MPTH-17CLINICAL AND MOLECULAR CHARACTERIZATION OF LONG-TERM GLIOBLASTOMA SURVIVORS

Abstract

BACKGROUND: Glioblastoma (GBM) is a challenging disease with ultimately fatal outcome in the majority of patients. Despite improved treatment modalities, median overall survival (OS) rates range between 15-18 months. However, some patients show remarkably longer OS, although the underlying factors associated with prolonged survival remain largely unknown. We here present the clinical and pathological characteristics of a cohort of patients considered long-term survivors. METHODS: Long-term survival (LTS) was defined as OS >3 years after initial diagnosis. Long-term survivors were retrospectively identified from a systematic departmental clinical database from a single institution, and both medical and pathology records were reviewed to identify demographic and clinical characteristics. Tumors were molecularly profiled using a standard clinical panel used for all glioma patients treated at our center. Kaplan-Meier and multivariate analysis was used to identify factors associated with LTS. RESULTS: We identified a total of 23 long-term survivors, including 14 cases with OS >5 years. Median age at initial diagnosis was 41 years (range 25-68). There was no difference in gender distribution. The majority of tumors were located in the frontal lobes (16/23, 69.5%). 13/23 (57%) of patients underwent gross-total resection. 9/23 tumors (39.1%) featured an oligodendroglial component in histopathological analysis. All patients received adjuvant concurrent radiation and temozolomide and subsequent chemotherapy (with regimens of either PCV, n = 2, gefitinib, n = 1, or temozolomide, n = 20). 9/23 patients showed MGMT-promoter methylation, 4 were non-methylated and 10 remained undetermined. The majority of patients (13/23, 56.6%) were TP53-wildtype. IDH1-mutation was present in 19/23 patients, 82.6% (17 R132H, 2 R132C). All IDH1-wildtype cases were both MGMT-promoter methylated and TP53-wildtype. CONCLUSIONS: IDH1-mutation, MGMT-promoter methylation, TP53-wildtype status, oligo-component, and frontal lobe location seem to be favorable prognostic factors for LTS. Interestingly, in our cohort gross-total surgical resection was not an absolute prerequisite for LTS and IDH1-wildtype status did not preclude long-term survival.