Overall survival. A: Complete cohort. B: Stratified by WHO grading. C: Stratified by treatment indication.

Abstract Purpose: Outcomes for grade 2 and 3 meningiomas are poor. A few studies suggest a benefit from radiotherapy dose escalation. This trial evaluates the safety and efficacy of dose escalation with intensity-modulated proton therapy (IMPT) for grade 2 and 3 meningiomas. Patients and Methods: This prospective single-arm phase I trial enrolled patients with grade 2 meningioma with residual disease or recurrence or patients with grade 3 meningioma after gross total resection. Patients underwent dose-escalated IMPT to 66 Gy relative biological effectiveness [Gy(RBE)] for grade 2 gross disease and 63 Gy(RBE) for grade 3 tumor beds. The primary endpoint was acute dose-limiting toxicity (DLT). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and late toxicity. Results: Twenty-one patients with 16 grade 2 and 5 grade 3 meningiomas were enrolled and treated between 2016 and 2023. The median clinical and radiographic follow-up periods were 3.4 and 3.2 years, respectively. No DLT was observed. Five new late grade 3 toxicities occurred in four patients. Three treatment failures were observed in two grade 2 and one grade 3 tumors. Two deaths occurred in patients with grade 2 meningiomas. The 1-, 2-, and 3-year PFS rates were 100%, 95%, and 88.2%, respectively. The corresponding OS rates were 100%, 95%, and 95%, respectively. Conclusions: This first prospective trial investigating dose-escalated IMPT for high-grade meningiomas demonstrated a favorable early safety profile and clinical outcomes. Phase II and III studies are warranted to confirm the superiority of dose escalation for high-grade meningiomas.

Local failure rates, progression-free survival, and overall survival.

Background and Objectives: Up to 40% of patients with cancer develop spinal metastases, and stereotactic spinal radiosurgery (SSRS) achieves high local control rates as definitive or postoperative treatment. Multiple tumor response assessments have been used but their compared clinical performance in post-surgical patients remains unclear. We sought to compare the applicability of RECIST1.1, MDACC and SPINO criteria. Materials and Methods: This IRB-approved retrospective study included patients with high-grade epidural spinal cord compression treated with decompressive surgery followed by adjuvant SSRS, with MRI follow-up available. Lesions were classified according to each of the scale’s objective (RECIST1.1 and MDACC) and subjective (SPINO [radiology reports]) criteria. Results: Ninety-four treated levels in 93 patients (median age 58.9 years) were analyzed. Most metastases were thoracic, and all cases had preoperative high-grade epidural spinal cord compression. Adjuvant SSRS was delivered in one or three fractions. Median follow-up was 16 months (range, 1–132), SPINO-based assessment was feasible in 100% of cases, RECIST1.1 in 43.6% and MDACC in 46.8%. Progressive disease criteria were met in 21.3% of cases using SPINO-based assessment, 19.5% using RECIST1.1, and 6.8% using MDACC. Conclusions: The SPINO recommendations provide a practical and comprehensive framework for radiographic response assessment in monitoring spinal metastases treated with a combination of surgical decompression and adjuvant SSRS.

Recent evidence supports incorporating 18 F-Fluciclovine PET for glioblastoma treatment planning and monitoring, as it better captures tumor infiltration compared to conventional MRI. However, the relationship between PET- and MRI-defined tumor volumes remains unclear, particularly in the post-treatment setting. This study prospectively compares tumor volumes on MRI and PET at multiple timepoints throughout the treatment course and evaluates volumetric changes with therapy. We prospectively enrolled 8 adults with IDH-wildtype glioblastoma treated with surgery and chemoradiation between September 2019 and 2021. Participants underwent paired 18 F-Fluciclovine PET/CT and conventional MRI at four timepoints: preoperatively, pre-radiation, and at one- and six-months post-radiation. Biological tumor volume (BTV) from PET, FLAIR, and post-contrast T1volumes (T1CV) were segmented. Volumetric changes were compared using the Friedman test. Participants (5 males, median age 63 years [IQR 54,66]) showed significantly larger BTVs compared to T1CV at diagnosis (median BTV = 27.2mL vs. T1CV = 13.3mL, adjusted P =.03), pre-radiation (BTV = 25.2mL vs. T1CV = 6.9mL, adjusted P =.03), and at one-month post-radiation (BTV = 27.3mL vs. T1CV = 12.1mL, P =.04). BTVs closely approximated yet were slightly smaller than their corresponding FLAIR volumes at all timepoints. After surgery, the median decrease in BTV (-4.4

