Effective treatment options remain limited for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), including patients who have progressed after platinum-based chemotherapy and systemic-therapy-naïve patients. This Phase Ib trial evaluates the efficacy and safety of finotonlimab, a PD-1 antibody, combined with SCT200, an EGFR antibody.

This prospective, multicenter, open-label study enrolled patients into two cohorts: Cohort A (previously treated with platinum-based chemotherapy and immune checkpoint inhibitors) and Cohort B (systemic therapy-naïve). Patients received finotonlimab (200 mg every 3 weeks) and SCT200 (6 mg/kg weekly for 12 weeks, then 8 mg/kg every 2 weeks). The primary endpoint was objective response rate (ORR).

Among 41 patients, Cohort A (n = 11) showed an ORR of 27.3%, median progression-free survival (PFS) of 5.8 months, and median overall survival (OS) of 10.6 months. Cohort B (n = 30) had an ORR of 56.7%, median PFS of 9.6 months, and an estimated median OS of 13.6 months. Common treatment-related adverse events included hypomagnesemia (63.4%), rash (41.5%), and acneiform dermatitis (36.6%), which were manageable.

The combination of finotonlimab and SCT200 demonstrates promising efficacy, particularly in systemic therapy-naïve patients, warranting further investigation.

ClinicalTrials.gov identifier: NCT05552807; Chinadrugtrials.org.cn identifier: CTR20220917.

Despite best clinical management, patients with meningiomas frequently experience tumor recurrence. During recent decades, efforts have been made to improve the prognostic stratification of meningiomas by incorporating molecular data. A subgroup of tumors harboring a homozygous CDKN2A deletion was identified, and a higher risk of tumor progression was observed, suggesting the potential use of cyclin-dependent kinases as biomarkers.

In this retrospective single-center study, the immunohistochemical staining for the cyclin-dependent kinases p16, phosphoRB1 (pRB1), CDK4 and CDK6 was analyzed in 1751 paraffin-embedded meningioma samples. For the assessment of p16, CDK4 and CDK6, a semi-quantitative score was applied, whereas an automated quantification tool was used for pRB1. The distribution and association with histopathological results, clinical data and progression-free survival (PFS)-defined by radiographic tumor recurrence-were assessed.

Of all meningioma samples, 14.9% (n = 261) expressed p16. Elevated pRB1 levels were found in 34.5% (n = 589) of tumor samples. CDK4 and CDK6 positive staining was observed in 41.9% and 42.2% of cases, respectively. Dichotomous stratification of meningiomas based on p16 and pRB1 expression levels suggested a significant influence on PFS in univariate analyses. Multivariate analysis determined elevated pRB1 expression, WHO grading, extent of resection, adjuvant radiotherapy, male gender, NF2-status and an elevated MIB1 index as independent prognostic factors.

High expression of pRB1 is an independent prognostic factor for shorter PFS. The prognostic impact of p16 is mostly attributed to the confounding increase of pRB1 expression.

Fast-track colonoscopy pathways detect colorectal cancer (CRC) but strain endoscopy capacity. We developed and externally validated multivariable risk models combining faecal immunochemical test (FIT) with clinical data to triage Swedish fast-track referrals.

We analysed 2,539 fast-track colonoscopies (2016-2020) and 723 as a validation cohort (2021-2022). Predictors were age, sex, eight symptoms, binary FIT, haemoglobin, and suspicious imaging. In development, missing predictors were imputed within training/test splits; validation used complete cases. Class imbalance was handled with oversampling to balance classes. Logistic regression and CatBoost models were built. External validation assessed AUC, calibration, and calibration slope. Variable influence was examined with feature contribution analysis. Decision-curve analysis (DCA) used the entry rule as a treat-all baseline.

CRC prevalence was 16% in both cohorts. Development AUCs were 0.81 (95% CI 0.78-0.83) for CatBoost and 0.77 (0.74-0.80) for logistic regression. In external validation, AUCs were 0.67 (0.61-0.74) and 0.66 (0.58-0.75), respectively. FIT status, suspicious imaging, and age were the main predictors. Calibration drift was observed. The entry rule functions as treat-all (specificity 0%). CatBoost DCA curves were near or above treat-all at common thresholds, but 95% bands overlapped; advantage over treat-all was not confirmed.

