatments, potentially leading to a more successful outcome.

Unraveling the Landscape of Pediatric Glioblastoma Biomarkers: A Comprehensive Review of Enhancing Diagnostics and Therapeutic Insights

“…It lessens the chance of recurrence and aids in the treatment of local illnesses. Juvenile glioblastoma has a significant level of microscopic polymorphism when viewed alongside adult GBM, but it also exists within its own subtype [ 34 ]. Resection by surgery is the most commonly used therapeutic option for pediatric glioblastoma.…”

“…Wyss et al, [34] 2022 Switzerland Specific as well as immunotherapeutic treatments should be included in innovative therapy regimens, perhaps leading to a better outcome in juvenile glioblastoma.…”

Updates on management of gliomas in the molecular age

“…Several therapies have been trialed for their effectiveness in improving overall survival and progression-free survival among children, including an assessment of their tolerance and toxicity profiles. Such therapies have included irinotecan, cilengitide, and sunitinib, all presenting with uncertain efficacy warranting further research[ 130 ].…”

Recent Advancements on the Use of Exosomes as Drug Carriers for the Treatment of Glioblastoma

“…On the other hand, plateletderived growth factor receptor A (PDGFRA) amplification appears to be a common feature of pediatric high-grade gliomas, possibly suggesting an early initiating role of this mutation in pediatric tumorigenesis [14]. Immunotherapeutic approaches are in development for pediatric high-grade gliomas, involving the use of therapeutic vaccination to redirect T-cells against tumor antigens [15]. However, the effectiveness of immunotherapeutic treatment is still to be thoroughly evaluated.…”