• Age-Associated Targetable Genomic Alterations and PD-L1 Expression in 2509 Patients With Pulmonary Ground-Glass Opacities.
    1 day ago
    To investigate the landscape of targetable genomic alterations and programmed cell death ligand 1 (PD-L1) expression in pulmonary ground-glass opacities (GGOs) and their association with age.

    A total of 2509 patients with GGOs were retrospectively analyzed. Tumor characteristics, PD-L1 expression, and prevalence of targetable alterations were compared across age groups.

    In GGOs, the mutation rates of EGFR (61.5%) and ERBB2 (12.0%) were relatively high, whereas those of KRAS (8.2%) and ALK rearrangements (2.3%) were relatively low. The patients exhibited a low tumor mutational burden (TMB), and PD-L1 expression was negative in 86.7% of cases. TMB, PD-L1 expression, and the mutation rates of EGFR, KRAS, and MET increased significantly with age, whereas the rates of ERBB2 mutations, ALK rearrangements, and RET rearrangements decreased significantly with age. Age was identified as an independent predictor for the above eight variables. The optimal age cutoff was determined to be 53 years. Compared with the younger age group (< 53 years), the older age group (≥ 53 years) showed a 31.6%, 130.4%, and 800.0% higher likelihood of harboring EGFR, KRAS, and MET mutations, respectively. Conversely, compared with the older age group, the younger age group showed a 289.1%, 94.1%, and 108.7% higher likelihood of harboring ERBB2 mutations, ALK rearrangements, and RET rearrangements, respectively.

    GGOs exhibit a distinct genomic and PD-L1 profile with significant age-related heterogeneity, providing insights for age-stratified therapeutic strategies.
    Non-Communicable Diseases
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  • Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?
    1 day ago
    Ovarian Cancer (OC), the deadliest gynecological malignancy, poses a major therapeutic challenge in advanced stages owing to its high recurrence rate and metastatic potential. In this regard, it is noteworthy that immunotherapy has recently gained significant attention in OC treatment, a phenomenon attributable to notable advances in over-the-counter Chimeric Antigen Receptor (CAR)-based cell therapy. At the heart of CAR-T Cell (CAR-T) immunotherapy is genetically modified CAR molecules that enable immune cells to target and recognize tumor antigens. Based on such strategies, CAR-T therapies have developed rapidly in hematological oncology and are gradually being extended to solid tumors. Despite their potential in OC treatment, several factors, including off-target effects attributable to the lack of Tumor-Specific Antigens (TSAs), as well as severe side effects such as tumor immune barriers, Cytokine Release Syndrome (CRS), and neurotoxicity, have been established to limit the clinical use of CAR-T therapies. Moreover, compared to CAR-T, CAR-Natural Killer (NK) and CAR-Macrophage (M) therapies have distinct advantages. The killing mechanism of NK cells integrates both CAR-dependent and non-dependent pathways, avoiding severe CRS and neurotoxicity. Furthermore, besides directly phagocytosing tumors due to its strong ability to infiltrate tumors, CAR-M therapy could also effectively improve the Immunosuppressive Microenvironment (IME) via immunomodulatory factor secretion to remodel M2-type Tumor-Associated Macrophages (TAMs) into the M1 phenotype with anti-tumor function. In this review, we systematically describe the research progress in CAR-T therapy for OC and compare the similarities and differences of three types of cellular therapies (CAR-T, CAR-NK, and CAR-M) regarding their mechanisms of action, clinical advantages, and technological bottlenecks. We hope that our findings will provide a theoretical basis for optimizing immunotherapeutic strategies for OC. Trial Registration: ClinicalTrials.gov identifier: NCT03585764.
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  • Differentiation of Fat-Poor Renal Angiomyolipoma From Clear Cell Renal Cell Carcinoma: Diagnostic Performance of a Novel Type of Color Contrast Enhanced Ultrasound.
    1 day ago
    The similar imaging characteristics of renal angiomyolipoma without visible fat (RAML.wvf) and clear cell renal cell carcinoma (ccRCC) are notable. Color Parameter Imaging (CPI) has emerged as an advanced contrast-enhanced ultrasound (CEUS) analysis tool that quantifies temporal perfusion dynamics.

    Evaluate the diagnostic value of CPI in distinguishing AML.wovf from ccRCC.

