Background Radiomics may preoperatively identify high-grade patterns (HGPs) in lung adenocarcinoma (ADC) and assist in clinical decision-making. Purpose To develop and evaluate a machine learning model based on preoperative contrast-enhanced CT images to predict HGPs and explore the model's prognostic value. Materials and Methods Patients with clinical stage I invasive ADC who underwent surgery (January 2017 to May 2025) were retrospectively enrolled from three centers. Binary (low risk: HGPs < 20%; high risk: HGPs ≥ 20%) and ternary (HGP0: HGPs = 0; HGP1: 0 < HGPs < 20%; HGP2: HGPs ≥ 20%) classification analyses were performed based on the proportion of HGPs. Multivariable logistic regression analysis was used to determine independent predictors of HGPs. XGBoost classifier-based radiomic models and combined models (radiomics-predicted probabilities plus clinical variables plus CT semantic features) were constructed and evaluated for discriminability, calibration ability, and clinical utility. Kaplan-Meier and Cox regression analyses were conducted to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Results A total of 1181 patients (median age, 61 years [IQR, 54-66 years]; 694 female) were allocated to the training (n = 667), internal test (n = 279), and external test (n = 235) sets. The combined model achieved the best discrimination in both binary (training: area under the receiver operating characteristic curve [AUC], 0.87 [95% CI: 0.84, 0.90]; internal test: AUC, 0.80 [95% CI: 0.74, 0.85]; external test: AUC, 0.84 [95% CI: 0.78, 0.90]) and ternary (training: microaverage AUC, 0.80 [95% CI: 0.78, 0.82]; internal test: microaverage AUC, 0.74 [95% CI: 0.70, 0.77]; external test: microaverage AUC, 0.72 [95% CI: 0.68, 0.76]) classification analyses. Model-predicted high-risk group was an independent prognostic factor for both OS (binary: hazard ratio [HR] = 1.98, P =.04; ternary: HR = 2.93, P =.03) and RFS (binary: HR = 3.33, P < .001; ternary: HR = 5.10, P < .001) and was consistently confirmed across subgroup analyses. Conclusion The combined model, integrating clinical variables, CT semantic features, and radiomics-predicted probabilities, effectively predicted high-grade patterns in lung ADC and showed strong potential for prognostic risk stratification. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Arita and Kocak in this issue.

Background Suboptimal nodal assessment in rectal cancer hampers pre- and postoperative assessment for treatment planning. A recently proposed standardized nodal evaluation system, Node Reporting and Data System 1.0 (Node-RADS), lacks robust evidence of diagnostic utility. Purpose To validate and optimize Node-RADS against European Society of Gastrointestinal and Abdominal Radiology (ESGAR) criteria in MRI-based nodal assessment in patients with rectal cancer, with subsequent patient-level external validation. Materials and Methods This retrospective study included consecutive patients with rectal cancer who underwent MRI and radical surgery between January 2016 and July 2025. Node-level analyses were performed in patients from center 1, and external patient-level validation was performed in patients from centers 2 and 3. Two radiologists independently evaluated mesorectal nodes according to Node-RADS and ESGAR criteria. The optimal threshold of the Node-RADS score for diagnosing malignancy was determined using the Youden index. Diagnostic performance and interobserver agreement were assessed using area under the receiver operating characteristic curve (AUC) and Cohen κ, respectively. Results This study included 780 patients (median age, 61 years [IQR, 53-68 years]; 477 men). Among 251 patients (1302 nodes) who underwent direct surgery, the optimal threshold of Node-RADS score was 3 or higher (Youden index, 0.65), enabling simplification to a modified model, the Simplified Nodal Assessment Process in Rectal Cancer (recSNAP). recSNAP outperformed the ESGAR criteria at both the node level (AUC, 0.83 vs 0.71; P < .001) and the patient level (AUC, 0.83 vs 0.71; P < .001). Similarly, among 284 patients (918 nodes) who received neoadjuvant chemoradiotherapy before surgery, Node-RADS with a threshold of 4 or higher outperformed the ESGAR criteria (AUC, 0.72 vs 0.66; P < .001). Interobserver agreement for Node-RADS at pre- and posttreatment MRI was substantial (Cohen κ, 0.76 and 0.64, respectively). Conclusion Node-RADS outperformed the ESGAR criteria for MRI-based rectal adenocarcinoma nodal assessment at both the node and patient levels and in external validation, and a simplified version of Node-RADS exhibited similar diagnostic performance. © RSNA, 2026 Supplemental material is available for this article.

The prevalence of major LARS and its associated risk factors remains variably reported in the literature. This meta-analysis aimed to assess the pooled prevalence of major LARS and to identify its predictive factors.

