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1. Incidence and Characteristics of Pseudoprogression in IDH-mutant High-Grade Gliomas: A POLA Network Study

Author: Antoine Seyve, Caroline Dehais, Olivier Chinot, Apolline Djelad, Elisabeth Cohen-Moyal, Charlotte Bronnimann, Carole Gourmelon, Evelyne Emery, Philippe Colin, Mathieu Boone, Elodie Vauléon, Olivier Langlois, Anna-Luisa di Stefano, Romuald Seizeur, François Ghiringhelli, Anne D’Hombres, Loic Feuvret, Jacques Guyotat, Laurent Capelle, Catherine Carpentier, Louis Garnier, Jérôme Honnorat, David Meyronet, Karima Mokhtari, Dominique Figarella-Branger, François Ducray, Hospices Civils de Lyon, Departement de Neurologie (HCL), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, and Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Subjects: Cancer Research, High-grade glioma, Oncology, pseudoprogression, Neurology (clinical), IDH-mutant, chemotherapy, radiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. Methods We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. Results In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. Conclusion In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.
Published: 2023

2. Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study

Author: Marine Lottin, Alexandre Escande, Luc Bauchet, Marie Albert-Thananayagam, Maël Barthoulot, Matthieu Peyre, Mathieu Boone, Sonia Zouaoui, Jacques Guyotat, Guillaume Penchet, Johan Pallud, Henry Dufour, Evelyne Emery, Michel Lefranc, Sébastien Freppel, Houman Namaki, Edouard Gueye, Jean-Jacques Lemaire, Bertrand Muckensturm, Robin Srour, Stéphane Derrey, Apolline Monfilliette, Jean-Marc Constans, Claude-Alain Maurage, Bruno Chauffert, Nicolas Penel, CHU Amiens-Picardie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Faculté de Médecine Henri Warembourg - Université de Lille, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Registre des Tumeurs de l'Hérault, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital saint Pierre, GH Sud Réunion, Hôpital de Perpignan, Centre Hospitalier Saint Jean de Perpignan, CHU Limoges, Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Régional d'Orléans (CHRO), Hôpitaux Civils de Colmar, Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'oncologie médicale (CHRU Lille), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: surgery, Cancer Research, intracranial, recurrence, Oncology, solitary fibrous tumour, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], hemangiopericytoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs.Methods: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS).Results: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03).Conclusion: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.
Published: 2023
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3. Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH-Mutant Gliomas: A French POLA Network Study

Author: Coline Montégut, Jean-Sébastien Guillamo, François Ducray, Caroline Dehais, Elisabeth Cohen-Jonathan Moyal, Christine Desenclos, Antoine Petit, Romuald Seizeur, Lien Bekaert, Claude Gaultier, Marie Jeannette Motuo Fotso, Marie Blonski, Jean-Sébastien Frenel, Elodie Vauléon, Olivier Langlois, Georges Noel, Antoine F. Carpentier, Anna Luisa Di Stefano, Charlotte Bronnimann, Dominique Figarella-Branger, Olivier Chinot, Emeline Tabouret, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Cancérologie de Strasbourg Europe (ICANS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Bordeaux [Bordeaux], Service d'Anatomie Pathologique et de Neuropathologie [Hôpital de la Timone - CHU - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Rôle et mécanismes d'action de l'adrenomedulline dans la croissance tumorale : Application au modèle des gliomes, Université de la Méditerranée - Aix-Marseille 2-IFR11-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, high grade glioma, Oncology, geriatric assessment, IDH mutation, elderly, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (
Published: 2022

4. The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas

Author: Guénaëlle Levallet, Fatéméh Dubois, Arthur Leclerc, Edwige Petit, Lien Bekaert, Maxime Faisant, Christian Creveuil, Evelyne Emery, Gérard Zalcman, Emmanuèle Lechapt-Zalcman, Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Anatomie Pathologique [CHU Caen], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and APRI 2012
Subjects: Brain Neoplasms, hypoxia, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organic Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Isocitrate Dehydrogenase, Catalysis, Computer Science Applications, Inorganic Chemistry, MicroRNAs, angiogenesis, glioma, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Mutation, Humans, miRNA, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract: CERVOXY; International audience; IDH (isocitrate dehydrogenase) mutation, hypoxia, and neo-angiogenesis, three hallmarks of diffuse gliomas, modulate the expression of small non-coding RNAs (miRNA). In this paper, we tested whether pro-angiogenic and/or pro-hypoxic miRNAs could be used to monitor patients with glioma. The miRNAs were extracted from tumoral surgical specimens embedded in the paraffin of 97 patients with diffuse gliomas and, for 7 patients, from a blood sample too. The expression of 10 pro-angiogenic and/or pro-hypoxic miRNAs was assayed by qRT-PCR and normalized to the miRNA expression of non-tumoral brain tissues. We confirmed in vitro that IDH in hypoxia (1% O2, 24 h) alters pro-angiogenic and/or pro-hypoxic miRNA expression in HBT-14 (U-87 MG) cells. Then, we reported that the expression of these miRNAs is (i) strongly affected in patients with glioma compared to that in a non-tumoral brain; (ii) correlated with the histology/grade of glioma according to the 2016 WHO classification; and (iii) predicts the overall and/or progression-free survival of patients with glioma in univariate but not in a multivariate analysis after adjusting for sex, age at diagnosis, and WHO classification. Finally, the expression of miRNAs was found to be the same between the plasma and glial tumor of the same patient. This study highlights a panel of seven pro-angiogenic and/or pro-hypoxic miRNAs as a potential tool for monitoring patients with glioma.
Published: 2022
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5. Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol

Author: Laurent Castera, William Kao, J. Lequesne, Bénédicte Clarisse, Elodie Coquan, J. Lacroix, Aurélie Capel, Marie Lange, Benoit Andre, Jean-Michel Grellard, Paul Lesueur, Anaïs Lelaidier, Julien Geffrelot, Audrey Emmanuelle Dugué, Evelyne Emery, Dinu Stefan, David Hassanein Berro, Nicolas Goardon, Angélique Léger, Alexandra Leconte, Pierre-Emmanuel Brachet, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacie [Baclesse Caen], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), This trial (NCT03212742) is granted by the French Cancer Institute and French Health Ministry (PHRC-K15–135). Astra-Zeneca provided olaparib. Olaparib is provided free of charge to enrolled patients by Astra Zeneca., and Bodescot, Myriam
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Radiosensitizer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Poly(ADP-ribose) Polymerase Inhibitors, olaparib, lcsh:RC254-282, Piperazines, Olaparib, 03 medical and health sciences, chemistry.chemical_compound, Study Protocol, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Internal medicine, Biopsy, Genetics, medicine, Temozolomide, Humans, Antineoplastic Agents, Alkylating, Chemotherapy, medicine.diagnostic_test, Radiotherapy, business.industry, Brain Neoplasms, Chemoradiotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, Radiosensitizer, olaparib, 030104 developmental biology, chemistry, Poly (ADP-ribose) polymerase (PARP), 030220 oncology & carcinogenesis, Concomitant, Phthalazines, Radiotherapy, Intensity-Modulated, business, Glioblastoma, medicine.drug
Abstract: International audience; BACKGROUND:Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM.METHODS:The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.DISCUSSION:Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.TRIAL REGISTRATION:NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.
Published: 2019

