Citations

ABSTRACT Background Radiotherapy is a cornerstone of treatment for pediatric central nervous system (CNS) tumors, but dose selection remains uniform despite interpatient variability in tumor radiosensitivity. This is consequential in children, for whom toxicity can have lifelong effects. Genomic-adjusted radiation dose (GARD) integrates tumor genomics with delivered radiation dose to quantify the biological effect of radiotherapy and has been validated across adult malignancies. Its relevance in pediatric CNS tumors is unknown. Methods We performed a cohort study using gene expression and data from 246 pediatric patients with high-grade glioma, medulloblastoma, or ependymoma from the Children’s Brain Tumor Network. GARD was calculated using a sequencing-adapted radiosensitivity index integrated with radiation dose through the linear–quadratic model. Associations of GARD and physical radiation dose with event-free and overall survival were evaluated using Cox proportional hazards models stratified by tumor type and anatomic location. Patients who did not receive radiotherapy comprised a negative control cohort (sham-GARD). Results Among patients receiving radiotherapy, physical dose was uniform, whereas GARD showed substantial interpatient variability in biological effect. Higher GARD was associated with improved event-free survival (hazard ratio [HR] 0·90, 95% CI 0·83–0·97; p=0·004) and overall survival (HR 0·90, 95% CI 0·83–0·99; p=0·018). Physical dose was not associated with either endpoint. Among patients who did not receive radiotherapy, sham-GARD was not associated with outcomes, supporting GARD as a treatment-specific predictor rather than a prognostic biomarker. Conclusions In pediatric CNS tumors, the biological effect of radiotherapy quantified by GARD was associated with outcomes, whereas physical dose was not. These findings challenge uniform radiotherapy dosing and support genomically informed dose individualization. Prospective evaluation of GARD-guided radiotherapy is warranted to optimize tumor control while minimizing long-term toxicity in children.

siRNA delivery to target cellular processes is an appealing area in lung diseases such as asthma. To realize this potential requires efficient, targeted cytosolic delivery without cellular toxicity or siRNA degradation. We demonstrate the efficacy of PONI-Guan nanoparticles in accessing airway epithelial and smooth muscle cells with specific siRNA targeting of mRNAs of interest while maintaining barrier integrity and avoiding cellular toxicity.

Background: Diffuse axonal brain injury (DABI) is a major component of traumatic brain injury, but the optimal timing of magnetic resonance imaging and histologic assessment after isolated DABI remains unclear. Because each method captures a different phase of injury, defining time-dependent diagnostic windows may improve experimental design and reduce animal use. Methods: Sixty-four Sprague-Dawley rats were randomized to moderate DABI or sham operation. Neurological Severity Score (NSS), 3 T diffusion tensor imaging (DTI), and histologic assessment were performed at early and late time points. Hippocampal fractional anisotropy (FA) was measured at 48 h and 1 month. β-amyloid precursor protein (β-APP) immunohistochemistry assessed acute axonal injury at 48 h, and hematoxylin and eosin (H&E) staining quantified hippocampal neuronal density at 1 month. Results: At 48 h, DABI rats had higher NSS, lower hippocampal FA, and greater β-APP-positive axonal accumulation than sham-operated rats. By 1 month, NSS and hippocampal FA no longer differed between groups, whereas hippocampal neuronal density remained significantly reduced in DABI rats, indicating persistent structural injury. Conclusions: In this rat model of isolated DABI, hippocampal FA and β-APP immunohistochemistry identified acute axonal pathology at 48 h, whereas conventional histology detected a persistent reduction in neuronal density at 1 month. These findings support a time-optimized diagnostic strategy using early DTI for noninvasive injury detection and late histology for long-term structural assessment.

