ABSTRACT Background Observational studies report an overall‐survival advantage for postoperative radioactive iodine (RAI) in lymph node–positive papillary thyroid carcinoma (PTC), but such estimates are vulnerable to confounding by indication and to bias from immortal time and the healthy‐user effect. We assessed the credibility of this apparent benefit rather than RAI efficacy itself. Methods Using SEER (2010–2015), we assembled a cohort of N1b, M0, totally thyroidectomized PTC patients and applied a 3‐month landmark analysis (sensitivity analyses at 1 and 6 months) with stabilized inverse‐probability‐of‐treatment weighting. We estimated RAI effects on overall survival, cancer‐specific survival, and relative survival, and on a negative‐control outcome—non–thyroid‐cancer death—that RAI cannot plausibly affect. Residual confounding was quantified with E‐values. Results Among 4275 patients, RAI showed an apparent survival benefit in direction across all three endpoints. However, the negative‐control outcome likewise showed an apparent benefit (IPTW hazard ratio 0.713, 95% CI 0.562–0.906), indicating residual confounding not removed by weighting. The apparent survival benefits therefore could not be distinguished from unmeasured confounding. Conclusions In registry data lacking key confounders, a negative control identifies the apparent RAI survival benefit as a candidate artifact of unmeasured confounding. The findings neither support nor refute RAI efficacy.
ABSTRACT Background Electronic patient‐reported outcome (ePRO) systems support symptom monitoring after chemotherapy; however, their integration into structured nurse‐led oncology workflows remains limited. In this study, we aimed to develop and evaluate the short‐term feasibility and usability of a nurse‐led ePRO system for home‐based postchemotherapy symptom monitoring and structured nursing triage for cancer patients. Methods This single‐arm feasibility study was conducted at a cancer center in Taiwan between April and September 2024 among adult patients requiring home‐based symptom monitoring after hospital‐based chemotherapy care. The nurse‐led digital system was designed to support weekly self‐reporting of 12 chemotherapy‐related symptoms using the Chemotherapy Toxicity Self‐Assessment Questionnaire. The system incorporated rule‐based triage categorization using green, orange, and red risk levels and predefined nurse response protocols. Feasibility outcomes included report adherence, triage alert management, and system performance. Usability was evaluated using the System Usability Scale. Results Forty‐two patients submitted 306 symptom reports during the 8‐week monitoring period, corresponding to an overall adherence rate of 91.1%. Among all reports, 16.3% generated orange alerts requiring nurse follow‐up and 6.5% generated red alerts requiring urgent review. Fatigue, pain, and hand–foot syndrome were the most frequently reported abnormal symptoms. All orange and red alerts had documented nursing review. The system met the predefined technical performance indicators during simulated load testing, and achieved a mean System Usability Scale score of 92.6 ± 6.46. Conclusions This nurse‐led ePRO system demonstrated favorable short‐term feasibility and usability for home‐based postchemotherapy symptom monitoring and structured nursing triage. These findings support the practicality of integrating structured ePRO monitoring into postchemotherapy nursing care. Further multicenter and comparative studies are warranted to evaluate long‐term engagement, scalability, and clinical outcomes.
ABSTRACT Background Existing deep learning models for predicting biochemical recurrence (BCR) after radical prostatectomy often ignore the biological context beyond the tumor. This study aims to develop and validate a transformer‐based model combining multi‐regional magnetic resonance imaging (MRI) features and clinical data to improve BCR prediction after radical prostatectomy in prostate cancer (PCa). Methods We enrolled 232 Pca patients from three medical centers between 2013 and 2020. Multi‐parametric MRI sequences, including T2‐weighted fat‐suppressed and diffusion‐weighted imaging, were collected before surgery. Patients from centers 1 and 2 were assigned to a discovery cohort (training: n = 146; internal validation: n = 36), and patients from center 3 (n = 50) formed an external test cohort. A transformer‐based deep learning (DL) model was developed using imaging features from intratumoral, peritumoral, and periprostatic regions, combined with clinical variables. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity with 95% confidence intervals (CI), and prognostic value was assessed via Kaplan–Meier (K‐M) survival analysis. Results The combined three‐region MRI‐based model demonstrated superior predictive performance for BCR risk across all sets, with an AUC of 0.801 (0.663–0.920) on the external test set and an AUC of 0.799 (0.715–0.872) on the validation set. Notably, the integrated DL model, which combined MRI data with clinical characteristics, outperformed the MRI‐based and clinical models. The three‐region with clinical combined model improved AUCs from 0.801 (95% CI: 0.663–0.920) to 0.863 (95% CI: 0.697–0.975) on the external test set and from 0.799 (95% CI: 0.715–0.872) to 0.832 (95% CI: 0.746–0.904) on the validation set. K‐M curve analysis revealed that the integrated model provided significantly better predictions than the MRI‐based and clinical models (p < 0.0001). Conclusion By combining intratumoral, peritumoral, and periprostatic regions from multi‐parametric MRI with clinical data, the transformer‐based DL model provides a multimodal approach for predicting BCR in PCa patients.
