Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging
Anne Laprie,
Soléakhéna Ken,
Thomas Filleron,
Vincent Lubrano,
Laure Vieillevigne,
Fatima Tensaouti,
Isabelle Catalaa,
Sergio Boetto,
Jonathan Khalifa,
Justine Attal,
Guillaume Peyraga,
Carlos Gomez-Roca,
Emmanuelle Uro-Coste,
Georges Noel,
Gilles Truc,
Marie-Pierre Sunyach,
Nicolas Magné,
Marie Charissoux,
Stéphane Supiot,
Valérie Bernier,
Muriel Mounier,
Muriel Poublanc,
Amandine Fabre,
Jean-Pierre Delord,
Elizabeth Cohen-Jonathan Moyal
Affiliations
Anne Laprie
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Soléakhéna Ken
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, INSERM, UPS
Thomas Filleron
Biostatistics Unit, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Vincent Lubrano
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, INSERM, UPS
Laure Vieillevigne
Department of Engineering and Medical Physics, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-OncopoleCancer de Toulouse-Oncopole
Fatima Tensaouti
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Isabelle Catalaa
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, INSERM, UPS
Sergio Boetto
Neurosurgery Department, Centre Hospitalier Universitaire de Toulouse
Jonathan Khalifa
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Justine Attal
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Guillaume Peyraga
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Carlos Gomez-Roca
Medical Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Emmanuelle Uro-Coste
Pathology department, Centre Hospitalier Universitaire de Toulouse
Georges Noel
Radiation Oncology Department, Centre Paul Strauss
Gilles Truc
Radiation Oncology Department Centre Georges-François Leclerc
Marie-Pierre Sunyach
Radiation Oncology Department- Centre Léon Bérard
Nicolas Magné
Radiation Oncology Department, Institut de Cancérologie de la Loire
Marie Charissoux
Radiation Oncology Department - Centre Val d’aurelle
Stéphane Supiot
Radiation Oncology Department, Institut de Cancerologie de l’Ouest
Valérie Bernier
Radiation Oncology Department, Institut de cancérologie de Lorraine centre Alexis Vautrin
Muriel Mounier
Clinical Research Department, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole
Muriel Poublanc
Clinical Research Department, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole
Amandine Fabre
Clinical Research Department, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole
Jean-Pierre Delord
Medical Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Elizabeth Cohen-Jonathan Moyal
Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole
Abstract Background Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival. Methods/design In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status. Discussion This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging. Trial registration NCT01507506, registration date December 20, 2011.
