Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings

Abstract

Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS).

Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis (N_LTS = 23) or <3 years (N_STS = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) (N_LTS = 23; N_STS = 74) and methylation analysis (N_LTS = 18; N_STS = 28). Pre-surgical MRI scans for a subset of LTS (N = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed.

Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMTp methylation and tumor protein 53 (TP53) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers.

Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis.

Keywords: glioblastoma; long-term survivor; methylation; predictors.

Figure 1.

Group criteria for clinical, molecular and imaging evaluation. Patients were screened for histological diagnosis of glioblastoma and then length of survival from diagnosis. Those with IDH wildtype status confirmed by NGS living ≥3 years comprise the LTS group (N = 23), those <3 years the STS group (N = 75). Groups were further refined by methylation diagnosis for molecular analysis (N_LTS = 18, N_STS = 28). For imaging, the availability of diagnostic imaging was required for both groups (N_LTS = 14, N_STS = 71). The “STS-imaging control” group was age, sex, and extent of resection matched 2:1 to the “LTS-imaging group” (N = 28; extent P = .342, CV = 0.21, OR = 2.5 E).