Angela M. Richardson

Purpose: Postoperative stereotactic radiation (SRT) is the standard-of-care for resected brain metastases. Implantation of cesium-131 collagen tiles (tile-based radiation therapy [TBRT]) initiates focal radiation immediately after resection, potentially offering therapeutic and logistical advantages. Radiation One and Done Study, a randomized, open-label, noninferiority, phase III trial (ClinicalTrials.gov identifier: NCT04365374 ), compared the safety and efficacy of resection with TBRT (R + TBRT) with resection with SRT (R + SRT) for patients with a newly diagnosed brain metastasis indicated for surgical resection. Methods: Across 32 US centers, patients were preoperatively randomly assigned 1:1 to R + TBRT or R + SRT. Any nonresected brain metastases received SRT postoperatively. Co-primary outcomes were time-to-surgical bed recurrence (SBR) and surgical bed recurrence-free survival (SB-RFS). Outcomes were analyzed using Cox proportional hazards models with stratification factors as covariates. Multiplicity was controlled by hierarchical testing. Analyses used the prespecified modified intention-to-treat (mITT) population (patients who underwent surgery, had pathologic confirmation of brain metastasis, and had follow-up information). Results: From April 2021 to August 2025, 230 patients were randomly assigned (115 per arm), 204 of whom (103 R + TBRT, 101 R + SRT) comprised the mITT population. The median follow-up was 12.9 months. The median time-to-SBR was not reached in R + TBRT versus 17.4 months in R + SRT (hazard ratio [HR]: 0.06 [95% CI, 0.01 to 0.46]; P = .0070). SB-RFS was improved with R + TBRT, with a median of not reached versus 10.9 months in R + SRT (HR, 0.48 [95% CI, 0.30 to 0.76]; P = .0021). Overall adverse events did not appear to differ: 83 patients (79.0% [95% CI, 70.0 to 86.4]) in R + TBRT versus 67 patients (80.7% [95% CI, 70.6 to 88.6]) in R + SRT. Conclusion: For patients with newly diagnosed brain metastases requiring resection, R + TBRT significantly improved SBR and SB-RFS, demonstrating both noninferiority and superiority.

Grief is an under-recognized yet pervasive experience in neurosurgery, arising not only from the death of patients and loved ones but also from losses related to professional identity, health, and personal relationships. Despite its relevance, grief is often conflated with burnout or overlooked entirely within surgical culture. When personal adversity strikes, such as loss, illness, or major life upheaval, the intensity of neurosurgical practice can amplify these challenges, influencing professional identity, performance, and overall resilience. As the field continues to evolve and diversify, it is increasingly important to foster open dialogue about vulnerability, personal hardship, and life beyond the operating room. This perspective examines how neurosurgeons experience and process loss, distinguishing grief from burnout and resilience, and highlighting the need for institutional and cultural change.

Background/Objectives: Glioblastoma is an aggressive primary brain tumor that develops within a chronically low-oxygen microenvironment, yet most preclinical studies are performed under atmospheric oxygen conditions that poorly reflect in vivo physiology. This study investigated how sustained culture under physiological oxygen tension (physioxia) influences glioblastoma cell behavior, signaling, and therapeutic response. Methods: Multiple patient-derived glioblastoma models were cultured under normoxia (21% O₂) or sustained physioxia (5% O₂) for at least seven days before experimentation. Cell migration, proliferation, cell cycle distribution, expression of the epithelial-to-mesenchymal transition-associated transcription factor Slug (SNAI2), PDGFRβ-associated signaling, and sensitivity to 5-fluorouracil were evaluated using transwell migration assays, cell counting, flow cytometry, RT-qPCR, immunoblotting, and BrdU incorporation assays. To examine the effects of oxygen history, we established and maintained additional patient-derived cultures grown under physioxia. Results: Sustained physioxia consistently increased migration across all glioblastoma models while reducing proliferation in normoxia-adapted cell lines through increased G0/G1 cell cycle arrest. Physioxia significantly increased Slug expression in all models and enhanced PDGFRβ, AKT, and ERK phosphorylation in a cell line-dependent manner. Therapeutic sensitivity to 5-fluorouracil was altered, with physioxia conferring increased resistance in some glioblastoma models but not universally. Patient-derived cell lines cultured continuously under physioxia retained enhanced migratory capacity and exhibited increased proliferation compared to cells grown in normoxia, suggesting that prior oxygen exposure influences proliferative responses while the pro-migratory phenotype remains conserved. Conclusions: Physiological oxygen tension is a major regulator of glioblastoma cell behavior, influencing migration, proliferation, signaling, and therapeutic response. These findings demonstrate that conventional normoxic culture conditions can obscure biologically relevant phenotypes and support the consideration of physioxia in experimental design. Such technical changes may improve the physiological and translational relevance of preclinical glioblastoma research.

Background/Objectives: Glioblastoma is an aggressive primary brain tumor that develops within a chronically low-oxygen microenvironment, yet most preclinical studies are performed under atmospheric oxygen conditions that poorly reflect in vivo physiology. This study investigated how sustained culture under physiological oxygen tension (physioxia; 5% O□) influences glioblastoma cell behavior, signaling, and therapeutic response. Methods: Multiple patient-derived glioblastoma models were cultured under normoxia (21% O□) or sustained physioxia (5% O□) for at least seven days before experimentation. Cell migration, proliferation, cell cycle distribution, expression of the epithelial-to-mesenchymal transition-associated transcription factor Slug (SNAI2), PDGFRβ-associated signaling, and sensitivity to 5-fluorouracil were evaluated using transwell migration assays, cell counting, flow cytometry, RT-qPCR, immunoblotting, and BrdU incorporation assays. Additional patient-derived cultures established and maintained continuously under physioxia were used to examine the effects of oxygen history. Results: Sustained physioxia consistently increased migration across all glioblastoma models while reducing proliferation in normoxia-adapted cell lines through increased G0/G1 cell cycle arrest. Physioxia significantly increased Slug expression in all models and enhanced PDGFRβ, AKT, and ERK phosphorylation in a cell line-dependent manner. Therapeutic sensitivity to 5-fluorouracil was also altered, with physioxia conferring increased resistance in selected glioblastoma models but not universally. Patient-derived cultures maintained continuously under physioxia retained enhanced migratory capacity and exhibited increased proliferation compared with normoxia, indicating that prior oxygen exposure influences proliferative responses while the pro-migratory phenotype remains conserved. Conclusions: Physiological oxygen tension is a major regulator of glioblastoma cell behavior, influencing migration, proliferation, signaling, and therapeutic response. These findings demonstrate that conventional normoxic culture conditions can obscure biologically relevant phenotypes and support incorporating physioxia into experimental design to improve the physiological and translational relevance of preclinical glioblastoma research.