6. Simultaneous mapping of vasculature, hypoxia and proliferation using DSC-MRI, 18F-FMISO PET, and 18F-FLT PET in relation to contrast enhancement in newly diagnosed glioblastoma

Author: Collet, Solène, Guillamo, Jean Sébastien, Berro, David Hassanein, Chakhoyan, Ararat, Constans, Jean-Marc, Lechapt-Zalcman, Emmanuèle, Derlon, Jean-Michel, Hatt, Mathieu, Visvikis, Dimitris, Guillouet, Stéphane, Perrio, Cécile, Bernaudin, Myriam, Samuel, Valable, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Neurology [UCLA], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), CHU Amiens-Picardie, Laboratoire d'Anatomie Pathologique [CHU Caen], Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Couteau, Florence, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT)
Subjects: [SDV] Life Sciences [q-bio], Glioblastoma, PET, Vascular, [SDV]Life Sciences [q-bio], Proliferation, [CHIM] Chemical Sciences, Vasculature, [CHIM]Chemical Sciences, Oncology: Brain, Hypoxia, MRI
Abstract: CERVOXY/LDM TEP COLL; International audience; Conventional MRI plays a key role in the management of patients with high grade glioma but multiparametric MRI and PET tracers could provide further information to better characterize the tumor metabolism and heterogeneity, by identifying the regions having a high risk of recurrence. In this study, we focused on the proliferation, hypervascularization and hypoxia, all factors considered as factors of poor prognosis. They were assessed by measuring the uptake of 18F-FLT, the rCBV maps and the uptake of 18F-FMISO, respectively. For each modality, the volumes and high uptake sub-volumes (hotspots) were semi-automatically segmented and compared to contrast enhancement (CE) volume on T1w-Gd images, commonly used in the management of patient with glioblastoma. Methods: DSC MRI (31 patients), 18F-FLT PET (20 patients) and/or 18F-FMISO PET (20 patients), for a total of 31 patients, were performed on pre-operative glioblastoma patients. Volumes and hotspots were segmented on SUV maps for 18F-FLT (using FLAB) and 18F-FMISO (using mean contralateral + 3.3 SD) PET and on rCBV maps (using mean contralateral + 1.96 SD) for DSC MRI and overlaid on T1w-Gd images. For each modality, the percentage of peripheral volumes and the peripheral hotspot outside the CE volume were calculated. Results: All tumors showed high proliferation, hypervascularization and hypoxic regions. Images also showed pronounced heterogeneity of both tracers uptake and rCBV maps, within each individual case. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularization and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were [1.6% - 155.5 %], [1.5% - 89.5%] and [3.1% - 78.0%] for 18F-FLT, rCBV and 18F-FMISO respectively. All patients had hyperproliferative hotspots outside CE volume, whereas hotspots of hypervasculature and hypoxia were mainly detected within the enhancing region. Conclusion: The spatial analysis of the multiparametric maps with the segmented volumes and hotspots provides valuable information to optimize the management and treatment of the patients with glioblastoma.
Published: 2021

7. Management of giant presacral schwannoma. Clinical series and literature review

Author: Augustin Huet, Arthur Leclerc, Evelyne Emery, G Lebreton, Arnaud Alves, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Radiologie [CHU Caen], Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Physiopathologie et imagerie des troubles neurologiques (PhIND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: Adult, Male, medicine.medical_specialty, Sacrum, Constipation, Intraoperative Complication, [SDV]Life Sciences [q-bio], Schwannoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Back pain, Dysuria, Humans, Aged, Retrospective Studies, Surgical team, business.industry, Disease Management, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, 3. Good health, Surgery, Bowel obstruction, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Neurilemmoma, Follow-Up Studies
Abstract: Purpose Presacral schwannomas are rare tumors. Due to their benign nature and slow growth, these tumors are often giant and become difficult to treat. Their removal is a surgical challenge with different strategies reported in the literature. This study presents the consecutives cases of presacral schwannomas operated on in our institution, our surgical strategy and literature review. Methods This retrospective study includes all consecutive patients operated on for a pre-sacral schwannoma in our department between 2006 and 2019, i.e. 6 patients. We report clinical features, pre and post-operative imaging, surgical data and post-operative outcomes. Results All patients had symptoms before surgery (constipation, dysuria, radicular or lower back pain) with an average duration of 7.4 months. All patients underwent an MRI and a CT scan before the surgery. Five patients had type III schwannoma according to Klimo classification and one patient had a type II. The average size was 504,9 cm3 (range 53,1-1495,4). All the patients were operated on by an anterior approach in a double team with an mean duration of 246 min. Intraoperative bleeding was less than 500 ml for 4 patients, 2 patients had significant bleeding (2700 and 2900 mL). Excision was total or subtotal in all cases. One patient had an intraoperative complication (air embolism). Follow up at 3 months was excellent with a disappearance of symptoms for all patients except one patient who retained constipation. One patient had a late complication (bowel obstruction due to tissue adhesions). At last follow-up after phone interview, no patient had clinical symptoms that could suggest a recurrence. Conclusion The anterior approach with a double surgical team is a great option for the treatment of presacral schwannoma. Combined with adequate preoperative imaging and intraoperative stimulation, it reduces the risk of intra and postoperative complications.
Published: 2021

8. New insights into the anatomo-functional architecture of the right sagittal stratum and its surrounding pathways: an axonal electrostimulation mapping study

