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

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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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This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy

    Davide Campana

  2. Hospices Civils de Lyon, University Hospital of Lyon, Lyon, France

    Thomas Walter, Emmanuelle Graillot & Marc Barritault

  3. Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS ‘Istituto Nazionale dei Tumori’, Milan, Italy

    Sara Pusceddu & Natalie Prinzi

  4. Department of Oncology and Haematology, Division of Oncology, University Hospital of Modena, Modena, Italy

    Fabio Gelsomino & Andrea Spallanzani

  5. Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy

    Michelangelo Fiorentino, Filippo Dall’Olio, Nicole Brighi & Guido Biasco

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  1. Davide Campana
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  2. Thomas Walter
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Correspondence to Davide Campana.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Campana, D., Walter, T., Pusceddu, S. et al. Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study. Endocrine 60, 490–498 (2018). https://doi.org/10.1007/s12020-017-1474-3

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