Abstract Introduction Cystoid macular edema (CME) is a recognized complication associated with penetrating keratoplasty (PK) and Endothelial Keratoplasty (EK). The purpose of this study was to determine the incidence of acute CME within the first 6 months after PK, Descemet stripping automated EK, or Descemet’s membrane EK. Methods A retrospective cohort analysis of the TriNetX United States collaborative database was conducted. Patients with a diagnosis of Fuchs dystrophy or keratoconus who underwent PK or EK between January 1, 2004 and August 30, 2024 were included. Those with a history of uveitis, retinal vascular occlusion, diabetic macular edema, or prior vitrectomy were excluded. Outcomes and diagnoses were defined using current procedural terminology and International Classification of Diseases, Tenth edition (ICD-10) codes. Cohorts were stratified based on a history of prior PK or EK with >6 months follow-up. Propensity score matching was performed on both cohorts to control for age at index, sex, race, ethnicity, and the diagnosis of Fuchs dystrophy and keratoconus. The incidence of acute CME during a 6-month postoperative follow-up period was assessed. Odds ratios were calculated between cohorts. Results A total of 2516 eyes were included in the study (PK: 1258; EK: 1258). At six months postoperatively, the incidence of acute CME in the EK cohort (46 of 1258) was significantly higher than in the PK cohort (20 of 1258) (P = 0.0012) (OR 0.426, 95% confidence interval 0.25–0.72). Conclusions Our findings suggest that the incidence of acute CME is higher in patients undergoing EK compared to PK.

PURPOSE Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects. MATERIALS AND METHODS The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and therapeutic cancer care. Applications underwent a structured, two-stage review, with GBO providing technical support, expert guidance, and training resources. RESULTS The RFP generated 218 applications reflecting strong demand for oncology QI funding in SSA. After review, 17 projects representing 10 African countries were selected and awarded $1.1 million USD. Funded initiatives reflected four themes: oncology training and clinical practice improvements, early detection and accurate diagnostics, pediatric cancer care, and oncology nursing and palliative medicine. As of March 2026, 11 (65%) of 17 projects are complete, with 4,565 health care professionals engaged through direct training, conference dissemination, system adoption, and sensitization activities, and program-supported services were delivered to more than 47,300 patients. CONCLUSION This initiative demonstrates the feasibility of a competitive, regionally guided grant program to strengthen cancer care capacity. Early implementation outcomes, including measurable improvements in diagnostic delay, treatment adherence, and care network expansion, confirm that locally led QI initiatives can generate meaningful results across diverse institutional settings. By centering African leadership and supporting diverse QI projects, it advances equitable access to funding, capacity building, and sustainability planning.

Abstract Background Multi-modality therapy has improved survival for many patients with brain metastases. However, neurocognitive sequelae remain a challenge. While advances in radiotherapy have reduced toxicity, the potential interaction with targeted therapy and immunotherapy and the consequent impact on neurocognitive outcomes remain poorly defined. We appraised the current evidence on neurocognitive outcomes in the era of modern combined-modality therapy. Methods This systematic review adhered to PRISMA guidelines and included clinical trials reporting neurocognitive outcomes in patients with brain metastases receiving radiotherapy ± concurrent systemic therapies. Studies published through December 31, 2024 were identified through PubMed/Medline, EMBASE, and Web of Science using pre-defined MeSH term-based search strings. Results 39 studies from 1997-2024 involving 6,617 patients met inclusion criteria (n = 27 whole-brain radiotherapy [WBRT]; n = 12 radiosurgery), including six studies evaluating combined-modality therapy in 1,161 patients. Baseline cognitive evaluation was performed inconsistently, but neurocognitive deficits were frequently observed prior to treatment. Most randomized trials reported improved cognitive outcomes and quality of life with advanced radiotherapy techniques (e.g., hippocampal avoidance, radiosurgery) vs WBRT. Among 20 randomized trials comparing radiotherapy with or without a concurrent investigational systemic therapy, only four included neurocognitive assessments. There was no evidence of cognitive sequelae with combined-modality therapy, though evaluable trials were limited due to inconsistent reporting of neurocognitive functioning. Conclusion As survival improves in patients with brain metastases, preserved cognition is an important outcome measure. The lack of neurocognitive endpoints in pivotal brain metastasis trials represents a critical evidence gap. The interaction between radiotherapy and novel systemic therapies, and their combined effects on neurocognition, remain unknown. To address this, we recommend 1) integrating sensitive, pragmatic, and tailored neurocognitive assessments into oncology trials to quantify additive toxicity, 2) early and systematically incorporating neuropsychology into care pathways, 3) expanding radiation dose-sparing and radioprotective strategies, and 4) evaluating the utility of cognitive rehabilitation programs.

