Originally published as JCO Early Release 10.1200/JCO.2006.06.3891 on September 5 2006

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Correlations Between O6-Methylguanine DNA Methyltransferase Promoter Methylation Status, 1p and 19q Deletions, and Response to Temozolomide in Anaplastic and Recurrent Oligodendroglioma: A Prospective GICNO Study

Alba A. Brandes, Alicia Tosoni, Giovanna Cavallo, Michele Reni, Enrico Franceschi, Laura Bonaldi, Roberta Bertorelle, Marina Gardiman, Claudio Ghimenton, Paolo Iuzzolino, Annalisa Pession, Valeria Blatt, Mario Ermani

From the Department of Medical Oncology and Pathology of Bellaria Hospital, Bologna; Department of Medical Oncology, Istituto Oncologico Veneto; Servizio Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto; Pathology, Neurological Sciences, Azienda Ospedale-Università of Padova, Padova; Department of Oncology, San Raffaele Hospital, Milan; Department of Pathology Verona Hospital, Verona; and the Department of Pathology, Belluno Hospital, Belluno, Italy

Address reprint requests to Alba A. Brandes, MD, Department of Medical Oncology, Bellaria Hospital, Via Altura 3, Bologna, Italy; e-mail: aa.brandes{at}yahoo.it

PURPOSE: To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting.

PATIENTS AND METHODS: From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m² of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction.

RESULTS: The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09).

CONCLUSION: TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

published online ahead of print at www.jco.org on September 5, 2006

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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