A multivariable approach using FIT, simple laboratory data, and clinical findings can support triage in a fast-track pathway. In validation, discrimination was modest, and superiority over the entry rule could not be shown because all referred patients underwent colonoscopy. External testing across regions, recording quantitative FIT, and routine recalibration are needed before implementation.

Prognostic models for resectable gastric cancer rarely integrate adipose tissue and immune-inflammatory parameters. This study evaluated the predictive value of preoperative relative fat mass (RFM) and the modified systemic inflammation score (mSIS), and explored their potential synergy with nanomedicine-based theranostics.

We retrospectively analyzed 518 patients who underwent radical gastrectomy across three tertiary centers in China (overall enrollment period: 2010-2019). Preoperative CT-derived waist circumference at L3 was used to calculate RFM, with the optimal cutoff determined by ROC analysis using the Youden index. Univariate and multivariate Cox regressions identified independent prognostic factors and constructed the nutritional-inflammatory composite parameter RFMmSIS. Predictive performance was assessed using AUC, AIC, BIC, NRI, IDI, and DCA. Postoperative follow-up was conducted every 3 months during the first 2 years, every 6 months during years 3 through 5, and annually thereafter.

Patients were randomly allocated to training (n = 362) and validation (n = 156) cohorts. RFM outperformed BMI for survival prediction (AUC: 0.584 vs. 0.503, P < 0.05) and was associated with worse 3-year overall survival (OS) (64.1% vs. 80.0%, P = 0.014) and disease-free survival (DFS) (57.7% vs. 78.4%, P = 0.005). Multivariate analysis identified RFM (HR: 2.355) and mSIS grade 2 (HR: 1.657) as independent prognostic factors. The composite RFMmSIS stratified patients into high-, intermediate-, and low-risk groups, with higher scores associated with increased severe complications (Clavien-Dindo ≥IIIa: 4.7% vs. 4.2% vs. 15.2%, P = 0.005 in training cohort) and poorer 3-year OS/DFS (high-risk: 44.3%/41.0%). RFMmSIS demonstrated superior predictive accuracy for OS and DFS compared with operative extent and pN stage (all P < 0.05).

Preoperative RFMmSIS is a clinically feasible predictor of short-term complications and long-term survival in gastric cancer, offering enhanced prognostic stratification beyond traditional parameters and providing a rationale for integrating nutritional-inflammatory risk assessment with nanomedicine-based theranostic strategies.

Data on the clinicopathological features of NRG1 fusion-positive non-small cell lung cancer (NSCLC) are limited. We conducted a retrospective, multicenter study and included patients with NRG1 fusion-positive NSCLC diagnosed between January 2018 and February 2025. Six patients were identified; five were female (83.3%), two were never-smokers (33.3%), and four were former smokers (66.7%). Adenocarcinoma was the predominant histology (n = 5), comprising mucinous (n = 2), enteric (n = 2), and not otherwise specified (n = 1) variants, while one patient had squamous cell carcinoma. All were PD-L1-negative, and CD74-NRG1 was the most common fusion (50%). Three patients received afatinib; only one achieved a partial response with a progression-free survival of 8.7 months. Median overall survival was 6.7 months. Our study demonstrates the histologic and molecular heterogeneity of NRG1 fusion-positive NSCLC, encompassing mucinous and enteric variants of adenocarcinoma. Responses to afatinib were variable, underscoring the need for more effective therapies, including zenocutuzumab and emerging agents.

Endocrine therapy with CDK4/6 inhibitor has been the main treatment for HR+/HER2- breast cancer in the adjuvant setting; however, the data on the application in the neoadjuvant setting is limited. We compared neoadjuvant efficacy and safety of sequential chemotherapy-CDK4/6 inhibitors with chemotherapy alone in HR+/HER2- breast cancer patients.

Female patients with HR+/HER2- breast cancer who received neoadjuvant therapy at the Fifth Medical Center of the PLA General Hospital from November 2019 to March 2025 were enrolled. The objective response rate (ORR), pathological complete response (pCR), and event-free survival (EFS) between the two treatment groups were analyzed.

