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Endocrine
Published in: Endocrine 3/2018

01-06-2018 | Original Article

Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study

Authors: Davide Campana, Thomas Walter, Sara Pusceddu, Fabio Gelsomino, Emmanuelle Graillot, Natalie Prinzi, Andrea Spallanzani, Michelangelo Fiorentino, Marc Barritault, Filippo Dall’Olio, Nicole Brighi, Guido Biasco

Published in: Endocrine | Issue 3/2018

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Abstract

Purpose

Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate.

Methods

In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy. MGMT promoter methylation status was evaluated with two techniques: methylation specific-polymerase chain reaction or pyrosequencing.

Results

Treatment with TEM-based therapy was associated with an overall response rate of 27.4% according to RECIST criteria (51.8% of patients with and 17.7% without MGMT promoter methylation). Response to therapy, progression free survival and overall survival was correlated to MGMT status at univariate and multivariate analysis. Methylation of MGMT promoter could be a strong predictive factor of objective response and an important prognostic factor of a longer PFS and OS.

Conclusion

According to our results, MGMT methylation status, evaluated with methylation specific-polymerase chain reaction or pyrosequencing, should have an important role in patients with metastatic NENs, in order to guide therapeutic options. These results need further confirmation with prospective studies.
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Metadata
Title
Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study
Authors
Davide Campana
Thomas Walter
Sara Pusceddu
Fabio Gelsomino
Emmanuelle Graillot
Natalie Prinzi
Andrea Spallanzani
Michelangelo Fiorentino
Marc Barritault
Filippo Dall’Olio
Nicole Brighi
Guido Biasco
Publication date
01-06-2018
Publisher
Springer US
Published in
Endocrine / Issue 3/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1474-3

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