TPS2105 Background: Glioblastoma remains a lethal primary brain tumor with limited therapeutic progress and a persistent unmet clinical need. Standard management requires maximal safe resection followed by external beam radiation therapy (EBRT) with concurrent temozolomide (TMZ); however, the required 4–6-week postoperative healing interval before initiating EBRT creates a vulnerable window for rapid early progression (REP), defined as radiographic tumor progression occurring between surgery and the start of chemoradiation. REP is detected in more than half of patients and is associated with inferior survival. Tile-based radiation therapy (TBRT) with cesium-131 brachytherapy sources (GammaTile, GT Medical Technologies, Tempe, AZ, USA), offers a strategy to eliminate this treatment gap by immediately initialing localized radiation at the time of resection. A feasibility and safety study (NCT05342883) evaluating TBRT implantation following EBRT has been fully accrued and supports randomized evaluation. The BRIDGES study (NCT07195591) builds on this foundation. Methods: NCT07195591 is a prospective, randomized, open-label, multicenter, phase 3 trial to evaluate whether immediate postoperative TBRT followed by abbreviated EBRT with concurrent and adjuvant TMZ improves outcomes compared with standard postoperative EBRT with concurrent and adjuvant TMZ. Eligible adults must have newly diagnosed, radiographic suspicion of glioblastoma, can undergo maximal safe resection, possess a Karnofsky Performance Status score ≥70, and be candidates for standard chemoradiation. Key exclusion criteria include multifocal or disseminated disease, prior cranial radiation or chemotherapy, inability to receive TMZ, and medical comorbidities that would interfere with protocol treatment or follow-up. Patients are randomized 2:1 to receive either TBRT implantation followed by a shortened EBRT course with concurrent and adjuvant TMZ or standard postoperative EBRT with concurrent and adjuvant TMZ. Randomization is stratified by age, sex, prior sub-maximal safe resection, and size of pre-operative tumor. A stratified log-rank test using Kaplan–Meier methods will be done using the stratification factors will be implemented for the primary endpoint. Additional time-to-event endpoints will be analyzed using Kaplan–Meier methods and Cox proportional hazards models, and the analyses will follow the intent-to-treat principle. The trial has two pre-planned interim analyses. A Data and Safety Monitoring Board will oversee the trial and conduct periodic safety reviews. Four of the 766 planned patients have enrolled. Clinical trial information: NCT07195591 .

2011 Background: Standard of care (SOC) of Glioblastoma (GBM) includes maximal safe resection followed by external beam radiation therapy (EBRT) with concomitant temozolomide (TMZ). This typically begins 4-6 weeks after surgery, during which rapid early progression (REP) occurs in ~50% of patients and is associated with worse survival, especially in unmethylated GBM (median OS ~13 months as per BN007). SOC treatment in BN007 showed ~38% ≥grade 3 treatment-related adverse events (TRAEs). GammaTile (GT Medical Technologies, Inc., Tempe, AZ), a tile-based radiation therapy (TBRT) with cesium-131 sources, immediately initiates radiation at resection, eliminating the 4-6-week delay. Methods: This is a prospective, single arm, open-label feasibility study across 15 US centers with a primary aim of assessing the safety and feasibility of combining resection + TBRT with an abbreviated course of EBRT with concurrent and adjuvant TMZ for newly diagnosed molecular GBM. Eligible patients were ≥18 years old; only patients with IDH-wildtype were included in survival analysis. MGMT and IDH underwent central lab review. Feasibility was defined as percent of patients who started EBRT+TMZ between 21-35 days post-surgery. Safety was assessed by incidence of ≥grade 3 TRAEs. REP was centrally reviewed. Additional aims included PFS and OS estimated using Kaplan-Meier. A planned sample size of 61 was chosen to ensure feasibility could be estimated with a ±10% degree of precision. Results are presented based on the modified intent to treat (mITT) population (enrolled patients who had surgery and confirmed GBM). Results: From 8/2022-8/2025, 70 patients were enrolled and had surgery; 67 of whom had confirmed GBM. Table 1 presents baseline characteristics. Median follow-up was 12.4 months. 93% started EBRT+TMZ; 74% started 21-35 days post-surgery. The median (range) of days from surgery to EBRT+TMZ was 29 (23-70) days. There were no delays due to EBRT planning. 39% of patients experienced a ≥grade 3 TRAE: 22% of patients were related to surgery only, 18% to radiation only, and 13% to surgery and radiation. 6.0% of patients showed REP. Median OS for patients with unmethylated MGMT was 16.5 months vs. 28.0 months for patients with methylated MGMT. The median PFS for patients with unmethylated MGMT was 9.3 months vs. not yet met for patients with methylated MGMT. Conclusions: Feasibility and safety are in line with SOC. REP had a notable reduction compared to literature. OS is encouraging. These data provide the basis for a phase 3 randomized trial (NCT07195591). Clinical trial information: NCT05342883 . Baseline characteristics. Parameter Detail n 67 Age, median 66 Male:Female, n 42:25 Ethnicity (Non-Hispanic), n 61 Race (White), n 56 EOR – GTR:not GTR, % 66:34 IDH-wildtype:mutated, n 66:1 MGMT promoter methylated:unmethylated, n 28:39

