August 17, 2021; 97 (7) Research Article
Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors
Giulia Berzero, Luisa Bellu, Capucine Baldini, François Ducray, David Guyon, Marica Eoli, Antonio Silvani, Caroline Dehais, Ahmed Idbaih, Nadia Younan, Ludovic Nguyen-Them, Stephan Gaillard, Francesco Pasqualetti, Coralie Lepage-Seydoux, Sakina Sekkate, Patricia Tresca, View ORCID ProfileAurélie Kas, Julie Gratieux, Samy Ammari, Edouard Saragoussi, View ORCID ProfileJulien Savatovsky, Jean-Yves Delattre, Khê Hoang-Xuan, David Meyronet, Chiara Villa, Franck Bielle, Marc Sanson, Mehdi Touat, Anna Luisa Di Stefano
First published June 4, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012330
Giulia Berzero
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Luisa Bellu
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Capucine Baldini
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
François Ducray
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
David Guyon
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Marica Eoli
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Antonio Silvani
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Caroline Dehais
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Ahmed Idbaih
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Nadia Younan
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Ludovic Nguyen-Them
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Stephan Gaillard
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Francesco Pasqualetti
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Coralie Lepage-Seydoux
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Sakina Sekkate
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Patricia Tresca
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Aurélie Kas
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Julie Gratieux
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Samy Ammari
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Edouard Saragoussi
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Julien Savatovsky
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Jean-Yves Delattre
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Khê Hoang-Xuan
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
David Meyronet
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Chiara Villa
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Franck Bielle
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Marc Sanson
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Mehdi Touat
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Anna Luisa Di Stefano
From Sorbonne Université (G.B., L.B., C.D., A.I., J.-Y.D., K.H.-X., F.B., M.S., M.T., A.L.D.S.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, and AP-HP Hôpitaux Universitaires La Pitié Salpêtrière–Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Radiation Therapy Unit (L.B.), Imaging and Medical Physics Department, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy; Drug Development Department (C.B.), Institut Gustave Roussy and Université Paris-Saclay, Villejuif; Department of Neuroncology (F.D.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurology (D.G., N.Y., A.L.D.S.), Department of Neurosurgery (S.G.), Service de Pharmacie (C.L.-S.), Department of Oncology (S.S.), Department of Neuroradiology (J.G.), and Department of Pathology (C.V.), Hôpital Foch, Suresnes, France; Neuro-oncology Unit (M.E., A.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Service de Neurologie (L.N.T.), Centre Hospitalier Perpignan, France; Radiation Oncology (F.P.), Department of Medicine and Oncology, University Hospital, Pisa, Italy; Clinical Research Unit (P.T.), Institut Curie, Paris; Department of Nuclear Medicine (A.K.), AP-HP GH Pitié-Salpêtrière, Paris; Department of Diagnostic Radiology (S.A.), Institut Gustave Roussy, Villejuif, France; Neuroradiology Unit (E.S., J.S.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; Department of Pathology (D.M.), Eastern Hospital Group, Lyon Civil Hospices; Department of Neuropathology (F.B.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Onconeurotek Tumor Bank (F.B., M.S.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. Dr. Berzero is currently at Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and Dr. Gaillard is currently at the Department of Neurosurgery, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris.
Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors
Giulia Berzero, Luisa Bellu, Capucine Baldini, François Ducray, David Guyon, Marica Eoli, Antonio Silvani, Caroline Dehais, Ahmed Idbaih, Nadia Younan, Ludovic Nguyen-Them, Stephan Gaillard, Francesco Pasqualetti, Coralie Lepage-Seydoux, Sakina Sekkate, Patricia Tresca, Aurélie Kas, Julie Gratieux, Samy Ammari, Edouard Saragoussi, Julien Savatovsky, Jean-Yves Delattre, Khê Hoang-Xuan, David Meyronet, Chiara Villa, Franck Bielle, Marc Sanson, Mehdi Touat, Anna Luisa Di Stefano
Neurology Aug 2021, 97 (7) e673-e683; DOI: 10.1212/WNL.0000000000012330
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Abstract
Objective To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600–mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort.
Methods We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600–mutant GGNTs treated with RAFi/MEKi.
Results Twenty-eight adults with recurrent or disseminated BRAF V600–mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of −78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival.
Conclusions Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600–mutant GGNTs and encourages rechallenge in responders.
Classification of Evidence This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.
Glossary
- CR=
- complete response;
- GGNT=
- glial and glioneuronal tumor;
- KPS=
- Karnofsky Performance Status;
- MEKi=
- MEK inhibitors;
- MGMT=
- O6-methylguanine-DNA methyltransferase;
- OS=
- overall survival;
- PD=
- progressive disease;
- PFS=
- progression-free survival;
- PR=
- partial response;
- PXA=
- pleomorphic xanthoastrocytoma;
- RAFi=
- RAF inhibitors;
- RANO=
- Response Assessment in Neuro-Oncology;
- SD=
- stable disease
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received December 17, 2020.
- Accepted in final form May 11, 2021.
- © 2021 American Academy of Neurology
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