Pediatric cancers represent a major public health challenge, particularly in low- and middle-income countries (LMICs). This study aimed to describe the epidemiological and clinical characteristics of pediatric cancers managed at a reference center in Tunisia, analyze treatment pathways, and identify prognostic factors associated with net survival.

Evidence-based medicine (EBM) was conceived to support decisions for individual patients by integrating the best available evidence, clinical expertise, and patient values. However, the application of EBM in many fields has become associated with rigid algorithms and guideline pathways, sometimes interpreted as prescriptive rather than as aids to decision-making. Hepatocellular carcinoma (HCC) offers an informative case study of this dichotomy. This paper traces the evolution of personalized decision-making in HCC over two decades and its implications for the future of EBM.

Since the introduction of sentinel lymph node biopsy, nodal assessment has expanded to nearly all women with endometrial cancer. However, evidence on the prognostic significance of isolated tumor cells (ITCs) and nodal tumor burden remains limited. We therefore investigated the association of ITCs and nodal tumor burden with survival.

Subtle differences between cancerous and normal regions in unstained tissue sections limit the performance of conventional diagnostic methods. Mueller matrix polarimetry provides comprehensive information on tissue polarization responses; however, the intrinsic coupling of optical effects in the original matrix elements complicates direct histological interpretation. In this study, a pixel-level polarization dataset from clinical lung cancer and basal cell carcinoma sections is established to systematically compare low-dimensional physical decomposition and high-dimensional combination mapping for cancer-region identification. Conventional decomposition approaches exhibit limited discriminative capability and significant class overlap in complex tissues. To address this limitation, a vectorial metric norm spectrum incorporating multi-order features is developed, enabling enhanced representation of polarization characteristics. The proposed high-dimensional mapping framework achieves accurate differentiation between cancerous and normal regions and demonstrates strong performance in cross-validated evaluations. This work establishes a progressive strategy from physical decomposition to high-dimensional representation for optical-assisted pathological analysis.

Berberine (BBR), a natural alkaloid, exhibits potent anti-tumor activity in colorectal cancer (CRC), but its mechanisms are not fully elucidated. Analysis of GEO datasets (GSE216908 and GSE184414) identified WDR54 as a key target of BBR treatment. In vitro, BBR treatment of CRC cell lines (HT-29 and SW480) markedly inhibited cell proliferation, DNA synthesis, and colony formation. Notably, BBR triggered G1-phase cell cycle arrest and promoted apoptosis, as validated by flow cytometry and molecular marker analysis. WDR54 overexpression partially rescued these anti-tumor effects, confirming its functional importance. Mechanistically, cellular thermal shift assays (CETSA) and mRNA stability assays revealed that BBR suppresses WDR54 expression via indirect transcriptional inhibition rather than direct protein binding or altered mRNA stability. Dual-luciferase reporter assays further confirmed that BBR dose-dependently inhibits WDR54 promoter activity. In vivo, an AOM/DSS-induced CRC mouse model showed that BBR reduced tumor number and size, alleviated pathological progression, and suppressed the WDR54/β-catenin axis. These findings suggest that BBR exerts significant anti-tumor effects in CRC by downregulating WDR54 and inhibiting Wnt/β-catenin signaling, highlighting WDR54 as a potential therapeutic target and BBR as a promising treatment for CRC.

Aurora-A is a potential therapeutic target in prostate cancer. In this study, virtual screening identified four Aurora-A-targeting peptides, among which Peptide-1 showed the most favourable profile. Molecular docking and MST assays demonstrated that Peptide-1 had the lowest predicted binding free energy and the strongest binding affinity towards Aurora-A (Kd = 0.72 ± 0.04 μM). MD simulation, MM/PBSA, and free-energy landscape analyses indicated that the Aurora-A-Peptide-1 complex was conformationally stable and mainly driven by electrostatic interactions. MTT assays showed that Peptide-1 inhibited the proliferation of PC3, DU145, and NCI-H660 cells, with weaker activity in RWPE-1 cells. Aurora-A knockdown reduced cellular sensitivity to Peptide-1, supporting its target-dependent activity. qRT-PCR further showed increased p53 and p21 mRNA expression after Peptide-1 treatment in PC3/p53WT cells. These findings suggest that Peptide-1 may act as an Aurora-A-targeting peptide with antiproliferative activity in prostate cancer cells.

Extensive-stage small cell lung cancer (SCLC) carries a poor prognosis and has limited therapeutic options. The addition of immune-checkpoint inhibitors (ICIs) to platinum-etoposide (PE) chemotherapy has become an important first-line treatment strategy. However, the comparative benefits and harms of different first-line chemotherapy-based regimens, including ICI-containing combinations, remain unclear.