Author: David Hassanein Berro, Hugues Duffau, Guillaume Herbet, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Brunaud, Carole, Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Histology, [SDV]Life Sciences [q-bio], Direct electrical stimulation, 050105 experimental psychology, Functional mapping, White matter, 03 medical and health sciences, 0302 clinical medicine, Fasciculus, medicine, Arcuate fasciculus, Humans, 0501 psychology and cognitive sciences, Thalamocortical radiations, Inferior longitudinal fasciculus, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Wakefulness, Vestibular system, Brain Mapping, Dysesthesia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Brain Neoplasms, General Neuroscience, 05 social sciences, Superior longitudinal fasciculus, Right sagittal stratum, Anatomy, Glioma, Middle Aged, biology.organism_classification, White Matter, Axons, Electric Stimulation, [SDV] Life Sciences [q-bio], Awake surgery, medicine.anatomical_structure, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Nerve Net, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: CERVOXY CLIN; International audience; The sagittal stratum (SS) is a large sheet-like structure where major axonal fiber tracts cross, though its anatomical delineations are still debated. Here we investigated the poorly studied anatomo-functional organization of the right SS using direct electrical stimulation (DES) in patients undergoing wide-awake surgery for a cerebral glioma. Seventeen patients were included. There were six males, the mean age was 38 years old. One patient underwent surgery twice. Fourteen patients were right-handed and one was ambidextrous. Behavior tasks were used to monitor online the patients’ functions during DES, including visual and somesthetic processes, semantics, language, spatial and social cognition. Beyond the cortical DES, the mapping of axonal pathways evoked various functional responses. At the level of the core of the right SS, there were visual disturbances, visual hemi-agnosia, semantic paraphasia, left spatial neglect, confusion and comprehension difficulties, anomia, and mentalizing disturbances. At the level of the surrounding axonal pathways, there were left spatial neglect, anomia, vertigo, dysesthesia, and hearing disturbances. Our functionally defined three-dimensional map indicates that this complex region has a multilayered functional architecture, and supports an organization founded on two anatomical systems: a core system formed by the optic radiations, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus, and a peripheral one composed of surrounding or intersecting white matter tracts, including the superior longitudinal fasciculus/arcuate fasciculus, thalamocortical radiations, auditory radiations, and parieto-insular vestibular system. These results should prompt neurosurgeons to achieve awake DES mapping within the right SS because of the likelihood of causing multiple and irreversible structural disconnections.
Published: 2021

9. Hyperplasie lymphoïde associée au VIH : une localisation orbitaire exceptionnelle

Author: Jean-Claude Quintyn, Marie-Alice Laville, Marie-Laure Quintyn, Camille Linard, Pierre Branger, Arthur Leclerc, Françoise Chapon, Evelyne Emery, Service de Neurochirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Ophthalmologie [CHU CAEN], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Service de Neurologie [CHU Caen]
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), medicine.disease_cause, medicine.disease, Lymphoid hyperplasia, 3. Good health, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Pseudolymphoma, Benign Lymphoid Hyperplasia, Intracranial lesions, Lymph, medicine.symptom, business
Abstract: HIV-related lymphoid hyperplasia has been exceptionally described outside lymph nodes. To our knowledge, 3 cases of nasopharyngeal localisation have been described in the literature. We report here an intracranial localisation with an important ophthalmological clinical impact. Our observation allows us to approach the differential diagnoses of intracranial lesions in the HIV-positive patient, to analyse the differential diagnoses of benign lymphoid hyperplasia and to discuss the therapeutic options.
Published: 2020

10. Overt speech feasibility using continuous functional magnetic resonance imaging: Isolation of areas involved in phonology and prosody

Author: Aram Ter Minassian, Jean-Michel Lemée, Evelyne Emery, David Hassanein Berro, Philippe Menei, Louis-Marie Leiber, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de radiologie, Physiopathologie et imagerie des troubles neurologiques (PhIND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie et réanimation chirurgicale, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurochirurgie [CHU Angers], and PRES Université Nantes Angers Le Mans (UNAM)
Subjects: 0301 basic medicine, Adult, Male, Computer science, Speech recognition, speech, [SDV]Life Sciences [q-bio], feedback, Lateralization of brain function, acoustic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, medicine, Humans, Prosody, Artifact (error), Brain Mapping, medicine.diagnostic_test, fMRI, Motor control, Contrast (statistics), Brain, Phonology, Magnetic Resonance Imaging, phonology, 030104 developmental biology, Acoustic Stimulation, Covert, overt, Feasibility Studies, Female, Functional magnetic resonance imaging, covert, 030217 neurology & neurosurgery
Abstract: CERVOXY CLIN; International audience; To avoid motion artifacts, almost all speech‐related functional magnetic resonance imagings (fMRIs) are performed covertly to detect language activations. This method may be difficult to execute, especially by patients with brain tumors, and does not allow the identification of phonological areas. Here, we aimed to evaluate overt task feasibility. Thirty‐three volunteers participated in this study. They performed two functional sessions of covert and overt generation of a short sentence semantically linked with a word. Three main contrasts were performed: Covert and Overt for the isolation of language‐activated areas, and Overt > Covert for the isolation of the motor cortical activation of speech. fMRI data preprocessing was performed with and without unwarping, and with and without regression of movement parameters as confounding variables. All types of results were compared to each other. For the Overt contrast, Dice coefficients showed strong overlap between each pair of types of results: 0.98 for the pair with and without unwarping, and 0.9 for the pair with and without movement parameter regression. The Overt > Covert contrast allowed isolation of motor laryngeal activations with high statistical reliability and revealed the right‐lateralized temporal activity related to acoustic feedback. Overt speaking during magnetic resonance imaging induced few artifacts and did not significantly affect the results, allowing the identification of areas involved in primary motor control and prosodic regulation of speech. Unwarping and motion artifact regression in the postprocessing step, seem to not be necessary. Changes in lateralization of cortical activity by overt speech shall be explored before using these tasks for presurgical mapping.
Published: 2020

11. Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients

Author: Guillaume Penchet, Serge Bracard, Lucas Troude, B. Irthum, P. Chassagne, Jean-Rodolphe Vignes, P.-H. Roche, Jean-Paul Lejeune, M. Lonjon, K. Mourier, Fashe investigators, Xavier Leclerc, Jérôme Berge, Thierry Civit, I. Pelissou-Guyotat, N. Aghakani, J. Drouineau, François Proust, Frédéric Ricolfi, J. Sedat, B. Bataille, Xavier Morandi, Elsa Magro, Evelyne Emery, Helene Cebula, Thomas Gaberel, Jean-Yves Gauvrit, P. David, Laurent Thines, Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de médecine gériatrique [CHU Rouen], CHU Bois Guiilaume-CHU Rouen, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Marseille, Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service médecine gériatrique Charles Nicolle [Rouen], Normandie Université (NU)-CHU Bois Guiilaume, and CCSD, Accord Elsevier
Subjects: Brain aneurysm, Male, medicine.medical_specialty, Microsurgery, Subarachnoid hemorrhage, Activities of daily living, Aneurysm, Ruptured, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Cognition, Quality of life, Surveys and Questionnaires, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prospective Studies, Pathological, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Significant difference, Endovascular Procedures, Intracranial Aneurysm, Recovery of Function, Subarachnoid Hemorrhage, medicine.disease, 3. Good health, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Personal Autonomy, Quality of Life, Observational study, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. Methods This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744 ) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. Results The 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio = 4.29; P = 0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. Conclusion Elderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.
Published: 2019

