Prognostic factors of brain metastases affecting survival: an Indonesian cohort
Main Article Content
Abstract
Background
Brain metastases (BMs) most frequently originate from primary tumors of the lung and breast, and significantly impact cancer patient prognosis. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The objective of this study was to identify key prognostic factors influencing survival in synchronous metastases (SM) and metachronous metastases (MM), focusing on metastatic duration, tumor volume response, and gamma knife radiosurgery.
Methods
A retrospective cohort study was conducted involving 100 patients with brain metastases (48 synchronous, 52 metachronous). Age, gender, primary tumor, gamma knife status, metastasis location, peritumoral index group, volume reduction, metastatic duration, metastasis characteristics, and intensity pattern based on MRI. A Cox proportional hazards regression was used to analyze the data. Based on the Cox regression coefficients, a prognostic index was constructed.
Results
Calculated HR comprised MM (HR=0.49;95% CI :0.24–0.97], gamma knife treatment (HR = 0.15;95% CI: 0.07–0.29], and volume response (HR=0.40;95% CI: 0.16–0.99), all indicating a significantly reduced mortality risk. A prognostic index was calculated for all patients; those with scores ≤–1.513 were classified as low risk. Kaplan-Meier analysis showed that the low-risk group had a significantly longer mean survival period (75.52 months) compared to the high-risk group (31.43 months) (p<0.001).
Conclusion
Metachronous presentation, gamma knife therapy, and greater tumor volume reduction independently predict better survival. The developed prognostic index provides a clinically useful tool for personalized risk assessment and treatment planning in patients with brain metastases.
Article Details
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References
1. Lamba N, Wen PY, Aizer AA. Epidemiology of brain metastases and leptomeningeal disease. Neuro Oncol 2021;23:1447–56. doi: 10.1093/neuonc/noab101.
2. Singh R, Stoltzfus KC, Chen H, et al. Epidemiology of synchronous brain metastases. Neurooncol Adv 2020;2:vdaa041. doi: 10.1093/noajnl/vdaa041.
3. Aninditha T, Pratama PY, Sofyan HR, et al. Adults brain tumor in Cipto Mangunkusumo General Hospital: a descriptive epidemiology. Ro J Neurol 2021;20:480-4. doi: 10.37897/RJN.2021.4.13.
4. Dewi PNA, Hermawan AN, Juli C, et al. Characteristics of brain imaging in intracranial tumor patients at neurology ward Dr. Hasan Sadikin General Hospital Bandung 2017–2019. Althea Med J 2021;8:204–9. doi: https://doi.org/10.15850/amj.v8n4.2361.
5. Jiang K, Parker M, Materi J, et al. Epidemiology and survival outcomes of synchronous and metachronous brain metastases: a retrospective population-based study. Neurosurg Focus 2023;55:E3. doi: 10.3171/2023.5.
6. Blazquez R, Proescholdt MA, Klauser M, et al. Breakouts—a radiological sign of poor prognosis in patients with brain metastases. Front Oncol 2022;12:849880. doi: 10.3389/fonc.2022.849880.
7. Baumgart L, Anetsberger A, Aftahy AK, et al. Single brain metastases – prognostic factors and impact of residual tumor burden on overall survival. Front Oncol 2024;14:1330492. doi: 10.3389/fonc.2024.1330492.
8. Li J, Zhang X, Wang Y, Jin Y, Song Y, Wang T. Clinicopathological characteristics and prognosis of synchronous brain metastases from non-small cell lung cancer compared with metachronous brain metastases. Front Oncol 2024;14:1400792. doi: 10.3389/fonc.2024.1400792.
9. Ho VKY, Gijtenbeek JMM, Brandsma D, Beerepoot LV, Sonke GS, van der Heiden-van der Loo M. Survival of breast cancer patients with synchronous or metachronous central nervous system metastases. Eur J Cancer 2015;51:2508-16. doi: 10.1016/j.ejca.2015.07.040.
10. Leone JP, Lee AV, Brufsky AM. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. Cancer Med 2015;4:989–94. doi: 10.1002/cam4.439.
11. Chu L, Ni J, Yang X, et al. Radiographic features of metastatic brain tumors from ALK-rearranged non-small cell lung cancer: implications for optimal treatment modalities. J Cancer 2019;10:6660–5. doi: 10.7150/jca.30091.
12. Kerschbaumer J, Bauer M, Popovscaia M, Grams AE, Thomé C, Freyschlag CF. Correlation of tumor and peritumoral edema volumes with survival in patients with cerebral metastases. Anticancer Res 2017;37:871-5. doi: 10.21873/anticanres.11392.
13. Du P, Chen H, Shen L, et al. Analysis of key clinical variables and radiological manifestations associated with the treatment response of patients with brain metastases to stereotactic radiosurgery. J Clin Med 2022;11:4529. doi: 10.3390/jcm11154529.
14. Phung HT, Le YT, Nguyen TV, et al. Treatment outcome of brain metastases from breast cancer following gamma knife radiosurgery: a retrospective study in Vietnam. Technol Cancer Res Treat 2025;24:15330338251328522. doi: 10.1177/15330338251328522.
