Chimeric antigen receptor (CAR) T-cell therapies are typically administered at high doses to maximize durable clinical responses. However, manufacturing constraints can limit the production of sufficient cells to achieve the intended dose. Although some patients experience durable responses after receiving lower CAR-T cell doses, the mechanisms underlying efficacy at these limited cell numbers remain poorly understood. To address this, we performed deep phenotyping of anti-CD19 CAR-T cell products and their corresponding leukapheresis starting materials from a phase I/II dose-escalation trial. We also report the primary and secondary clinical outcomes of the diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma cohorts of the HD-CAR-1 basket trial (NCT03676504; EudraCT 2016-004808-60). Patients responding to low-dose CAR-T therapy showed dose-dependent enrichment of functional effector and effector memory-like CAR-T cells. The absolute number of these cells emerged as a robust biomarker of therapeutic response, valid across dose levels and CAR-T targets. Effective low-dose products were associated with high T-cell numbers and T-cell-supportive myeloid states in leukapheresis materials, whereas regulatory myeloid states promoted dysfunctional CAR-T cells and treatment failure. Our study provides insights into the phenotype, mechanisms, and biomarkers of CAR-T cells that drive therapeutic responses at low doses, with medical and socioeconomic implications.

Radiologists classify breast density using the Breast Imaging Reporting and Data System (BI-RADS) as required by the 2024 Mammography Quality Standards Act (MQSA), which mandates disclosure of breast density in all mammography reports. FDA-approved AI software now provides objective, reproducible breast density assessments to improve workflow and guide supplemental screening. This study examines concordance between AI-based systems (Volumetric density measurement by Volpara/Lunit) and radiologist assessments and explores potential clinical and economic implications.

A retrospective cohort study with IRB approval was conducted at Avera Health using 54,819 mammograms between February 2024 and June 2025. Radiologists assessed breast density with the option to override AI-generated assessments. Density classifications were compared and categorized as "agreement" or "substantial change." Effects on Tyrer-Cuzick (TC) lifetime risk scores, patient referrals, and prospective healthcare costs were analyzed.

Overall, AI and radiologist assessments had agreement rates of 92-97% for BI-RADS B and C and 85-90% for A and D. Most discrepancies involved BI-RADS B and C categories, leading to misclassification of breast density and potential repercussions for patient care. Overestimation resulted in unnecessary procedures, radiation, costs, and anxiety, while underestimation risked delayed detection of aggressive cancers.

Current AI software demonstrates concordance with radiologist assessments, though notable variability persists at critical diagnostic thresholds. Utilizing standardized protocols, periodic AI model updates, and radiologist oversight are crucial to minimizing misclassification, enhancing workflow efficiency, optimizing patient outcomes, and fostering trust in AI-assisted breast imaging.

Objective: To investigate the clinical characteristics and prognostic factors of pediatric precursor lymphoid neoplasms with KMT2A gene rearrangement. Methods: In this retrospective cohort study, clinical data of 47 children with KMT2A gene rearrangement precursor lymphoid neoplasms diagnosed at the Children's Hospital Affiliated to Zhengzhou University from January 2018 to November 2024 were collected, so as to describe their clinical characteristics. According to whether hematopoietic stem cell transplantation (HSCT) was performed during first complete remission (CR1), children were divided into CR1 transplantation group and CR1 chemotherapy group, survival rates comparison and prognostic factor analysis were performed between two groups. For relapsed children in the CR1 chemotherapy group, they were further subdivided into a transplantation salvage group and a chemotherapy salvage group based on salvage therapy modality, and post-relapse survival rates were compared between the two subgroups. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were analyzed using the Cox proportional hazards regression model. Results: Among the 47 patients, there were 27 males and 20 females, with the age of 0.8 (0.4, 2.4) years. B-cell acute lymphoblastic leukemia accounted for 85% (40 cases). The initial white blood cell count was 89×10⁹ (27×10⁹, 302×10⁹)/L. Central nervous system leukemia was diagnosed in 10 children(22%, 46 children had central nervous system assessment). A total of 43 children were included in the efficacy evaluation, with a follow-up of 30.1 (13.8, 47.7) months. The 3-year overall survival and event-free survival (EFS) rates were (68.2±7.3) % and (51.7±8.0) %, respectively. The CR1 transplantation group (17 children) had significantly better 3-year overall survival and EFS rates than the CR1 chemotherapy group (26 children)(100.0% vs. (47.2±10.1) %, (84.7±10.3) % vs. (29.6±9.1) %, χ²=12.68 and 16.03, both P<0.001). The transplantation salvage group (4 children) had a higher 18-month overall survival rate than the chemotherapy salvage group (14 children) (100.0% vs. (8.9±8.4)%, χ²=10.07, P=0.002). Multivariate analysis showed that negativity of minimal residual disease detected by quantitative real-time PCR (qPCR-MRD) at week 12 of induction therapy (HR=0.29, 95%CI 0.10-0.83, P=0.022) and HSCT (HR=0.15, 95%CI 0.05-0.44, P<0.001) were both independent protective factors for EFS. Conclusion: Pediatric KMT2A gene rearrangement precursor lymphoid neoplasms are clinically highly aggressive and have a poor prognosis, but negative qPCR-MRD at week 12 of induction therapy and HSCT are independent protective factors for EFS.