PURPOSE:Recurrence in glioblastoma (GBM) is common, and the success of salvage strategies, including re-resection and reirradiation, is limited. Brachytherapy with Cs-131 collagen tiles enables intraoperative focal dose intensification with rapid dose fall-off and limited normal brain radiation exposure. We report the outcomes of Cs-131 collagen tile implantation at the time of resection for recurrent GBM. METHODS AND MATERIALS:We reviewed 15 adults with previously irradiated, recurrent isocitrate dehydrogenase (IDH) wild-type GBM who underwent maximal safe resection followed by intraoperative Cs-131 collagen tile implantation at a single institution. Candidates had surgically accessible, primarily enhancing recurrences ≥6 months after prior external beam radiation therapy, and were anticipated to have a gross total resection. The prescription dose was 60 Gy at a depth of 5 mm. We assessed overall survival, progression-free survival, toxicity, and patterns of failure (local ≤0.5 cm from the cavity, marginal 0.5-1 cm, and distant >1 cm) after implantation. RESULTS:Patients (median age, 63 years; range, 39-76) had good performance status (median Karnofsky Performance Status score, 90; range, 70-100) and prior chemoradiation (most to 60 Gy/30 fractions). Tiles (median, 6.5/patient; range, 3-13) were implanted at first recurrence in 12 of 15 patients (80%) and at second recurrence in 3 (20%), at a median of 15 months after external beam radiation therapy (range, 8.9-47). At 13 months median follow-up (range, 1.4-21), the median overall survival after Cs-131 implantation was not reached (NR) (95% CI, 6.7-NR months); the median time to progression after Cs-131 implantation was 9 months (95% CI, 6.0-NR); and the cumulative incidence of first progression (local or distant) after Cs-131 implantation was 53.3% over the follow-up period. The first failures were local (n = 2), marginal (n = 2), distant (n = 3), and combined local and distant (n = 1). One patient developed symptomatic grade 3 radionecrosis, which improved with bevacizumab. No patients required reoperation for Cs-131 toxicity. CONCLUSIONS:Intraoperative Cs-131 tile brachytherapy for recurrent GBM is feasible and well tolerated. Distant failures remain common. Integrating effective systemic therapy and careful patient selection may optimize outcomes.

Glioblastoma (GBM) is a highly aggressive brain tumor with poor outcomes, most commonly affecting older adults. Young adults (YA; ages 18–39), though less frequently affected, demonstrate distinct clinical and biological characteristics that may influence treatment response and survival. This study aimed to evaluate treatment patterns and outcomes in YA GBM relative to older adults in a national dataset. This retrospective cohort analysis of the National Cancer Database (NCDB) from 2004 to 2021 identified GBM patients aged 18 years and older. Baseline demographics, tumor characteristics, and treatment patterns were compared between YAs and patients aged ≥ 40 years. Survival analysis was limited to isocitrate dehydrogenase (IDH)-wildtype GBM diagnosed in 2018 or later. Multivariable Cox regression was used to identify factors associated with overall survival (OS). Of 179,854 GBM patients, 6,941 (4.2

Purpose: There is marked variability in treatment fields for glioblastoma. We performed a retrospective study comparing outcomes of patients treated according to MD Anderson Cancer Center (MDACC) or Radiation Therapy Oncology Group (RTOG) guidelines and identified differences in treatment-related toxicity. Methods and Materials: Adult patients with glioblastoma treated with surgery and adjuvant radiation treatment were included in this study. Primary outcomes were local control, progression-free survival (PFS), overall survival (OS), and radiation-related toxicity. PFS and OS were estimated using the Kaplan-Meier estimator. Univariate and multivariate analyses were conducted using Cox regression models. Results: In total, 257 patients met the inclusion criteria with a median age of 60.1 years at diagnosis. There were 162 and 95 patients treated according to the MDACC or RTOG guidelines, respectively. Despite having similar gross tumor volumes, the RTOG cohort had a larger median planning target volume (303.2 cm³ vs 430.7 cm³, P < .001) and worse PFS (6 months vs 9 months, P = .031). There was no difference in OS between treatment techniques. Patients treated according to RTOG guidelines experienced higher rates of radionecrosis (34% vs 21%, P = .024) and severe lymphopenia (15% vs 7%, P = .044). Conclusions: Patients treated according to MDACC guidelines had smaller treatment volumes, improved PFS, and lower rates of radionecrosis and severe lymphopenia. However, when adjusting for prognostic factors, treatment type was not associated with PFS in multivariate analysis. Prospective investigation is warranted to confirm these differences in outcomes.