12. Resting‐state functional magnetic resonance imaging versus task‐based activity for language mapping and correlation with perioperative cortical mapping

Author: Aram Ter Minassian, Jean-Michel Lemée, Louis-Marie Leiber, Florian Bernard, Philippe Menei, Eva Chinier, David Hassanein Berro, Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Politecnico di Torino = Polytechnic of Turin (Polito), Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'anesthésie et réanimation chirurgicale, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), and Politecnico di Torino [Torino] (Polito)
Subjects: Male, genetic structures, brain surgery, Computer science, Language mapping, Neurosurgical Procedures, Task (project management), Correlation, Behavioral Neuroscience, 0302 clinical medicine, Task Performance and Analysis, Original Research, Language, Brain Mapping, medicine.diagnostic_test, Brain Neoplasms, 05 social sciences, fMRI, Brain, Middle Aged, Magnetic Resonance Imaging, Semantics, Female, psychological phenomena and processes, brain tumor, Adult, Adolescent, Rest, Brain tumor, behavioral disciplines and activities, 050105 experimental psychology, Perioperative Care, lcsh:RC321-571, 03 medical and health sciences, Young Adult, medicine, Humans, 0501 psychology and cognitive sciences, [INFO]Computer Science [cs], Wakefulness, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, Functional Neuroimaging, Perioperative, medicine.disease, Electric Stimulation, Resting state functional magnetic resonance imaging, nervous system, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: Introduction Preoperative language mapping using functional magnetic resonance imaging (fMRI) aims to identify eloquent areas in the vicinity of surgically resectable brain lesions. fMRI methodology relies on the blood‐oxygen‐level‐dependent (BOLD) analysis to identify brain language areas. Task‐based fMRI studies the BOLD signal increase in brain areas during a language task to identify brain language areas, which requires patients' cooperation, whereas resting‐state fMRI (rsfMRI) allows identification of functional networks without performing any explicit task through the analysis of the synchronicity of spontaneous BOLD signal oscillation between brain areas. The aim of this study was to compare preoperative language mapping using rsfMRI and task fMRI to cortical mapping (CM) during awake craniotomies. Methods Fifty adult patients surgically treated for a brain lesion were enrolled. All patients had a presurgical language mapping with both task fMRI and rsfMRI. Identified language networks were compared to perioperative language mapping using electric cortical stimulation. Results Resting‐state fMRI was able to detect brain language areas during CM with a sensitivity of 100% compared to 65.6% with task fMRI. However, we were not able to perform a specificity analysis and compare task‐based and rest fMRI with our perioperative setting in the current study. In second‐order analysis, task fMRI imaging included main nodes of the SN and main areas involved in semantics were identified in rsfMRI. Conclusion Resting‐state fMRI for presurgical language mapping is easy to implement, allowing the identification of functional brain language network with a greater sensitivity than task‐based fMRI, at the cost of some precautions and a lower specificity. Further study is required to compare both the sensitivity and the specificity of the two methods and to evaluate the clinical value of rsfMRI as an alternative tool for the presurgical identification of brain language areas., We compared task‐based and resting‐state fMRI for the identification of language network in patient surgically treated for a brain tumor. fMRI data were then compared to the standard, the electric cortical stimulation. Resting‐state fMRI was able to detect brain language areas during CM with a sensitivity of 100% compared to 64% with task fMRI.
Published: 2019

13. Comparison between MRI-derived ADC maps and 18FLT-PET in pre-operative glioblastoma

Author: Jean-Sébastien Guillamo, Samuel Valable, J M Derlon, David Hassanein Berro, Louisa Barré, Solène Collet, Evelyne Emery, Jean-Marc Constans, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Départment de Neuroradiologie [CHU Caen], GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], and CCSD, Accord Elsevier
Subjects: Percentile, Cellularity, [SDV]Life Sciences [q-bio], 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Medicine, Radiology, Nuclear Medicine and imaging, Multiparametric Magnetic Resonance Imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Radiological and Ultrasound Technology, business.industry, medicine.disease, Pre operative, nervous system diseases, [SDV] Life Sciences [q-bio], body regions, ADC, MESH: Glioblastoma, MRI, ADC, 18FLT-PET, Cellularity, 18FLT-PET, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), business, Nuclear medicine, Glioblastoma, 030217 neurology & neurosurgery, MRI
Abstract: Background and purpose Among principal MRI sequences used for a better pre-therapeutic characterization of glioblastoma (GBM), DWI-derived ADC is expected to be a good parameter for the evaluation of cellularity, due to restricted water diffusivity. We aimed here to compare ADC maps to 18FLT-PET, a proliferation tracer, in GBM cases. Materials and methods Patients underwent 18FLT-PET, followed by multiparametric magnetic resonance imaging (MRI) just prior to surgery. We analysed in this study twenty GBM confirmed patients. The 5th percentile (5p) of the ADC values were thresholded to define the ADCmin ROI, while the 95th percentile (95p) of the SUV FLT values were used to define the FLTmax ROI. The statistical and spatial correlations between these two groups of ROIs were analyzed. Results We did not observe any significant correlations between ADCmin and FLTmax cut-off values (R2 = 0.0285), neither between ADCmin and FLTmax ROIs (mean Dice = 0.09 ± 0.12). Mean ADC values in the FLTmax defined ROI were significantly higher than the values in the ADCmin ROI (P Conclusions When comparing ADC maps to 18FLT uptake, we did not observe significant anatomical overlap nor correlation, between the regions of low ADC and high FLT disabling to clearly link ADC values to cellular proliferation. The exact significance of ADC maps in GBM has yet to be elaborated.
Published: 2019

14. Efficacy and Tolerance of Post-operative Hypo-Fractionated Stereotactic Radiotherapy in a Large Series of Patients With Brain Metastases

