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An ANOCEF genomic and transcriptomic microarray study of the response to irinotecan and bevacizumab in recurrent glioblastomas.

Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, France. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France ; INSERM, U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France ; Faculté de Médecine Pitié-Salpêtrière, Université Pierre & Marie Curie Paris VI, CNRS UMR 7225 and UMR-S975, Paris, France ; Neuro-Oncology Unit, C. Mondino National Neurological Institute, Pavia, Italy. Assistance Publique-Hôpitaux de Marseille, Service de Neuro-Oncologie, Centre Hospitalier Universitaire Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France ; Aix-Marseille Université, Inserm, CRO2 UMR_S 911, 13385 Marseille, France ; ANOCEF (Association des Neuro-Oncologues d'Expression Française (French Speaking NeuroOncologists' Association)), France. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France ; INSERM, U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France ; Faculté de Médecine Pitié-Salpêtrière, Université Pierre & Marie Curie Paris VI, CNRS UMR 7225 and UMR-S975, Paris, France ; ANOCEF (Association des Neuro-Oncologues d'Expression Française (French Speaking NeuroOncologists' Association)), France. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France ; INSERM, U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France ; Faculté de Médecine Pitié-Salpêtrière, Université Pierre & Marie Curie Paris VI, CNRS UMR 7225 and UMR-S975, Paris, France. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France ; INSERM, U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France ; Faculté de Médecine Pitié-Salpêtrière, Université Pierre & Marie Curie Paris VI, CNRS UMR 7225 and UMR-S975, Paris, France ; Medical Oncology 1, Venetian Oncology Institute-IRCCS, Padua, Italy. Aix-Marseille Université, Inserm, CRO2 UMR_S 911, 13385 Marseille, France ; ANOCEF (Association des Neuro-Oncologues d'Expression Française (French Speaking NeuroOncologists' Association)), France ; APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, 13385 Marseille, France. ANOCEF (Association des Neuro-Oncologues d'Expression Française (French Speaking NeuroOncologists' Association)), France ; Service de Neuro-oncologie, Hôpital Neurologique, Hospices Civils de Lyon, 59 Boulevard Pinel, 69394 Lyon Cedex 3, Lyon, France ; Université de Lyon, Claude Bernard Lyon 1, Lyon, France ; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Lyon, France.

BioMed research international. 2014;:282815
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Abstract

BACKGROUND We performed a retrospective study to assess whether the initial molecular characteristics of glioblastomas (GBMs) were associated with the response to the bevacizumab/irinotecan chemotherapy regimen given at recurrence. RESULTS Comparison of the genomic and gene expression profiles of the responders (n = 12) and nonresponders (n = 13) demonstrated only slight differences and could not identify any robust biomarkers associated with the response. In contrast, a significant association was observed between GBMs molecular subtypes and response rates. GBMs assigned to molecular subtype IGS-18 and to classical subtype had a lower response rate than those assigned to other subtypes. In an independent series of 33 patients, neither EGFR amplification nor CDKN2A deletion (which are frequent in IGS-18 and classical GBMs) was significantly associated with the response rate, suggesting that these two alterations are unlikely to explain the lower response rate of these GBMs molecular subtypes. CONCLUSION Despite its limited sample size, the present study suggests that comparing the initial molecular profiles of responders and nonresponders might not be an effective strategy to identify biomarkers of the response to bevacizumab given at recurrence. Yet it suggests that the response rate might differ among GBMs molecular subtypes.

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