Preoperative stereotactic radiation therapy (SRT) vs postoperative SRT logistics and toxic effects provides clinically significant data on management outcomes. To determine preoperative SRT logistics and safety profile compared with postoperative in patients with brain metastases. This single-institution phase 3 randomized clinical trial included patients 18 years and older and undergoing a planned surgical resection. Patients were required to have an Eastern Cooperative Oncology Group Performance Status score of 2 or greater and be candidates for SRT within 30 days of surgical resection. Patients with radiosensitive histologies (eg, small cell lung cancer and lymphoma), brain metastasis of unknown primary, and/or radiographic evidence of leptomeningeal disease were excluded. Data were collected from December 2018 to August 2023, and data were analyzed from September 2023 to December 2024. Patients were randomized 1:1. Patients randomized to the preoperative SRT cohort underwent SRT (in 1 to 5 fractions) followed by surgical resection within 1 month of radiation therapy. Patients randomized to the postoperative SRT cohort underwent resection followed by postoperative SRT within 1 month of surgery. Outcomes reported focus on nonprimary end point analysis of the trial, including comparative toxic effect outcomes of preoperative vs postoperative SRT postprocedural events, feasibility of preoperative SRT, and radiation therapy management. Of 103 patients, 56 (54.4%) were male, and the median (range) age was 59 (26-83) years. Of 103 patients, 83 (80.6%) completed both radiation and surgery for brain metastases while in the study. Of these, 70 patients (84%) had 1 to 4 brain metastases at enrollment, 11 (13%) had 5 to 10 lesions, and 2 (2%) had more than 10 lesions. In the preoperative stereotactic radiosurgery (SRS)/SRT cohort, 45 (88%) completed both treatments compared with 38 (73%) in the postoperative SRS/SRT arm. There were no statistically significant differences between treatment groups in 30-day postoperative morbidity or postprocedural events. The median (range) time between surgery and SRT was significantly shorter in the preoperative arm (6 [0-24] days) compared with the postoperative arm (22 [12-42] days; P < .001). The median (range) time from randomization to receiving both brain-directed therapies was 10 (4-31) days in the preoperative arm compared with 32.5 (19-55) days for the postoperative arm (P < .001). In this randomized clinical trial, preoperative SRT had comparable safety to postoperative SRT and resulted in shorter time to treatment completion, potentially facilitating expedited care. ClinicalTrials.gov Identifier: NCT03741673

OBJECTIVE:Spinal stereotactic radiosurgery (SSRS) is an established treatment modality for spinal metastatic disease. A common complication of SSRS is postradiation pathologic fracture. The authors evaluated the risk of pathologic fracture in sacral SSRS. METHODS:All patients receiving SSRS in 1 to 5 fractions to 1 or more sacral levels between 2011 and 2020 at participating institutions were included. Demographic, histological, anatomical, and outcome data were obtained from electronic medical records. Data were analyzed using SPSS version 28. RESULTS:Of 67 total patients, 50 (74.6%) were men and 17 (25.4%) were women. The most common tumor histologies were prostate adenocarcinoma (n = 16 [23.9%]) and renal cell carcinoma (n = 12 [17.9%]). Median (range) age at treatment was 63 (8-87) years. The mean ± SD (range) number of levels treated was 1.5 ± 0.7 (1-4) levels. Mean ± SD (range) bone density at S1 was 208.0 ± 74.4 (-3.0 to 443.3) Hounsfield units (HUs). Median (range) follow-up was 16.6 (1.5-132) months, median ± SD (range) overall survival was 24 ± 21.0 (1.7-83.3) months, and the 1-year local control rate was 83.6%. Fourteen patients (20.9%) experienced fracture within the radiation field. There was no association between fracture and patient sex (p = 0.32), age (p = 0.40), S1 HU (p = 0.28), tumor location according to Denis classification (p = 0.87), presence of pain (p = 0.66), single versus multifraction radiation (p = 0.44), or number of levels treated (p = 0.52). Patients experiencing in-field progression were more likely to experience fracture (61.5% vs 10.2%, p < 0.001), and patients experiencing fracture had a higher average Spine Instability Neoplastic Score than patients without fracture (5.7 vs 4.3, p = 0.049). Only local control remained as a factor associated with sacral fracture in the multivariate analysis. Of the patients experiencing fracture, 10 (71.4%) were symptomatic and 3 of those (30.0%) underwent post-SSRS surgical intervention. CONCLUSIONS:Pathologic fracture may occur after sacral SSRS in a significant number of patients and is significantly associated with failure of local control.

