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Medline ® Abstract for Reference 43

of 'Clinical features, pathology, and prognostic factors for oligodendroglial tumors'

MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951.
van den Bent MJ, Erdem-Eraslan L, Idbaih A, de Rooi J, Eilers PH, Spliet WG, den Dunnen WF, Tijssen C, Wesseling P, Sillevis Smitt PA, Kros JM, Gorlia T, French PJ
Clin Cancer Res. 2013;19(19):5513. Epub 2013 Aug 15.
PURPOSE: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.
EXPERIMENTAL DESIGN: We conducted genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status.
RESULTS: We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years, both P<0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex, performance score, and review diagnosis in the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27 methylated samples, it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P = 0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response.
CONCLUSIONS: MGMT-STP27 may be used to guide treatment decisions in this tumor type.
Authors' Affiliations: Departments of Neurology, Biostatistics, and Pathology, Neuro-Oncology Unit Erasmus MC, Rotterdam; AP-HP, Groupe Hospitalier Pitie Salpêtrière, Service de Neurologie 2 Mazarin and UniversitéPierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), Paris, France; Department of Pathology, UMCU, Utrecht; Department of Pathology, UMCG, Groningen; Department of Neurology, St. Elisabeth Hospital, Tilburg; Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen; Department of Pathology, Free University Medical Center, Amsterdam, the Netherlands; and European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.