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Updated: Mar 2, 2026
Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: a pilot study
Stefano Guadagni1, Giammaria Fiorentini, Marco Clementi
1Departments of aApplied Clinical Sciences and Biotechnology bLife, Health and Environmental Sciences, University of L'Aquila cDepartment of Pathology, S. Salvatore Hospital, L'Aquila dDepartment of Oncology and Hematology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro eIstituto Tumori Milano, Milano fDepartment of Surgical Sciences, University of Verona, Verona, Italy.
Abstract:
Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan-Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.
Insights
For stage III melanoma patients receiving melphalan chemotherapy, MGMT promoter methylation status significantly impacts survival outcomes. Higher MGMT methylation levels correlate with improved survival, suggesting its potential as a predictive biomarker.
Area of Science:
- Oncology
- Epigenetics
- Melanoma Research
Background:
- Approximately 25% of melanoma patients with locoregional metastases are resistant to current targeted and immunotherapies.
- Melphalan hypoxic perfusion is an option for pelvic metastases, and MGMT promoter methylation can enhance alkylating agent efficacy.
Purpose of the Study:
- To investigate the correlation between MGMT promoter methylation status and survival in stage III melanoma patients treated with melphalan regional chemotherapy.
Main Methods:
- Examined metastatic tissues from 27 stage III melanoma patients undergoing melphalan hypoxic pelvic perfusion.
- Assessed MGMT promoter methylation using MS-MLPA probes and BRAF V600E mutation via CAST-PCR.
- Estimated survival using Kaplan-Meier curves, stratified by clinicopathological factors.
Main Results:
- Overall median survival was 17 months, with 1, 3, and 5-year survival rates of 66.7%, 18.5%, and 7.4%, respectively.
- Disease stage, burden, and MGMT methylation percentage significantly influenced survival.
- An MGMT promoter methylation cut-off of at least 14% was associated with significantly longer survival.
Conclusions:
- MGMT promoter methylation is a significant factor in predicting survival for melanoma patients receiving melphalan regional chemotherapy.
- Further larger studies are needed to clarify the prognostic significance of MGMT methylation in clinical practice.