Background: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety. Purpose: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement thresholds and assess the role of baseline shift correction adaptative planning in improving treatment delivery efficiency. Methods: Twelve patients underwent two MRI sessions on the MRL. The optimal registration structure was identified, and intrafraction motion was assessed to calculate delivery efficiency. Baseline shift (BLS) simulations were applied for five cases that showed significant motion and suboptimal delivery efficiency, and the dosimetric impact of the BLS was evaluated. The simulated BLS-based plan adaptation was implemented via a segment aperture morphing adapt-to-position workflow. Results: The most stable registration structure was the spinal canal plus three adjacent vertebrae. Cine imaging revealed average intrafraction motion (95th to 5th percentiles) of 0.8 ± 0.5 mm in the right-left (RL) direction, 0.9 ± 0.6 mm in the anterior–posterior (AP) direction, and 0.7 ± 0.5 mm in the SI direction. Simulated BLS improved delivery efficiency to >80% in all but one case, with a ±1 mm displacement threshold tolerance. While target coverage remained consistent after BLS simulation, the spinal cord dose increased by 7–60%, exceeding the 14 Gy constraint in three of the five simulated cases. Conclusions: Cine imaging and BLS can enhance delivery efficiency in spine SBRT but may increase spinal cord dose. These findings underscore the need for careful patient selection, advanced motion management, and patient-specific BLS protocols.

Background. Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT). Methods. A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses. Results. Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12). Conclusions. This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.

Background:Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments. Case Description:Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed. Conclusions:We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.

Abstract Background: Many patients develop brain metastasis during the course of their disease and it represents the cause of death in more than half of them. The prognosis and survival of patients with brain metastases remains poor with limited palliative treatment options. Thus, there is a need to develop new strategies for the therapeutic management of patients with brain metastases. Inflammatory stimuli originating from CNS tumors may increase the permeability of the blood-brain barrier and promote immune cell activation and infiltration into tumors. Several studies have demonstrated now the efficacy of immune checkpoint inhibitors in patients with melanoma with active brain metastases. The modulation of VEGF-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. Lenvatinib is an oral, potent multiple receptor tyrosine kinase inhibitor that selectively inhibits VEGFRs, VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), in addition to other pro-angiogenic and oncogenic pathway-related receptor tyrosine kinases. The combination of lenvatinib and pembrolizumab is approved for patients with metastatic endometrial carcinoma and renal cancer, and it is investigated in other tumor types with promising preliminary results. We hypothesize that pembrolizumab and lenvatinib will be an effective treatment for TNBC, NSCLC, and other solid tumor types with brain metastases by decreasing angiogenic tumor activity and improving antitumor T-cell activity. Methods: This is a single-center, open-label, multi-cohort Phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with solid tumors and brain metastases. The study has 3 cohorts: triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and other solid tumor types with established or preliminary clinical evidence of efficacy of programmed cell death-1 (PD-1) and angiogenesis inhibitors. Eligible patients will have at least 1 unirraditated or progressing brain metastasis of 0.5-2 cm on brain MRI. The study is conducted using a Simon’s optimal two-stage design, and approximately 87 patients will be enrolled concurrently (n=29 per cohort). Pembrolizumab (200 mg intravenously on Day 1 of each cycle) and lenvatinib (20 mg orally once daily) are administered in 21-day cycles for a maximum of 24 months. The primary endpoint is intracranial objective response rate at 4 months as assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Exploratory analyses will include evaluation of tissue and blood-based immune-related correlates of response to the pembrolizumab and lenvatinib combination. The first patient was enrolled in January 2022 and accrual of patients is ongoing (NCT05064280). Citation Format: Ecaterina E. Dumbrava, Emma J. Montazari, Uyen M. Vu, Tiantian Cai, Mehmet Altan, Nuhad K. Ibrahim, Debra N. Yeboa, Jing Li, Frederick F. Lang, Gisela Sanchez, Isabella C. Glitza, Barbara J. O'Brien, Rashmi K. Murthy, Jianbo Wang, Tanisha T. Darko, Denisse Velazquez, Komal Shah, Funda Meric-Bernstam, Hussein Tawbi, Jordi Rodon. Phase II study of pembrolizumab in combination with lenvatinib in patients with triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and other tumor types and brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT292.

