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.

Background: Prostaglandin E2 (PGE2) suppresses perinatal breathing. Reducing antenatal PGE2 concentrations with paracetamol could stimulate spontaneous breathing in premature infants at birth. We aimed to assess feasibility and potential effects of antenatal paracetamol. Methods: In this randomised, placebo-controlled, triple-blind feasibility trial, pregnant women <31 weeks’ gestation were randomised to receive either intravenous paracetamol (intervention) or placebo (control). Multiple pregnancies were also eligible, and the number of infants could exceed the number of enrolled women. The primary outcome was feasibility of administering study medication within 30–120 min prior to birth. Secondary exploratory outcomes included measures of breathing and other physiological parameters of infants during the first 1–10 min after birth and were compared between infants from mothers who received paracetamol and infants from mothers who received a placebo irrespective of timing of administration. Planned enrolment was 40 women. Results: The trial enrolled 23 women before termination due to low recruitment. Five women did not receive study medication, while 18 did (9 per group). Overall, 11 of the 23 enrolled women (48%) received study medication within the specified timeframe. The nine women in the intervention group gave birth to 13 infants, while the nine women in the control group gave birth to 12 infants. Among infants, average minute volume did not differ significantly between groups (intervention (n = 13) vs. control (n = 12); mean ± SEM; 147 ± 12 vs. 114 ± 14 mL/kg/min, p = 0.093). However, the intervention group had a significantly higher area under the curve for minute volume, greater inspiratory drive, and a higher heart rate (1120 ± 410 vs. 707 ± 346 mL/kg, p = 0.020; 11.8 ± 1.0 vs. 8.4 ± 1.3 mL/kg/breath/s, p = 0.046; 137 ± 5 vs. 121 ± 5 beats/min, p = 0.037). Conclusions: Antenatal paracetamol administration 30–120 min prior to birth was feasible in only half of the women, below the pre-specified threshold of 80%, but the exploratory findings suggest that it may improve the breathing effort of premature infants.

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 Immunosuppression is a recognized risk factor for severe and disseminated coccidioidomycosis; however, data describing outcomes in patients with inflammatory bowel disease (IBD) receiving advanced therapy, including biologics and small molecules, remain limited. We aim to describe the prevalence, clinical presentation, treatment patterns, and outcomes of coccidioidomycosis in IBD patients receiving advanced therapy at an endemic tertiary care center. Methods We performed a retrospective observational study of adult patients with IBD at Mayo Clinic Arizona diagnosed with coccidioidomycosis between 2023 and 2026. Patients were included if IBD diagnosis preceded coccidioidomycosis diagnosis and advanced therapy had been active for at least 4 weeks before infection. Cases were classified as proven, probable, or possible based on microbiologic, clinical, radiographic, and serologic criteria. Clinical outcomes included antifungal treatment duration, hospitalization related to coccidioidomycosis or IBD, IBD treatment modification after diagnosis, re-emergence of coccidioidomycosis symptoms, and IBD-related surgery. Results A total of 48 patients met inclusion criteria. Among 1083 tested IBD patients receiving advanced therapy, coccidioidomycosis positivity prevalence was 4.4% when including all serologically positive patients and 1.9% when restricted to proven or probable cases. The median age at coccidioidomycosis diagnosis was 40 years (range 19-87 years), and 30 (62.5%) of 48 had Crohn’s disease. Proven or probable infection was identified in 21 (43.8%) of 48 patients, while 14 (29.2%) of 48 patients were classified as possible. Antifungal therapy was prescribed in 32 (66.7%) of 48 patients, including all proven cases, 15 (88.2%) of 17 probable cases, 9 (64.3%) of 14 possible cases, and 3 (25.0%) of 12 nondiagnostic cases. Among proven/probable/possible cases, the median antifungal treatment duration was 174 days (range 8-831 days). Advanced IBD therapy was continued in 3 (75.0%) of 4 proven cases, 9 (52.9%) of 17 probable cases, 12 (85.7%) of 14 possible cases, and all nondiagnostic cases. Hospitalization occurred in 6 (12.5%) of 48 of the cohort, all of which were proven/probable cases. Most patients remained on advanced therapy after diagnosis, although tumor necrosis factor α inhibitors were the most interrupted or discontinued agents. Conclusions In this endemic tertiary care cohort, management decisions varied according to diagnostic certainty. Patients with proven or probable coccidioidomycosis were more likely to receive antifungal therapy and undergo advanced IBD therapy modification, whereas most patients with possible or nondiagnostic serologic findings remained on advanced therapy without major IBD-related complications. Prolonged antifungal treatment was common, highlighting the complexity of managing coccidioidomycosis in immunosuppressed patients with IBD.

