• The role of MGMT promoter methylation as a predictive factor for temozolomide-based treatment in neuroendocrine neoplasms: a prospective observational study.
  • Brighi, Nicole <1985>

Subject

  • MED/06 Oncologia medica

Description

  • 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.

Date

  • 2022-03-18

Type

  • Doctoral Thesis
  • PeerReviewed

Format

  • application/pdf

Identifier

urn:nbn:it:unibo-28132

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.

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