2026 Background: Stereotactic radiosurgery (SRS) is an ablative modality for focal treatment of brain metastases (BM) and is standard of care for limited BM. Suitability for SRS has historically been linked to number of BM, with up to 4 BM considered amenable to SRS. JLGK0901 revealed no difference in overall survival (OS) and similar rates of adverse events for patients with 5-10 vs. 2-4 BM. Evidence supporting for SRS for >10 BM is limited. As systemic treatments have evolved to include agents with improved central nervous system (CNS) efficacy and OS, the role of SRS warrants re-evaluation. Methods: We retrospectively reviewed patients from a single institution with ≥5 BM treated with SRS with no prior history of brain radiation 2015-2022 on an IRB-approved protocol. Clinical history, including sex, histology, Karnofsky performance status (KPS), extracranial disease status and systemic regimen used before and after diagnosis of BM, was reviewed. Systemic regimens were categorized based on potential for CNS efficacy as 1) none: no evidence, 2) weak: single agent immunotherapy or known but limited data on CNS efficacy, or 3) strong: multiple agents with known CNS efficacy, single agents with strong CNS efficacy. Kaplan-Meier method was used to estimate survival with log-rank test used to evaluate differences in survival curves. Cox proportional hazards modeling was used to evaluate differences in CNS progression-free survival (CNS-PFS) and OS. Results: 558 patients (48% female) who received SRS to ≥5 BM (range 5-23) were identified. Primary histologies included: 36% non-small cell lung cancer; 22% melanoma; 14% breast; 7% renal; 5% gastrointestinal; 15% other. Median OS was 11.0 months and did not differ between patients with 5-9 (n=441) vs ≥10 BM (n=117) (median OS 11.1 vs. 10.0 months; p=0.53). Median CNS-PFS was 6.6 months and did not differ between 5-9 vs ≥ 10 BM (median CNS-PFS 6.4 vs. 7.7 p=0.86). On univariate analysis, high KPS (HR 0.96; p<0.001) was associated with improved OS. Histology ( p=0.14), BM number ( p=0.53); average BM volume ( p=0.48), and systemic disease status ( p=0.17) were not associated with OS. Change of systemic therapy at time of SRS was associated with improved OS (HR 0.58; p<0.001) and CNS-PFS (HR 0.63; p<0.001). Amongst patients with systemic therapy change, regimens with increased CNS efficacy compared to prior therapy were associated with improved OS (HR 0.59; p<0.001) and CNS-PFS (HR 0.65; p=0.002). Conclusions: In this large, retrospective analysis of patients with ≥ 5 previously untreated BM treated with SRS, we found no association between BM number and CNS-PFS or OS. Change in systemic therapy, particularly to agents with CNS efficacy, was associated with improved outcomes. While limited by biases inherent to retrospective analyses, these results suggest patients with larger number of BM (≥10) are appropriate for SRS, especially when changing to systemic therapy with CNS penetrance.

Purpose/Objective(s) There is marked variability defining treatment fields for the treatment of glioblastoma (GBM). We performed a retrospective study comparing outcomes of patients treated according to the MD Anderson Cancer Center (MDACC) or Radiation Therapy Oncology Group (RTOG) guidelines and identified differences in treatment-related toxicity. Materials/Methods Adult patients with GBM treated with surgery and adjuvant radiation treatment (RT) between 2013–2016 were included in this study. Patients were treated according to institutional preference. Primary outcomes were local control rates, survival outcomes, and radiation-related toxicity. Radionecrosis was characterized through either surgical pathology or MRI, utilizing available perfusion and diffusion techniques. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator. Univariate and multivariate analyses were conducted using the Cox regression models. Results In our study, 257 patients met inclusion criteria with a median age of 60.1 at the time of diagnosis. There were 162 and 95 patients treated according to the MDACC and RTOG guidelines, respectively. Although the gross tumor volumes were similar between the groups, the RTOG cohort had a larger median planning target volume (303.2 cc vs 430.7 cc, P = < 0.001) and worse PFS (P = 0.031). There was not a statistically significant difference in OS between treatment strata. Patients treated according to the RTOG protocol experienced higher rates of radionecrosis (34% vs 21%, P = 0.024) and grade 3+ lymphopenia (15% vs 7%, P = 0.044). Conclusion Patients treated according to the MDACC protocol had smaller treatment volumes, improved PFS, and lower rates of radiation-related toxicity. Prospective investigation is warranted to confirm the differences in outcomes.

