Glioma

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Cell competition among neighboring cells in a tissue gauges relative fitness in terms of growth and proliferation, which results in the death of cells with suboptimal fitness and the dominance of optimally or supraoptimally fit cells. It is conserved across multiple taxa and has indispensable functions in development, homeostasis, aging, and prevention of neoplastic growth, both in Drosophila and mammals. However, similar to how several key developmental pathways are subverted in cancer, cell competition mechanisms are often co-opted in the oncogenic transformation of cells in homeostatically stable tissues, and the role of this phenomenon in human cancer is attracting increasing interest. Grade IV glioblastomas (GBMs) are the most aggressive brain tumors that occur in adults. GBMs arise from glial cells and invariably result in tumor recurrence and death. Treatment of GBMs is complicated by the unique features of the anatomical context, including the dura, blood–brain barrier, glioma stem cells, necrosis, and extensive genetic and epigenetic heterogeneity. In this review, we discuss the evidence for cell competition elicited by genomic alterations in several key genes involved in early or late gliomagenesis, as well as activation of specific signaling pathways that aid competitive interactions with nonglial cell types like neurons to gain leverage in the colonization of brain niches. The role of intratumoral heterogeneity in conferring clonal dominance or cooperation resulting in therapeutic resistance in GBMs is also discussed.

This narrative review summarizes the current status of the use of particle radiation therapy on the treatment of adult malignant gliomas. Due to the unique physical property, particle (e.g., proton or carbon-ion) beam radiation therapy can improve radiation dose distribution, thereby therapeutic radio for patients with brain malignancy. Therefore, particle beam radiation therapy is associated with low adverse events which have implications for improving quality of life for long-term survivors. In addition, there is a potential for safe dose escalation in selected patients. Malignant glioma is considered radioresistant; thus, particle beams of higher relative biological effectiveness, carbon-ion beam, for example, may further improve disease control in theory. Data on carbon-ion beam RT alone for the management of brain tumor are scarce. Most literature described proton beam alone or the use of combined proton/photon and carbon-ion beam boost for the treatment of glioma. Existing clinical evidence describes virtually no acute high-grade toxicities and limited late effects. Prospective clinical trials are needed to confirm the improved efficacy and favorable toxicity profile of particle beam radiation therapy on adult malignant glioma described in retrospective studies. Currently, multiple prospective trials are ongoing to answer such questions.

Spread along nerve fiber bundles is one of the most important modes of glioma invasion; however, the current guidelines for radiotherapy target areas recommend a 1–2-cm margin in all directions from the tumor border based on pretreatment imaging findings. In this article, we analyzed the relationship between edema and nerve fiber bundles in 60 glioma patients and aimed to clarify the effect of including edema on delineation of the target volume.

Background and Aim: Mutations in isocitrate dehydrogenase (IDH), co-deletion of 1p and 19q, loss or expression of the transcription regulator ATRX, and mutations in telomerase reverse transcriptase (TERT) gene promoters are intimately linked with diffuse gliomas. We further explored the roles of the key molecules in adulthood diffuse gliomas and their prognosis. Materials and Methods: A total of 413 patients who underwent primary surgery between 2009 and 2015 at Xuanwu Hospital, Beijing, China, were included in this observational study. All specimens from the patients were fixed in 10% neutral buffered formalin and embedded in paraffin. The mutational status of IDH1/2 and the TERT promoter was determined using polymerase chain reaction-based direct sequencing. The assay for the 1p and 19q co-deletion was conducted using fluorescence in situ hybridization. Overall- and progression-free survival was calculated using the Kaplan–Meier method and the log-rank test. The study was approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University, China (approval No. [2019]004) on May 22, 2019. Results: We found that tumors characterized by multiple lesions were predominantly free of IDH mutations (P < 0.001). Gliomas with IDH mutations arose more often in the frontal and insular lobes than in the other lobes (P < 0.001). Rates of IDH mutations were higher in patients who had seizures or were without discomfort than in those who had other clinical symptoms (P = 0.0003). Of 119 patients with complete molecular information according to the 2016 World Health Organization classification of central nervous system tumors, 5 had oligoastrocytomas that had multiple genotypes – IDH1 mutation, loss of ATRX expression, and 1p/19q co-deletion – but lacked TERT promoter mutations. Patients with seizures or without discomfort who had IDH mutations had better outcomes than did other patients (P < 0.001). Patients whose tumors had IDH and TERT promoter mutations had a better prognosis than did other patients (P < 0.001). Among patients whose tumors had wild-type IDH, those with loss of ATRX survived longer than did others (P = 0.005). Conclusions: The status of both ATRX and the TERT promoter can indicate the prognosis in patients with IDH wild-type gliomas. The diagnosis that is based on clinical symptoms, histologic findings, and molecular analysis should be implemented as the diagnostic standard for patients with oligoastrocytomas.

Glioblastoma is the most common primary brain tumor in adults. There is no standard treatment for residual or recurrent glioblastoma and the prognosis is poor. Here, we report the case of a 72-year-old woman with a glioblastoma who underwent subtotal resection, after which her tumor recurred rapidly. Adaptive hypofractionated radiotherapy combined with temozolomide and bevacizumab was administered, resulting in a long progression-free survival. The study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, China.

Online since 6^th Sep 2017.