The Response to Chemo Radiation Therapy in Unresectable Glioblastoma Multiforme Patients in Relation to MGMT Promoter Methylation Status: A Study from a Single Saudi Center

Abstract

Background: The optimal therapy for Glioblastoma Multiforme (GBM) constitutes of maximal safe resection followed by adjunctive concurrent radiation and chemotherapy with Temozolomide (TMZ). However, in certain cases safe maximal resection is not practically amenable. The methylation of the MGMT promoter is being used as a prognostic and predictive factor for the GBM response to TMZ therapy. In the present study, we aimed to measure the outcome of GBM Saudi patients who underwent tumor biopsy followed by radiation therapy with or without chemotherapy based on the MGMT promoter methylation status. Methods: The methylation-specific PCR assay was used to study the methylation status of the MGMT promoter in 77 formalin-fixed paraffin-embedded tissues of high grade glioblastoma. Results: MGMT promoter methylation was detected in 48 samples (62%). Interestingly, significant difference (p=0.0073) was found in overall survival between patients treated with surgery, radiotherapy and temozolomide and those treated with surgery and radiotherapy only, irrespective of MGMT promoter status. The survival rate for patients with MGMT methylated tumor was significantly different favoring the plus temozolomide group (p=0.0107). However, for the patients with MGMT unmethylated tumor, there was no significant difference (p=0.1453) between the two groups. Using the Cox proportional-hazards model, the methylation status of the MGMT promoter emerged as a significant (p=0.0234) clinically relevant predictor of benefit from temozolomide. Conclusion: Here, we have demonstrated that MGMT methylation has significantly improved the survival rate in Saudi patients with unresectable GBM who received concomitant radiation therapy and TMZ. However, MGMT methylation status did not impact the response to radiation therapy.