Author: Xavier Mirabel, Geoffrey Martinage, Raphaëlle Mouttet-Audouard, Emilie Bogart, Evelyne Emery, Samira Makhloufi-Martinage, Eric Lartigau, Erwan Rault, David Pasquier, Dinu Stefan, Julien Geffrelot, Laurent Basson, Nicolas Reyns, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Stereotactic radiation therapy, Gastroenterology, lcsh:RC254-282, surgery, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cyberknife, Internal medicine, medicine, Clinical endpoint, brain metastasis, radiotherapy, Original Research, hypofractionated stereotactic radiation therapy, business.industry, Retrospective cohort study, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Metastasectomy, business, Brain metastasis
Abstract: International audience; Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs).Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT.Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22–83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions (n = 52, 33%) and 30 Gy in 5 fractions (n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81–93%] and 81% [95%CI, 70–88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81–93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0–17.9 months] and the OS rate at 1 year was 58% [95% CI, 50–65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis.Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients.
Published: 2019

15. Promoter hypermethylation of genes encoding for RASSF/Hippo pathway members reveals specific alteration pattern in diffuse gliomas

Author: Gaëtane Planchard, Sylvie Lecot-Cotigny, Guénaëlle Levallet, Gérard Zalcman, Jean-Sébastien Guillamo, Emmanuèle Lechapt-Zalcman, Lien Bekaert, Christian Creveuil, Evelyne Emery, Elodie A. Pérès, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de Biostatistique et de Recherche Clinique (UBRC), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurochirurgie [CHU Caen], Laboratoire d'Anatomie Pathologique [CHU Caen], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and GHU Paris Psychiatrie et Neurosciences
Subjects: 0301 basic medicine, Adult, Male, Adolescent, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Protein Serine-Threonine Kinases, Pathology and Forensic Medicine, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Recurrence, medicine, Gene silencing, Humans, Hippo Signaling Pathway, Gene Silencing, Promoter Regions, Genetic, Gene, Aged, Neoplasm Staging, Aged, 80 and over, Hippo signaling pathway, business.industry, Tumor Suppressor Proteins, Astrocytoma, Promoter, Methylation, Glioma, DNA Methylation, Middle Aged, medicine.disease, Prognosis, 030104 developmental biology, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, Molecular Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Oligodendroglioma, Neoplasm Grading, business, Signal Transduction
Abstract: Ras association domain family (RASSF)/Hippo pathway alterations are poorly characterized in diffuse gliomas. We assayed promoter methylation of LATS1/2, MST1(STK4)/MST2(STK3), RASSF1, RASSF2, Nore1A/RASSF5, RASSF6, and RASSF10 genes in 133 diffuse gliomas. The RASSF/Hippo pathway was highly silenced in gliomas, particularly RASSF1A (79.4%) and LATS2 (35.9%). The most frequent combination of promoter hypermethylation of one RASSF gene and one Hippo pathway member's gene was RASSF1/LATS2-coupled hypermethylation [n = 44 (33.08%)]. Hypermethylated profiles were related to IDH mutation, yet not randomly in IDH-mutated gliomas, because LATS2 promoter hypermethylation was more frequent in oligodendroglioma than in astrocytoma. RASSF1 and LATS2 promoter hypermethylation predicted a longer overall survival (OS). Considering hypermethylation of these two promoters, Cox proportional hazard regression analysis categorized the patients into three prognostic groups: i) high risk of death (n = 24; both RASSF1 and LATS2 unmethylated promoters; median OS, 13 months); ii) intermediate risk of death (n = 65; RASSF1 or LATS2 hypermethylated promoter; median OS, 50.5 months; HR = 3.3; 95% CI, 1.6–6.4; P = 0.001); and iii) low risk of death (n = 44; both RASSF1 and LATS2 hypermethylated promoters; median OS, 119 months; HR = 75.1; 95% CI, 3.3–15.1; P = 0.001). We have thus highlighted a simple two-gene (RASSF1/LATS2) methylation signature as a tool to stratify different prognostic groups of patients with diffuse glioma, adding further prognostic information within the IDH-mutated group.
Published: 2019

16. Proton therapy for treatment of intracranial benign tumors in adults: A systematic review

Author: Paul Lesueur, Jacques Balosso, Juliette Thariat, Dinu Stefan, Abdulhamid Chaikh, Jean Louis Habrand, K.I. Cao, Thomas Tessonnier, Evelyne Emery, Valentin Calugaru, Catherine Nauraye, Yves Reznik, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Institut Curie [Paris], Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service Endocrinologie - Diabétologie [CHU Caen], Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Département de cancérologie et radiothérapie, CHU Grenoble, and ARCHADE (Advanced Resource Centre for HADrontherapy in Europe)
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, Neurinoma, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiosurgery, 03 medical and health sciences, 0302 clinical medicine, Paraganglioma, Pituitary adenoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Spinal canal, Proton therapy, business.industry, Brain Neoplasms, General Medicine, medicine.disease, Craniopharyngioma, 3. Good health, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Benign Meningioma, Benign meningioma, Radiology, Para ganglioma, business
Abstract: Introduction The depth-dose distribution of a proton beam, materialized by the Bragg peak makes it an attractive radiation modality as it reduces exposure of healthy tissues to radiations, compared with photon therapy Prominent indications, based on a long-standing experience are: intraocular melanomas, low-grade skull-base and spinal canal malignancies. However, many others potential indications are under investigations such as the benign morbid conditions that are compatible with an extended life-expectancy: low grade meningiomas, paragangliomas, pituitary adenomas, neurinomas craniopharyngioma or recurrent pleomorphic adenomas. Materials Given the radiation-induced risk of secondary cancer and the potential neurocognitive and functional alteration with photonic radiotherapy, we systematically analyzed the existing clinical literature about the use of proton therapy as an irradiation modality for cervical or intracranial benign tumors. The aim of this review was to report clinical outcomes of adult patients with benign intracranial or cervical tumors treated with proton therapy and to discuss about potential advantages of proton therapy over intensity modulated radiotherapy or radiosurgery. Results Twenty-four studies were included. There was no randomized studies. Most studies dealt with low grade meningiomas (n = 9). Studies concerning neurinoma (n = 4), pituitary adenoma (n = 5), paraganglioma (n = 5), or craniopharyngioma (n = 1) were fewer. Whatever the indication, long term local control was systematically higher than 90% and equivalent to series with conventional radiotherapy. Conclusion Proton-therapy for treatment of adult benign intracranial and cervical tumors is safe. Randomized or prospective cohorts with long term cognitive evaluations are needed to assess the real place of proton-therapy in the treatment of adults benign head and neck tumors.
Published: 2019

17. Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer)

