title: Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma.
abstract: Bevacizumab is used to treat glioblastoma; however, no current biomarker predicts its efficacy. We used an exploratory cohort of patients treated with the radiochemotherapy then bevacizumab or chemotherapy at recurrence (N = 265). Bevacizumab use increased median overall survival (OS) 18.7 vs 11.3 months, p = 0.0014). In multivariate analysis, age, initial surgery, neutrophil count, Karnofsky status >70% and bevacizumab administration were independent prognostic factors of survival. We found an interaction between bevacizumab use and baseline neutrophil count. The cut-off value for the neutrophil count was set at 6000/mm3. Only patients with a high neutrophil count benefited from the bevacizumab treatment (17.3 vs 8.8 months p < 0.0001). We validated this result using data from the TEMAVIR trial, which tested the efficacy of neoadjuvant bevacizumab plus irinotecan versus radiochemotherapy in the first-line treatment of glioblastoma. Transcriptomic data from TCGA underlined that CSF3 expression, the gene encoding G-CSF, the growth factor for neutrophils, correlated with VEGF-A-dependent angiogenesis. In another independent cohort (BELOB trial), which compared lomustine versus lomustine plus bevacizumab at recurrence, bevacizumab only benefited patients with high CSF3 expression in the tumor. These data suggest that only patients with a high peripheral neutrophil count before bevacizumab treatment benefited from this therapy.
authors.affiliation: Biostatistics unit Georges Francois Leclerc Cancer Center, Dijon, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bertaut
authors.affiliation: CLIPP, Research Center, University of Burgundy, Dijon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Truntzer
authors.affiliation: Department of Neurosurgery, CHU, Dijon, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Madkouri
authors.affiliation: Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France.
authors.forename: Coureche Guillaume
authors.initials: CG
authors.lastname: Kaderbhai
authors.affiliation: Platform of Transfer in Cancer Biology Genetic and histology, Georges Francois Leclerc Cancer Center, Dijon, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Derangère
authors.affiliation: Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Vincent
authors.affiliation: Department of Medical Oncology, University Hospital Amiens, Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.affiliation: Department of Pathology, CHU, Dijon, France.
authors.forename: Marie Hélene
authors.initials: MH
authors.lastname: Aubriot-Lorton
authors.affiliation: Department of Neurosurgery, CHU, Dijon, France.
authors.forename: Wahlid
authors.initials: W
authors.lastname: Farah
authors.affiliation: Department of Neurosurgery, CHU, Dijon, France.
authors.forename: Klaus Luc
authors.initials: KL
authors.lastname: Mourier
authors.affiliation: Platform of Transfer in Cancer Biology Genetic and histology, Georges Francois Leclerc Cancer Center, Dijon, France.|INSERM U866, Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France.|Platform of Transfer in Cancer Biology Genetic and histology, Georges Francois Leclerc Cancer Center, Dijon, France.|INSERM U866, Dijon, France.|University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D000367:Age Factors; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D017567:Karnofsky Performance Status; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009504:Neutrophils; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D054316:Biomarkers, Pharmacological; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D000068258:Bevacizumab
keywords: bevacizumab; glioblastoma; prognosistic factor