    In this prospective study, 88 patients (35 with AML and 53 with ccRCC) underwent CEUS and CPI. Junior and senior radiologists independently analyzed the CEUS and CPI images. Three diagnostic approaches were compared: (1) CPI alone, (2) CEUS alone, and (3) CEUS combined with CPI. The diagnostic sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curves of resident and staff radiologists were analyzed.

    The CPI features of ccRCC and AML.wovf analyzed by the junior and senior radiologist groups showed significant differences: the mosaic sign and the Cold sign (both p < 0.001) were more indicative of AML.wovf, whereas the Warm sign was more suggestive of ccRCC (both p < 0.05). The area under the curve (AUC) for the combined CEUS+CPI diagnosis in the junior radiologist group was higher than that for CEUS alone (p = 0.012). Regarding diagnostic confidence between the two radiologist groups, the proportion of uncertain cases in the CPI group was significantly lower than in the CEUS group for both the senior radiologist group and the junior radiologist group (both p < 0.05).

    CPI technology can enhance the diagnostic performance of contrast-enhanced ultrasound in differentiating ccRCC from AML.wovf, particularly offering an advantage in improving the diagnostic accuracy of junior radiologists.
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  • Predicting Prognosis for Gastric Cancer Patients Receiving Neoadjuvant Treatment With Body Composition-Based Deep Learning.
    1 day ago
    This study sought to develop an innovative body composition (BC)-based deep learning (DL) model to precisely evaluate survival in gastric cancer (GC) patients undergoing neoadjuvant treatment (NT).

    This retrospective study included GC patients undergoing NT from two centers. CT images both pre-NT and post-NT were preprocessed, focusing on the automatic segmentation of subcutaneous fat, visceral fat, and skeletal muscle regions using TotalSegmentator. Delta Radiomics features were extracted using Pyradiomics. After feature fusion and selection, the optimal model is Naive Bayes (Rad model). A hybrid DL model was developed by combining ResNet18 and Transformer networks for feature extraction. The Clinic_Rad_DL model was constructed by combining clinical features, radiomic signatures, and DL signatures. The ExtraTree classifier was used for the Clinic_Rad_DL model, while a separate Cox regression model was developed for survival analysis using the same features.

    A total of 356 patients (mean age, 59 ± 10 years; 264 males [74.2%]) were enrolled and divided into training, validation, and test sets in a 7:2:1 ratio. The DL model outperformed the Rad model. The Clinic_Rad_DL model outperformed both Rad model and DL model, with AUC of 0.915, 0.890, and 0.890 in training, validation, and test sets, respectively. The Cox proportional hazards model showed C-index of 0.806, 0.803, and 0.819, effectively stratifying patients into high- and low-risk groups with significant survival differences.

    The study developed and validated a BC-based DL model to predict survival in GC patients undergoing NT, offering potential for personalized treatment strategies in clinical practice.
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  • Extent of Pelvic Lymph Node Dissection at Partial Cystectomy: Effect on Cancer-Specific Mortality.
    1 day ago
    We assessed the extent of pelvic lymph node dissection (PLND) at partial cystectomy (PC) according to PC eligibility (≤cT2 stage, tumor ≤ 3 cm and segmental resection possible) and tested its effect on cancer-specific mortality (CSM).

    Within the SEER database (2004-2021), we identified PC patients undergoing PLND and tabulated the number of lymph nodes (LNs) removed according to PC eligibility. Multivariable Cox-regression models tested the effect of PLND extent on CSM after adjusting for age, sex, T stage, N stage, and chemotherapy.

    Of 1017 PC patients undergoing PLND, 197 (19.4%) were eligible vs. 820 (80.6%) ineligible according to PC eligibility criteria. Median number of LNs removed at PLND was 6 (IQR: 3-11) in eligible versus 7 (IQR: 3-14) in ineligible patients (p = 0.09). Mean numbers of LNs removed at PLND increased over the study period, from 7 to 16 (p = 0.007) in PC-eligible and from 8 to 13 (p = 0.001) in PC-ineligible patients. In 1017 patients regardless of PC eligibility, 5-year CSM-free survival rate was 65.6%, and PLND extent predicted lower CSM (multivariable hazard ratio [mHR]: 0.99, p = 0.036). In 197 PC-eligible patients, 5-year CSM-free survival rate was 84.2%, and the PLND extent was not associated with CSM (mHR: 0.96, p = 0.2). Conversely, in 820 PC-ineligible patients, 5-year CSM-free survival rate was 61.1%, and PLND extent predicted lower CSM (mHR: 0.99, p = 0.043).

