Abstract
The clinical behavior and optimal management of IDH-wildtype diffuse astrocytic tumors, not elsewhere classified (NEC), remain poorly understood. This study aimed to investigate the clinical, molecular, imaging characteristics, and prognosis of histological grade 2 and 3 IDH-wildtype diffuse astrocytic tumors, NEC. A retrospective chart and imaging review was conducted for 46 patients diagnosed with NEC tumors at a single institution. Clinical data, histopathological and molecular markers including next-generation sequencing (NGS) results, MRI features, and extent of surgical resection were collected. Univariable and multivariable Cox proportional hazards analyses were performed to assess factors associated with overall survival (OS). The median OS was 45.0 months (95% CI, 27.7–62.4). On multivariable analysis, 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) were independently associated with shorter OS. Amplification of KIT (P = 0.024) and PDGFRA (P = 0.034), as well as ATM mutation (P = 0.050), were significantly associated with higher Ki-67 index, suggesting a link to increased proliferative activity. In addition, higher histological grade (P < 0.001) and infiltrative MRI appearance (P = 0.029) were also associated with increased Ki-67 index. Our results support the importance of maximal safe resection and suggest that adjuvant temozolomide therapy in combination with radiotherapy may be beneficial, particularly for patients with high Ki-67 indices. Furthermore, the molecular association of KIT, PDGFRA, and ATM alterations with increased proliferative activity highlights the need to explore targeted therapeutic strategies against these genetic alterations in future studies.