Integrating molecular and clinical determinants of survival in a real-world glioblastoma cohort

Year 2026, Volume: 7 Issue: 1, 34 - 39, 20.02.2026

Mehmet Salim Demir , Gözde Ağdaş , Erdoğan Şeyran , Gürkan Güner

https://izlik.org/JA48ZS42LX

Abstract

Aims: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with limited survival despite multimodal treatment. This retrospective study evaluated the prognostic impact molecular markers and clinical factors on survival outcomes in a real world GBM cohort.
Methods: We conducted a retrospective analysis of 60 patients diagnosed with GBM between 2020 and 2023. Clinical, radiological, surgical, and molecular data were retrospectively collected. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves, with compared with log-rank test. Multivariable Cox regression analysis was performed to identify independent prognostic factors.
Results: Median OS and PFS for the entire cohort were 16.5 and 9.8 months, respectively. Molecular markers were the strongest prognostic factors: IDH-mutant and MGMT-methylated tumors showed significantly prolonged OS and PFS compared to their wild-type/unmethylated counterparts (p<.001). Surgical outcomes followed a clear gradient, with gross total resection (GTR) yielding the best survival, followed by subtotal resection (STR) and biopsy. Concurrent TMZ use was also associated with a significant improvement in OS (p<.001). Survival dynamics were further detailed using Kaplan-Meier analysis.
Conclusion: This study confirms the critical prognostic role of IDH mutation and MGMT promoter methylation status in GBM, while also validating the significant survival benefit associated with maximal surgical resection and concurrent TMZ. Our real-world outcomes translate effectively into long-term survival gains, reinforcing current treatment paradigms as reliable benchmarks for clinical management.

Keywords

Glioblastoma , IDH mutation , MGMT methylation , survival analysis , temozolomide , extent of resection

Ethical Statement

Ethics Approval This study was conducted in accordance with the Declaration of Helsinki and approved by the Van Training and Research Hospital (GOKAEK: 10-25, 19.12.2025 dated) local institutional ethics committee. Due to the retrospective design, informed consent was waived.

Thanks

Dear Editor-in-Chief, We would like to submit our manuscript entitled “Integrating Molecular and Clinical Determinants of Survival in a Real-World Glioblastoma Cohort” for consideration in the Journal of Medicine and Palliative Care. In this retrospective real-world study of 60 glioblastoma patients, we evaluated key molecular, clinical, and surgical factors influencing overall and progression-free survival. Our findings demonstrate that IDH mutation status, MGMT promoter methylation, and extent of resection provide clear prognostic stratification, resulting in markedly different survival trajectories among patients. Given the uniformly poor prognosis of glioblastoma, accurate survival estimation and early identification of patient subgroups are essential for appropriate treatment intensity, patient selection, and timely integration of palliative and supportive care. We believe our results offer clinically meaningful insights that may assist physicians in prognostic counseling and individualized care planning. This manuscript is original, has not been published elsewhere, and is not under consideration by another journal. All authors have approved the submission. Thank you for your consideration. Sincerely, Mehmet Salim Demir, MD Corresponding Author on behalf of all authors

References

• Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2021;142(2):141-162. doi:10.1007/s00401-021-02226-7
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. doi:10.1056/NEJMoa043330
• Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. doi:10.1056/NEJMoa043331
• Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773. doi:10.1056/NEJMoa0808718
• Cancer Genome Atlas Research Network. Comprehensive genomic characterization of glioblastoma. Nature. 2008;455(7216):1061-1068. doi:10.1038/nature07385
• Molinaro AM, Hervey-Jumper S, Morshed RA, et al. Association of IDH mutation with survival in glioma patients: a contemporary analysis. JAMA Oncol. 2020;6(4):495-503. doi:10.1001/jamaoncol.2019.6143
• Weller M, Felsberg J, Hartmann C, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6(1):39-51. doi:10.1038/nrn2730
• Wick W, Platten M, Weller M, et al. MGMT testing—the challenges for biomarker-based glioma treatment. Nat Rev Neurol. 2014;10(6):372-385. doi:10.1038/nrneurol.2014.100
• Sanai N, Berger MS. Extent of resection influences survival in glioblastoma. Neurosurgery. 2018;62(Suppl 1):1-15. doi:10.1227/01.neu. 0000310449.40911.93
• Grabowski MM, Recinos PF, Nowacki AS, et al. Residual tumor volume after resection impacts overall survival in glioblastoma. J Neurooncol. 2014;119(2):567-578. doi:10.1007/s11060-014-1503-y
• Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: RTOG 0525. J Clin Oncol. 2013;31(32): 4085-4091. doi:10.1200/JCO.2013.50.9430
• Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy–temozolomide for glioblastoma. N Engl J Med. 2014;370(8):709-722. doi: 10.1056/NEJMoa1308345
• Stupp R, Taillibert S, Kanner AA, et al. Tumor-treating fields for newly diagnosed glioblastoma. JAMA. 2015;314(23):2535-2543. doi:10.1001/jama.2015.16669
• Wirsching HG, Weller M. Systemic therapy of glioblastoma: achievements, challenges, and next steps. Nat Rev Clin Oncol. 2023;20(3): 173-186. doi:10.1038/s41571-022-00736-9
• Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: state of the art and future directions. CA Cancer J Clin. 2020;70(4):299-312. doi:10.3322/caac.21613
• Caccese M, Piga I, Bellu L, et al. Treatment of glioblastoma in the elderly: updated evidence. Front Oncol. 2021;10:608250. doi:10.3389/fonc.2020.608250
• Shergalis A, Bankhead A 3rd, Luesakul U, Muangsin N, Neamati N. Current challenges and opportunities in treating glioblastoma. Pharmacol Rev. 2018;70(3):412-445. doi:10.1124/pr.117.014944
• Olar A, Wren D, Zadeh G, et al. Molecular markers and survival in glioblastoma: integrating IDH, MGMT, and TERT. Acta Neuropathol. 2015;130(4):593-604. doi:10.1007/s00401-015-1445-2
• Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas. Lancet Oncol. 2021;22(3): e281-e291. doi:10.1016/S1470-2045(20)30891-4
• Le Rhun E, Preusser M, Roth P, et al. Molecular targeted therapy of glioblastoma. Cancer Treat Rev. 2019;80:101896. doi:10.1016/j.ctrv.2019. 101896
• Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology (RANO) working group. J Clin Oncol. 2010;28(11):1963-1972. doi:10.1200/JCO.2009.24.6627
• Brown TJ, Brennan MC, Li M, et al. Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016;2(11):1460-1469. doi:10.1001/jamaoncol.2016.1373
• Nabors LB, Portnow J, Ahluwalia M, et al. Central nervous system cancers, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020;18(11):1537-1570. doi:10.6004/jnccn.2020. 0052