Georges-Francois Leclerc Cancer Center, Dijon, France
Aurelie Bertaut , Romain Boidot , Rachid Madkouri , Coureche guillaume Kaderbhai , Julie Vincent , Bruno Chauffert , Francois Ghiringhelli
Background: Bevacizumab is frequently used at recurrence of glioblastoma. However, no biomarker could predict its efficacy. Methods: Exploratory cohort consisted in all patients treated with Stupp regimen for a glioblastoma in Dijon cancer center (N = 265). A validation cohort was TEMAVIR trial which compared 120 patients suffering from glioblastoma treated with Stupp regimen versus bevacizumab plus irinotecan followed by Stupp regimen plus bevacizumab. CSF3 expression was determined in a cohort of 202 patients from the cancer genome atlas. Prognosis role of CSF3expression was next determined in an independent cohort of 23 patients treated with bevacizumab for a recurrent glioblastoma. Results: In the exploratory cohort, bevacizumab increased median overall survival (OS) 18.7 vs 11.3 months, p = 0.0014. Upon multivariate analysis, the age, type of initial surgery, neutrophil count, Karnofsky status > 70%, bevacizumab administration were an independent prognosis factors of survival. We detected an interaction between bevacizumab use and neutrophil count at baseline. Cut off value of neutrophil count was set at 6000/mm3. Only patients with a high level of neutrophil benefited in term of overall survival from the bevacizumab administration (17.3 months (CI95% 14.6-20.4) for patients that received bevacizumab versus vs 8.8 months CI95% 6.4-10.3) for others (p < 0.0001)). Overall survival was not significantly improved for remaining patients treated with bevacizumab with low neutrophil count (21.6 months (CI95% 18.0-23.3) for patients that received bevacizumab versus 15.9 months (CI95%12.0-19.9) for the others (p = 0.7313)).Similar results were obtained in the TEMAVIR trial. Transcriptomic data underlined that expression of CSF3, the gene encoding G-CSF, was correlated with VEGF-A expression. In another independent cohort, we also observed this association between high CSF3expression in tumor and a better survival in patients treated with bevacizumab at recurrence. Conclusions: Only patients with a high level of neutrophil before initiation of bevacizumab treatment benefited from this therapy. Neutrophil count at baseline is a predictive biomarker of efficacy of bevacizumab for glioblastoma bearing patients
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