Delays in research protocol development may be a single factor that hinders the career progression of academic faculty. Structured educational guidance during this phase proves crucial in mitigating setbacks in Institutional Review Board (IRB) approval and expediting trial implementation. To address this, the Protocol-in-a-Day (PIAD) workshop, a comprehensive 1-day event involving members from six critical facets of RO clinical trial implementation, was established, offering significant input to individual protocols. Efficacy and satisfaction of the PIAD workshop were assessed through a 5-question survey and the average time from submission to IRB initial approval. The normality of the data was analyzed using the Shapiro-Wilk Test. Nonparametric data was analyzed using a Mann-Whitney U test for significance. A total of 18 protocols that went through the PIAD workshop were activated. The mean time to IRB approval for protocols that went through PIAD was 39.8 days compared to 58.4 days for those that did not go through the PIAD workshop. Based on survey results, 100% of PIAD participants said the PIAD workshop was useful and 94% of participants stated that the PIAD workshop improved the overall quality of their protocol. Participant surveys further highlighted substantial improvements in trial quality, language, and statistical design and revealed that all participants found the workshop helpful. Therefore, both junior and senior faculty benefitted from this educational program during protocol development, as both groups demonstrated shorter times to IRB approval than non-participants. This acceleration not only fosters efficient trial implementation but also supports academic faculty in their career development.

Purpose/Objective(s) There are no stereotactic radiosurgery (SRS) dose constraint guidelines for the motor cortex and tracts as this region of interest (ROI) is difficult to delineate using conventional imaging techniques and anatomic landmarks. Navigated transcranial magnetic stimulation (nTMS) is a novel non-invasive tool using electromyographic signal and magnetic resonance diffusion tensor imaging (DTI) to functionally map cortical motor tracts (MT). While nTMS is used to identify the MT before tumor resection, it has not been implemented in SRS planning. The objectives of this study were to (i) determine the feasibility of performing nTMS-based DTI in patients with previously SRS treated brain metastases in or near the MT, (ii) measure concordance of nTMS seeded MT (TMS-MT) versus anatomically seeded MT (A-MT) and (iii) evaluate the relationship between radiation dose to TMS-MT and patient outcomes measured by objective hand function testing and patient reported outcomes (PROs). Materials/Methods 15 patients with brain metastases proximal to anatomically defined MT previously treated with single-fraction SRS were enrolled on an IRB-approved cross-sectional study. At a median 4.9 months after SRS, patients underwent nTMS testing of the upper extremities and brain DTI. Functional outcomes testing (Grip Dynamometer) and quality-of-life (QOL) PROs (EQ-5D-5L) were acquired. Tractography was generated on treatment planning software and imported as an ROI into the treatment planning system for volumetric and dosimetric evaluation. Results Functional testing, PRO questionnaires, and nTMS scheduling was successful for 15/15 (100%) of enrolled patients and TMS-MT was successful in 14/15 (93.3%). Examination of size and location of A-MT versus TMS-MT revealed that A-MT were larger (median volume 17.85cc versus 7.1cc for TMS-MT). There was a median volumetric overlap of 4.16cc (32.1%) between the TMS-MT and A-MT on the patient's treated side (range = 16.4-46.3%). Strength deficits occurred in 5/10 (50%) patients treated unilaterally (unaffected extremity testing measures used as a baseline control), and 60% of patients experienced coordination deficits. Median Dmax to TMS-MT was 12.5Gy for patients with deficits in grip strength compared to 4.2Gy for those without detected deficits. For all patients, a decrease in EQ5D5L score trended linearly with increase in Dmax to the TMS-MT. Conclusion In this completed feasibility study, nTMS testing in the radiation oncology clinic met criteria for feasibility. Dmax to the TMS-MT correlated with magnitude of negative impact in motor function and overall QOL. The notable differences in location and size of the TMS-MT vs. A-MT suggest that additional functional imaging may improve MT delineation to inform clinical decision making and SRS treatment planning.