    In all PC patients regardless of eligibility status, more extensive PLND was associated with improved cancer-specific survival.
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  • Efficacy of Fertility-Sparing Treatment With Progestin Is Associated With Different Molecular Classification in Endometrial Carcinoma and Atypical Endometrial Hyperplasia.
    1 day ago
    To investigate the impact of various molecular characteristics on the outcomes of fertility-preserving therapy in patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH).

    A total of 14 EC cases and 60 AEH cases were retrospectively analyzed at the Women's Hospital, Zhejiang University from January 2013 to October 2022.

    This study investigated the molecular profiles and outcomes of fertility preservation in 74 cases. The most prevalent molecular profile was NSMP type (63.9%), followed by p53abn type (21.3%) and MMRd type (14.8%). After 6 months of progesterone therapy, the cumulative CR rates were 100% for NSMP type, 83.3% for MMRd type, and 33.3% for p53abn type (p = 0.006). The CR rate in the p53abn group was significantly lower than in the other two groups (p = 0.006), with a notably higher recurrence rate (p = 0.006). ER and PR expression was significantly lower in the MMRd and p53abn groups (p = 0.002). A total of 26 pregnancies (42.6%) were observed. In the EC group, the pregnancy rate of p53abn was lower than that of the NSMP group (0% vs. 83.3%, p = 0.02). In the AEH group, pregnancy rates of p53abn and MMRd were not significantly different from the NSMP group (0% vs. 50%, p = 0.16; 33.3% vs. 50%, p = 0.20).

    Molecular classification may serve as a predictive tool for the efficacy of fertility preservation therapy in patients with EC and AEH and was found to be particularly useful for identifying p53 mutants, which are associated with a high risk of recurrence, as well as MMRd types, which are known to lead to poor responses to progesterone treatment.
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  • The Clinical Benefits of Nutritional Supplementation Across the Chemotherapy Journey in Cancer Patients: A Multicenter Prospective Cohort Study.
    1 day ago
    This study aimed to explore the clinical benefits of receiving nutritional supplementation (NS) throughout the whole course of chemotherapy.

    This multicenter prospective cohort study totally included 251 cancer patients requiring nutritional support and scheduled for chemotherapy. Primary outcomes included energy intake (EI), protein intake (PI), body mass index (BMI), NRS 2002 and PG-SGA scores. Short-term efficacy was the secondary outcome.

    Among the study participants, 168 received NS, whereas 83 opted for dietary advice (DA) alone. In the NS group, EI and PI demonstrated a gradual upward trend across the six cycles of chemotherapy, with no significant changes in the DA group. The BMI remained stable in both groups. The proportion of patients with or at risk of malnutrition showed a declining trend in the NS group but an increasing trend in the DA group. The generalized estimating equation results indicated that NS significantly improved PI (coefficient = 0.19, 95% CI: 0.11 to 0.27, p < 0.001), NRS 2002 (coefficient = -0.13, 95% CI: -0.23 to -0.03, p = 0.005), and PG-SGA (coefficient = -0.18, 95% CI: -0.28 to -0.08, p < 0.001). The improvements in PI, NRS 2002, and PG-SGA scores occurred from cycle 1, cycle 3, and cycle 2, respectively. Multivariate logistic analysis confirmed NS as a favorable factor associated with higher disease control rate (OR = 4.65, 95% CI: [1.88, 12.01], p = 0.001).

    The incorporation of NS yielded several clinical benefits beyond adequate EI and stable weight. It contributes to higher protein intake and good nutritional status in patients with cancer throughout the whole course of chemotherapy, ultimately improving treatment efficacy.

    Patient-Reported Outcome Management Including Surveillance and Intervention in Nutritional Group (PROMISING) Study (registration number: ChiCTR2100047535).
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  • Comparing the quality of dying for patients with hematological malignancy and solid tumors: A bereavement study in Japan.
    1 day ago
    Although research on palliative care in hematological malignancies has increased, research examining quality of death (QOD) and quality of care (QOC) in this population remains limited. This study compared QOD and QOC between patients with hematological malignancies and those with solid tumors.

