GEN-06 CLINICAL COURSE AFTER TUMOR RECURRENCE OF MGMT HYPERMETHYLATED GLIOBLASTOMA

Abstract

MGMT methylation in glioblastoma is a biomarker for determining treatment responsiveness and predicting prognosis. We analyzed whether there were differences in the prognosis between glioblastoma with MGMT hypermethylation and other glioblastomas after tumor recurrence. We enrolled 184 patients who underwent radiation therapy and temozolomide chemotherapy after tumor resection for newly diagnosed glioblastoma. MGMT methylation was quantitatively analyzed using methylation-specific high resolution melting analysis. The cut-off value for MGMT methylation had a difference of 35% from the previous values. The subjects were split into three groups according to their MGMT methylation levels, 122 in the low (L) methylation group (levels of 0–34%), 40 in the medium (M) methylation group (levels of 35–69%), and 22 in the high (H) methylation group (levels of 70% or more). We mainly focused on and compared the progression after recurrence. The progression-free survival (PFS) rate and overall survival (OS) rate were significantly longer in the M and H groups than in the L group. There was no difference in PFS between group M and group H, but OS was significantly longer in group H. The details of treatment for the 16 of 22 patients who had recurrences in group H are as follows: temozolomide, n = 1; bevacizumab, n = 8; investigational drugs (peptide vaccines and immune checkpoint inhibitors), n = 3; and supportive care, n = 4. The median survival rate for these 16 patients after recurrence was 18 months. Even patients who received only supportive care had a median survival time ranging between 9 and 17 months. Our results indicate that MGMT hypermethylation in glioblastoma is effective to a certain degree with other treatments even after recurrence. Even patients who underwent only supportive care survived for a relatively longer period of time. Biologically, MGMT hypermethylation may be associated with a moderately slow-growing tumor.