Local failure and leptomeningeal disease (LMD) are both poor outcomes that can occur after resection and post-operative radiosurgery for newly diagnosed brain metastases (BM). There is increasing utilization of collagen-embedded Cesium-131 brachytherapy (GammaTile®) as a method of providing immediate adjuvant radiation therapy. Post-operative LMD rates following GammaTile implantation for newly diagnosed BMs has yet to be reported. The objective was to evaluate the incidence of LMD rates, local control (LC), and survival following resection and GammaTile for newly diagnosed BMs. An ongoing, multicenter, prospective, observational Phase IV non-interventional registry (NCT0442738) was queried to analyze rates of LMD following surgical resection of newly diagnosed BMs. Following resection and GammaTile implantation, we evaluated LMD rates, LC, and overall survival (OS). The Kaplan-Meier method was used to analyze time-to-event outcomes. Fifty-one patients with 55 BMs were analyzed. The median follow-up was 12.4 months. The majority of BMs were in the supratentorial brain (87.3

Purpose The standard of care (SOC) for newly diagnosed glioblastoma (GBM) consists of maximal safe resection (MSR) followed by external beam radiation therapy (EBRT) and chemotherapy and subsequent courses of adjuvant chemotherapy. The prognosis for GBM is typically poor, with a 5-year survival rate of <10% and median survival ranging from 12 to 16 months with SOC treatment. Rapid early progression (REP) is the regrowth or progression of tumor between MSR and start of EBRT, which occurs in ∼45% of patients, and is associated with worse survival. A multicenter trial is underway (GESTALT, NCT05342883) to investigate the safety and feasibility of immediately initiating radiation delivery at time of resection using permanently implanted low dose rate brachytherapy (LDR-BT) administered with 3.5 U cesium-131 seeds embedded in collagen (GammaTile, GT Medical Technologies, Tempe, AZ, USA) followed by a 20-fraction course of EBRT. The goal of EBRT is to provide the remaining dose, on a voxel-by-voxel basis, so that the composite biologically effective dose (BED) from LDR-BT and EBRT closely approximate the BED from SOC radiation. The trial employs an experimental method to convert LDR-BT dose to a “base dose” which was derived so that the sum of base dose and dose from an ideal EBRT plan, optimized using standard treatment planning software (TPS), results in a composite BED that matches the BED from the SOC. This aim of this work is to demonstrate the feasibility of generating acceptable EBRT plans using the experimental method. Materials and Methods For 22 consecutive patients enrolled on the GESTALT trial, MIM Software (MIM Software Inc., Cleveland, OH, USA) was used to fuse EBRT planning CT and MRI images, contour a low-risk target (PTV-LR), a high-risk target (PTV-HR), and organs at risk (OARs), calculate dose from LDR-BT, and convert LDR-BT dose to base dose using a custom MIM Workflow. The enrolling site’s TPS was used to optimize an EBRT plan using TPS-specific base or background dose planning tools so that the composite of the base dose and EBRT dose satisfactorily fulfilled composite dose objectives specified as part of the experimental method. The summations of base dose and EBRT dose for each subject were analyzed to investigate feasibility. Specifically, the number of subjects was determined for which the composite doses covering 95% (D95%) of the PTV-LR and PTV-HR were within 5% of the prescribed composite doses of 44.90 Gy and 55.65 Gy, respectively. Similarly, the number of subjects was obtained for which the composite dose met the composite dose objective for all specified OARs. Results Composite D95% for both PTV-LR and PTV-HR (Figure 1A) were within 5% of the prescribed composite doses for 19/22 (86%) subjects. Composite D95% was >5% below prescription for both target volumes for subject 16 and for the PTV-LR for subject 8. In both cases, the target volumes overlapped OARs and target coverage was intentionally sacrificed (i.e., OAR goals were prioritized per protocol). For subject 18, the composite D95% was >5% higher than the prescription for the PTV-HR but could have been decreased through monitor unit normalization to meet all dose objectives. For 19/22 (86%) subjects, the composite D95% met the stated composite dose objective for all OARs (Figure 1B). Conclusions This is the first reported analysis demonstrating the feasibility of generating EBRT plans that account for dose from LDR-BT that results in desired composite BED distributions, as per the GESTALT trial protocol for GBM. The method resulted in high rates of compliance for target volume coverage and OAR protection. Feasibility and safety of this method will be further investigated using additional subjects enrolled in the GESTALT trial.

