Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases : A comparative analysis.

BACKGROUND: Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. PATIENTS AND METHODS: Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy3 and 249.6 Gy3). No toxicity-related risk factors were identified. CONCLUSION: SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment.

Outcome and toxicity profile of salvage low-dose-rate iodine-125 stereotactic brachytherapy in recurrent high-grade gliomas.

BACKGROUND: The aim of this study was to provide an outcome and toxicity profile of salvage low-dose-rate iodine-125 (I-125) stereotactic brachytherapy (SBT) in patients with small, circumscribed malignant glioma recurrences. METHODS: Patients with malignant glioma recurrences consecutively undergoing salvage SBT from 2003 to 2011 were identified from our prospective tumor database. SBT was considered a potentially suitable treatment strategy for adult mostly multimodally pretreated patients (Karnofsky score of ≥ 70) with biopsy-proven, circumscribed, small (diameter ≤ 3.5 cm) recurrences. Exclusively temporary I-125 seeds were used (reference dose: 50 Gy, dose rate: < 15 cGy/h). Study endpoints were time-to-treatment failure (TTF) after SBT, postrecurrence survival (PRS), and toxicity. Survival was assessed with the Kaplan-Meier method. Adverse events were categorized according to the RTOG/EORTC classification. Prognostic factors were obtained from proportional hazards models. RESULTS: Sixty-eight patients (28 WHO grade III, 40 WHO grade IV gliomas) were included. Fifty-nine patients had previously received external beam radiation. Median TTF and PRS were 8.3 months and 13.4 months, respectively. TTF and PRS were longer for grade III gliomas than for glioblastomas (15.0 vs. 6.2 months and 28.1 vs. 9.3 months, respectively). Patients with grade III tumors were younger (p = 0.002). Favorable factors for TTF and PRS were age ≤ 50 years and a methylated O(6)-methylguanine-DNA methyltransferase (MGMT)-promoter. Alternative models including tumor grade instead of age reached a similar good fit. Three patients suffered from grade I, one from grade II, and two from grade IV toxicity. CONCLUSIONS: Salvage SBT is feasible and safe even after previously performed external beam radiation. Favorable outcome measurements in particular for grade III recurrences deserve further prospective evaluation.

Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas.

BACKGROUND: This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. METHODS: This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. RESULTS: For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1-5), and a median total implanted activity of 21.8 mCi (range 4.2-43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). CONCLUSION: SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.