Among the 181 enrolled patients, 142 received chemotherapy alone (NCT cohort) and 39 received CDK4/6 inhibitors plus endocrine therapy (NCT-ET cohort) after chemotherapy as preoperative therapy. Overall pCR was similar across cohorts (3.5% in NCT cohort vs. 2.6% in NCT-ET cohort, p = 1.000), as was ORR (72.5% vs. 69.2%, p = 0.685). The 3-year EFS rate was numerically higher in the NCT-ET cohort (96.7% vs. 83.6%, p = 0.111). However, among patients who failed to achieve partial response (PR) within 4 cycles of chemotherapy, switching to endocrine therapy was associated with improved ORR (61.3% vs. 30.4%, p = 0.005). Overall pCR (3.2% vs. 0.0%, p = 0.356) and 3-year EFS rate (95.7% vs. 78.0%, p = 0.105) were numerically higher in the NCT-ET cohort. The total incidence of grade ≥ 3 adverse effects was higher in the NCT-ET cohort (69.2% vs. 47.8%). However, for patient received endocrine therapy after chemotherapy, grade ≥ 3 events decreased from 66.7% during chemotherapy phase to 20.5% after switching to endocrine therapy.

Despite no statistically significant differences in observed overall pCR and 3y-EFS between patients treated with NCT or NCT-ET, the sequential endocrine strategy was associated with improved ORR among patients who did not achieve PR after four cycles of chemotherapy and a lower incidence of adverse events during endocrine therapy.

Semantic interoperability in health care, essential for seamless integration of information systems, is partially achieved through the use of terminologies and common data standards that define the semantic structure of data. Various complexities arise when using real-world health care data, including different interpretations of terms and concepts and gaps in domain coverage in standard terminologies. However, ensuring compatibility becomes increasingly challenging when big data are distributed across diverse repositories that use heterogeneous health care standards and overlapping terminologies. Ontologies are key solutions to bridge these gaps, enabling consistent semantic interoperability and data harmonization.

We aim to develop and validate a hyperontology within the EUCAIM (Cancer Image Europe) project to semantically integrate and harmonize clinical, biological, and imaging metadata, along with associated data from heterogeneous, disparate cancer image data models, to achieve semantic interoperability in oncology and medical imaging. The hyperontology will be used to support several EUCAIM components, including the extract, transform, and load process; federated query; image annotation and segmentation; and ultimately, AI-federated processing.

The ontology development process combines real-world data from a network of European projects on cancer imaging (AI for Health Imaging) with their semantic mappings, as well as conceptual unpacking and modeling of the Minimal Common Oncology Data Elements (mCODE) specifications. The mCODE is a core set of structured data elements for oncology electronic health records. The building process is supported by ontology grounding, layering, and modularization. We adopted this hybrid approach to simplify ontology design, semantically reflect oncology's essential entities and their interactions, and enhance the extensibility and reusability of the hyperontology. We initiated ontology development with a set of competency questions derived from the provided knowledge, which helped clarify the ontology's scope and requirements and identify inconsistencies or incomplete information. We also assessed whether the requirements were fulfilled by formalizing the competency questions using SPARQL.

We developed a FAIR hyperontology that semantically integrates and harmonizes clinical, biological, and imaging metadata and data spread across disparate sources. The ontology also captures and accurately represents oncology and medical imaging. The hyperontology, which covers various cancer types, is rich in axiomatizations and patterns, supporting the semantic understanding and harmonization of heterogeneous data. Additionally, semantic mappings are established across data models and standards, ensuring the efficient and meaningful sharing and integration of health care data. Finally, we evaluated the ontology model and demonstrated its applicability using real-world prostate and breast cancer use cases.

EUCAIM's hyperontology is a valuable effort that provides a unifying framework for the essentials of oncology and medical imaging, facilitating communication among disparate and heterogeneous cancer image data models. The ontology model is evaluated and validated using multiple methods, demonstrating compliance with the specified ontological requirements. Challenges include ensuring that the ontology is scalable, extensible, and applicable, given the complexity and dynamic nature of the application domain.

