Surgically targeted radiation therapy (STaRT) using Cesium-131 collagen tile brain brachytherapy (GammaTile®, GT Medical Technologies, Tempe, Arizona, USA) is FDA cleared for operable newly diagnosed intracranial malignant neoplasms and recurrent intracranial neoplasms. To assess the rate of infection after brain tumor resection (R) and permanent implantation of STaRT on a prospective, multi-institutional observational study. The prospective, observational registry (NCT04427384) evaluates clinical outcomes that measure the effectiveness and safety of R+STaRT. As a secondary endpoint of the registry, wound infections are pre-specified as an adverse event (AE) of particular focus and are tracked and attributed using Common Terminology for Adverse Events version 5. The first 250 consecutive patients undergoing R+STaRT from 30 centers were chosen for evaluation to help ensure adequate follow up, and these patients were treated with brain tumor resection and STaRT between 11/2020 and 10/2023. 73.6% of cases were for recurrent tumors and 26.4% were for newly diagnosed tumors. 46.3% were glioblastomas, 34.3% were brain metastases, 12.4% were meningiomas, and 7.0% were “other.” Median follow-up was 11.9 months (range 0-36.3 months). There were surgical wound infections among 5 patients, four Grade 3 and one Grade 4. From the day of surgery, 4 infections were noted within the first 30 days, none occurred between 31-90 days, and 1 was noted 117 days after surgery. This interim data analysis of the first 250 consecutive patients from 30 centers show an infection rate (Grade 3 or 4) of 2%, which is consistent with what would be expected with craniotomy without STaRT. This data supports the safety of STaRT in a wide variety of clinical scenarios.

Determining true recurrence versus necrosis alone after previous radiotherapy (RT) for brain metastasis based on imaging alone is challenging. Accurate diagnosis is critical to patient management, as further RT is contraindicated in the setting of radiation necrosis without tumor (TUM-). Rates of intraoperative frozen section pathology reporting tumor +/- necrosis (TUM+) or necrosis without tumor (TUM-) were examined in patients undergoing resection for presumed RBM after prior same-site RT. All cases were prospectively enrolled on a multi-institutional registry for patients undergoing resection and intraoperative cesium-131 collagen tile brachytherapy (NCT04427384)(GammaTile, GT Medical Technologies, Tempe AZ, USA). Preoperative evaluation varied by center, and patient demographics, primary site, lesion size, and prior therapies were also examined. From 10/2020 to 2/2024, 60 patients (64 lesions) underwent resection and intraoperative frozen section pathologic evaluation. Per patient, primary sites were 53% lung, 15% melanoma, 13% breast, 7% renal, and 10% other. Median age was 62, median preoperative maximum diameter was 2.9 cm, F:M ratio was 31:29, and median time from prior RT was 15.4 months. Across all histologies, TUM+ was seen in 88% (53/60) and TUM- in 12% (7/60). Rates of TUM- by primary type were highest for lung (16%), breast (13%), and melanoma (11%). The TUM- rate for lung metastasis was 16% vs 7% for non-lung origin. All TUM- patients received RT and prior chemotherapy, immunotherapy, or both. For all previously irradiated metastasis, pathologic evaluation at time of presumed radiographic recurrence demonstrated an actual 12% rate of TUM-. These findings underscore the importance of pathologic tumor confirmation before considering re-RT for presumed radiographic recurrence.