High-quality cytopreparation is essential for the morphological analysis of circulating tumor-associated cells (C-TACs). While the Soft Micro Pore Filter (S-MPF) method is effective for cell recovery, technical challenges such as air bubble entrapment and uneven cell distribution remain. We aimed to establish a stable and reproducible cytopreparation protocol by precisely controlling airflow and fluid dynamics using a three-way stopcock.

A modified preprocessing workflow was developed integrating a three-way stopcock to eliminate air bubbles through priming. We evaluated: (i) processing time and leukocyte residual rate, (ii) recovery and transfer rates using spiked HeLa cells, and (iii) the preservation of large 3D C-TAC clusters from lung cancer patient samples compared to a provisional method.

The modified method substantially improved filtration time (from 2.91 to 0.39 min) and reduced the leukocyte residual rate (from 7.3% to <0.1%). The cell transfer rate to slides was highly stable at 98.7% [coefficient of variation (CV)=11.8%]. Furthermore, large 3D clusters consisting of ≥15 cells were successfully transferred from clinical samples while maintaining their diagnostic morphological features.

The integration of a three-way stopcock provides a robust and standardized workflow for S-MPF-based cytopreparation. This protocol substantially enhances the reliability of C-TAC morphological diagnostics in routine clinical practice.

Pediatric osteosarcoma is a rare and aggressive malignancy with limited treatment options in cases of progression or metastasis. Regorafenib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and other kinases, currently approved in Japan for certain gastrointestinal cancers. Its clinical use in osteosarcoma, especially in pediatric patients, has not been well established.

We retrospectively analyzed six pediatric patients with advanced osteosarcoma who were treated with regorafenib at our institution. All patients had previously received standard treatment, including neoadjuvant and adjuvant chemotherapy as well as surgery, and were considered to have disease progression or resistance prior to regorafenib administration. Clinical background, treatment response, adverse events, and progression-free survival (PFS) were evaluated. Tumor response was assessed using RECIST criteria, and adverse events were graded according to CTCAE v5.0.

The average age was 16 years (range=12-18 years), and all patients had received prior surgery and chemotherapy. Regorafenib was administered at adult equivalent doses, with dose reductions required in 3 of 6 patients. Four patients (66.7%) achieved stable disease for at least eight weeks. The longest PFS exceeded 12 months. Common toxicities included diarrhea and hematuria; no grade ≧3 adverse events were observed. All patients underwent genomic testing to guide treatment planning.

This case series suggests that regorafenib may provide disease control with acceptable safety in pediatric patients with advanced osteosarcoma. Further studies are needed to evaluate its efficacy and tolerability in this population as well as in adult patients.

To develop a simple preoperative prognostic score that integrates symptom burden, tumor biology, and nutritional status [symptom-tumor-nutrition (STN) score] in patients with stage II-III colorectal cancer (CRC) undergoing laparoscopic curative resection.

We retrospectively analyzed 455 consecutive patients with stage II-III CRC who underwent laparoscopic colorectal resection between 2008 and 2018. The STN score (0-3) assigned 1 point each for the following: preoperative obstructive findings requiring decompression, carcinoembryonic antigen ≥5.0 ng/ml, and Prognostic Nutritional Index ≤40. The patients were stratified into low (0), mid (1), and high (2, 3) STN groups. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models.

The DFS and OS scores of the high-STN group were significantly worse than those of the low- and mid-STN groups (both log-rank p<0.01). In the multivariable analysis, high-STN independently predicted poorer DFS [hazard ratio (HR)=2.21, 95% confidence interval (CI)=1.05-4.61; p=0.035] and OS (HR=2.29, 95%CI=1.01-5.15; p=0.045).

The STN score is a practical preoperative tool that stratifies recurrence risk and long-term survival after laparoscopic resection of stage II-III CRC.

Pulmonary resection is associated with decline in respiratory function and exercise tolerance, thereby influencing postoperative complications and patient prognosis. Recently, attention has been paid to the importance of perioperative rehabilitation. However, its efficacy and optimal methods remain unclear. Therefore, this review aimed to comprehensively examine the effects of pre- and postoperative rehabilitation on exercise tolerance, postoperative complications, length of hospital stay, readmission rates, and survival rates.

A literature search was performed in the PubMed database, focusing on randomized controlled trials (RCTs) reported in English. The search identified 103 articles. After screening, 14 RCTs were included in the analysis. The intervention details, implementation timing, outcomes, and their effects were summarized.

Rehabilitation was implemented preoperatively, postoperatively, or both. Preoperative rehabilitation, including aerobic exercise, resistance training, and respiratory training for ≥1 week, was associated with improved exercise tolerance, reduced postoperative pulmonary complications, and shorter hospital stay. Furthermore, even a short-term intervention of three days was associated with improved respiratory function and walking ability. In postoperative rehabilitation, educational interventions were associated with improved exercise compliance and reduced postoperative complications. However, the effects of these interventions were inconsistent, and no clear effects on long-term outcomes, such as readmission or survival rates, were observed.