Purpose The standard of care (SOC) for newly diagnosed glioblastoma (GBM) consists of maximal safe resection (MSR) followed by external beam radiation therapy (EBRT) and chemotherapy and subsequent courses of adjuvant chemotherapy. The prognosis for GBM is typically poor, with a 5-year survival rate of <10% and median survival ranging from 12 to 16 months with SOC treatment. Rapid early progression (REP) is the regrowth or progression of tumor between MSR and start of EBRT, which occurs in ∼45% of patients, and is associated with worse survival. A multicenter trial is underway (GESTALT, NCT05342883) to investigate the safety and feasibility of immediately initiating radiation delivery at time of resection using permanently implanted low dose rate brachytherapy (LDR-BT) administered with 3.5 U cesium-131 seeds embedded in collagen (GammaTile, GT Medical Technologies, Tempe, AZ, USA) followed by a 20-fraction course of EBRT. The goal of EBRT is to provide the remaining dose, on a voxel-by-voxel basis, so that the composite biologically effective dose (BED) from LDR-BT and EBRT closely approximate the BED from SOC radiation. The trial employs an experimental method to convert LDR-BT dose to a “base dose” which was derived so that the sum of base dose and dose from an ideal EBRT plan, optimized using standard treatment planning software (TPS), results in a composite BED that matches the BED from the SOC. This aim of this work is to demonstrate the feasibility of generating acceptable EBRT plans using the experimental method. Materials and Methods For 22 consecutive patients enrolled on the GESTALT trial, MIM Software (MIM Software Inc., Cleveland, OH, USA) was used to fuse EBRT planning CT and MRI images, contour a low-risk target (PTV-LR), a high-risk target (PTV-HR), and organs at risk (OARs), calculate dose from LDR-BT, and convert LDR-BT dose to base dose using a custom MIM Workflow. The enrolling site’s TPS was used to optimize an EBRT plan using TPS-specific base or background dose planning tools so that the composite of the base dose and EBRT dose satisfactorily fulfilled composite dose objectives specified as part of the experimental method. The summations of base dose and EBRT dose for each subject were analyzed to investigate feasibility. Specifically, the number of subjects was determined for which the composite doses covering 95% (D95%) of the PTV-LR and PTV-HR were within 5% of the prescribed composite doses of 44.90 Gy and 55.65 Gy, respectively. Similarly, the number of subjects was obtained for which the composite dose met the composite dose objective for all specified OARs. Results Composite D95% for both PTV-LR and PTV-HR (Figure 1A) were within 5% of the prescribed composite doses for 19/22 (86%) subjects. Composite D95% was >5% below prescription for both target volumes for subject 16 and for the PTV-LR for subject 8. In both cases, the target volumes overlapped OARs and target coverage was intentionally sacrificed (i.e., OAR goals were prioritized per protocol). For subject 18, the composite D95% was >5% higher than the prescription for the PTV-HR but could have been decreased through monitor unit normalization to meet all dose objectives. For 19/22 (86%) subjects, the composite D95% met the stated composite dose objective for all OARs (Figure 1B). Conclusions This is the first reported analysis demonstrating the feasibility of generating EBRT plans that account for dose from LDR-BT that results in desired composite BED distributions, as per the GESTALT trial protocol for GBM. The method resulted in high rates of compliance for target volume coverage and OAR protection. Feasibility and safety of this method will be further investigated using additional subjects enrolled in the GESTALT trial.

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.

