Citations

PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

ABSTRACT Introduction Operating room (OR) noise during holmium laser enucleation of the prostate (HoLEP), particularly from laser activation, may impair surgical workflow and staff performance. Methods 84 HoLEP procedures were recorded at three academic institutions between June 2024 and January 2026. Laser platforms included Lumenis Moses 2.0, Quanta Litho 150, Quanta Magneto, and Dornier Thulio. Sound measurements were obtained using a standardized smartphone‐based system during three phases: laser‐off (baseline), idle (not firing), and active lasing. Acoustic metrics included average sound level (LAeq), peak sound level (Lcpeak), and sound levels exceeded for 10%, 50%, and 90% of the recording time (L10, L50, and L90). Background noise correction was performed using baseline measurements to account for ambient noise and isolate laser‐related sound. OR staff completed a validated survey assessing perceived noise burden (0–10 scale). Results Background‐corrected noise during active lasing differed significantly by platform. Litho demonstrated lower mean noise levels compared to Thulio for LAeq (60.6 vs. 68.2 dB, p = 0.023) and L10 (61.5 vs. 70.6 dB, p = 0.023), while Moses had higher LAeq compared to Litho (63.1 vs. 60.6 dB, p = 0.043). Overall, Litho had the lowest noise levels, whereas Thulio had the highest. Survey responses paralleled these findings. Litho was associated with lower perceived overall effort (2.1 ± 0.9), while Moses demonstrated higher overall effort (3.6 ± 1.2) for communication and concentration (Figure 2). Significant pairwise differences were observed between Moses and Litho (all p < 0.05). Trends were consistent across sites. Conclusions Noise levels during HoLEP varied by laser technology and correlated with differences in perceived communication and cognitive effort. Litho demonstrated the lowest acoustic burden, while Moses and Thulio had higher noise exposure. These findings highlight the impact of laser selection on the OR environment and intraoperative team performance.

Background: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed and new treatments have become available. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP. Methods: ASH formed a multidisciplinary guideline panel including two patient representatives that was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to July 19, 2025). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and identification of areas with new data or where application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on recommendations in adults with primary ITP regarding initial therapy and second-line treatment in patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy. Conclusions: Novel recommendations of these guidelines include: (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

ABSTRACT Many real‐world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ‐1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first‐line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ‐1‐in (meeting all inclusion criteria) or TOPAZ‐1‐out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression‐free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ‐1‐out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ‐1‐in , and 446 (32.9%) as TOPAZ‐1‐out . After a median follow‐up of 14.5 months (95% CI: 13.7–36.5), OS was 16.1 months in TOPAZ‐1‐in and 12.5 months in TOPAZ‐1‐out (HR 0.69, 95% CI: 14.6–16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1–8.1, p < 0.0001). Median OS in the TOPAZ‐1‐out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93–1.42; p = 0.09). Among TOPAZ‐1‐out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ‐1‐out patients experienced no significant increase in adverse events compared with the TOPAZ‐1‐in group. Real‐world data suggest CGD may be effective in TOPAZ‐1‐out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.

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.

Objective Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre‐existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). Methods All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. Results We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Conclusion Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision‐making and close monitoring.

Abstract Colorectal cancer develops through a normal-adenoma-carcinoma sequence, yet only 5-10% of adenomas progress to malignancy, and the cellular programs governing that sequence remain poorly defined. Here we generate a spatial multi-omics atlas of human colon adenomas, combining Visium CytAssist and protein co-detection across 24 nonadvanced and advanced tubular adenomas with single-cell resolution Xenium Prime 5K profiling of 101 patient-matched normal, adenoma, and carcinoma cores from 16 patients. Integrating whole-transcriptome and 31-plex protein data identifies nine spatial clusters and two dysplastic epithelial populations that co-express stemness, proliferation, and senescence programs. These programs occupy a shared, spatially confined epithelial niche that expands from adenoma to carcinoma. Spatial analysis revealed GDF15, a senescence-associated secretory factor, mediated the coupling between senescence and stemness in advanced adenomas, and that GDF15-high epithelium locally excludes CD8+ T cells in adenoma and, more broadly, in carcinoma. These findings position senescence as a spatially instructive rather than merely tumor-suppressive program during colorectal carcinogenesis and suggest GDF15 might be a potential candidate target for cancer prevention and interception in the colon.

Background: The study aims to evaluate the postoperative outcomes of hiatal hernia repair with cruroplasty alone compared to the addition of fundoplication. We theorize that previously reported inferiority with crural-only repairs resulted from a lack of real-time feedback regarding the effectiveness of the repair. EndoFLIP TM allows for intraoperative assessment of the gastroesophageal junction. We predict equivalent postoperative outcomes will be achieved between hiatal hernia repairs performed by cruroplasty alone and with fundoplication when the final distensibility index (DI) is similar. Methods: This retrospective cohort review includes patients who underwent hiatal hernia repair with intraoperative EndoFLIP TM between 2020 and 2022. Propensity score-matching was utilized to identify cruroplasty alone and fundoplication patients with a final DI within 0.5 mm 2 /mmHg of one another. Postoperative development of dysphagia, reflux, or hernia recurrence were primary outcomes of interest. Results: Forty-two patients were included in the analysis. While the cruroplasty-alone cohort had an increased age at the time of surgery, 50% more redo repairs, and a slightly higher BMI, there were no significant preoperative or intraoperative differences between groups. Overall, the median duration of follow-up was 111 (IQR 213) days. During that time, there were no differences in the development of postoperative reflux or dysphagia between cohorts ( P = .228 and P = .451, respectively). Kaplan-Meier curve analysis did not demonstrate a significant difference in time-to-event for either outcome. There were 3 radiographic recurrences, with 2 occurring after fundoplication ( P = .000). Conclusions: This is the first study to utilize intraoperative EndoFLIP TM to determine the need for fundoplication during hiatal hernia repair. The results demonstrate no additional short-term benefit from fundoplication performance. These findings argue against routine fundoplication when an acceptable DI can be achieved after cruroplasty. Further research is needed to validate these results.