• Five-Year Survival Analyses on Non-Pathological Complete Response Esophageal Squamous Cell Carcinoma Patients After Neoadjuvant Regimens Plus Surgery: A Propensity Score Matching, Real-World Cohort Study.
    2 weeks ago
    Non-pathological complete response (non-pCR) is common in esophageal squamous cell carcinoma (ESCC) patients after neoadjuvant therapy, yet evidence guiding long-term outcomes and postoperative risk stratification in the immunotherapy era remains limited.

    We retrospectively enrolled consecutive ESCC patients treated with neoadjuvant immunochemotherapy (nICT) or chemotherapy alone (nCT) followed by esophagectomy and restricted analyses to non-pCR cases. Primary endpoints were five-year overall survival (OS) and event-free survival (EFS). A 1:1 optimal propensity score matching (PSM) procedure and administrative censoring at 60 months were applied. Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazards analyses.

    Among 366 patients with non-pCR disease, 164 matched pairs were generated. After matching, nICT demonstrated a higher major pathological response (MPR) rate (19.5% vs. 6.1%), a lower ypT4 proportion (3.7% vs. 22.0%), and fewer recurrence/metastasis rate (40.2% vs. 58.5%), all p < 0.001. In the matched multivariable Cox model, nICT was independently associated with a lower risk of EFS events (HR 0.55, 95% CI 0.36-0.84; p = 0.005), whereas no independent association with OS was observed (HR 0.94, 95% CI 0.70-1.27; p = 0.707). Open esophagectomy (OE), ypN2-3 disease, and perineural invasion (PNI) were associated with worse EFS, whereas lower Ki-67 expression and postoperative adjuvant treatment were associated with better EFS. PNI was associated with worse OS, and postoperative adjuvant treatment was associated with better OS.

    Among non-pCR ESCC patients after neoadjuvant therapy and surgery, nICT was associated with lower recurrence risk and improved five-year EFS compared with nCT, whereas a significant OS advantage was not observed. Pathological factors (PNI, high Ki-67, and residual nodal burden) and postoperative treatment may help inform risk stratification, although the observational treatment associations should be interpreted cautiously.
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  • Despite improved overall stratification, the 9th edition stage IIIA category remains prognostically heterogeneous: insights from a T3N2a subgroup analysis.
    2 weeks ago
    The 9th edition TNM staging system refines N2 subclassification into single-station (N2a) and multi-station (N2b) metastases, leading to substantial stage migration within the previously heterogeneous stage IIIA category. While the 9th edition has demonstrated improved overall prognostic performance, it remains unclear whether the newly defined stage IIIA category is prognostically homogeneous. This study aimed to address this question in a real-world cohort of resected occult N2 NSCLC.

    Data of NSCLC patients who underwent surgery at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University from January 2014 to December 2017 were retrospectively analyzed. Patients were staged according to the 8th and 9th editions of the AJCC TNM guidelines. Kaplan-Meier analysis was used to assess the impact of clinicopathological factors on survival, and Cox regression analysis was performed for multivariate analysis. The Receiver Operating Characteristic (ROC) curve was utilized to evaluate the predictive performance of the two TNM staging systems.

    A retrospective study analyzed 550 T1-4N2M0 NSCLC patients post-surgery. 262 (47.6%) had stage reclassifications: 93 downstaged from IIIA to IIB, 36 downstaged from IIIB to IIIA, and 133 upstaged from IIIA to IIIB. The 9th edition demonstrated significantly improved three-tier prognostic discrimination across stages IIB, IIIA, and IIIB (p < 0.001). However, significant prognostic heterogeneity was observed within the newly defined stage IIIA category: patients with T3N2a disease (downstaged from 8th edition IIIB) had a 5-year OS of only 28.8%, compared to 51.2% for other stage IIIA patients (p < 0.05). The 9th edition demonstrated superior prognostic performance, as reflected by a larger area under the ROC curve (AUC: 0.606 vs. 0.550 for 5-year OS). Multiple mediastinal lymph node metastases emerged as an independent risk factor for reduced DFS and OS.

