title: Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients.
abstract: BACKGROUND
  To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications).
  
  
  METHODS
  From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted.
  
  
  RESULTS
  The median progression-free survival was 10.3 months (95% CI, 10.0-11.0). The median overall survival was 19.7 months (95% CI, 18.5-21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1-9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS.
  
  
  CONCLUSIONS
  Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.
authors.affiliation: Department of Radiation Oncology, INSERM 1030 "Molecular Radiotherapy", Gustave Roussy, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: guillaume.louvel@gustaveroussy.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Louvel
authors.affiliation: Department of Neurosurgery, Clairval Private Hospital, Marseille, France; UMR911, CRO2, Aix-Marseille Université, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Metellus
authors.affiliation: Department of Radiotherapy, Centre de Lutte Contre le Cancer Paul Strauss, Strasbourg, France; Radiobiology Laboratory, Federation of Translationnal Medicine de Strasbourg (FMTS), Strasbourg University, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Noel
authors.affiliation: Department of Neurosurgery, Sainte-Anne Hospital, Paris, France; Paris Descartes University, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Peeters
authors.affiliation: Lyon Civil Hospitals, Pierre Wertheimer Neurological and Neurosurgical Hospital, Service of Neurosurgery D, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Guyotat
authors.affiliation: Department of Neurosurgery, Maison Blanche Hospital, Reims University Hospital, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Duntze
authors.affiliation: Department of Neurosurgery, University Hospital Pontchaillou, Rennes, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Le Reste
authors.affiliation: Department of Neurosurgery, University Medical Center, Faculty of Medicine, University of Brest, France.
authors.forename: Phong
authors.initials: P
authors.lastname: Dam Hieu
authors.affiliation: Department of Neurosurgery, APHP Beaujon Hospital, Clichy, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Faillot
authors.affiliation: Department of Neurosurgery, Maison Blanche Hospital, Reims University Hospital, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Litre
authors.affiliation: Department of Neurosurgery, Sainte Anne Military Teaching Hospital, Toulon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desse
authors.affiliation: Department of Neurosurgery, University Hospital Jean Minjoz, Besançon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Petit
authors.affiliation: Departement of Neurosurgery, University Hospital of Caen, University of Lower Normandy, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Emery
authors.affiliation: Department of Neurosurgery, Pasteur Hospital, Colmar, France.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Voirin
authors.affiliation: Department of Neurosurgery, Amiens University Hospital, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Peltier
authors.affiliation: Department of Neurosurgery, CHU de Limoges, France.
authors.forename: François
authors.initials: F
authors.lastname: Caire
authors.affiliation: Department of Neurosurgery A, CHU Pellegrin, Bordeaux Cedex, France.
authors.forename: Jean-Rodolphe
authors.initials: JR
authors.lastname: Vignes
authors.affiliation: Department of Neurosurgery, Clairval Private Hospital, Marseille, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Barat
authors.affiliation: Department of Neurosurgery, Rouen University Hospital, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Langlois
authors.affiliation: Department of Neurosurgery, CHU d'Angers, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
authors.affiliation: Department of Neurooncology, Gustave Roussy, Villejuif, France.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Dumont
authors.affiliation: Department of Neurosurgery, Sainte-Anne Hospital, Paris, France; Paris Descartes University, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Zanello
authors.affiliation: Department of Neurosurgery, Sainte-Anne Hospital, Paris, France; Paris Descartes University, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Dezamis
authors.affiliation: Department of Radiation Oncology, INSERM 1030 "Molecular Radiotherapy", Gustave Roussy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dhermain
authors.affiliation: Department of Neurosurgery, Sainte-Anne Hospital, Paris, France; Paris Descartes University, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Pallud
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013995:Time
chemical_list: D018906:Antineoplastic Agents, Alkylating
keywords: Glioblastoma; Prognostic factors; Radiotherapy; Standard combined chemoradiotherapy; Temozolomide; Time interval