Recurrent Grade IV gliomas are difficult to treat, particularly in patients who have already received definitive radiotherapy. Surgically targeted radiation therapy (STaRT) using Cesium-131 (Cs-131) collagen-tile brain brachytherapy (GammaTile®, GT Medical Technologies, Tempe, Arizona, USA), delivers immediate, localized radiation to the surgical cavity at higher doses than conventional adjuvant therapies, potentially improving clinical outcomes. The prospective observational registry (NCT04427384) is a multicenter study that evaluates clinical outcomes that measures effectiveness and safety of patients receiving brain tumor resection and STaRT. Herein, prospectively collected data from 122 patients with recurrent Grade IV glioma treated at 27 USA institutions were analyzed. Baseline demographic, clinical, and operative data were collected, including isocitrate dehydrogenase (IDH) mutation, O6-methylguanin-DNA methyltransferase (MGMT) promoter methylation status, extent of resection, and treatment-related toxicity. Patients were followed longitudinally to assess survival, recurrence, and toxicity. Kaplan-Meier curves and Cox regression were used for survival analysis. The cohort included 71 males and 51 females (median age 61) and preoperative Karnofsky Performance Scale (KPS) of 80, but recovered by one month. Most patients (91.8%) had prior radiotherapy (median dose 60 Gy). Gross total resection was achieved in 66.7% of cases. A 12.2% toxicity rate occurred within 30 days; one patient experienced Grade 4 toxicity, there were no Grade 5 events. Median follow-up was 7.5 months, with overall median survival from STaRT of 13.6 months. IDH-mutant patients had longer survival than IDH wild-type (18.9 versus 13.1 months; p=0.045). MGMT methylation status was not associated with survival differences. Six- and 12-month progression-free survival rates were 74.6% and 56.6%, with local control (LC) at 91.8% and 87.7%, respectively. STaRT was well-tolerated, demonstrating promising survival and LC outcomes, with median survival from STaRT exceeding published operative series. These results support further investigation of STaRT as part of a multimodal strategy for recurrent glioblastoma.

Abstract PURPOSE/OBJECTIVE(S) Determining true recurrence versus necrosis alone after previous radiation therapy (RT) for brain metastasis based on imaging alone is difficult. Proper diagnosis is essential, as further radiation is contraindicated in the setting of radiation necrosis without tumor (TUM-). To better understand the rate of pathologic tumor positivity (TUM+) vs TUM-, we examined frozen section results from a cohort of patients with prior same-site RT undergoing resection of presumed recurrent brain metastasis (RBM). MATERIALS/METHODS Rates of intraoperative frozen section pathology disclosing tumor +/- necrosis (TUM+) or necrosis without tumor (TUM-) were examined in patients undergoing resection for presumed RBM after prior same-site RT. All cases had been prospectively enrolled on a multi-institution registry for patients undergoing resection and intraoperative cesium-131 collagen tile brachytherapy (NCT04427384)(GammaTile, GT Medical Technologies, Tempe AZ, USA). Preoperative evaluation varied by center, and patient demographics, primary site, lesion size, and prior therapies were also examined. RESULTS From 10/2020 to 2/2024 60 patients (64 lesions) underwent resection and intraoperative frozen section pathologic evaluation. Per patient, primary sites were 53% lung, 15% melanoma, 13% breast, 7% renal, and 10% other. F:M ratio was 31:29; median age 62, maximum preoperative diameter 2.9 cm, and median time from prior RT 15.4 months. Across all histologies TUM+ was seen in 88% (53/60) and TUM- in 12% (7/60). Rates of TUM- by primary type were highest for lung (16%), breast (13%), and melanoma (11%). The TUM- rate for lung metastasis was 16% vs 7% for non-lung origin. All TUM- patients received RT and prior chemotherapy, immunotherapy, or both. CONCLUSION For all previously irradiated metastasis, pathology demonstrated a 12% rate of TUM-. As all cases necessitated surgery, the adverse event grading would be ≥ Gr 4. These findings highlight the importance of pathologic confirmation before undertaking re-irradiation for presumed radiographic recurrence.

