Background: This study evaluates prognostic factors influencing survival outcomes for 60 patients with permanent iodine-125 implants in the primary treatment of non-glioblastoma multiforme (GBM) high-grade gliomas. Methods: Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/h with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan-Meier method for univariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 34 patients received external radiation therapy (5,000–6,000 cGy) before the implant; 13 patients were implanted without additional external beam radiation, and 13 patients underwent external radiation therapy before implant placement. Results: With a mean follow-up of 77.6 months (range 3.5–164 months), 1-, 3-, 5- and 10-year survival were 86.7% (±0.05%), 60% (±0.07%), 50% (±0.07%) and 45.7% (±0.7%), respectively. The median survival time was 57 months. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%) and brain abscess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky score and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location and preoperative Karnofsky score greater than 70. RPA classification was used to define this group of patients. In RPA classes I and II (n = 43), 1-year survival was 93%, while 3-, 5- and 10-year survival was 67.4, 60.5 and 55.5%, respectively, and median survival time was 91 months. In RPA class III (n = 7), 1-year survival was 71.4%, while 3- and 5-year survival was 42.9 and 28.6%, respectively, and median survival time was 47 months. In RPA class IV (n = 10), 1-year survival was 60%, while 3-, 5- and 10-year survival was 50, 22.2 and 11.1%, respectively, and median survival time was 37 months. Conclusion: Brachytherapy with permanent implant of 125I appears promising in the treatment of primary non-GBM malignant gliomas. It improved survival time and reduced the incidence of complications and provided good quality of life. In order to further confirm these results, multicenter randomized prospective studies are needed. RPA analysis is a valid tool to define prognostically distinct survival groups. In this study, 2-year survival and median survival time were improved in all prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with 125I implants. Further randomized studies with effective stratification are needed.

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