Abstract
AB003. Clinical analysis of central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas with IDH-mutant versus IDH-wildtype focused on CDKN2A homozygous deletion
Da Hyun Park, Young Zoon Kim
Division of Neuro-Oncology, Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
Correspondence to: Young Zoon Kim, MD, PhD. Division of Neuro-Oncology, Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, 158 Paryong-ro, Masan Hoewon-gu, Changwon 51353, Gyeongnam, South Korea. Email: yzkim@skku.edu.
Background: We are primarily investigating the prognostic role of cell-cycle-dependent kinase inhibitor (CDKN)-2A homozygous deletion in central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas. Additionally, traditional prognostic factors for grade 4 gliomas will be examined, and our results will be validated.
Methods: We conducted a retrospective analysis of glioma cohorts in our institute. Medical records were reviewed for 142 glioblastoma patients for 15 years, and pathological slides were examined again for the updated diagnosis according to the 2021 WHO classification of CNS tumors. The isocitrate dehydrase (IDH) mutation and CDKN2A deletion were examined by next generation sequencing (NGS) analysis using ONCO accuPanel®. Traditional prognostic factors including age, WHO performance status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation were examined.
Results: After the exclusion of 6 patients with poor status of pathologic samples, 136 glioblastoma that were diagnosed by previous WHO criteria were changed into 29 (21.3%) astrocytoma, IDH-mutant, CNS WHO grade 4 and 107 (78.7%) glioblastoma, IDH-wildtype, CNS WHO grade 4. Among them, 61 patients (56.0%) had CDKN2A deletion. Group A with IDH-wildtype and CDKN2A deletion had a mean overall survival (OS) of 15.70 months [95% confident interval (CI): 13.86–17.54], group B with IDH-mutant and CDKN2A deletion had a mean OS of 19.37 months (95% CI: 13.43–25.30), group C with IDH-wildtype and intact CDKN2A had a mean OS of 22.63 months (95% CI: 20.10–25.17), and group D with IDH-mutant and intact CDKN2A had a mean OS of 33.38 months (95% CI: 29.35–37.40). Multifactor analysis showed following factors were independently associated with OS: age [≥50 vs. <50 years; hazard ratio (HR) 4.642], extent of resection (gross total resection vs. others; HR 5.523), WHO performance (0, 1 vs. 2; HR 5.007), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.075), IDH mutation (mutant vs. wildtype; HR 6.358), and CDKN2A deletion (absence vs. presence; HR 13.452).
Conclusions: The presenting study suggests that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low-grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcomes due to CDKN2A deletion.
Keywords: Glioma; CDKN2A deletion; isocitrate dehydrase mutation (IDH mutation); glioblastoma; prognosis
Acknowledgments
The authors appreciate Kyeong Hwa Ryu and Mi-Ok Sunwoo (Department of Radiology, Samsung Changwon Hospital) for their review of the neuroradiological images, Ki Soo Kim and Eun Hee Lee (Department of Pathology, Samsung Changwon Hospital) for the interpretation of the histopathological features, and Tae Gyu Kim (Department of Radiation Oncology, Samsung Changwon Hospital) for administering radiotherapy.
Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (The Ministry of Science and ICT) (No. NRF 2019R 1F1A 1054681). This paper was also financially supported by Sungkyun Research Fund, Sungkyunkwan University (2016) and Samsung Changwon Hospital Research Fund (2020).
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab003/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by Sungkyunkwan University Samsung Changwon Hospital Institutional Review Board (SCMC 2024-05-010). Because of the retrospective nature of the research and minimal hazard to the participants, the requirement for informed consent was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Cite this abstract as: Park DH, Kim YZ. AB003. Clinical analysis of central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas with IDH-mutant versus IDH-wildtype focused on CDKN2A homozygous deletion. Chin Clin Oncol 2024;13(Suppl 1):AB003. doi: 10.21037/cco-24-ab003