Abstract BACKGROUND Resection and intraoperative brachytherapy for operable recurrent brain metastasis allows for pathologic confirmation of recurrent disease, mass effect relief, and immediate initiation of radiotherapy (RT). In this analysis, we report patterns-of-use and treatment-related adverse events (AEs) for rBM patients treated with Cs-131 collagen tiles, an FDA-cleared intracranial brachytherapy device. METHODS Patients with rBM who underwent resection and surgically-targeted radiation therapy (GammaTile, GT Medical Technologies Inc., Tempe, AZ USA) on a prospectively enrolling phase 4 registry study (NCT04427384) were analyzed. AEs were graded per CTCAE v5.0. RESULTS Between 11/2020 and 2/2024, 56 rBM in 51 consecutive patients underwent STaRT at 19 centers, with 5 patients having 2 metastases implanted concurrently. 44 patients (86%) had prior same-site RT (median interval 14.5 mo, range 3-56). Primary tumor histologies were lung (27), melanoma (8), breast (7), renal (4), colon (2), and “other” (3). Median pre-operative maximum diameter was 3.0 cm (range 1.4-5.7); age 63 (range 28-81); 53% females; KPS median 90 (range 40-100); and median implantation time 3 minutes. 26 patients were implanted at a 1st, 15 at a 2nd, and 10 at ≥ 3rd same-site recurrence (range 1-9). At a median follow-up of 6.2 months (range <1-35.1), 6/51 patients (11.8%) experienced ≥Gr 3 AEs at a median of 12 (range 1-69) days postoperatively (POD). No radiation necrosis (RN) events were observed, and no AEs occurred in multi-implant cases or where STaRT was the initial form of RT. CONCLUSIONS In this prospective multi-institutional study, STaRT demonstrated an excellent safety profile in a cohort of larger rBM, even in the setting of multi-recurrent disease. Accrual and follow-up are on-going and will provide data on tumor control and long-term RN rates.

Abstract INTRO This is the first observational registry study of R+STaRT, delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers, for patients with intracranial tumors. METHODS Since October 2020, 37 sites to-date have enrolled 359 patients with primary & metastatic intracranial tumors into the R+STaRT registry to assess the safety & efficacy of the addition of Gamma Tile to medically needed resection. Local control, overall survival, QOL, neurocognition, functional decline, and surgical and radiation associated AE’s are collected at 1, 3, 6, 9,12, 18 and 24 months, then every 6 months through 5 years. RESULTS Demographics include 359 patients, avg. age 57 y.o.. 162 malignant gliomas, 125 metastatic tumors, 38 meningiomas, and 34 rare other tumors. 197 Males (163 White, 23 Black, 5 Asian, and other races) and 157 Females (White 121, 28 Black, 0 Asian, and 8 other races). No unexpected outcomes reported in the hands of experienced providers have occurred, although close clinical-radiographic follow-up, to ensure early detection of possible treatment-effects, is paramount. Steroid-use, and above endpoints, continue to be collected. CONCLUSIONS In this observational registry of Gamma Tiles (Cs-131 source brachy-therapy) added to medically needed resections for patients with primary and metastatic intracranial tumors continues. Data will be used to benchmark clinical outcomes of R+STaRT therapy and allow for comparisons to existing standard-of-care treatments. The outcome measures captured will allow for evaluation of the potential risks and benefits of this treatment approach for patients in a real-world setting.