Platelets, traditionally recognized for their role in hemostasis, are now understood to actively contribute to tumor progression, angiogenesis, and metastasis. Through dynamic bidirectional interactions with cancer cells, platelets undergo measurable alterations in count, mean platelet volume, and molecular cargo, including proteins and mRNAs, supporting their potential utility as liquid biopsy biomarkers for early cancer detection. Within the tumor microenvironment, platelets contribute to immune evasion, support tumor cell intravasation and extravasation, enhance the survival of circulating tumor cells, and promote neovascularization. In addition, they can physically shield malignant cells from immune surveillance, thereby increasing metastatic potential. Although context-specific anti-tumor effects have been reported, the predominant evidence supports a largely pro-tumorigenic and pro-metastatic role for platelets. Elucidating the molecular mechanisms underlying platelet-tumor interactions is therefore essential for improving cancer risk stratification, prognostic evaluation, and therapeutic development. This review summarizes current advances in platelet-derived biomarkers and discusses emerging therapeutic strategies targeting platelet-mediated pathways to suppress metastasis and improve clinical outcomes in cancer patients.

SETD2-mediated H3K36me3 reprogramming is involved in homologous recombination (HR) repair; however, the dynamics of this repair process remain unclear. Here, we report that the scaffold protein menin, encoded by the Men1 gene, plays a crucial bridging role in H3K36-mediated HR repair. Genetic ablation of Men1 resulted in spontaneous lung carcinogenesis and was accompanied by severe genomic instability. Mechanistically, menin directly recognizes histone H2A.X via its Val371-Gln400 motif, and DNA damage markedly promotes the specific interaction between menin and γH2A.X. Subsequently, SETD2 is recruited to DNA damage sites by menin and acts as a writer to catalyze H3K36me3 reprogramming at local chromatin. LEDGF, as a reader, recognizes the H3K36me3 marker and further recruits CtIP as an effector to perform DNA end resection, ultimately activating the RPA2/Rad51 pathway. Restoring H3K36me3 via pharmacological intervention rescued impaired HR repair in Men1-deficient cells, further validating that menin governs HR repair in an H3K36me3-dependent manner. The results of the present study provide the detailed molecular mechanism underlying the previously described functions of H3K36me3 remodeling in HR repair.

The evolution of radical prostatectomy has resulted in excellent oncologic outcomes; however, postoperative erectile dysfunction remains a clinical constraint. While oncologic control in focal therapy remains its main limitation, Menon Precision Prostatectomy, also referred to as Millimeter Precision Prostatectomy (MPP) was developed to bridge this therapeutic gap. The purpose of this review is to summarize the rationale, development, and future direction of MPP.

We report the case of a 75-year-old man with conjunctival squamous cell carcinoma in his anophthalmic socket that had resulted from enucleation at age 5. He had a 6-week history of a palpable, right orbital mass and periocular pain. Examination revealed a right inferolateral orbital mass and keratinization of the inferior fornix. Magnetic resonance imaging revealed an extensive mass in the inferolateral orbit. Biopsy showed squamous cell carcinoma. The patient underwent exenteration with temporalis flap reconstruction followed by adjunctive radiotherapy. A metastasis to the right parotid was excised at 6 months. This case illustrates the potential for extensive orbital invasion and perineural spread by ocular surface squamous neoplasia in an anophthalmic socket despite minimal conjunctival signs.

Immune escape remains a major barrier to durable benefit from immunotherapy in breast cancer, particularly in immune-cold tumors and those with an immune-excluded architecture. Emerging evidence from cancer neuroscience suggests that nerves are not passive bystanders of the tumor microenvironment, but active regulators of stromal remodeling, myeloid polarization, T-cell dysfunction, metastatic adaptation, and neuroendocrine stress biology.

Immune checkpoint blockade (ICB) therapy has dramatically improved the survival outcomes of patients with locally advanced unresectable and metastatic non-small cell lung cancer (NSCLC). In particular, accumulated clinical trials and systematic reviews have further verified that induction ICB regimen following surgery confers superior benefits for IIIB-N3 NSCLC. Herein, we present a clinical case of a patient diagnosed with bulky contralateral mediastinal N3 (cT1bN3M0) left upper lung adenocarcinoma and devoid of actionable driver gene alterations. The patient achieved pathological complete response following anti-PD-1 treatment and subsequently underwent left upper lobectomy, followed by anti-PD-1 therapy for three consecutive years. To date, the patient has maintained a recurrence-free survival status for more than 5 years. Notably, we dynamically monitored the T-cell receptor (TCR) repertoire throughout the entire treatment course. Further analysis of TCR profiles revealed distinct dynamic patterns of certain specific T-cell clonotypes during treatment. These clonal alterations may help interpret sustained immune responses and warrant further exploration as candidate indicators for therapeutic outcome.

