OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm (range 0.21-76.2 cm). Gross-total resection was achieved in 81% of the cases. The median number of I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p< 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

Purpose RTOG 0321 is the first multi-institutional cooperative group HDR prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity. Methods and Materials Patients are treated with EBRT 45 Gy and one HDR implant with 19 Gy in 2 fractions. Implants are done with TRUS guidance, and CT-compatible non-metallic catheters. HDR planning is done on ≤ 3 mm-thick CT slices. The “mean DVH” of the PTV, implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation of the volume at ten-percentage-point intervals from 10%–200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters/implant, and patients/institution are calculated. Multivariate analysis and Hazard Ratios calculation of all the variables against reported Grade ≥ 2 (G2+) GU adverse events (CTCAEv3) are performed. Results Dosimetry data is based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters/implant, and patients/institution are: 54 cc, 63 cc, 19 and 9. The mean of %V100PTV, V80Bladder, V80Rectum, and V120Urethra were: 94%, 0.40cc, 0.15cc, and 0.25cc. There are too few G2+ GI AE for correlative analysis, thus the analysis has been performed on the more common G2+ GU AE. There are positive correlations noted between both acute and late G2+ GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2+ acute and late AE. Conclusions Higher urethral dose, larger high dose volumes and lower dose homogeneity are associated with greater toxicities. A mean DVH comparison at all dose levels should be used for quality control and future research comparison.

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