Objective: To evaluate the safety and feasibility of combining resection with immediate initiation of radiation and subsequent Stupp protocol in newly diagnosed GBM. Background: GBM is highly proliferative, with rapid early local progression (REP) after surgical resection, prior to the initiation of concurrent EBRT/TZM documented in 25–50% of patients. This high rate of REP supports initiation of an effective postoperative treatment as early as safely possible. FDA cleared GammaTiles (GT)(GT Medical Technologies, Inc, Tempe, AZ) consist of Cesium-131 radiation sources precisely imbedded in bio-resorbable collagen tiles. Intraoperatively tiles are permanently placed to line the at-risk areas of the resection bed achieving an immediate initiation of surgically targeted radiation therapy (STaRT). Design/Methods: GESTALT is a single arm 61 patient multi-center trial. Adults with suspected or confirmed GBM consented pre-operatively undergo a maximum safe resection and GT placement. Subjects with confirmed molecular GBM (WHO 2021 criteria) start concurrent EBRT/TMZ beginning 25±4 days post-surgery. Subsequent EBRT (20 fractions, 4 weeks) to low and high-risk PTV takes GT dose into account to a combined biologically equivalent dose of 46 and 60 Gy delivered in 2Gy/fraction, respectively. Adjuvant TMZ (6 cycles) begins 28±7 days after EBRT/TMZ; TTF is allowed. IDH-mutated tumors will be followed for safety. Outcomes include feasibility of incorporating GT without delay of Stupp protocol, consent/attrition rates, safety, OS, progression free survival, local control, functional decline (ECOG-PS) and immune competence (absolute lymphocyte counts). Results: The trial opened for enrollment in August of 2022 at 3 sites with 12 additional sites pending (NCT05342883). Clinical results to-date will be presented. Conclusions: This is the first trial in newly diagnosed GBM patients combining resection, GT, and the Stupp protocol, and attempts to reduce REP. The outcomes of this trial, if suggestive, will be used as the basis for a subsequent randomized trial. Disclosure: Dr. Dunbar has nothing to disclose. Dr. McCracken has received personal compensation for serving as an employee of GT Medical. Dr. McCracken has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GT Medical. Dr. McCracken has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GT Medical. Dr. Nowlan has received personal compensation for serving as an employee of GT Medical. Dr. Nowlan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GT Medical. Kathryn Dusenbery has nothing to disclose. Dr. Ferreira has nothing to disclose. Dr. Lee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GT Medical. Dr. Lee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure. Dr. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GT Medical. Dr. Lee has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Huff Powell Bailey Law Firm. An immediate family member of Dr. Lee has stock in Remedy Pharmaceuticals. An immediate family member of Dr. Lee has stock in Martin Pharmaceuticals. An immediate family member of Dr. Lee has stock in Critical Diagnostics. An immediate family member of Dr. Lee has stock in Woolsey Pharmaceuticals. An immediate family member of Dr. Lee has stock in Monogram Orthopaedics. An immediate family member of Dr. Lee has stock in Cytonics. An immediate family member of Dr. Lee has stock in 20-20 Gene Systems. Dr. Peach has nothing to disclose. Dr. Corns has nothing to disclose. Clark Chen has nothing to disclose.

Abstract BACKGROUND Recurrent glioblastoma is an aggressive disease with dismal prognosis despite advances in standard therapy, making the maintenance of functional status and quality of life (QOL) in patients an important endpoint during treatment. Here, we report functional status (KPS) and QOL metrics (LASA and FACT-Br) at 6-months post-treatment for recurrent glioblastoma patients treated with maximal safe resection followed by intraoperative placement of collagen tile brachytherapy with Cesium-131 (Surgically Targeted Radiation Therapy or STaRT), a novel brachytherapy carrier. OBJECTIVE To assess the impact of STaRT on KPS and QOL among patients with recurrent glioblastoma (rGBM) at 6-months post-treatment. METHODS Patients were treated between 10/2020 and 05/2023 as part of a multi-institutional registry study (NCT#04427384). KPS was used to measure functional status. Linear Analog Self-Assessment (LASA) and Functional Assessment of Cancer Therapy – Brain (FACT-Br) were used to measure QOL. All assessments were collected at pre-surgery, and 1,3, and 6-months post-treatment. RESULTS 57 rGBM patients were treated on the Registry between 10/2020 and 05/2023. Of the 57 participants, 47 participants remain in the study, with 21 participants reaching the 6-month time point (5 exits, 5 deaths). Median age was 60 years (range 28-81). Methylguanine methyltransferase (MGMT) promoter was methylated in 17.5%, unmethylated in 38.5%, and unknown in 44%. Gross total resection was achieved in 72% of participants. Median KPS was 80% (range 40%-100%) at screening versus 70% (range 40%-90%) at 6 months post-treatment. Median LASA was 37 (range 8-50) at pre-surgery versus 34 (range 5-48) at 6-months post-treatment. Minimally important differences (MID) were noted between pre-surgery (136.9 ± 29.5) and 6-months post-treatment (112.5 ± 35.7) for the FACT-Br Total Score. CONCLUSION This interim data analysis supports further investigation of STaRT as a treatment for recurrent glioblastomas as a means of providing stable functional status and quality of life.