    The authors conducted a secondary analysis of a nationwide mortality follow-up survey of bereaved family members in Japan (2017-2018). The study included 3575 decedents with hematological malignancies and 50,592 with solid tumors. Propensity score matching was performed to adjust for demographic and clinical characteristics. QOD and QOC were assessed using the Good Death Inventory (GDI) and the Care Evaluation Scale 2.0 (CES). Bivariate analyses compared the matched groups.

    Overall, QOD and QOC were comparable between groups. However, among the GDI subdomains, patients with hematological malignancies had slightly lower scores for "good relationships with family" (mean difference, 0.2; 95% confidence interval [CI], 0.03-0.3) and "preparation for death" (mean difference, 0.2; 95% CI, 0.04-0.3). In addition, patients with hematological malignancies were less likely to die in palliative care units than those with solid tumors (mean difference, 3.9%; 95% CI, 0.4%-7.4%).

    Although overall quality measures were similar, specific QOD domains related to family relationships and preparation for death were slightly lower among patients with hematological malignancies. These findings may reflect limited opportunities for end-of-life discussions due to the unpredictable and rapidly progressive course of hematological malignancies. Enhancing communication about prognosis and goals of care and early integration of palliative care may improve end-of-life experiences.
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  • Perioperative Outcomes of Robot-Assisted Partial Nephrectomy Using Hinotori Compared With da Vinci Xi: A Propensity Score-matched Analysis.
    1 day ago
    Robot-assisted partial nephrectomy (RAPN) using the da Vinci Surgical System (DVSS) is broadly performed globally. In Japan, the Hinotori Surgical Robot System (HSRS) has recently been developed. However, few studies have compared perioperative outcomes between HSRS-RAPN and DVSS-RAPN. This study aimed to compare perioperative outcomes between these two robotic platforms.

    Clinical data from 86 patients who underwent RAPN from April 2023 to November 2025 were prospectively collected and retrospectively analysed. Propensity score matching (1:1) based on preoperative variables yielded 31 matched pairs. Perioperative outcomes, including trifecta achievement, were compared.

    Following matching, baseline characteristics were well balanced. Operative parameters, perioperative complications, positive surgical margins, postoperative renal function, and trifecta rates did not significantly differ between the groups.

    HSRS-RAPN can be safely and effectively performed, achieving perioperative outcomes comparable to those of DVSS-RAPN. These findings suggest that HSRS is a feasible alternative robotic platform for RAPN.
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  • Single-Cell Dissection of Malignant Cell Heterogeneity Reveals Functional Programs and Clinically Relevant Subtypes in Head and Neck Squamous Cell Carcinoma.
    1 day ago
    Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis and limited predictive biomarkers for therapy response. Characterizing malignant cell heterogeneity may improve prognostic and therapeutic stratification. We integrated single-cell RNA sequencing (scRNA-seq) data from 58 HNSCC patients (181,003 cells) to define malignant cell subpopulations, their differentiation states, developmental trajectories, cell-cell interactions, and spatial localization. Coexpression gene modules and meta-programs were identified using hdWGCNA and NMF. These programs were projected onto bulk RNA-seq datasets to classify HNSCC subtypes and examine associations with clinical outcomes, tumor microenvironment (TME), genomic instability, and predicted response to immune checkpoint inhibitors (ICIs). Twelve malignant clusters were identified with distinct clinical and molecular features. MC-5 exhibited a stem-like phenotype associated with poor prognosis, while MC-7 and MC-11 showed high TME communication and immune engagement. Coexpression analysis revealed 16 modules and eight meta-programs encompassing proliferation, differentiation, stress response, and immune activity. Translation to bulk RNA-seq defined three HNSCC subtypes (MS-1, MS-2, MS-3) with divergent survival, immune infiltration, stromal composition, and genomic features. MS-2, an immune-enriched subtype, demonstrated superior survival, high HPV positivity, and predicted ICI responsiveness. A 25-gene malignant cell score (MCScore) robustly predicted both prognosis and immunotherapy response. This study provides a comprehensive map of malignant cell heterogeneity in HNSCC, identifies key functional expression programs, and defines molecular subtypes with clinical and therapeutic relevance. Malignant cell-specific signatures, such as MCScore, offer promising tools for patient stratification and precision immunotherapy.
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