Abstract Introduction Patients with metastatic spine disease (MSD) present with varying degrees of systemic illness and frailty. Given the palliative intent of surgery and radiation treatment for MSD, treatment risks must be judiciously weighed against potential benefits. We sought to examine the impact of peroperative nutritional status as measured by the PG-SGA on survival in patients undergoing surgery and radiation for MSD. Methods This study involved an international, multicenter prospective, observational registry of patients with MSD: AO Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON). Variables including baseline demographics, oncologic data, adverse events (medical adverse events and surgical complications), length of stay, and nutritional status were prospectively collected. The Patient-Generated Subjective Global Assessment (PG-SGA) was used to evaluate nutritional status. Results A total of 589 patients were included in this study; 469 (80%) of whom underwent surgery and radiation and 120 (20%) of whom underwent radiation alone. The majority of patients (362, 61%) were classified as well nourished, however, 68 patients (12%) were classified as severely malnourished. Among patients that underwent surgery and radiation, the median overall survival of well nourished patients was 491 days compared to 117 days in the severely malnourished patients (p < 0.001). A multivariate analysis demonstrated severe malnourishment and ECOG performance status of 3 or 4 were associated with worse overall survival. Conclusion Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with perioperative survival in patients with MSD. Further studies that investigate optimal pre-treatment optimization for patients with MSD in order to mitigate morbidity and mortality risk are essential.

Abstract Introduction As the incidence of metastatic spine disease (MSD) increases, treatments to manage refractory pain, pathologic vertebral body fractures, and spinal cord compression are becoming increasingly common. Given the palliative nature of surgical intervention used to achieve tumor control and thus mitigate loss of neurologic function and compromised ambulatory function, it is essential to mitigate the risk of such procedures. Methods The AO Spine Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON), an international, prospective registry for patients with spinal metastases, was used for this query. Prospective collection included baseline health and demographic information, oncologic data (including Spinal Instability Neoplastic Score (SINS) score and Bilksy epidural compression classification), and baseline functional status (preoperative American Spinal Injury Association (ASIA) and ECOG scores). Health related quality of life (HRQoL) data included Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) and Euro-QoL measures. Surgery related adverse events (AE’s) were collected using the Spine Adverse Events Severity (SAVES V2) framework. Kaplan-Meir curves were used to assess survival. Results The cohort consisted of 1267 patients, 701 male (55.3%). A total of 245 (19.3%) experienced at least one postoperative AE, the majority of which were considered minor (grade 3 or less). Among the most common were deep wound infections (3.2%), wound dehiscence (2.5%), and urinary infections (2.4%). A multivariate analysis demonstrated that age, smoking status, ECOG performance, prior radiotherapy, presence of multiple metastases at other sites, and multiple spine metastases were significant risk factors for a postoperative AE. Postoperative AE’s (p = 0.049) and major postoperative AE’s (p = 0.0038) were found to be related to survival as well as a significant change in HRQoL scores (p < 0.001). Conclusion Postoperative AE’s are extremely relevant to the care of patients with MSD and impact both HRQoL and survival.

ABSTRACT Prolonged operative time is associated with increased surgical complications, resource utilization, and cost. While factors such as surgeon experience and patient habitus are well recognized, the impact of anatomical anomalies and variations remains poorly quantified. This systematic review evaluates the influence of abdominal structural anomalies and anatomical variations on operative time. Following PRISMA 2020 guidelines, a search of PubMed (2000–2025) identified 82 eligible studies. Operative‐time impact was assessed using added operative time relative to reference benchmarks. The unit of analysis was the procedure‐level observation. Observations were stratified by procedure category and surgical complexity and summarized using median added operative time and range. Among procedure‐level observations with available benchmarks, 13 of 14 (92.9%) structural anomalies, 48 of 54 (88.9%) situs inversus cases, and 10 of 11 (90.9%) other anatomical variants demonstrated increased operative time relative to baseline. Structural anomalies were associated with larger median increases, particularly in colorectal procedures, whereas anatomical variations demonstrated a more heterogeneous effect across procedural systems. Higher‐complexity procedures, including pancreatic operations, showed greater absolute increases in operative time. Preoperative identification of anatomical differences was associated with attenuation of operative delays. Structural anomalies are frequently associated with increased operative duration, whereas anatomical variations demonstrate a more variable and context‐dependent effect. The magnitude of operative time impact is influenced by procedural complexity and preoperative planning. Incorporating anatomical variability into surgical planning may reduce avoidable operative delays and improve operative efficiency.