Clinical and molecular characteristics and prognostic factors of diffuse astrocytoma, IDH-wildtype, not elsewhere classified

Abstract

Purpose The clinical nature of IDH-wildtype astrocytoma, not elsewhere classified (NEC), is poorly understood. To this end, we aimed to investigate the clinical, molecular, imaging, and prognosis of histological grade 2 and 3 IDH-wildtype diffuse astrocytoma, NEC. Methods Retrospective chart and imaging reviews were performed for 46 patients with IDH-wildtype diffuse astrocytoma, NEC. Data regarding clinical, histopathological, molecular markers, MRI findings, and the extent of resection were collected. Univariable and multivariable Cox analyses were performed for overall survival (OS). Results The median OS was 45.0 months (95% CI 27.7-62.4). Multivariable analysis identified older age at diagnosis (hazard ratio [HR] = 1.10, P = 0.007), higher Ki-67 index (HR = 1.09, P = 0.002), and non-gross total resection (HR = 3.57, P = 0.042) as independent predictors of unfavorable OS. Tumors with genetic alterations such as amplification of KIT (P = 0.024) and PDGFRA (P = 0.034), and mutations in ATM (P = 0.050) showed an increased Ki-67 index. Tumors with higher histological grade (P < 0.001) and infiltrative appearance on MRI (P = 0.029) also showed an increased Ki-67 index. For patients with Ki-67 index >= 5, addition of adjuvant temozolomide therapy resulted in a survival benefit (P = 0.014). Conclusion Our findings support the importance of maximal safe resection and prognostic value of the Ki-67 index in this tumor. KIT, PDGFRA amplification and ATM mutations were associated with the increased Ki-67 indices, and targeted therapies against these alterations warrant further investigation.