Author: Evelyne Emery, Jean-Louis Habrand, Paul Lesueur, William Kao, Jean-Michel Grellard, J. Lequesne, V. Barraux, Juliette Thariat, Brigitte Marie, Dinu Stefan, Julien Geffrelot, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre de recherche clinique [CHU Caen] (CRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Aliments Bioprocédés Toxicologie Environnements (ABTE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Radiation Tolerance, 0302 clinical medicine, Stereotactic radiotherapy, Fractionation, Melanoma, Aged, 80 and over, education.field_of_study, Brain Neoplasms, Incidence (epidemiology), Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Kidney Neoplasms, Progression-Free Survival, Tumor Burden, 3. Good health, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Renal Cancer, Female, Radiation Dose Hypofractionation, France, Radiology, Adult, lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, lcsh:R895-920, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radioresistant, Radiosurgery, lcsh:RC254-282, Young Adult, 03 medical and health sciences, medicine, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, education, Aged, Retrospective Studies, business.industry, Research, Cancer, Retrospective cohort study, Brain metastases, medicine.disease, Radiation therapy, business, 030217 neurology & neurosurgery
Abstract: Background Until 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS). Methods Between 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data. Results After a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65–2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively. Conclusion Fractionation does not decrease LPFS. Even for small radioresistant brain metastases (
Published: 2018

18. A randomized controlled study assessing outcome, cognition, autonomy and quality of life in over 70-year-old patients after aneurysmal subarachnoid hemorrhage

Author: Proust, F., Bracard, S., Lejeune, J.-P., Thines, L., Leclerc, X., Penchet, G., Bergé, J., Morandi, X., Gauvrit, Jean-Yves, Mourier, K., Ricolfi, Frédéric, Lonjon, M., Sedat, J., Bataille, B., Droineau, J., Civit, T., Magro, E., Pelissou-Guyotat, I., Cebula, H., Lallouche, K., David, P., Emery, E., Courtheoux, P., Vignes, J.-R., Bénichou, J., Aghakani, N., Roche, P.-H., Gay, E., Bessou, P., Guabrillargues, J., Irthum, B., Investigators, Fashe, Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [HUS, Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Neurochirurgie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Neurochirurgie[Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurochirurgie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurochirurgie A [Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Service de neurochirurgie [CHU Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neurochirurgie [Hôpital Pasteur de Nice], Hôpital Pasteur [Nice] (CHU), Service de Neurochirurgie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de neurochirurgie [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de biostatistiques [CHU Rouen], Service de Neurochirurgie Fonctionnelle, Centre douleur chronique, APHM, Timone, 13385, Marseille, France, Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurochirurgie [CHRU de Besançon], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [CHU de Dijon], Service de Neurochirurgie [Poitiers], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand
Subjects: Male, Aging, Pediatrics, medicine.medical_specialty, Activities of daily living, Subarachnoid hemorrhage, medicine.medical_treatment, Population, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, Cognition, 0302 clinical medicine, Elderly, Randomized controlled trial, Quality of life, law, Modified Rankin Scale, Randomized controlled study, Activities of Daily Living, Humans, Medicine, education, Aged, Aged, 80 and over, education.field_of_study, Endovascular coiling, business.industry, Incidence (epidemiology), medicine.disease, Intracranial aneurysm, 3. Good health, Treatment Outcome, Research Design, Quality of Life, Female, Surgery, Neurology (clinical), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, 030217 neurology & neurosurgery
Abstract: Background Current aging of the population with good physiological status and the increasing incidence of subarachnoid hemorrhage (SAH) in elderly patients has enhanced the benefit of treatment in terms of independence and long-term quality of life (QoL). Methods From November 1, 2008 to October 30, 2012, 351 patients aged 70 years or older with aneurysmal SAH underwent adapted treatment: endovascular coiling (EV) for 228 (65%) patients, microsurgical clipping (MS) for 75 (29.3%) or conservative treatment for 48 (13.7%). Forty-one of these were randomized to EV (n = 20) or to MS (n = 21). The objectives were to determine the proportion of patients with modified Rankin Scale score ≤ 2 (independence) at 1 year, and, secondarily, to compare cognitive function on the Mini-Mental State Examination (MMSE), autonomy on the Activities of Daily Living Index (ADLI) and Instrumental Activities of Daily Living scale (IADL), and QoL, in the prospective and randomized arms, at 1 year. Results At 1 year, with 1 loss to follow-up in the EV arm, 11 patients (55%) were independent after EV occlusion and 8 (38.1%) after MS exclusion, without significant difference (P = 0.29). Mortality was higher after MS during the first 2 postoperative months, and thereafter the difference between MS and EV ceased to be significant. Cognitive function and autonomy scores were similar in both arms. Conclusion In elderly patients treated for aneurysmal SAH, approximately 50% were independent at 1 year, with conserved cognition and autonomy. EV and MS are valid procedures in this population, with similar results at 1 year in terms of independence, cognition, autonomy, and QoL.
Published: 2018

19. Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model

Author: Edouard Dezamis, Phong Dam Hieu, Johan Pallud, Luc Bauchet, Renata Ursu, J. Duntze, Olivier Langlois, Jean-Luc Barat, Alexandre Roux, Georges Noël, Marc Zanello, Elodie Sorbets, Jimmy Voirin, Jacques Guyotat, Antoine Petit, Philippe Menei, Robert Corns, Evelyne Emery, Johann Peltier, Fabien Litre, Nicolas Desse, Adeline Riondel, Sonia Zouaoui, François Caire, Pierre-Jean Le Reste, Pascale Fabbro-Peray, Jean-Rodolphe Vignes, Philippe Metellus, Antoine F. Carpentier, Anaïs Chivet, Etienne Audureau, Thierry Faillot, Emmanuelle Lechapt-Zalcman, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Avicenne [AP-HP], Hôpital Privé Clairval [Marseille], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Paul Strauss, CRLCC Paul Strauss, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département de Pathologie [CHU Caen], CHU Amiens-Picardie, Hôpital pasteur [Colmar], Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Neurochirurgie [CHU Limoges], CHU Limoges, Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, BESPIM, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de neurochirurgie [Rouen], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut des Neurosciences de Montpellier (INM), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Neurology, Prognostic models, medicine.medical_treatment, Conditional random forest, Recursive partitioning, [SDV.CAN]Life Sciences [q-bio]/Cancer, Karnofsky performance status, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Decision tree, Medicine, Humans, Overall survival, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, Adult patients, business.industry, Proportional hazards model, Brain Neoplasms, Decision Trees, Random survival forest, Retrospective cohort study, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Cox model, Disease Progression, Female, Surgery, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Recursive partitioning analysis, business, Glioblastoma, 030217 neurology & neurosurgery, Chemoradiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p
Published: 2018