ABSTRACT Background The global burden of liver cancer has been increasing over recent decades, whereas the incidence in Switzerland has remained relatively stable. This study assessed long‐term trends in incidence, mortality, and 1‐ and 5‐year relative survival of primary liver cancer in the Swiss canton of Zurich from 1980 to 2022, stratified by sex and age. Methods This population‐based retrospective analysis included all primary liver cancer cases diagnosed in the canton of Zurich and registered in the Cancer Registry of the cantons of Zurich, Zug, Schaffhausen and Schwyz between 1980 and 2022. Mortality data were obtained from the Federal Statistical Office. Cases were classified according to ICD‐O‐3 topography and morphology and, from 2003 onward, TNM stage. Age‐standardised incidence and mortality rates were calculated using the 1976 European standard population. Temporal trends were analysed using Joinpoint regression and reported as Average Annual Percentage Changes (AAPCs) with 95% confidence intervals (CIs). Relative survival was estimated using the Ederer II method and standardised according to international standards. Results Among 3866 incident cases, 71.3% were hepatocellular carcinomas and 70.7% occurred in men. Overall age‐standardised incidence remained stable in both men (AAPC −0.1%, 95% CI −0.6 to 0.3%) and women (−0.2%, −0.9% to 0.4%). However, incidence increased significantly among individuals younger than 65 years, particularly in women (AAPC 2.3%, 1.3%–3.3%) and men (1.2%, 0.6%–1.9%). Mortality remained broadly stable in men and increased modestly in women. One‐ and five‐year relative survival improved substantially, from 13.8% and 3.5% in 1980–1999 to 53.9% and 25.8% in 2016–2022, respectively. Improvements were greater in men than women. Conclusion These findings reflect major advances in liver cancer diagnosis and treatment over the past four decades. Continued prevention, targeted screening of high‐risk groups, and epidemiological monitoring remain important.
ABSTRACT Background Cysteine‐rich angiogenic inducer 61 (CYR61), a matricellular protein, has been implicated in gastric cancer aggressiveness through activation of integrin‐mediated NF‐κB signaling; however, effective pharmacological strategies targeting this axis remain limited. Cyclopiane, a bioactive small‐molecule compound, has shown potential anti‐tumor activity, but its role and underlying mechanisms in gastric cancer have not been fully elucidated. This study aimed to investigate whether Cyclopiane suppresses gastric cancer invasion and angiogenesis via modulation of the CYR61/αvβ3 integrin/NF‐κB signaling pathway. Methods Human gastric cancer cell lines AGS and MKN45 were treated with increasing concentrations of Cyclopiane. Cell viability was assessed using MTT assays, while invasive capacity was evaluated using Matrigel‐coated Transwell assays. TUNEL staining was used to assess changes in apoptosis in tumor cells. The expression of invasion‐, angiogenesis‐, and inflammation‐related proteins was analyzed by Western blot (WB) and enzyme‐linked immunosorbent assay (ELISA). Transcriptomic profiling of AGS cells treated with Cyclopiane versus vehicle control was performed to identify differentially expressed genes and enriched signaling pathways. CYR61 overexpression was achieved via adeno‐associated virus (AAV‐CYR61), with its pathway involvement further validated using integrin αvβ3 antagonists. The conventional anticancer drug 5‐fluorouracil (5‐FU) was employed to compare Cyclopiane's therapeutic effects. In vivo experiments utilized a nude mouse xenograft model to evaluate changes in tumor growth, angiogenesis, and inflammatory responses following Cyclopiane treatment. Results We found that Cyclopiane significantly reduced cell viability, invasive capacity of AGS and MKN45 cells and promoted apoptosis in a dose‐dependent manner, with its high‐dose effects comparable to those of 5‐FU. Transcriptomic analysis revealed that Cyclopiane downregulated CCN1/CYR61, ITGAV and ITGB3 expression, with pathway enrichment identifying integrin signaling, ECM‐receptor interaction, focal adhesion and NF‐κB pathways as the top modulated terms. In vivo experiments demonstrated that Cyclopiane significantly inhibited tumor growth and progression. Both in vivo and in vitro studies showed Cyclopiane significantly downregulated vascular endothelial growth factor (VEGF), matrix metalloproteinase‐2 (MMP‐2), and MMP‐9 expression while inhibiting integrin αvβ3 expression and NF‐κB activation, as evidenced by reduced phosphorylation levels of p65 and IκBα. Overexpression of CYR61 partially reversed the inhibition of invasion, angiogenic factor production, and NF‐κB signaling mediated by Cyclopiane. The αvβ3/αvβ5 integrin antagonist Cilengitide also exhibited tumor‐suppressive effects, and the co‐treatment of Cyclopiane with Cilengitide achieved the strongest tumor‐suppressive effect. Conclusion These findings suggest that modulation of the CYR61/integrin/NF‐κB signaling axis contributes, at least in part, to the anti‐invasive and anti‐angiogenic effects of Cyclopiane in preclinical gastric cancer models. Further studies are required to establish its molecular target specificity, safety, selectivity, and translational potential.
