Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study
| Autor: | Sara Pusceddu, Natalie Prinzi, Marc Barritault, Fabio Gelsomino, Michelangelo Fiorentino, Andrea Spallanzani, Davide Campana, Nicole Brighi, Guido Biasco, Emmanuelle Graillot, Thomas Walter, Filippo Gustavo Dall'Olio |
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| Přispěvatelé: | Campana, Davide, Walter, Thoma, Pusceddu, Sara, Gelsomino, Fabio, Graillot, Emmanuelle, Prinzi, Natalie, Spallanzani, Andrea, Fiorentino, Michelangelo, Barritault, Marc, Dall'olio, Filippo, Brighi, Nicole, Biasco, Guido |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Oncology Lung Neoplasms Endocrinology Diabetes and Metabolism 0302 clinical medicine Endocrinology Promoter Regions Genetic DNA Modification Methylases Aged 80 and over Melanoma Methylation Middle Aged Prognosis Survival Rate Diabetes and Metabolism Neuroendocrine Tumors Treatment Outcome 030220 oncology & carcinogenesis DNA methylation Female MGMT medicine.drug Adult medicine.medical_specialty 030209 endocrinology & metabolism Capecitabine Young Adult 03 medical and health sciences Internal medicine medicine Temozolomide Humans Chemotherapy Progression-free survival Survival rate neoplasms Aged Retrospective Studies business.industry Tumor Suppressor Proteins DNA Methylation medicine.disease Carcinoid Pancreatic Neoplasms Neuroendocrine neoplasm DNA Repair Enzymes Neuroendocrine neoplasms Pharmacogenetics business |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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