20. [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis

Author: Lien Bekaert, Alain Manrique, Karim Bordji, Emmanuèle Lechapt-Zalcman, Keven F. Ponte, Louisa Barré, Pierre Branger, Jean-Marc Constans, Guénaëlle Levallet, Evelyne Emery, Myriam Bernaudin, Solène Collet, Samuel Valable, Edwige Petit, Jean-Sébastien Guillamo, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], Département de Pathologie [CHU Caen], Départment de Neuroradiologie [CHU Caen], Service de médecine nucléaire [CHU Caen], Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT)
Subjects: Adult, Male, [18F]-FMISO PET, medicine.medical_specialty, Angiogenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Radiosurgery, Disease-Free Survival, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Glioma, medicine, Biomarkers, Tumor, Cerebral Blood Volume, Humans, Radiology, Nuclear Medicine and imaging, Misonidazole, Hypoxia, Aged, Aged, 80 and over, Chemotherapy, Tumor hypoxia, medicine.diagnostic_test, Neovascularization, Pathologic, business.industry, Brain Neoplasms, Biological Transport, General Medicine, Hypoxia (medical), Middle Aged, medicine.disease, 3. Good health, Surgery, Radiation therapy, Positron emission tomography, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Immunohistochemistry, Tumor Hypoxia, Female, medicine.symptom, business, Glioblastoma
Abstract: Hypoxia in gliomas is associated with tumor resistance to radio- and chemotherapy. However, positron emission tomography (PET) imaging of hypoxia remains challenging, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival. In this prospective single center clinical study, 33 glioma patients (grade IV: n = 24, III: n = 3, and II: n = 6) underwent [18F]-FMISO PET and MRI including relative cerebral blood volume (rCBV) maps before surgery. Maximum standardized uptake values (SUVmax) and hypoxic volume were calculated, defining two groups of patients based on the presence or absence of [18F]-FMISO uptake. After surgery, molecular quantification of CAIX, VEGF, Ang2 (rt-qPCR), and HIF-1α (immunohistochemistry) were performed on tumor specimens. [18F]-FMISO PET uptake was closely linked to tumor grade, with high uptake in glioblastomas (GB, grade IV). Expression of biomarkers of hypoxia (CAIX, HIF-1α), and angiogenesis markers (VEGF, Ang2, rCBV) were significantly higher in the [18F]-FMISO uptake group. We found correlations between the degree of hypoxia (hypoxic volume and SUVmax) and expression of HIF-1α, CAIX, VEGF, Ang2, and rCBV (p
Published: 2017

21. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

Author: Johan, Pallud, Etienne, Audureau, Georges, Noel, Robert, Corns, Emmanuèle, Lechapt-Zalcman, Julien, Duntze, Vladislav, Pavlov, Jacques, Guyotat, Phong Dam, Hieu, Pierre-Jean, Le Reste, Thierry, Faillot, Claude-Fabien, Litre, Nicolas, Desse, Antoine, Petit, Evelyne, Emery, Jimmy, Voirin, Johann, Peltier, François, Caire, Jean-Rodolphe, Vignes, Jean-Luc, Barat, Olivier, Langlois, Edouard, Dezamis, Eduardo, Parraga, Marc, Zanello, Edmond, Nader, Michel, Lefranc, Luc, Bauchet, Bertrand, Devaux, Philippe, Menei, Philippe, Metellus, Anne, Vital, Centre Hospitalier Sainte-Anne, Université Paris Descartes - Paris 5 ( UPD5 ), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Universitaire de Caen, CHU Caen, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), CHU Pontchaillou [Rennes], Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurochirurgie, CHU Caen-Caen University Hospital, CHU Amiens-Picardie-Hôpital Nord - Amiens, Laboratoire de Neurochirurgie, Centre hospitalier Sainte-Anne (Paris), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Micro et nanomédecines biomimétiques ( MINT ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Bretagne Loire ( UBL ), CHU Angers, Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Leeds General Infirmary (LGI), Leeds Teaching Hospitals NHS Trust, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital pasteur [Colmar], CHU Strasbourg, CHU Amiens-Picardie, Service de Neurochirurgie [CHU Limoges], CHU Limoges, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Privé Clairval [Marseille], Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Réseau d'Etude des Gliomes, REG, Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Università degli studi di Napoli Federico II, CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Neurochirurgie [CHU Angers], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Biomimétiques, and Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Survival, [SDV]Life Sciences [q-bio], Clinical Investigations, Kaplan-Meier Estimate, Disease-Free Survival, Cohort Studies, Young Adult, medicine, Humans, Progression-free survival, Young adult, Antineoplastic Agents, Alkylating, Aged, Aged, 80 and over, Carmustine, [ SDV ] Life Sciences [q-bio], Brain Neoplasms, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, carmustine wafers, Chemoradiotherapy, Middle Aged, 3. Good health, Surgery, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, Cohort, Propensity score matching, Female, Neurology (clinical), business, Glioblastoma, medicine.drug, Cohort study
Abstract: CERVOXY COLL; International audience; BACKGROUND: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. METHODS: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. RESULTS: The median progression-free survival was 12.0 months (95% CI: 10.7-12.6) in the implantation group and 10.0 months (9.0-10.0) in the standard group and the median overall survival was 20.4 months (19.0-22.7) and 18.0 months (17.0-19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63-0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60-0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80-1.13], P = .574; HR, 1.06 [0.87-1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44-0.76], P \textless .0001; HR, 0.54 [0.41-0.70], P \textless .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40-0.78], P \textless .0001; HR, 0.46 [95% CI: 0.33-0.64], P \textless .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. CONCLUSIONS: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit
Published: 2015