Abstract Implantation of collagen tile brachytherapy GammaTile (GT Medical Technologies Tempe, AZ) allows for targeting of radiation to residual malignancy following surgical resection of gross disease. Radiation necrosis (RN) can develop after radiotherapy or brachytherapy. We sought to determine outcomes in recurrent glioblastoma patients with RN after treatment with Gammatile. All patients were previously treated with surgical resection followed Stupp protocol chemoradiation. At recurrence, patients underwent repeat surgical resection and implantation of GammaTile. Subsequent MRIs were assessed for stability, presumed RN or progression. Symptomatic RN patients were treated with corticosteroids or bevacizumab. From December 2020 to February 2023, 19 patients were treated. Median time from initial radiation to GammaTile therapy was 270 days. A total of 8 patients (42%) developed RN at a median time of 81 days from GammaTile. In RN patients vs those that did not develop RN, pathological tumor viability was lower (20% vs 50%, p=0.3), age was lower (54 vs 63, p=0.06), tumor volume was lower (10.8 cc vs 51.9 cc, p=0.02), time from initial surgery was longer (470 days vs 299 days, p=0.46), number of GammaTiles placed was lower (5 vs 8, p=0.045), rate of gross total resection (GTR) was higher (100% vs 64%, p=0.04), and MGMT methylation rate was higher (63% vs 11%, p=0.03). No patients in the RN group experienced radiographic progression (0% vs 45%, p=0.009) and 3 (38%) required bevacizumab therapy. Median overall survival from GammaTile surgery in the RN group was 325 days vs 188 days (p=0.03). Our series demonstrates a significant survival benefit in patients who develop RN following GammaTile implantation after glioblastoma recurrence. RN developed in younger patients with smaller tumor volumes, lower pathological tumor viability, and higher rates of GTR and MGMT methylation status.

Abstract OBJECTIVE To evaluate the safety and feasibility of combining resection with immediate initiation of radiation and subsequent Stupp protocol in newly-diagnosed glioblastoma (GBM). BACKGROUND Rapid early local progression (REP) after resection, prior to the initiation of EBRT+/-chemotherapy, occurs in 25-50%. This high-rate of REP supports initiation of an effective postoperative treatment as early as safely possible. Bio-resorbable collagen tiles with imbedded cesium-131 radiation sources (Gammatiles™) are FDA cleared for this use. Intraoperatively, tiles are placed within the resection bed, thus achieving an immediate initiation of surgically targeted radiation therapy (STaRT). DESIGN/ METHODS GESTALT is a single-arm 61 patient multi-center trial. Consented adults with suspected or confirmed GBM undergo a maximum safe resection with Gammatile™ (STaRT). Patients with molecular GBM (WHO 2021 criteria) start concurrent EBRT/Temozolomide beginning 25±4 days post-surgery. Subsequent EBRT (20 fractions, 4 weeks) to low and high-risk PTV takes Gammatile™ dose into account to a combined biologically equivalent dose of 46 and 60 Gy delivered in 2Gy/fraction, respectively. Adjuvant TMZ (6 cycles) begins 28±7 days after EBRT/Temozolomide. TTF is allowed. IDH-mutated gliomas are followed for safety. Outcomes include feasibility of incorporating Gammatile™ without delay of Stupp protocol, consent/attrition rates, safety, performance status trajectory (ECOG, KPS), immune competence (absolute lymphocyte counts), local control, PFS, and OS. RESULTS The trial opened in Fall 2022 at 4 sites. 12 additional sites are onboarding (NCT05342883). 16 patients are on trial as of abstract submission. Currently, this trial appears feasible and without any unexpected intolerances/toxicities. CONCLUSIONS This is the first trial in newly diagnosed GBM patients to combine resection, Gammatile™, and the Stupp protocol, in an attempt to reduce REP, as well as possibly, improve other outcomes. RESULTS will inform the routine and investigational use of Gammatile™, and if suggestive, will form the basis for a subsequent randomized trial.

