Background Historically, creating patient-derived models of lower grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. Methods In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. Results Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1-4), and a success rate of 87% (13/15) for WHO Grade 1-3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. Conclusions We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study glioma-genesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

Introduction: Glioblastoma is the most common primary brain tumor in adults. Standard of care includes maximal surgical resection of the tumor followed by concurrent chemotherapy and radiation. The treatment of glioblastoma must account for an increased disease severity and treatment intensity compared to other cancers which places a significant cost burden on the patient and health system. Cost assessments of glioblastoma treatment have been sparse in comparison to other solid cancer subtypes. This study evaluates all current available cost literature with an emphasis on the modern treatment paradigm to properly assess the economic implications of this disease.Methods: A critical review of 21 studies from 13 different countries measuring direct costs related to glioblastoma management was performed. Evaluated data included itemized costs, total costs of treatment regimens from diagnosis until death, the cost of second-line care after recurrence, and the incremental costs and cost-effectiveness of emerging therapies.Results: The average cost of a craniotomy was $10,042 across studies. Imaging for the duration of glioblastoma care had a mean cost of $2,788±3,719. Studies examined different combinations of treatment modalities. Utilization of the modern treatment paradigm led to a survival of 16.3 months across studies and had a mean cost of $62,602. Surgery for recurrent disease had an average cost of $27,442±18,992.Limitations and Conclusions: Direct cost estimates for glioblastoma varied substantially between institutions and countries and often failed to uniformly describe direct cost estimates associated with care for glioblastoma. The limitations of these studies make true economic assessment of standards of care, costs of recurrence, and incremental costs associated with adjunctive therapy uncertain.