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. 2025 May 29:noaf133.
doi: 10.1093/neuonc/noaf133. Online ahead of print.

Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4

Aleksandra B Lasica  1   2 , Zhou Lan  2   3 , Julie J Miller  2   4 , Albert Jiao  5 , Ian Pan  5 , Loai Aker  5 , Prem Prabhakar  6 , Julia Japo  6 , Alyssa Russ  1 , Catharina Westergaard  1 , Elisa Aquilanti  1   2 , Ugonma Chukwueke  1   2 , L Nicolas Gonzalez Castro  1   2   7 , J Ricardo McFaline Figueroa  8   9 , Eudocia Quant Lee  1   2 , Lakshmi Nayak  1   2 , Rameen Beroukhim  1   2 , Tracy T Batchelor  2   7 , Daniel P Cahill  2   10 , Vihang Nakhate  1   2   4 , Tyler Lanman  1   2   4 , Juan Pablo Ospina  1   2   4 , Natalie Stec  1   2   4 , Ruchit V Patel  2   10 , David M Meredith  2   6 , Wenya Linda Bi  2   10 , David A Reardon  1   2 , Keith L Ligon  2   6 , Raymond Y Huang  2   5 , Patrick Y Wen  1   2 , Gilbert Youssef  1   2
Affiliations

Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4

Aleksandra B Lasica et al. Neuro Oncol. .

Abstract

Background: Astrocytoma, isocitrate dehydrogenase-mutant, WHO grade 4 (Astro4), is a new tumor type in the 2021 WHO classification of central nervous system tumors that has been poorly characterized in the literature. This study evaluates predictors of prognosis in a large cohort of newly diagnosed Astro4.

Methods: We retrospectively identified 128 consecutive adult patients who presented with an initial diagnosis of Astro4 at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021. Clinical, molecular, and radiological characteristics were recorded, and their associations with overall survival (OS) and progression-free survival (PFS) were measured by log-rank test and Cox proportional hazards model.

Results: The median age at diagnosis was 37.1 years, and 61.7% were men. The median OS was 5.9 years (95% confidence interval, 4.4 - 7.3), while the median PFS was 2.7 years (1.8 - 3.6). Age ≥50 and homozygous CDKN2A/B deletion were independent negative prognosticators of OS on univariate and multivariate analyses [hazard ratio (HR), 2.21 (1.16 - 4.21), p=0.019; HR, 2.61 (1.27 - 5.38), p=0.013]. Maximal resection of enhancing disease was associated with longer PFS on univariate and multivariate analyses [HR, 0.48 (0.26 - 0.87), p=0.019]. There were no significant differences in OS or PFS based on MGMT promoter methylation status, T2/FLAIR extent of resection, T2/FLAIR mismatch, radiological pseudoprogression, or enhancement on the pre-operative scan.

Conclusions: Our study comprehensively characterizes a large cohort of newly diagnosed patients with Astro4, emphasizing the prognostic value of CDKN2A/B deletion, age, and the extent of resection of enhancing disease in these patients.

Keywords: CDKN2A/B deletion; IDH-mutant; WHO Grade 4; astrocytoma; prognosis.

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