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Purpose <p>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.</p> Methods <p>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).</p> Results <p>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, <i>P</i> = 0.007), higher Ki-67 index (HR = 1.09, <i>P</i> = 0.002), and non-gross total resection (HR = 3.57, <i>P</i> = 0.042) as independent predictors of unfavorable OS. Tumors with genetic alterations such as amplification of <i>KIT</i> (<i>P</i> = 0.024) and <i>PDGFRA</i> (<i>P</i> = 0.034), and mutations in <i>ATM</i> (<i>P</i> = 0.050) showed an increased Ki-67 index. Tumors with higher histological grade (<i>P</i> &lt; 0.001) and infiltrative appearance on MRI (<i>P</i> = 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 (<i>P</i> = 0.014).</p> Conclusion <p>Our findings support the importance of maximal safe resection and prognostic value of the Ki-67 index in this tumor. <i>KIT</i>, <i>PDGFRA</i> amplification and <i>ATM</i> mutations were associated with the increased Ki-67 indices, and targeted therapies against these alterations warrant further investigation.</p>

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

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Woo Jong Cho,
  • Kaeum Choi,
  • Kyunghwa Han,
  • Seo Hee Choi,
  • Hong In Yoon,
  • Sung Soo Ahn,
  • Jong Hee Chang,
  • Seok-Gu Kang,
  • Se Hoon Kim,
  • Seung-Koo Lee,
  • Chan Woo Wee,
  • Yae Won Park

摘要

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.