title: Relationship between magnetic resonance imaging characteristics and plasmatic levels of MMP2 and MMP9 in patients with recurrent high-grade gliomas treated by Bevacizumab and Irinotecan.
abstract: Matrix metalloproteases MMP2 and MMP9 are involved in cancer angiogenesis and invasion. We recently demonstrated that plasma MMP2 and MMP9 levels could both predict response to bevacizumab in patients with recurrent high-grade glioma (HGG). We examined the potential relationship between MMP2/MMP9 plasma levels and glioma imaging characteristics. In this retrospective, monocentric study, MRI before bevacizumab administration for HGG patients was independently analyzed for contrast enhancement (CE) and FLAIR sequences. Contemporary MMP2 and MMP9 plasma levels were assessed using ELISA kits. We analyzed 28 patients with a median Karnofsky Performance Status of 70 (range 50-80). A diffuse pattern was observed in 14 patients (50%). We did not observe any correlation between baseline imaging features and plasma levels of MMP2 or MMP9. We found no association between baseline MMP levels and diffuse MRI patterns. In univariate analyses, diffuse pattern, multi-focal disease, tumor diameter, surface area, and volume had no impact on outcome, while the number of lobes involved in CE and crossing of the midline by CE were associated with a worse progression-free survival (p = 0.072 and p = 0.012, respectively) and overall survival (p = 0.012 and p < 0.001, respectively). In patients with recurrent high-grade glioma treated with a bevacizumab-based regimen, our exploratory analysis of multiple MRI tumor characteristics at baseline failed to detect a relationship between imaging feature and plasma levels of MMP2 and MMP9. Our results suggests that number of lobes involved in CE and crossing of the midline by CE are associated with outcome although the potential prognostic versus predictive role of these markers warrant further investigation.
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farina
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.|AMU, CRO2, UMR911, 13005, Marseille, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Tabouret
authors.affiliation: Department of Neuro-Radiology, Aix-Marseille Univ, AP-HM, 13005, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehmann
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Barrie
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Petrirena
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Campello
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Boucard
authors.affiliation: Department of Neuro-Surgery, Aix-Marseille Univ, AP-HM, 13005, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Graillon
authors.affiliation: Department of Neuro-Radiology, Aix-Marseille Univ, AP-HM, 13005, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Girard
authors.affiliation: Department of Neuro-Oncology, Hopital de la Timone, Aix-Marseille Univ, AP-HM, 264 rue Saint Pierre, 13005, Marseille, France. olivier.chinot@ap-hm.fr.|AMU, CRO2, UMR911, 13005, Marseille, France. olivier.chinot@ap-hm.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000077146:Irinotecan; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D002166:Camptothecin
keywords: Bevacizumab; Glioma; Imaging; Matrix metalloproteases