PATH-18. MOLECULAR AND GENETIC ANALYSIS IDENTIFIES IDH MUTATION AS A KEY FACTOR OF LONG-TERM SURVIVAL IN GLIOBLASTOMA PATIENTS

Abstract

Despite improved treatment modalities, glioblastoma multiforme (GBM) remains the most malignant brain tumor with a median overall survival (OS) of 15-18 months. However, some patients show remarkably longer OS, although the underlying factors associated with prolonged survival remain largely unknown. Mutations of isocitrate dehydrogenase (IDH) have been associated with improved prognosis in low-grade gliomas. Here, we investigate the influence of IDH-mutational status and other molecular-genetic factors on long-term survival in GBM patients. Long-term survival (LTS) was defined as OS >3 and very long-term survival (VLTS) as >5 years after initial diagnosis. Long-term survivors were identified retrospectively and their clinical and pathology data were analyzed. Molecular-genetic and pathological factors were determined via standard genetic profiling methods. Kaplan-Meier and multi-variate analysis were used to identify factors associated with LTS/VLTS. We identified a total of 65 LTS (including 26 VLTS) patients. Median age was 45.5 years (range 18.5-72.4). Patients were predominantly male (62.5%). Tumors were located mainly in the frontal lobes (52.3%) and the right hemispheres (64.4%). IDH-mutation was present in the majority of LTS (75.4%) and nearly all (92.3%) of VLTS patients, and included mainly R132H mutations and only two R132C mutations. 60% of LTS and 69.3% of VLTS patients showed MGMT promoter methylation. 1p/19q co-deletion was found in 36.9% of LTS and 46.1% of VLTS. The majority of LTS (58.5%) and VLTS (53.8%) were TP53-wildtype. The confirmed IDH-wildtype cases were mostly MGMT promoter methylated and TP53-wildtype. IDH-mutation seems to be a key factor in long-term survival and especially very-long-term survival of GBM patients. Other molecular factors such as MGMT promoter methylation, TP53-wildtype status and 1p/19q-co-deletion also appear to be favorable prognostic factors for LTS and VLTS, underscoring the value of molecular analysis of tumor tissue for patient management and prognostication.