Association for NeuroOncology (EANO) (2017). European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncology, 18(6):e315-e329. DOI: https://doi.org/10.1016/ S1470-2045(17) Implementing this guideline requires multidisciplinary and multiprofessional structures of care and defined processes of diagnosis and treatment.

This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures. AF and DF report no conflicts of interest. FundingThe preparation of this guideline was not funded. The members of the task force did not receive compensation for their participation. 5 SummaryThis guideline provides recommendations for the diagnostic and therapeutic procedures for patients with malignant gliomas. It differentiates evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein shall provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline will contribute to a critical appreciation of concurrent medications with a focus on the controlled use of anticonvulsants and steroids. It shall serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarized here will require interdisciplinary structures of care for brain tumor patients and structured processes of diagnostic and therapeutic procedures. Key wordsAnaplastic, glioma, glioblastoma, surgery, radiotherapy, temozolomide, bevacizumab Search strategy and selection criteriaThis guideline was prepared by a task force assembled by the Executive Committee of the European Association for Neuro-Oncology (EANO) in 2013. The task force was designed to represent the different disciplines involved in the diagnosis and care of malignant glioma patients as well as to reflect the multinational composition of EANO.References for this review were identified through searches of PubMed with the search terms "glioma", "anaplastic", "glioblastoma", "trial", "clinical", "radiotherapy" 6 and "chemotherapy" from January 2005 to January 2013. Articles were also identified through searches of the authors` own files. Onl...

Integrins are extracellular matrix receptors involved in tumour invasion and angiogenesis. Although there is evidence that inhibiting integrins might enhance the efficiency of radiotherapy, little is known about the exact mechanisms involved in the integrin-dependent modulation of tumor radiosensitivity. The purpose of this study was to investigate the role of avb3 and avb5 integrins in glioblastoma cell radioresistance and overall to decipher the downstream biological pathways. We first demonstrated that silencing avb3 and avb5 integrins with specific siRNAs significantly reduced the survival after irradiation of 2 glioblastoma cell lines: U87 and SF763. We then showed that integrin activity and integrin signalling pathways controlled the glioma cell radiosensitivity. This regulation of glioma cell response to ionising radiation was mediated through the integrin-linked kinase, ILK, and the small GTPase, RhoB, by two mechanisms. The first one, independent of ILK, consists in the regulation of the intracellular level of RhoB by avb3 or avb5 integrin. The second pathway involved in cell radiosensitivity consists in RhoB activation by ionising radiation through ILK. Furthermore, we demonstrated that the avb3/avb5 integrins/ILK/ RhoB pathway controlled the glioma cells radiosensitivity by regulating radiation-induced mitotic cell death. This work identifies a new biological pathway controlling glioblastoma cells radioresistance, activated from the membrane through avb3 and/or avb5 integrins via ILK and RhoB. Our results are clues that downstream effectors of avb3 and avb5 integrins as ILK and RhoB might also be promising candidate targets for improving the efficiency of radiotherapy and thus the clinical outcome of patients with glioblastoma. ' 2008 Wiley-Liss, Inc.Key words: glioblastoma; radiosensitivity; integrin; ILK; RhoB Despite recent advances in diagnostic imaging, neurosurgical techniques, radiation therapy and chemotherapy, 1 glioblastoma, one of the most common primary brain tumours, is still associated with a dismal prognosis. Almost all of the patients will die of a relapse in the radiation field as a result of low tumour sensitivity to ionising radiation. The low tumour sensitivity to radiotherapy is not only due to the modulation of different biological signal transduction pathways in tumour cells but also due to a cross-talk between the tumour cells and their microenvironment. Our previous results have shown that factors controlling the microenvironment, such as basic fibroblast factor (FGF-2), modulate the tumour cell radioresistance via the small GTPase RhoB which itself also regulates angiogenesis via metalloproteinase 2 (MMP2) and hypoxia in the glioblastoma U87 cell model. Cell adhesion to extracellular matrix (ECM) is known to confer a cell-adhesion-mediated chemotherapeutic drug resistance for hematopoietic and solid tumours.9 Among integrins, the b1 integrin has been largely involved in cell survival after a genotoxic injury by modulating DNA repair 10 or protecting cells from apoptosis. 11Fe...

Hypoxia is a crucial factor in tumor aggressiveness and resistance to treatment, particularly in glioma. Our previous results have shown that inhibiting the small GTPase RhoB increased oxygenation of U87 human glioblastoma xenografts, in part, by regulating angiogenesis. We investigated here whether RhoB might also control a signaling pathway that would permit glioma cells to adapt to hypoxia. We first showed that silencing RhoB with siRNA induced degradation and inhibition of the transcriptional activity of the hypoxiainducible factor by the proteasome in U87 hypoxic cells. This RhoB-dependent degradation of hypoxia-inducible factor-1A in hypoxic conditions was mediated by the Akt/glycogen synthase kinase-3B pathway. While investigating how hypoxia could activate this signaling pathway, using the GST-Rhotekin RBD pulldown assay, we showed the early activation of RhoB by reactive oxygen species under hypoxic conditions and, subsequently, its participation in the ensuing cellular adaptation to hypoxia. Overall, therefore, our results have not only highlighted a new signaling pathway for hypoxia controlled by the small GTPase RhoB, but they also strongly implicate RhoB as a potentially important therapeutic target for decreasing tumor hypoxia. (Cancer Res 2006; 66(1): 482-9)