Abstract Cellular senescence has been implicated in the pathophysiology of radiotherapy-associated bone loss. Based on our previous work, clearance of senescent cells using genetic and pharmacological tools alleviates the anomalies associated with radiation-associated bone deterioration. The pro-inflammatory senescence associated secretome referred to as senescence associated secretory phenotype (SASP), is a hallmark of cellular senescence. The modulation of SASP by senomorphic drugs, potentially can suppress the pro-inflammatory secretome of senescent cells, irrespective of the underlying senescence mechanism. In this study we tested a senomorphic drug, ruxolitinib, a Janus kinase inhibitor (JAKi), during acute and chronic radiotherapy related effects on the bone. Our clinical data indicate an early increase in several pro-inflammatory SASP proteins following radiotherapy of spinal metastasis in prostate cancer patients. Longitudinal assessment of SASP-related genes confirmed this acute elevation in several SASP markers in systemic circulation following irradiation of male mouse femurs. In studies done in male mice, following three preclinical radiotherapy regimens of 30Gy (5 x 6Gy), 60Gy (5 x 12Gy) and a single dose of 24Gy, suppression of SASP by JAKi was efficacious in suppressing radiation-induced bone damage. In comparison and as shown before, the senolytic combination of D+Q was also able to alleviate radiation-associated bone loss. Early and intermittent suppression of SASP using JAK inhibitors in male mice alleviated chronic bone deterioration, diminished telomere dysfunction, lowered senescence and SASP marker expression and reduced bone-marrow adiposity. Overall, our study shows that early targeting of SASP proteins could be a potential therapeutic to prevent radiotherapy-related chronic bone loss and risk of fractures.

Abstract INTRODUCTION Associations of arterial stiffness, measured through pulse wave velocity (PWV), with incident dementia may be driven by age‐related structural changes to the arterial wall or by elevated blood pressure. METHODS Dementia‐free White or Black participants in the community‐based Atherosclerosis Risk in Communities (ARIC) cohort study with measures of PWV were examined. The associations of carotid‐femoral PWV (cfPWV) and total, structural, and load‐dependent PWV with dementia were estimated using Poisson regression models and Cox proportional hazards models. Dementia cases were defined by physician‐adjudicated review, telephone interviews, hospitalization records, and death certificates. RESULTS Of 4818 participants included in the study population (mean age: 75 years; 41% male, 21% Black), 1067 (22%) developed dementia over a median follow‐up of 9.0 years. Higher cfPWV, total PWV, structural PWV, and load‐dependent PWV were associated with greater dementia risk. DISCUSSION Both structural and pressure‐related arterial stiffness mechanisms may underlie the link between PWV and dementia.

Background and Goals: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with cirrhosis and ascites, with additional risks posed by multidrug-resistant organisms (MDRO). This real-world study evaluated clinical outcomes in patients with SBP and the impact of MDRO. Methods: This study identified US adults with SBP receiving guideline-recommended treatment with antibiotics and albumin from January 2012 to June 2022. Antibiotic utilization trends, health care resource utilization, and clinical outcomes [in-hospital and ICU mortality and hospital and ICU length of stay (LOS)] were assessed and stratified by MDRO status. Results: A total of 10,956 patients with 12,570 encounters were identified. Median age was 57.0 years (IQR=49.0 to 65.0), and 62.4% were male; suspected MDRO infections occurred in 15% of encounters. Third-generation cephalosporins were used in 71.6%, 49.2% had acute kidney injury, and 20.0% and 7.2% had hepatorenal syndrome and hepatic encephalopathy, respectively. Median hospital LOS was 7.2 days (IQR=4.3 to 12.9), with 17.7% in-hospital mortality. ICU care was required in 14.5% of encounters, with a median ICU LOS of 3.6 days (IQR=1.7 to 6.7) and ICU mortality of 29.7%. MDRO infections were associated with increased in-hospital mortality (OR=2.24, P <0.001) and decreased hazard of hospital discharge (ie, prolonged LOS; HR=0.43, P <0.001). Receiving albumin within 24 hours of admission was associated with a 72% higher hazard of hospital discharge (ie, shorter LOS; HR=1.72, P <0.001). Conclusion: This study highlights the clinical and resource burden of SBP, emphasizing the impact of MDRO infections and the importance of timely albumin administration concordant with clinical guidelines.

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only). Updates are published regularly and can be found on the ASCO Publications website .

Vascular abnormalities are significant and often underdiagnosed conditions that can have profound implications for athletic performance, limb function, and even life, and multimodality imaging plays an essential role in timely recognition, characterization, and management.