Resection and Surgically Targeted Radiation Therapy for the Treatment of Larger Recurrent or Newly Diagnosed Brain Metastasis: Results From a Prospective Trial

Abstract

Introduction Achieving durable local control (LC) for larger (e.g., >2-3 cm) brain metastasis whether newly diagnosed or recurrent remains problematic. Resection (R) alone is typically insufficient and adding radiation therapy (RT) still results in a 12-month recurrence rate of 20% or more in many series. Hypothesizing that R plus immediate radiation utilizing brachytherapy may improve outcomes for this cohort of patients, we designed and prospectively evaluated a permanently implanted surgically targeted radiation therapy (STaRT) device consisting of cesium-131 (Cs-131) seeds positioned within a collagen carrier (GammaTile, GT Medical Technologies, Tempe, AZ). The device was designed to prevent direct source-to-brain contact and maintain inter-source spacing after closure. Methods This was a subgroup analysis of a cohort of patients with either recurrent or previously untreated brain metastases enrolled in a prospective, multi-histology single-arm trial (ClinicalTrials.gov, NCT#03088579), conducted between February 2013 and February 2018, of resection and tumor bed brachytherapy with Cs-131 containing permanently implanted collagen tiles to deliver 60 Gray (Gy) at .5 cm depth. No additional local therapy was given without progression. Results A total of 16 metastases in 11 patients were treated; 12 tumors were recurrent and four were previously untreated. The median preoperative maximum diameter was 3.2 cm (range: 1.9-5.1 cm). Histology was seven breasts, six lungs, and three sarcomas. The median age was 60 years (range: 41-80 years); the Karnofsky Performance Status (KPS) was 70 (range: 70-90). The cohort consisted of seven females and four males. The mean time for implantation completion was five minutes. The median overall survival (OS) was 9.3 months. At a median radiographic follow-up of 9.5 months' treatment, site progression was found in 1/16 (6%) at 10.9 months, and the median treatment site time-to-progression (TTP) has not been reached [95% confidence interval (CI): >10.9 months]. At 12 months, the Kaplan-Meier (K-M) estimates for LC after R+STaRT for all tumors was 83%; for previously untreated tumors, LC at 12 months was 100% and for recurrent tumors, it was 80%. Two tumor beds (12.5%) experienced radiation brain changes: one had grade two and the other grade three. No surgical adverse events occurred. Conclusion In this single-arm precommercial study, R+STaRT demonstrated excellent safety and LC in this cohort. The device has recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis, and randomized clinical trials vs. standard of care treatments in both settings are scheduled to open in 2020.

Surgical Outcomes of Novel Collagen Tile Cesium Brachytherapy for Recurrent Intracranial Tumors at a Tertiary Referral Center

“…They demonstrated that 131Cs brachytherapy was able to provide durable local control (89% PFS at one year) with no cases of radiation necrosis, though these patients had not had any previous treatment for their intracranial disease [ 30 ]. Results from the same group with a smaller cohort of patients who had previously had radiation treatment of their metastatic intracranial disease demonstrated similar results in terms of efficacy and safety, which is consistent with other similar studies [ 25 , 31 ]. Likewise, Brachman et al demonstrated the safety and efficacy of 131Cs brachytherapy in a cohort of 19 patients with previously irradiated meningiomas, with only two cases of local progression at 15 months and two cases of radiation necrosis that were amenable to medical management [ 29 ].…”

Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles

“…Overall, this leads to very conformal and localized treatment plans. Previous studies evaluated the use of these implanted Cs-131 seeds in brain metastases, meningiomas, and gliomas and showed a favorable toxicity profile [4,5,[13][14][15]. Additional benefits of this technique include immediate post-resection initiation of radiation in a rapidly proliferating tumor and the relative ease of use when applying the tiles [3].…”

The evolving role of neurosurgery for central nervous system metastases in the era of personalized cancer therapy

“…Although these approaches may have shown success in terms of maintenance of local control, many have been associated with a higher risk of radiation-related complications than what has been reported for WBRT or radiosurgery. A more recently developed technology combines the use of cesium-131 radiation seeds with an implanted substrate that improves dosimetry [105]; how this will compare over time to more established techniques remains to be determined. Yet another technology which is increasingly used is MR-guided laser induced hyperthermia (LITT) to ablate abnormal tissue e frequently metastases e for which different devices are available allowing precise thermometry [106].…”