    While the 9th edition TNM system improves overall prognostic stratification for resected occult N2 NSCLC, the stage IIIA category remains prognostically heterogeneous. T3N2a patients have outcomes more consistent with IIIB than IIIA, suggesting that further refinement of stage grouping may be warranted.
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  • Minimally invasive versus open emergency right-sided colectomy for malignant obstruction: a nationwide propensity score-matched cohort study.
    2 weeks ago
    Minimally invasive surgery (MIS) improves short-term outcomes in elective colectomy, however, the choice of surgical approach in hemodynamically stable patients with obstructing right-sided colon cancer remains unclear in emergency settings. MIS could be considered and the present study aims to evaluate short-term outcomes of MIS in bowel obstructed patients compared with open surgery (OPEN).

    A retrospective nationwide study including patients from the nationwide Swedish Colorectal Cancer Registry (SCRCR) undergoing emergency right-sided colectomy in Sweden (2017-2023) was conducted. Propensity score matching (1:1) was performed based on sex, age, ASA class, hospital size, and operative timing (on-call vs. daytime). Outcomes included length of stay (LOS), postoperative complications, and surgical quality indicators. Analysis was performed according to intention-to-treat.

    A total of 1147 patients were identified. Of the 1,147 included patients, 99 (8.6%) underwent an initially minimally invasive approach. After matching, 99 patients remained in each group. The conversion rate was 34%. Median LOS was 9 days (IQR 6;14) after OPEN and 6 days (IQR 5;10) after MIS. In quantile regression with bootstrap standard errors, MIS was associated with a 3-day shorter median LOS (median difference - 3.0 days, 95% CI - 4 to - 2, p = 0.002). Postoperative complications (Clavien-Dindo ≥ 2) occurred in 38.8% after OPEN and in 23.2% after MIS. Logistic regression analysis with robust standard errors showed significantly lower odds of postoperative complications after MIS (OR 0.48, 95% CI 0.27-0.83, p = 0.009). No significant differences were observed in re-admission, 90-day mortality, R0 resection, lymph node yield, blood loss or operative time.

    In this nationwide observational cohort, an initially minimally invasive approach was associated with shorter length of stay and fewer postoperative complications. No statistically significant differences were observed in the available short-term surgical and pathological quality indicators. Given the limited number of MIS procedures and potential for residual confounding, these findings support further evaluation of MIS in carefully selected patients.
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  • Serous cystadenocarcinoma of the pancreas: a population-based study.
    2 weeks ago
    Serous cystadenocarcinoma (SCAc) of the pancreas is an exceptionally rare malignant pancreatic neoplasm, and its clinical characteristics, treatment patterns, and prognosis remain poorly defined. The aim of this population-based study was to characterize the demographic and clinical features, treatment patterns, and survival of patients with pancreatic SCAc.

    Patients with microscopically confirmed SCAc were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Demographic, tumor-related, treatment, and survival data were analyzed using descriptive statistics and Kaplan-Meier survival analysis.

    Twenty-one patients with SCAc were identified. Median age at diagnosis was 69 years, and 13 patients (62%) were female. Tumors most frequently involved the pancreatic body or tail. Disease was localized in 4 patients (19%), regional in 6 (29%), distant in 9 (43%), and unstaged in 2 (10%). Surgical resection was performed in 12 patients (57%), and 6 (29%) received chemotherapy. Estimated 5-year overall survival (OS) was 60.5% for the overall cohort. Five-year OS was 73.3% among patients who underwent resection and 44.4% among those who did not.

    Pancreatic SCAc is a rare malignancy with frequent involvement of the pancreatic body or tail. Surgical resection was the most common treatment, whereas chemotherapy was used in a minority of patients. Population-based data suggest relatively favorable long-term survival.
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  • Combined radiological approach for characterization of solid renal masses: a proposed strategy for integrating the RENAL nephrometry score into the clear cell likelihood score.
    2 weeks ago
    To systematically evaluate whether the combined application of RENAL nephrometry and clear cell likelihood score (ccLS) could improve the diagnostic reliability of the ccLS in distinguishing clear cell renal cell carcinoma (ccRCC).