Difficult-to-diagnose melanocytic neoplasms often require additional diagnostic tools beyond histopathological assessment to reach a definitive diagnosis. The 23-gene expression profile (GEP) test provides additional diagnostic information, returning a result of suggestive of benign, intermediate, or suggestive of malignant. Here, we present a real-world cohort of ambiguous melanocytic lesions where the 23-GEP test was used to arrive at a definitive diagnosis with long-term follow-up. Melanocytic lesions were included in this study if 23-GEP testing was performed as part of their original diagnostic workup (n = 267). Long-term follow-up to determine disease recurrence and/or metastasis (ie, an event) was obtained (median, 6 years). Following 23-GEP testing, 89.5% of difficult-to-diagnose lesions were provided definitive diagnoses. Event rates were 11.5% for lesions with malignant 23-GEP results, 2.9% for lesions with intermediate results, and 1.3% for lesions with benign results (Fisher exact, P = 0.002). Lesions with at least 5 years of clinical follow-up and/or an event (n = 163) had similar results to the overall cohort (P = 0.007). A benign 23-GEP result is associated with a low risk of recurrence/metastasis, whereas a malignant 23-GEP result is associated with a significantly higher risk of recurrence/metastasis, supporting the value of 23-GEP in guiding clinical management decisions for ambiguous melanocytic lesions.

This study aimed to verify the efficacy and safety of a novel all-in-one device for colorectal hybrid endoscopic submucosal dissection (ESD). We further evaluated its clinical outcomes and cost- effectiveness compared with conventional ESD.

All In One (AIO) assisted hybrid ESD was prospectively performed on 161 patients (173 colorectal neoplasms) across five centers from November 2021 to November 2022.The primary outcome was the en bloc resection rate. Secondary outcomes were the complete resection rate and the incidences of adverse events. For the secondary retrospective comparative analysis, 345 patients (362 colorectal neoplasms) who underwent conventional ESD in the lead center during the same period were retrospectively identified and include to compare with the AIO group for outcomes and cost-effectiveness.

In the prospective study, the en bloc resection rate was 97.7% (169/173), and the complete resection rate was 94.2% (163/173). The intraoperative and postoperative bleeding rates were 4.6% (8/173) and 1.2% (2/173). No perforation or abdominal pain was observed, and the incidence of fever was 1.2% (2/173). In the propensity score-matched retrospective comparison, the en bloc resection rates were 97.8% in AIO groups and 96.3% in conventional group (p=0.722). The complete resection rates were 94.8% in both groups. There was no difference between the adverse events rates (all p>0.05). It also demonstrated significantly reduced procedural time and costs with AIO assisted hybrid ESD (both p<0.001).

The novel AIO device for colorectal hybrid ESD is safe and effective. It also reduced the procedural time and cost compared to convention ESD.

Cellular plasticity and epithelial-mesenchymal transition (EMT) promote the initiation and progression of non-small cell lung cancer (NSCLC). Thioredoxin reductase 1 (TXNRD1), a key redox enzyme, has been linked to malignancy, but its mechanism in NSCLC remains unclear. We examined whether TXNRD1 regulates TGF-β1 autocrine signaling to drive EMT and stemness.

Stage-progression gene profiles were analyzed in the TCGA and GEO databases with an emphasis on redox gene families. TXNRD1 was manipulated by overexpression or knockdown in A549, H226, and H1299 cells, followed by migration/invasion, spheroid assays, ELISA for cytokines, and RT-qPCR/Western blot for EMT markers. RNA-seq with pathway enrichment analyses was used to identify downstream programs. An orthotopic lung cancer mouse model was established using TXNRD1-WT cells, TXNRD1-deficient cells, and TXNRD1-deficient cells treated with TRi-1. Tumor progression was monitored by bioluminescence imaging at 6 and 12 weeks after transplantation.

TXNRD1 expression was ~2-fold higher in advanced-stage NSCLC and was validated in tumor tissues. CRISPR/Cas9 or siRNA knockdown reduced EMT-associated genes and decreased TGF-β1 production in A549 and H226 cells. TXNRD1 overexpression increased EMT and stemness markers and produced larger, more compact spheres with higher sphere numbers in H1299 cells. RNA-seq indicated the TXNRD1 pathway activates the TGF-β1 pathway to promote EMT, motility, and stemness via an autocrine loop; knockdown or TXNRD1 inhibition suppressed metastatic tumor growth in vivo.

Our study identifies TXNRD1 as a crucial regulator of cellular plasticity and metastasis in NSCLC via the TGF-β1 pathway, suggesting that targeting TXNRD1 may reduce metastatic potential and improve patient survival.