Management of recurrent, aggressive meningiomas remains problematic. We undertook this analysis to evaluate the efficacy of maximal safe surgical resection (R) plus cesium-131collagen tile brachytherapy (CTBT) in the management of these difficult cases. To report the final results from a pre-FDA clearance trial of R plus CTBT (GammaTile, GT Medical Technologies, Tempe, Arizona, USA) for the treatment of recurrent, aggressive meningiomas. Patients with recurrent aggressive meningiomas were enrolled preoperatively in a prospective, nonrandomized, single-center trial (NCT03088579) between June 2013 and January 2018. Treatment included maximal safe resection and intraoperative CTBT palcement. Local progression (defined as tumor recurrence ≤1.5 cm of the operative bed) was determined on follow-up imaging. Hazard ratios (HR) were utilized to compare the efficacy of R plus CTBT to prior same-site treatment for each case. There were 29 recurrent aggressive meningiomas treated in 27 patients. Median age was 66 (range 37-82) years and World Health Organization Grade at the time of R+CTBT was Grade 1 in 1 (3%) patient, Grade 2 in 26 (90%) patients, and Grade 3 in 2 (7%) patients. Prior same-site treatment was R plus radiation therapy (RT) in 76%, 21% R alone, and 3% RT alone. Median radiographic follow-up was 34.8 (0.03-70.9) months. Local control (LC) following R plus CTBT was 79%/73%/48% at 36/48/60 months, compared to 28%/21%/17% with prior treatment (HR=0.14, p=0.0004). Surgically related complications occurred in 4 (13.7%) cases; 1 (3.4%) case of early postoperative infection and delayed onset wound breakdown and infection in 3 cases (10.3%). Symptomatic radiation injury occurred in 4 (13.7%) patients, and all resolved with medical therapy. Maximal safe resection plus CBCT using a now FDA-cleared device significantly improved LC outcomes with acceptable complication rates in patients with recurrent, aggressive meningiomas when compared with the prior same-site treatments.

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.

Purpose/Objective(s) In newly-diagnosed glioblastoma (nGBM) rapid early progression (REP) is defined as tumor progression/regrowth between resection and start of external beam radiation (EBRT) with temozolomide (EBRT+TMZ). This occurs in 45% of patients per a recent multi-institutional meta-analysis. We hypothesized the rate of REP may be decreased in the setting of immediate post-resection brachytherapy (BT) in newly diagnosed GBM. We also describe rapid early response (RER), which is regression of residual tumor in the setting of BT. Materials/Methods Occurrence of REP and RER were investigated by record and imaging review of patients with nGBM who enrolled pre-operatively on an ongoing single arm multi-center prospective trial (NCT05342883) of resection and intraoperative placement of cesium-131 collagen tile brachytherapy (CTBT)] GT Medical Technologies, Tempe AZ, USA), and subsequent EBRT+ temozolomide. Records were analyzed for demographics, resection type, methylation status, and occurrence of REP/RER. Results From 8/22 to 2/24, 22 patients with nGBM (all IDH wild type) underwent resection and CTBT. All patients had both a post-operative MRI and a pre-EBRT MRI for treatment planning with a median inter-MRI interval of 17 days (range = 12-56). 14 patients (64%) had MRI-confirmed gross total resections (GTR). MGMT was methylated in 7 and unmethylated in 15. Overall, 6/22 (27%) had evidence of REP at a median inter-MRI interval of 16.5 days (range = 13-20). REP was adjacent to the cavity in 5 patients and distant in 1. In 3/8 (38%) cases of sub-total resection or near total resection the residual tumor showed a RER on MRI (median inter-MRI interval 17 days, range 12-22). At time of analysis, median follow-up was 5.9 months (range = 0.5-16). Conclusion In the setting of post-resection brain BT, we found an REP rate of 27% and RER rate 38% (3/8 <GTR patients). To our knowledge, this is the first report on the incidence of REP and the first description of RER in nGBM patients treated with post-resection BT. The trial is continuing to accrue to a total of 61 participants. Additional enrollment and follow-up will provide further data on REP, RER, and impact on other outcomes as well as data on the primary endpoints of feasibility and safety.

Malignant and benign brain tumors with a propensity to recur continue to be a clinical challenge despite decades-long efforts to develop systemic and more advanced local therapies. GammaTile (GT Medical Technologies Inc., Tempe AZ) has emerged as a novel brain brachytherapy device placed during surgery, which starts adjuvant radiotherapy immediately after resection. GammaTile received FDA clearance in 2018 for any recurrent brain tumor and expanded clearance in 2020 to include upfront use in any malignant brain tumor. More than 1,000 patients have been treated with GammaTile to date, and several publications have described technical aspects of the device, workflow, and clinical outcome data. Herein, we review the technical aspects of this brachytherapy treatment, including practical physics principles, discuss the available literature with an emphasis on clinical outcome data in the setting of brain metastases, glioblastoma, and meningioma, and provide an overview of the open and pending clinical trials that are further defining the efficacy and safety of GammaTile.

