The Chinese Glioma Cooperative Group (CGCG) Guideline Panel for adult diffuse gliomas provided recommendations for diagnostic and therapeutic procedures. The Panel covered all fields of expertise in neuro-oncology, i.e. neurosurgeons, neurologists, neuropathologists, neuroradiologists, radiation and medical oncologists and clinical trial experts. The task made clearer and more transparent choices about outcomes considered most relevant through searching the references considered most relevant and evaluating their value. The scientific evidence of papers collected from the literature was evaluated and graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence and recommendations were given accordingly. The recommendations will provide a framework and assurance for the strategy of diagnostic and therapeutic measures to reduce complications from unnecessary treatment and cost. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China.

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Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long‐term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. The CSCs are thought to be largely responsible for tumor initiation, maintenance, dissemination, and relapse; therefore, their pivotal roles have revealed them to be promising targets in MB therapy. Our growing understanding of the major medulloblastoma molecular subgroups and the derivation of some of these groups from specific stem or progenitor cells adds additional layers to the CSC knowledge base. Herein we review the current knowledge of MB stem cells, highlight the molecular mechanisms relating to MB relapse and leptomeningeal dissemination, and incorporate these with the need to develop more effective and accurate therapies for MB patients.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

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AimsTumor electric fields therapy (TTFields) is emerging as a novel anti‐cancer physiotherapy. Despite recent breakthroughs of TTFields in glioma treatment, the average survival time for glioblastoma patients with TTFields is <2 years, even when used in conjugation with traditional anti‐cancer therapies. To optimize TTFields‐afforded efficacy against glioblastoma, we investigated the cancer cell‐killing effects of various TTFields paradigms using in vitro and in vivo models of glioblastoma.MethodsFor in vitro studies, the U251 glioma cell line or primary cell cultures prepared from 20 glioblastoma patients were treated with the tumor electric field treatment (TEFT) system. Cell number, volume, and proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, or 220 kHz), durations (24, 48, or 72 h), field strengths (1.0, 1.5, or 2.2V/cm), and output modes (fixed or random sequence output). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary glioblastoma cells. For in vivo studies, the therapeutic effect and safety profiles of random sequence electric field therapy in glioblastoma‐transplanted rats were assessed by calculating tumor size and survival time and evaluating peripheral immunobiological and blood parameters, respectively.ResultsIn the in vitro settings, TEFT was robustly effective in suppressing cell proliferation of both the U251 glioma cell line and primary glioblastoma cell cultures. The anti‐proliferation effects of TEFT were frequency‐ and “dose” (field strength and duration)‐dependent, and contingent on the field sequence output mode, with the random sequence mode (TEFT‐R) being more effective than the fixed sequence mode (TEFT‐F). Genetic tests were performed in 11 of 20 primary glioblastoma cultures, and 6 different genetic traits were identified them. However, TEFT exhibited comparable anti‐proliferation effects in all primary cultures regardless of their genetic traits. TEFT also inhibited the invasiveness of primary glioblastoma cells in transwell experiments. In the in vivo rat model of glioblastoma brain transplantation, treatment with TEFT‐F or TEFT‐R at frequency of 200 kHz and field strength of 2.2V/cm for 14 days significantly reduced tumor volume by 42.63% (TEFT‐F vs. control, p = 0.0002) and 63.60% (TEFT‐R vs. control, p < 0.0001), and prolonged animal survival time by 30.15% (TEFT‐F vs. control, p = 0.0415) and 69.85% (TEFT‐R vs. control, p = 0.0064), respectively. The tumor‐bearing rats appeared to be well tolerable to TEFT therapies, showing only moderate increases in blood levels of creatine and red blood cells. Adverse skin reactions were common for TEFT‐treated rats; however, skin reactions were curable by local treatment.ConclusionTumor electric field treatment at optimal frequency, strength, and output mode markedly inhibits the cell viability, proliferation, and invasiveness of primary glioblastoma cells in vitro independent of different genetic traits of the cells. Moreover, a random sequence electric field output confers considerable anti‐cancer effects against glioblastoma in vivo. Thus, TTFields are a promising physiotherapy for glioblastoma and warrants further investigation.