    This retrospective single-center study encompassed 140 histopathologically confirmed solid renal masses in 130 patients who underwent preoperative MRI between March 2011 and January 2025. Two radiologists independently assigned the RENAL nephrometry and ccLS for each lesion. The diagnostic performance of the ccLS and the combined radiological approach was assessed using receiver operating characteristic curve analysis in the whole study cohort and two subgroups stratified by lesion diameter (≤ 4 cm vs. >4 cm). Interreader consistency was evaluated using the kappa coefficient.

    Overall, 74 (52.9%) ccRCC and 66 (47.1%) non-ccRCC lesions were enrolled. Diagnostic performance analysis yielded a negative predictive value of 90.9%, a specificity of 30.3%, and an AUC of 0.638 for excluding ccRCC when lesions with a ccLS of 2 or lower were accepted as non-ccRCC. With the combined approach, considering low-complexity lesions per the nephrometry score with ccLS of 3 as non-ccRCC improved diagnostic performance using a ccLS cut-off of ≤ 2 for excluding ccRCC (AUC = 0.684, p = 0.022). The combined approach exhibited better performance in lesions ≤ 4 cm for excluding ccRCC among ccLS 3 lesions (p = 0.042). Interobserver consistency was found to be near-perfect (κ = 0.927) and substantial (κ = 0.70) for the nephrometry and ccLS, respectively.

    In this preliminary single-center cohort, the combined radiological approach was systematically evaluated for both predicting and excluding ccRCC. Its benefit was concentrated in excluding ccRCC among indeterminate ccLS 3 lesions ≤ 4 cm, reducing false-positive outcomes and enhancing diagnostic confidence and suggesting a role in risk stratification rather than detection; external validation is required before clinical adoption.
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  • A Comparison of Mechanisms Driving Lesion Outcomes During Lung Tumor and Tuberculosis Granuloma Formation.
    2 weeks ago
    Small cell lung cancer (SCLC) and tuberculosis (TB) are both deadly diseases that present with spatially complex lung lesions. These lesions share similarities, including spatial interactions between T cells and macrophages. Both SCLC and TB exhibit heterogeneous disease progression and responses to treatment; current experimental methods have few tools to investigate the spatiotemporal evolution of these lesions within human lungs. We have applied our computational agent-based model (ABM), GranSim, to extensively study heterogeneity of TB granuloma formation and treatment efficacy. We introduce TumorSim, an analogous ABM designed to understand heterogeneity of SCLC lung tumors. TumorSim mechanistically captures immune-tumor interactions, many of which are well-studied in isolation, including cytokine-based recruitment of immune cells and PD-1/PD-L1-based inhibition of cytotoxic T cells. Drawing from lung immunology literature, we define and explore wide parameter ranges to characterize TumorSim behavior using global sensitivity analysis. We compare factors that drive both tumor and granuloma outcomes. As model validation, sensitivity analysis captures several well-known correlates of improved SCLC outcomes including macrophage-mediated cytotoxic T-cell recruitment. Surprisingly, both models predict a two-phase formation process occurring with an abrupt change in tumor/granuloma dynamics upon arrival of adaptive immune cells into the lung. Simulations suggest that while C-C motif chemokine ligand 5 (CCL5) is associated with improved tumor control later during tumor growth, CCL5 plays a pro-tumor role early during tumor growth by recruiting regulatory T cells. We find that, like virtual granulomas, TumorSim tumors become enlarged when immunosuppressive mechanisms outweigh pro-inflammatory responses. This novel tumor model enables future studies of both immunotherapeutics and anti-cancer drugs.
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  • Optimising ovarian cancer care: An embedded mixed methods evaluation of a national nurse-led telehealth program.
    2 weeks ago
    A nationwide nurse-led telehealth case management program was established providing personalised supportive care to individuals and families experiencing ovarian cancer. The program was evaluated using the RE-AIM framework. This paper focuses on the effectiveness findings of the evaluation.

    Using mixed methods design, participants completed four surveys over 12 months assessing symptom burden, psychological distress, supportive care needs, quality of life, and self-efficacy. Service experiences were further explored through interviews.