Pre- and postpulmonary resection rehabilitation, particularly preoperative intervention, reduces postoperative pulmonary complications, shortens hospital stay, and prevents decline in exercise tolerance. Even short-term preoperative intervention may be clinically beneficial. However, evidence on its impact on long-term prognosis remains limited. Future studies should investigate long-term outcomes.

The mucosal barrier, regulated by cytokines and cell adhesion molecules, is critical to colorectal cancer (CRC) progression. Interleukin (IL)-22 regulates intestinal homeostasis, whereas interleukin-22 binding protein (IL-22BP) functions as its soluble decoy receptor. We aimed to elucidate the clinical significance of IL-22BP and its association with cell adhesion molecules in advanced CRC.

We retrospectively analyzed data from 178 patients with stage II and III CRC who underwent curative resection. The protein expression of IL-22, IL-22BP, claudin-1, and β-catenin was evaluated using immunohistochemistry on tissue microarrays. We investigated the associations between these markers and clinicopathological features and survival outcomes.

High IL-22BP expression was significantly associated with claudin-1 expression (p=0.043). Patients with low IL-22BP expression demonstrated shorter recurrence-free survival (RFS) (p=0.015) and overall survival (OS) (p=0.037). Multivariate analysis identified low IL-22BP expression as an independent predictor of poor RFS [hazard ratio (HR)=2.265; 95% confidence interval (CI)=1.209-4.242; p=0.011] and OS (HR=2.502; 95%CI=1.174-5.335; p=0.018). In contrast, IL-22 and β-catenin expression was not associated with prognosis.

IL-22BP expression correlates with claudin-1 and serves as an independent prognostic biomarker in patients with advanced CRC. Our findings suggest that the IL-22/IL-22BP axis may modulate tight junction integrity to prevent tumor progression, implicating IL-22BP as a potential therapeutic target.

Accurate assessment of the longitudinal tumor extension is essential for determining the surgical strategy for distal bile duct cancer (DBDC). Although multidetector-row computed tomography (MDCT) is widely used for preoperative imaging, endoscopic retrograde cholangiopancreatography (ERCP) is still frequently performed despite its invasiveness. This study aimed to compare the diagnostic performance of MDCT and ERCP for assessing the longitudinal extension of DBDC.

Among 60 patients who underwent pancreatoduodenectomy for DBDC over an eight-year period, 43 patients who underwent both MDCT and ERCP before preoperative biliary drainage were retrospectively analyzed. According to the bile duct sections classification defined in the Anatomical Matters of the Regulations for the Management of Japanese Classification of Biliary Tract Carcinoma (the 2nd English Edition), the proximal margin of the longitudinal extension was independently evaluated based on MDCT and ERCP images. Imaging findings were compared with the pathological findings of the resected specimens.

The sensitivity, specificity, and accuracy of MDCT were 93.0%, 93.0%, and 86.0%, respectively. Those of ERCP were 92.1%, 76.9%, and 65.1%, respectively. Overestimation occurred in nine of 43 patients (20.9%) on ERCP alone, whereas no patients were overestimated on MDCT alone. In two patients with marked epithelial extension, it was underestimated on both MDCT and ERCP.

MDCT demonstrated higher diagnostic accuracy and a lower risk of overestimation than ERCP for assessing the longitudinal extension of DBDC. An MDCT-first approach may therefore be appropriate for routine preoperative assessment.

Metastatic triple-negative breast cancer (TNBC) is characterized by an aggressive clinical course and poor prognosis relative to other breast cancer subtypes. Real-world palliative care (PC) utilization patterns in this population remains poorly characterized. This study examined the sociodemographic, policy, and facility-level factors associated with PC utilization in metastatic TNBC.

Adults with metastatic TNBC (2018-2023) were identified from the National Cancer Database. PC was defined as non-curative intent surgery, radiation, systemic therapy, pain management, or any combination. Multivariable logistic regression evaluated sociodemographic and facility-level factors associated with PC utilization.

Among 9,211 patients with metastatic TNBC, 1,798 (19.5%) received PC. The most common modalities were systemic therapy (42.9%), multimodal combinations (24.5%), and radiation (22.8%). Medicaid-expansion states were associated with higher PC utilization [adjusted odds ratios (aORs)=1.39-1.83 across expansion timing categories; all p<0.05]. Uninsured patients had higher odds of PC utilization than privately insured patients [aOR=1.53, 95% confidence interval (CI)=1.14-2.07; p=0.005]. Treatment at academic/research programs was associated with higher PC utilization than community cancer centers (aOR=1.31, 95%CI=1.01-1.71; p=0.041). Geographic variation was observed, with higher odds of PC utilization in the Northeast, South, and Midwest than the West (all p<0.05).

In this largest population-level study to date, we found that PC utilization remains low among patients with metastatic TNBC, and was associated with insurance coverage, facility type, and geographic region. These findings highlight disparities in access to PC and underscore the need for more equitable and timely integration of PC among patients with metastatic TNBC.