Current challenges in the treatment of gliomas:The molecular era

Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric glioma.Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis.Molecular characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of treatment.Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma.However,improvements in survival have been modest.Currently,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular biomarkers.Furthermore,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.

Updates on management of gliomas in the molecular age

Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.

ERBB1 Is Amplified and Overexpressed in High-grade Diffusely Infiltrative Pediatric Brain Stem Glioma

PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,

Concise review of stereotactic irradiation for pediatric glial neoplasms:Current concepts and future directions

Brain tumors,which are among the most common solid tumors in childhood,remain a leading cause of cancer-related mortality in pediatric population.Gliomas,which may be broadly categorized as low grade glioma and high grade glioma,account for the majority of brain tumors in children.Expectant management,surgery,radiation therapy(RT),chemotherapy,targeted therapy or combinations of these modalities may be used for management of pediatric gliomas.Several patient,tumor and treatment-related characteristics including age,lesion size,grade,location,phenotypic and genotypic features,symptomatology,predicted outcomes and toxicity profile of available therapeutic options should be considered in decision making for optimal treatment.Management of pediatric gliomas poses a formidable challenge to the physicians due to concerns about treatment induced toxicity.Adverse effects of therapy may include neurological deficits,hemiparesis,dysphagia,ataxia,spasticity,endocrine sequelae,neurocognitive and communication impairment,deterioration in quality of life,adverse socioeconomic consequences,and secondary cancers.Nevertheless,improved understanding of molecular pathology and technological advancements may pave the way for progress in management of pediatric glial neoplasms.Multidisciplinary management with close collaboration of disciplines including pediatric oncology,surgery,and radiation oncology is warranted to achieve optimal therapeutic outcomes.In the context of RT,stereotactic irradiation is a viable treatment modality for several central nervous system disorders and brain tumors.Considering the importance of minimizing adverse effects of irradiation,radiosurgery has attracted great attention for clinical applications in both adults and children.Radiosurgical applications offer great potential for improving the toxicity profile of radiation delivery by focused and precise targeting of well-defined tumors under stereotactic immobilization and image guidance.Herein,we provide a concise review of stereotactic irradiation for pediatric glial neoplasms in light of the literature.

Genetic variants in XPD gene and glioma susceptibility in Chinese children:A multicenter case–control study

Background:Glioma is one of the central nervous system(CNS)tumors in children,accounting for 80%of malignant brain tumors.Nucleotide excision repair(NER)is a vital pathway during DNA damage repair progression.Xeroderma pigmentosum group D(XPD)or excision repair cross‐complementing group 2(ERCC2)is a critical factor in the NER pathway,playing an indispensable role in the DNA repair process.Therefore,the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair.Methods:We are the first to conduct a multi‐center case‐control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk.We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay.Results:Although there is no significant association of these genetic variations with glioma susceptibility,the stratified analysis revealed that in the subtype of astrocytic tumors,the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype,and carriers with two to three genotypes also elevated the tumor risk than 0‐1 genotypes.Conclusion:In conclusion,our findings provided an insight into the impact of XPD genetic variants on glioma risk.