The overarching objective of this multicenter, prospective, observational registry study is to evaluate "real-world" clinical outcomes and patient-reported outcomes measuring safety and efficacy of a permanently implanted device with Cs-131 seeds embedded in a collagen carrier tile for intracranial neoplasms.

Abstract Background For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy (EBRT),. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy methods have been limited by uneven dose distributions, complicated workflows, extended procedural times, the cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, including brain metastases, and has demonstrated excellent safety and local control in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study [NCT04427384] are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the device. Methods Subjects (N=600) at up to 50 enrolling sites undergoing resection of brain tumors of any pathology with intra-operative GammaTile placement are eligible for enrollment. We project 40% of enrollees to have brain metastasis. Tumor pathology, overall survival, radiation- and surgery-related adverse events, quality of life, serial MRIs, and timing of surgical bed recurrence and/or distant recurrence will be collected. The powered primary endpoint for recurrent brain metastases, surgical bed-progression free survival, will compare STaRT to standard-of-care benchmarks. This study will be the first observational study of resection plus GammaTile. Results will be used to benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, and facilitate the design of future clinical trials.

Abstract BACKGROUND For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy has been limited by uneven dose distributions, complicated workflows, extended procedural times, cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and efficacy in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the GammaTile. METHODS Patients undergoing resection (R) of brain tumors with intra-operative GammaTile placement are eligible for enrollment. Planned sample size is 600 at up to 50 enrolling sites. First subject was enrolled 10/14/2020. Tumor pathology, overall survival, radiation- and surgery-related adverse events, patient- and provider-reported quality of life, serial MRIs, and timing of surgical bed and/or distant recurrence are collected. Powered primary endpoints for recurrent brain metastases, recurrent glioblastoma, and recurrent meningioma (surgical bed-progression free survival (PFS), overall survival, and PFS, respectively), compare STaRT to standard-of-care benchmarks. Results will be used to improve awareness and access to this treatment, benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, facilitate the design of future clinical trials, and contribute to the optimal sequencing of treatments for intracranial neoplasms.

Abstract BACKGROUND Resection (R) followed by single- or multi-fraction stereotactic radiosurgery (SRT) of brain metastases (BMs) lowers resection bed recurrence compared to R alone. Nevertheless, for larger BMs, 12-month recurrence rates after R+SRT can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy device (GammaTile, GT Medical Technologies, Tempe, AZ) utilizing Cs-131 seeds embedded within a bioresorbable collagen tile was developed and is described as Surgically Targeted Radiation Therapy (STaRT) to distinguish it from external beam radiotherapy. STaRT allows rapid, intense localized radiation dose delivery directly to the tumor bed with predictable dosimetry immediately at the time of R, which may confer reduced risk for radiation necrosis compared to other therapies. It is hypothesized that R+ STaRT will increase surgical bed recurrence-free survival (SB-RFS), while reducing impact on functional and neurocognitive status compared to R+SRT. METHODS Multicenter, randomized, comparison trial of patients with resectable, previously untreated “index” BMs (≥ 2.5–5cm), and 0–3 other tumors, will be preoperatively randomized 1:1 to undergo R+SRT or R+STaRT to the index lesion; unresected tumors in both groups will receive SRT. Planned sample size is 180 from 14 sites. Enrollment opened 03/31/2021. First subject was enrolled 04/07/2021. Primary endpoint is SB-RFS. Secondary endpoints include overall survival, quality of life, neurocognition, functional status, imaging findings and adverse events. Follow-up will be through 24 months. This will be the first randomized trial comparing R+SRT versus R+STaRT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures captured will elucidate the potential risks and benefits of these two RT delivery methods in the setting of newly diagnosed BMs. We will present trial accrual progress, available data, experience and lessons learned.