Oncotarget

Clinical Research Papers:

Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma

Aurélie Bertaut, Caroline Truntzer, Rachid Madkouri, Coureche Guillaume Kaderbhai, Valentin Derangère, Julie Vincent, Bruno Chauffert, Marie Hélene Aubriot-Lorton, Wahlid Farah, Klaus Luc Mourier, Romain Boidot and Francois Ghiringhelli _

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Oncotarget. 2016; 7:70948-70958. https://doi.org/10.18632/oncotarget.10898

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Abstract

Aurélie Bertaut1, Caroline Truntzer2, Rachid Madkouri3, Coureche Guillaume Kaderbhai4, Valentin Derangère5, Julie Vincent4, Bruno Chauffert6, Marie Hélene Aubriot-Lorton 7, Wahlid Farah3, Klaus Luc Mourier3, Romain Boidot5,8 and Francois Ghiringhelli4,5,8,9

1 Biostatistics unit Georges Francois Leclerc Cancer Center, Dijon, France

2 CLIPP, Research Center, University of Burgundy, Dijon, France

3 Department of Neurosurgery, CHU, Dijon, France

4 Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France

5 Platform of Transfer in Cancer Biology Genetic and histology, Georges Francois Leclerc Cancer Center, Dijon, France

6 Department of Medical Oncology, University Hospital Amiens, Amiens, France

7 Department of Pathology, CHU, Dijon, France

8 INSERM U866, Dijon, France

9 University of Bourgogne Franche-Comté, Dijon, France

Correspondence to:

Francois Ghiringhelli, email:

Keywords: glioblastoma, bevacizumab, prognostic factor

Received: April 11, 2016 Accepted: July 10, 2016 Published: July 28, 2016

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.


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