title: Input of molecular analysis in medical management of primary brain tumor patients.
abstract: Primary brain tumors comprise a large group of malignant and non-malignant tumors including heterogeneous entities with various biological and clinical behaviors. Up till recently, diagnosis of brain cancers, that drives treatment decision-making, was based on integration of clinical, radiological and pathological features of patients and tumors. Over the last years, practical neuro-oncology has entered an era of molecular-based personalized medicine. Indeed, molecular features of tumors provide critical information to physicians for daily clinical management of patients and for design of relevant clinical research. Sporadic gliomas or glial tumors are the most common primary brain tumors in adults. Recently, their medical management has been revolutionized by molecular data. Indeed, optimal therapeutic management of grade III glioma patients now requires assessment of chromosome arms 1p/19q copy number and IDH mutational statuses as predictive and prognostic biomarkers. Indeed, two large phase III clinical trials have demonstrated that early chemotherapy plus radiotherapy, versus radiotherapy alone, doubles median overall survival of patients suffering from 1p/19q co-deleted and/or IDH mutated anaplastic oligodendroglial tumor. Interestingly, both biomarkers have been identified in a large proportion of WHO grade II gliomas. Their clinical value, in this population, is under investigation through multiple phase III clinical trials. In sporadic WHO grade I gliomas, and specifically in pilocytic astrocytomas, MAPK signaling pathway activation is a frequent event, mainly due to genetic alterations involving BRAF gene. This characteristic opens new therapeutic perspectives using MAPK signaling pathway inhibitors. Finally, in the most aggressive gliomas, WHO grade IV gliomas, two critical biomarkers have been identified: (i) MGMT promoter methylation associated with longer survival and better response to chemotherapy and (ii) IDH mutations predicting better prognosis. Although, further studies are needed, MGMT promoter methylation will undoubtedly be transferred soon to clinical practice. Molecular characteristics are beginning to be valuable and indispensable in neuro-oncology for better management of brain tumors patients. The near future will be marked by identification of novel molecular biomarkers and their validation for clinical practice.
authors.affiliation: AP-HP, Hopital Universitaire La Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UM 75, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; Inserm, U 1127, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; CNRS, UMR 7225, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; ICM, 47, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: ahmed.idbaih@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: AP-HP, Hopital Universitaire La Pitié-Salpêtrière, Service de neurologie 2-Mazarin, 47-83, boulevard de l'Hôpital, 75013 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UM 75, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; Inserm, U 1127, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; CNRS, UMR 7225, ICM, 47, boulevard de l'Hôpital, 75013 Paris, France; ICM, 47, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Duran-Peña
authors.affiliation: Service de Neuro-oncologie, Hôpital Neurologique, Hospices Civils de Lyon, 3, quai des Célestins, 69002 Lyon, France; Université Claude-Bernard Lyon 1, 43, boulevard du 11 Novembre 1918, 69100 Villeurbanne, France.
authors.forename: C
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: Service de Neuro-oncologie, Hôpital Neurologique, Hospices Civils de Lyon, 3, quai des Célestins, 69002 Lyon, France; Université Claude-Bernard Lyon 1, 43, boulevard du 11 Novembre 1918, 69100 Villeurbanne, France.
authors.forename: F
authors.initials: F
authors.lastname: Ducray
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Biomarqueur; Brain tumor; Glioma; Gliome; Traitement; Treatment; Tumeur cérébrale