15. Gupta S, Singh S, Chophy A, et al. Analysis of prognostic factors in patients with brain metastases affecting survival. J Egypt Natl Canc Inst 2022;34:45. doi: 10.1186/s43046-022-00146-z.
16. Lwanga K, Lemeshow S. Sample size determination in health studies: a practical manual. Geneva: World Health Organization; 1991.
17. Ulu EMK, Ozturk B, Atalay K, et al. Diffusion-weighted MRI of metastatic brain tumors: relation of diffusion parameters with histologic type. Turk Neurosurg 2022;32:58-68. doi: 10.5137/1019-5149.JTN.32084-20.4.
18. Zhu D, Shao Y, Yang Z, et al. Magnetic resonance imaging characteristics of brain metastases in small cell lung cancer. Cancer Med 2023;12:15199-206. doi: 10.1002/cam4.6206.
19. Mourad AF, Mohammad HEDG, Sayed MM, Ragae MA. What’s the clinical significance of adding diffusion and perfusion MRI in the differentiation of glioblastoma multiforme and solitary brain metastasis? Egypt J Radiol Nucl Med 2017;48:661–9. doi: 10.1016/j.ejrnm.2017.04.002.
20. Huang Y, Huang J, Guan C, Liu T, Que S. Volumetric measurement of cranial cavity and cerebral ventricular system with 3D Slicer software based on CT data. BMC Med Imaging 2025;25:64. doi: 10.1186/s12880-025-01591-7.
21. Ocaña-Tienda B, Pérez-Beteta J, Romero-Rosales JA, et al. Volumetric analysis: rethinking brain metastases response assessment. Neurooncol Adv 2023;6:vdad161. doi: 10.1093/noajnl/vdad161.
22. Barton B, Peat J. Medical statistics: A guide to SPSS, data analysis and critical appraisal. 2nd ed. Oxford UK: John Wiley & Sons Ltd ;2014.
23. Chen K, Zhang F, Fan Y, Cheng G. Lung-molGPA index predicts survival outcomes of non-small-cell lung cancer patients with synchronous or metachronous brain metastases. Onco Targets Ther 2020;13:8837-44. doi: 10.2147/OTT.S255478.
24. Omoto Y, Kurosumi M, Hozumi Y, et al. Immunohistochemical assessment of primary breast tumors and metachronous brain metastases, with particular regard to differences in the expression of biological markers and prognosis. Exp Ther Med 2010;1:561-7. doi: 10.3892/etm_00000088.
25. Bander ED, Yuan M, Carnevale JA, et al. Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies. Cancer 2021;127:2062–73. doi: 10.1002/cncr.33459.
26. Li M, Hou X, Sai K, et al. Immune suppressive microenvironment in brain metastatic non-small cell lung cancer: comprehensive immune microenvironment profiling of brain metastases versus paired primary lung tumors (GASTO 1060). Oncoimmunology 2022;11:2059874. doi: 10.1080/2162402X.2022.2059874.
27. Crisà FM, Leocata F, Arienti VM, et al. Adaptive staged-dose gamma knife radiosurgery for the treatment of large brain metastases: report of 40 consecutive cases and analysis of literature. Neurol India 2023;71(Suppl 1):S146–52. doi: 10.4103/0028-3886.373643.
28. Noyama T, Katano A, Shinya Y, et al. Prognostic factors for patients with brain metastases treated with single-fraction gamma knife radiosurgery. Anticancer Res 2021;41:3179-85. doi: 10.21873/anticanres.15104.
29. Xiang Z, Chen J, Zhang H, Shen L, Wei Q. Whole brain radiotherapy-based combined modality treatment of brain metastases from non-small cell lung cancer: a retrospective analysis of prognostic factors. Oncol Res Treat 2015;38:35-40. doi: 10.1159/000371501.
30. Zhou MH, Wu Y, Sun JZ. Clinical features and prognostic factors in 190 cancer patients with brain metastases. Transl Cancer Res 2020;9:1160-6. doi: 10.21037/tcr.2019.12.98.
31. Tan SS, Van Putten E, Nijdam WM, et al. A microcosting study of microsurgery, LINAC radiosurgery, and gamma knife radiosurgery in meningioma patients. J Neuro Oncol 2011;101:237–45. https://doi.org/10.1007/s11060-010-0243-4.
32. Ahmad S, Ricco A, Brown R, et al. Single institutional experience of stereotactic radiosurgery alone for first brain metastatic event and salvage of second brain metastatic event in a community setting with review of the literature. Front Oncol 2017;7:32. doi: 10.3389/fonc.2017.00032.
33. Sperduto PW, Fang P, Li J, et al. Estimating survival in patients with gastrointestinal cancers and brain metastases: an update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA). Clin Transl Radiat Oncol 2019;18:39-45. doi: 10.1016/j.ctro.2019.06.007.
34. Bankole NDA, Melhaoui A, Arkha Y, et al. Outcomes of single brain metastasis treated with gamma knife stereotaxic radiosurgery (GKSR). Our experience on 103 cases. IBRO Neurosci Rep 2023;14:138-45. doi: 10.1016/j.ibneur.2023.01.007.