22. Incorporating BCNU wafers into malignant glioma treatment: European case studies

Author: Anne Balossier, H. Maximilian Mehdorn, Evelyne Emery, Oliver Heese, Philippe Menei, Jagmohan Singh, Lutz Dörner, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), and Univ Angers, Okina
Subjects: Adult, Male, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Disease-Free Survival, Pharmacotherapy, Internal medicine, Glioma, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Antineoplastic Agents, Alkylating, ComputingMilieux_MISCELLANEOUS, Drug Implants, Carmustine, Chemotherapy, Temozolomide, Brain Neoplasms, business.industry, General Medicine, medicine.disease, Combined Modality Therapy, Surgery, Europe, Clinical trial, Radiation therapy, [SDV] Life Sciences [q-bio], Treatment Outcome, Concomitant, Female, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Carmustine (BCNU: N,N'-bis[2-chloroethyl]-N-nitrosourea) wafers are a local chemotherapeutic agent for the treatment of malignant glioma. They avoid the problems of high toxicity and short half-life associated with systemic delivery, and can bridge the traditional 'treatment gap' between surgery and subsequent conventional chemo- or radiotherapy. Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation. In practice, clinicians may use BCNU wafers in conjunction with other radio- and chemotherapies, in order to maximize the chance of a beneficial patient outcome. The purpose of these case reports is to exemplify how four experienced European clinicians employ BCNU wafers for the management of malignant glioma, and to illustrate how BCNU wafers can be effectively incorporated into treatment regimens. Four patients are described in whom BCNU wafers were implanted during the course of treatment for glioblastoma multiforme, the most severe and common type of malignant glioma. These include three patients with recurrent disease, and a single patient with a newly diagnosed tumour. All four patients received additional radio- and chemotherapy as appropriate. Treatment was well tolerated and patient survival from diagnosis ranged from 56 to 132 weeks. This compared favourably with the survival of approximately 58 weeks seen in the recent EORTC-NCIC clinical trial of combined radiotherapy with concomitant and adjuvant temozolomide. BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours.
Published: 2010

23. ADAMTS proteoglycanases in the physiological and pathological central nervous system

Author: Sighild Lemarchant, Jari Koistinaho, Denis Vivien, Katja M. Kanninen, Mathilde Pruvost, Evelyne Emery, Joan Montaner, BMC, Ed., Department of Neurobiology, University of Eastern Finland-A. I. Virtanen Institute for Molecular Sciences-Biocenter Kuopio, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurovascular Research Laboratory, Universitat Autònoma de Barcelona (UAB)-Vall d’Hebron Research Institute (VHIR), Service de Neurochirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Department of Oncology, Kuopio University Hospital, This work was supported by the University of Eastern Finland and the ERANET-Neuron research program 'ProteA: Proteases before, during and after stroke', 2012-2015, European Commission, and University of Eastern Finland
Subjects: Central Nervous System, Angiogenesis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Review, chemistry.chemical_compound, 0302 clinical medicine, Spinal cord injury, 0303 health sciences, General Neuroscience, ADAMTS, ADAMTS4 Protein, A disintegrin and metalloproteinase with thrombospondin motifs, Stroke, Chondroitin sulfate proteoglycans, medicine.anatomical_structure, Neurology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Angiogenesis Neurorepair, Chondroitin sulfate proteoglycan, [SDV.IMM] Life Sciences [q-bio]/Immunology, Central nervous system, Immunology, ADAMTS9 Protein, Synaptic plasticity Inflammation, Biology, Synaptic plasticity, 03 medical and health sciences, Cellular and Molecular Neuroscience, ADAMTS1 Protein, Neurorepair, medicine, Animals, Humans, 030304 developmental biology, Inflammation, Thrombospondin, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, ADAM Proteins, chemistry, Proteoglycanases, ADAMTS5 Protein, Procollagen N-Endopeptidase, Neuroscience, 030217 neurology & neurosurgery
Abstract: ADAMTS-1, -4, -5 and -9 belong to ‘a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)’ family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries., This work was supported by the University of Eastern Finland and the ERANET-Neuron research program ‘ProteA: Proteases before, during and after stroke’, 2012–2015.
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24. Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

Author: Raymond J, Benomar A, Gentric JC, Magro E, Nico L, Bacchus E, Klink R, Iancu D, Weill A, Roy D, Bojanowski MW, Chaalala C, Eker O, Pelissou-Guyotat I, Piotin M, Aldea S, Barbier C, Gaberel T, Papagiannaki C, Derrey S, Nguyen TN, Abdalkader M, Cognard C, Januel AC, Sabatier JF, Jecko V, Barreau X, Costalat V, Le Corre M, Gauvrit JY, Morandi X, Biondi A, Thines L, Desal H, Bourcier R, Beaujeux R, Proust F, Viard G, Gevry G, and Darsaut TE
Subjects: Humans, Patient Selection, Treatment Outcome, Brain, Retrospective Studies, Intracranial Arteriovenous Malformations surgery, Embolization, Therapeutic, Radiosurgery methods
Abstract: Background: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients., Methods: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients., Results: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%)., Conclusions: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs., (Copyright © 2023 Elsevier Inc. All rights reserved.)
Published: 2023
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25. The in vivo metabolic investigation of brain gliomas with positron emission tomography.

Author: Derlon JM
Subjects: Amino Acids metabolism, Animals, Brain Neoplasms diagnostic imaging, Glioma diagnostic imaging, Glucose metabolism, Humans, Nucleic Acids metabolism, Oxygen metabolism, Brain Neoplasms metabolism, Cerebrovascular Circulation physiology, Glioma metabolism, Tomography, Emission-Computed
Published: 1998
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25 results on '"Service de Neurochirurgie [CHU Caen]"'

1. Incidence and Characteristics of Pseudoprogression in IDH-mutant High-Grade Gliomas: A POLA Network Study

2. Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study

3. Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH-Mutant Gliomas: A French POLA Network Study

4. The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas

5. Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol

6. Simultaneous mapping of vasculature, hypoxia and proliferation using DSC-MRI, 18F-FMISO PET, and 18F-FLT PET in relation to contrast enhancement in newly diagnosed glioblastoma

7. Management of giant presacral schwannoma. Clinical series and literature review

8. New insights into the anatomo-functional architecture of the right sagittal stratum and its surrounding pathways: an axonal electrostimulation mapping study

9. Hyperplasie lymphoïde associée au VIH : une localisation orbitaire exceptionnelle

10. Overt speech feasibility using continuous functional magnetic resonance imaging: Isolation of areas involved in phonology and prosody

11. Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients

12. Resting‐state functional magnetic resonance imaging versus task‐based activity for language mapping and correlation with perioperative cortical mapping

13. Comparison between MRI-derived ADC maps and 18FLT-PET in pre-operative glioblastoma

14. Efficacy and Tolerance of Post-operative Hypo-Fractionated Stereotactic Radiotherapy in a Large Series of Patients With Brain Metastases

15. Promoter hypermethylation of genes encoding for RASSF/Hippo pathway members reveals specific alteration pattern in diffuse gliomas

16. Proton therapy for treatment of intracranial benign tumors in adults: A systematic review

17. Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer)

18. A randomized controlled study assessing outcome, cognition, autonomy and quality of life in over 70-year-old patients after aneurysmal subarachnoid hemorrhage

19. Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model

20. [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis

21. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

22. Incorporating BCNU wafers into malignant glioma treatment: European case studies

23. ADAMTS proteoglycanases in the physiological and pathological central nervous system

24. Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

25. The in vivo metabolic investigation of brain gliomas with positron emission tomography.

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