    Of the 652 individuals enrolled in the program, 112 (17%) participated in the evaluation. Predominant baseline moderate to severe symptoms were fatigue (65%); anxiety (56%); and sleep issues (50%). Key unmet needs included: uncertainty about the future (54%); fear of cancer spread (48%); and anxiety (42%). 43% reported high distress; 27% lacked confidence self-managing fatigue, 23% self-managing distress. All participants received symptom and needs assessment; 80% received information support, and one-third accessed specialised psychosocial care. Those with greater symptom burden, distress, lower quality of life and self-efficacy at baseline received more services. Over 12 months, overall wellbeing and satisfaction with information improved significantly. 30 interview participants consistently valued the program for: being seen and heard as a whole person; trusted information and advice; meaningful emotional support; and flexible and timely services.

    Participation in this nurse-led telehealth program was associated with improved outcomes and positive experiences among individuals with ovarian cancer who are at high risk of poorer outcomes. These findings support continued investment in person-centred tailored supportive care delivered via telehealth prioritising emotional wellbeing, symptom management, and quality of life.
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  • Benchmarking copy number alteration inference methods for spatial transcriptomics.
    2 weeks ago
    Copy number alterations (CNAs), gains or losses of genomic regions, contribute to malignant progression and tumor heterogeneity. Advances in spatial transcriptomics have expanded opportunities to study clonal structure in situ, but direct spatial genomic profiling remains difficult in practice, motivating the increasing use of computational methods to infer CNAs from spatial transcriptomics data. However, their performance across diverse spatial transcriptomics settings remains unclear. Here, we present a benchmark of nine CNA inference methods across 69 spatial transcriptomics tissue sections from six cancer types and four spatial transcriptomics platforms. By evaluating these methods across four key tasks, we show that no single method consistently outperforms all others, with performance depending on the analytical goal and data characteristics. We therefore provide task-specific and data-aware guidance to help users select appropriate methods in practical settings. More broadly, this benchmark provides a basis for the future development and optimization of CNA inference methods.
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  • Rapid Whole Genome Sequencing Enhances Pediatric Cancer Diagnosis.
    2 weeks ago
    Whole-genome sequencing (WGS) has been shown to improve diagnosis beyond standard-of-care genetic tests and guide precision treatment for childhood cancer. While WGS is now offered for children with suspected cancer in England, clinical workflows typically return results after several weeks whereas clinical decisions are often required within days. Here we evaluate feasibility and efficacy of a rapid WGS (rWGS) research workflow with streamlined bioinformatics to deliver clinical genomic findings (NCT07201038, Active, not recruiting). In 54 children with suspected or confirmed malignancy, rWGS reduces mean end-to-end turnaround time from 42 to 3 days, whilst increase variant detection rate. Whereby rWGS detected 147 of 155 (95%) clinically actionable variants identified in the cohort, standard of care testing detected 138 of 155 (89%) variants. In a subset of 35 patients assessed prospectively, clinicians report that in 17 (49%), rWGS either (i) facilitates faster access to targeted therapy and risk stratification, or (ii) avoids unnecessary investigations and treatment escalation. These findings indicate feasibility and suggest clinical utility of rWGS when deployed as a first line diagnostic test in pediatric oncology.
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  • Cadonilimab plus lenvatinib in advanced endometrial cancer: the multicenter single-arm phase II CLEAR-EC trial.
    2 weeks ago
    Treatment options are limited for women with advanced endometrial cancer after platinum-based chemotherapy. In this single-arm, multicenter phase II CLEAR-EC trial with a safety run-in, we evaluated cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus lenvatinib as second-line or later therapy (ClinicalTrials.gov: NCT05824481). Three patients were enrolled in the safety run-in, followed by 29 additional patients after the recommended phase II dose was established. The primary endpoint was objective response rate; secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, and safety. Prespecified exploratory analyses assessed circulating tumor DNA in relation to efficacy, with additional post-hoc biomarker analyses. No dose-limiting toxicities occurred, establishing lenvatinib 16 mg once daily plus cadonilimab 10 mg/kg every three weeks as the recommended phase II dose. The trial met its prespecified primary endpoint, with an objective response rate of 40.6% (95% confidence interval, 23.7-59.4). Disease control rate was 81.3% (95% confidence interval, 63.6-92.8), median progression-free survival was 13.8 months, and median overall survival was not reached. Grade ≥3 treatment-related adverse events occurred in 40.6% of patients. Early on-treatment circulating tumor DNA levels were associated with progression-free and overall survival.
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