gms | German Medical Science

Objective: Despite a variety of new treatment modalities in recurrent malignant glioma, the patients' overall survival (OS) and time-to-progression (TTP) remain limited. This pivotal study evaluates the effectiveness and risks of low-dose rate Iodine-125 SBT in selected patients (pts) with recurrent WHO III and IV gliomas.

Method: Data were prospectively collected and retrospectively analyzed. All patients suffered from histological recurrences of WHO III or IV gliomas, which were verified by stereotactic biopsy. In addition, the biomarker status was determined (MGMT methylation, IDH1/2 mutation, LOH 1p/19q). Indications for SBT were circumscribed lesions with a diameter of <4cm based on MRI and/or [18F]FET-PET. SBT was performed via temporary iodine-125 seed implantation between 2000 and 2011. The reference dose was 50 Gy. The dose rate was low (< 15 cGy/h). Date of last follow-up (FU) was 04/2012. Survival analysis was performed with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models.

Results: 73 patients (37 m and 36 f) were included. The median FU was 18.0 months. The mean age at seed implantation was 48 (range 17-76) yrs with a median KPS of 90 (range 80–90). All pts had received prior treatment with 62 (84.9%) having undergone previous percutaneus radiotherapy. Histological evaluation revealed 37 (50.7%) GBM WHO IV (61.5% MGMT methylated), 2 (2.7%) Gliosarcoma WHO IV (0.0% MGMT methylated), 25 (34.2%) astrocytomas WHO III (65.0% MGMT methylated), 8 (11.0%) oligoastrocytoma WHO III (87.5% MGMT methylated) and 1 (1.4%) oligodendrogliomas WHO III (100.0% MGMT methylated). The mean tumor volume was 2.5 cm³. Median TTP – either local or distant progression – and survival after SBT were 10.0 (95% CI, 6.6–13.4) and 25.0 (95% CI, 10.4–39.6) mths. Favorable prognostic factors for TTP were: MGMT methylation (methylated vs unmethylated: 12.0 vs 5.0 mths, p=0.04), KPS (90 vs 80: 11.0 vs 2.0 mths, p=0.05), IDH mutation (both IDH1 or IDH2) vs none (20.0 vs 2.0 mths, p=0.001), and age at SBT (<50 vs >50 yrs : 15.0 vs 6.0 mths, p=0.03). Treatment-associated complications were radionecrosis (n=1), wound healing deficits (n=5) and an intracranial abscess (n=1). In one patient the seed position had to be corrected by a second surgical procedure.

Conclusions: Iodine-125 low-dose rate SBT is a safe and attractive treatment option for selected patients with recurrent malignant glioma, who had previously undergone multimodal therapy including external beam radiation.