The role of MGMT promoter methylation as a predictive factor for temozolomide-based treatment in neuroendocrine neoplasms: a prospective observational study.

Brighi, Nicole (2022) The role of MGMT promoter methylation as a predictive factor for temozolomide-based treatment in neuroendocrine neoplasms: a prospective observational study., [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia, ematologia e patologia, 34 Ciclo. DOI 10.48676/unibo/amsdottorato/10068.
Documenti full-text disponibili:
[img] Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (1MB)

Abstract

Temozolomide-based treatments have been demonstrated active in advanced NETs. However, treatment selection and sequencing are based solely on clinical parameters, since no biomarker is currently available to guide clinical management. MGMT-promoter methylation status is a good predictive factor for TEM treatment response in glioblastomas and melanomas and it is currently used in clinical practice. Differently, in NET patients, evidence on MGMT-promoter methylation status role is scarce. The aim of this study was to prospectively evaluate the role of MGMT status in predicting response to TEM-based treatment in NET patients. Primary endpoint was correlation of MGMT promoter methylation with PFS; secondary endpoints were correlation with OS, ORR, DCR, safety and cost analysis. A single-center, prospective observational trial has been conducted at ENETS Center-of-Excellence Outpatient Clinic of Policlinico-Sant’Orsola (Bologna). Patients with advanced, well-differentiated NETs of gastro-entero-pancreatic and lung origin candidate to TEM-based treatment, with tissue available for MGMT-promoter methylation analysis were enrolled. MGMT-promoter methylation status was analyzed by pyrosequencing on tumor tissue. Data of 22 patients were analyzed. Five patients (23%) presented MGMT-promoter methylation. In the MGMT-methylated population, median PFS was 34 months [IQR:15-58], compared to 14 [IQR:8-38] in non-methylated patients. MGMT-promoter methylation status was the only independent variable related to PFS. Better outcomes were observed in the MGMT-methylated group, also for OS (34vs21 months), DCR (100%vs88%) and ORR (80%vs24%). TEM-based treatment resulted a safe treatment, with low rate of adverse events (G≥3<10%). The cost of MGMT-promoter methylation testing by pyrosequencing is affordable (60 euros/patient) and the test is widely available. This study has prospectively demonstrated the role of MGMT-promoter methylation status as good predictive factor for TEM-based treatment in NET patients. Due to its promising predictive role, the wide availability and low costs of the assay, this biomarker could be implemented in clinical practice to guide treatment selection in NET patients.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Brighi, Nicole
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
34
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Neuroendocrine tumors, temozolomide, predictive factors, biomarkers, pyrosequencing, methylation, capecitabine.
URN:NBN
DOI
10.48676/unibo/amsdottorato/10068
Data di discussione
18 Marzo 2022
URI

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi

^