Chemoresistance and the immune-cold tumor microenvironment are major barriers to durable cancer control, yet they frequently emerge from overlapping mitochondrial adaptations selected by cytotoxic stress. In resistant tumors, mitochondria regulate oxidative phosphorylation (OXPHOS), redox buffering, apoptosis thresholds, organelle quality control, and metabolite overflow, while also shaping how antitumor immune cells experience nutrient deprivation, hypoxia, acidosis, and chronic danger signaling. Rather than assuming a single causal chain, this review distinguishes three non-equivalent relationships: direct suppression by mitochondria-derived signals, parallel emergence under shared selective pressures, and reverse causation in which immune exclusion itself facilitates mitochondrial adaptation. Within this framework, we synthesize evidence that mitochondrial adaptations support residual disease through OXPHOS dependence, mitochondrial dynamics, mitophagy, redox control, and metabolite-driven epigenetic remodeling, while concurrently reshaping T-cell, macrophage, and dendritic-cell function through lactate and acid stress, succinate, fumarate, 2-hydroxyglutarate (2-HG), adenosine, and mitochondrial DNA (mtDNA)-dependent innate immune signaling. We further highlight key determinants that influence whether mtDNA-STING signaling becomes immunogenic or suppressive, including timing, cell source, subcellular localization, and the dominant responding immune compartment. Finally, we discuss translational strategies to disrupt this mitochondria-immune interface, with emphasis on host and tumor heterogeneity, biomarker-guided selection, and treatment timing when combining with chemotherapy, mitochondrial targeting, and immunotherapy.

Ovarian cancer (OC) is the most lethal gynecological malignancy. A deeper insight into tumor microenvironment (TME) interactions is essential for developing novel therapeutic approaches. leukocyte immunoglobulin-like receptor B4 (LILRB4) is a receptor involved in multiple biological and pathological processes in hematological malignancies; however, its role in the progression of solid tumors remains largely unexplored. In particular, the function within the OC is still unclear.

Post-translational modifications (PTMs) are pivotal in tumor biology, yet their role in papillary thyroid cancer (PTC) remains unclear. We integrated bulk and single-cell transcriptomes with clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to analyze 17 PTMs and construct a prognostic model using 12 machine learning algorithms for predicting the thyroid cancer-free interval (TCFi). Enrichment analysis, single-cell analysis, and immune-related analysis were performed to elucidate the biological role of PTMs. Therapeutic responses of PTC patients were predicted based on the model. We validated the expression of model genes and identified the key signature associated with the malignant phenotypes of PTC. We filtered out 12 genes to construct a post-translational modification index (PTMI) and identified three molecular clusters of PTC. Shapley additive explanations (SHAP) and nomogram models confirmed the predictive efficacy of PTMI. Integrated analyses revealed significant associations between PTMI and immune features. High-PTMI patients showed sensitivity to FDA-approved drugs and chemotherapeutics but resistance to radioactive iodine therapy. Notably, we identified TYMS as a key functional PTMI signature. The PTMI proposed in this study holds strong potential as a prognostic biomarker and therapeutic predictor, offering valuable insights for personalized management of PTC patients.

CD73 is an enzyme that generates extracellular adenosine and has been implicated in tumor-associated immune suppression, but its biological and clinical significance in pancreatic ductal adenocarcinoma (PDAC) remains incompletely understood. We investigated the prognostic relevance and biological functions of CD73 in PDAC using transcriptomic analyses, in vitro functional assays, and in vivo mouse models. Transcriptomic analyses consistently showed that CD73 expression was correlated with hypoxia, glycolysis related, and cell-cycle programs. In agreement with these findings, hypoxic exposure induced CD73 mRNA expression in a subset of PDAC cell lines, and CD73 knockdown modestly affected glycolysis related extracellular acidification (ECAR) in a cell line dependent manner, and modulation of CD73 expression altered PDAC cell growth. CD73 expression was also associated with reduced intratumoral CD8+ T cell infiltration and cytolytic activity in human PDAC cohorts. In vivo, CD73 overexpression accelerated cancer progression and shortened survival in immunocompetent mice, whereas this effect was abrogated in immunodeficient NSG mice. Flow cytometric analysis further demonstrated reduced intratumoral CD8+ T cell infiltration in CD73 overexpressing tumors. Clinically, high CD73 expression was consistently associated with worse survival in multiple PDAC cohorts. Collectively, these findings suggest that CD73 is associated with multiple features of PDAC progression, including hypoxia-related metabolic programs, tumor growth, and suppression of anti-tumor immunity. CD73 may therefore represent a biologically relevant biomarker and a potential therapeutic target in PDAC.