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

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

doi:10.1093/neuonc/noaf133

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

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

Authors

Aleksandra B Lasica^{1

2}, Zhou Lan^{2

3}, Julie J Miller^{2

4}, Albert Jiao⁵, Ian Pan⁵, Loai Aker⁵, Prem Prabhakar⁶, Julia Japo⁶, Alyssa Russ¹, Catharina Westergaard¹, 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

¹ Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.
² Harvard Medical School, Harvard University, Boston, MA, United States.
³ Center for Clinical Investigation, Brigham and Women's Hospital, Boston, MA, United States.
⁴ Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, United States.
⁵ Division of Neuroradiology, Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States.
⁶ Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.
⁷ Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States.
⁸ Brain & Spine Tumor Center, Perlmutter Cancer Center, NYU Langone Health, New York, NY, United States.
⁹ Department of Neurology, Grossman School of Medicine, New York University, New York, NY, United States.
¹⁰ Department of Neurosurgery, Mass General Brigham, Boston, MA, United States.

PMID: 40440464
DOI: 10.1093/neuonc/noaf133

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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