Abstract INTRODUCTION Collagen tile brachytherapy (CTBT) was cleared by the FDA in 2018 for all recurrent intracranial neoplasms and in 2020 for newly diagnosed intracranial neoplasms. We sought to describe usage trends of CTBT by evaluating the first 1000 consecutive orders since CTBT became commercially available in 2019 with respect to tumor type (glioma, brain metastasis, meningioma) and CTBT treatment setting (newly diagnosed, recurrence with prior radiation, recurrence without prior radiation). METHODS Commercial data was accessed using Salesforce, Inc. Coefficient of correlation (r2) was estimated as a measure of orders over time. 1000 orders were divided into 4 time cohorts (Cohort 1 for 1st 250 orders, Cohort 2 for 2nd 250 orders, Cohort 3 for 3rd for 250 orders and Cohort 4 for 4th 250 orders). Order proportions were compared among time cohorts using X2 tests. RESULTS Time period for 1000 orders among 93 centers was 1/23/19–5/11/23. Over these 17 completed yearly quarters there was a positive trend in ordering frequency (r2=0.97). Tumor type was known for 917 orders, of which 52.2% were glioma, 37.4% metastases, and 10.4% meningioma. Proportions of orders for tumor type did not change over time cohorts (p=0.26). Treatment setting was known for 816 orders, of which 80.3% were in recurrence with previous radiation, 14.3% newly diagnosed, and 5.4% recurrence without previous radiation. For glioma and meningioma, treatment setting did not change over time cohorts (p=0.5, p=0.3, respectively). However, for metastases, the proportion of orders for use in the newly diagnosed setting increased over time: 6.4% in Cohort 1, 19.2% in Cohort 2, 21.6% in Cohort 3, 34.7% in Cohort 4 (p< 0.001). CONCLUSION CTBT usage is increasing over time. Proportions of orders among tumor types (glioma, meningioma, metastases) has not changed. However, use of CTBT is increasing in the newly diagnosed setting for brain metastases.

2038 Background: Surgically targeted radiation therapy (STaRT), using a novel bioresorbable collagen brachytherapy device containing 4 Cesium-131 sources, is FDA-cleared for use as adjuvant radiation therapy (RT) post-resection in both newly diagnosed and recurrent intracranial neoplasms. Intraoperative initiation of brachytherapy potentially minimizes post-resection tumor regrowth with a favorable dosimetric profile compared to external beam radiation. This work sought to determine early patterns of care and the safety of this approach in recurrent GBM. Methods: This prospective multi-institutional observational study (NCT04427384) included recurrent GBM patients who underwent maximum safe resection (MSR) and permanent implantation of the device(s) (GammaTile, GT Medical Technologies, Tempe, AZ, US). Descriptive and comparative analyses regarding patient characteristics and early clinical outcomes were performed. Toxicities were categorized using the CTCAE v5.0 adverse event (AE) criteria. Results: During 10/2020–01/2023, 14 participating sites enrolled 45 patients with recurrent GBM for STaRT; 2 patients had two sites treated for a total of 47 implants. 67% of patients were treated at the first recurrence, 24% at the second, and 13% at the third, respectively. The median age was 61 (range 28-75), 36% were female, and 23% were > 65 years. 85% of patients received prior same-site RT with the median time from last RT to implantation of 14.6 months (range 3.5-57). The median maximum preoperative size was 4.2 cm (range 1.6-7.0) and the median volume was 20.8 cm 3 (range 0.8-130). 68% of resections were gross-total, 17% near-total, and 15% sub-total; the median time needed for device implantation was 5 minutes (range 1.0-13). Median follow-up was 5.2 months (range 0.6-23.2). Median Karnofsky performance status (KPS) at screening, at initial postoperative assessment, and 3 months were all 80 (range 40-100). 7 attributed AEs occurred in 13% (6/45) of patients, all grade 3 AEs: 2 CSF leaks, 2 seizures, 1 cerebral edema, 1 pseudomeningocele, and 1 left hemiparesis. All except one were coded as related to both radiation and surgery; the patient with pseudomeningocele experienced a seizure at 47 days that was considered related to radiation alone. Conclusions: Early data from this prospective registry demonstrate the feasibility and safety of STaRT in recurrent GBM. Data on 6-month progression-free survival will be presented at the conference. A prospective randomized trial of adjuvant systemic therapy (AST) +MSR+STaRT versus MSR+AST is planned for initiation in 2023.

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.

Early results from this prospective multi-center trial demonstrate the feasibility and safety of STaRT. The lack of radiation-related AE, even with short follow-up, is intriguing given the relatively large lesion size and proportion of patients treated for recurrent, previously irradiated disease. Additional follow-up will provide data on tumor control outcomes and radiation necrosis rates using this novel technique.

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.