The ARTSCAN 2 randomised controlled trial compares accelerated fractionation (AF) radiotherapy (RT) in a preoperative setting with conventional fractionation (CF) RT postoperatively for oral cavity cancer (OCC). Current results indicate no advantage for preoperative AF RT, thereby reinforcing postoperative CF RT as the "gold standard" of care. This analysis of the trial focuses on health-related quality of life (HRQoL) and conducts a health-economic evaluation from a societal perspective.

240 patients formed the intention-to-treat population. Preoperative AF RT was given twice daily during 4.5 weeks to a total dose of 68 Gy followed by surgery 4-6 weeks later. Postoperative CF RT was given to a total dose of 60 or 66 Gy during 6-7 weeks. In the per protocol population, HRQoL was assessed with the EORTC QLQ-C30, QLQ-H&N35, and HADS questionnaires at five occasions during the five-year follow-up period. Direct and indirect costs were retrieved, and a cost-utility analysis (CUA) was conducted using quality-adjusted life years (QALYs) as outcome measure.

HRQoL was analysed in 218 patients (i.e., the per-protocol population), of whom 204 were included in the CUA. Up until two years after treatment, the preoperative AF RT-group featured significantly worse HRQoL in a few of the QLQ-H&N35 scales compared to the postoperative CF RT-group. In the CUA, preoperative AF RT was less effective and more expensive than postoperative CF RT.

Postoperative CF RT is associated with fewer symptoms in selected head-and-neck-specific domains and is more cost-effective than preoperative AF RT in the treatment of OCC.

Plasticity, the capability of tumor cells to go through phenotypic transitions, promotes colorectal cancer (CRC) progression and treatment resistance. Although plasticity is evident in advanced CRCs, little is known about plasticity in early-stage tumors and tumor stem cells. Here, we demonstrate that a plastic cell state (PCS) is present already in polyps from patients with familial adenomatous polyposis and in mouse intestinal adenomas, in which PCS is associated with PROX1⁺ tumor stem cells. We furthermore analyzed progressive plasticity upon loss of the canonical wingless-related integration site (Wnt) effector Tcf7 or Lef1 in Apc mutant mice. Deletion of either gene led to emergence of new plastic tumor cell populations, failure of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) tumor stem cell differentiation into enterocyte-like cells, enhanced Myc pathway activation, and increased tumor cell proliferation and tumorigenesis. Together, we demonstrate that PCS is associated with early CRC development and identify multiple potentially druggable mechanisms activated during progressive tumor cell plasticity.

Humoral immunity, mediated by B cells that mature in germinal centers in lymph nodes (LNs), is essential for adaptive immune responses, but its role in antitumor immunity and responses to immunotherapy remain unclear. Here, we show that activation of B cells in tumor-draining deep cervical LNs (dcLNs) is necessary for the efficacy of CTLA-4 (cytotoxic T lymphocyte-associated protein 4) immune checkpoint blockade in glioma in vivo. Anti-CTLA-4 therapy enhanced T follicular helper cell (T_FH cell) expansion in dcLNs, leading to germinal center B cell responses, immunoglobulin G (IgG) class switching, and the generation of glioma-reactive antibodies. Glioma-bearing mice lacking antibody-secreting cells did not benefit from CTLA-4 blockade. Distally secreted IgG accumulated in the tumor microenvironment and promoted glioma cell phagocytosis in vivo. These findings define a B cell-dependent mechanism underlying CTLA-4-mediated control of glioma and provide a conceptual framework for future therapeutic strategies in tumor.

Accurate segmentation and classification of lung nodules in computed tomography (CT) scans remains a critical challenge in early lung cancer detection within distributed healthcare Internet of Things (IoT) environments. This paper presents a novel two-stage framework called Adaptive Geometric-Attention Network (AGA-Net) that integrates geometric constraints with multi-scale attention mechanisms for precise nodule segmentation followed by uncertainty-aware malignancy classification in federated learning scenarios. Unlike existing approaches that rely on traditional convolutional architectures, our method introduces a Geometric-Constrained Attention Module (GCAM) that leverages the spherical nature of lung nodules and a Multi-Scale Uncertainty Quantification Network (MUQ-Net) for robust classification under privacy-preserving constraints. The proposed framework demonstrates superior performance across three benchmark datasets: LUNA16, LIDC-IDRI, and NSCLC-Radiomics, achieving a Dice coefficient of 0.927 for segmentation and AUC of 0.951 for malignancy classification while maintaining computational efficiency validated on IoT-class edge hardware including the NVIDIA Jetson AGX Orin and Jetson Orin Nano. The integration of geometric priors with attention mechanisms, uncertainty quantification, and federated learning capabilities provides both high accuracy and clinical interpretability, making it suitable for next-generation computer-aided diagnosis systems deployable on healthcare IoT edge devices.

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary tumor of the central nervous system. MicroRNAs (miRNAs) are key post transcriptional regulators of gene expression, and increasing evidence suggests that miRNA relationships may contribute to regulatory complexity in cancer biology. In this study, we combined in silico analyses of ten independent miRNA expression datasets (TCGA and GEO) with functional validation in GBM cell models to investigate the association between miR-132 and miR-21 in GBM. Differential expression analysis consistently demonstrated significant overexpression of miR-21-5p and downregulation of miR-132-3p in GBM tissues compared with normal brain. These findings were validated in U87 and C6 GBM cell lines using qRT-PCR, confirming consistent dysregulation of both miRNAs in vitro (p < 0.05). Functional experiments demonstrated that miR-132 overexpression is associated with reduced miR-21 expression and increased expression of established miR-21 target genes, including BMPR2 and BCL11B at both mRNA and protein levels. These molecular changes were accompanied by reduced metabolic activity, impaired wound closure, and increased apoptotic cell death in both U87 and C6 GBM models. Collectively, these findings support a strong functional association between miR-132 expression and miR-21 related regulatory networks and phenotypic changes in GBM. However, the present study does not provide evidence for a direct physical or fundamental interaction between miR-132 and miR-21. Further mechanistic studies, including rescue experiments and direct binding assays, are required to clarify the underlying regulatory mechanisms.

Lung cancer is one of the leading causes of cancer-related deaths globally, with smoking being the primary risk factor, though environmental exposures and genetic mutations also play significant roles. Lung cancer arises when abnormal lung cells grow uncontrollably, leading to over 2 million new cases and nearly 1.8 million deaths globally. Drug resistance, especially to targeted therapies, is a key challenge, as tumours often adapt and become unresponsive. Multitargeted drug design, which targets multiple pathways involved in tumour growth, offers a promising solution to overcome resistance and improve treatment efficacy. In this study, we identified several lung cancer-associated proteins: CK2, Ran-Importin β complex, HNGF, Human Survivin, CRK-II adaptor protein, AKR1B10, and tRNA dihydrouridine synthase 2, with respective PDB IDs 1JWH, 1IBR, 1SG1, 1XOX, 2DVJ, 4XZL, and 4XP7. We conducted molecular docking using DrugBank's library, employing HTVS, SP, and XP, followed by pose processing with MM/GBSA. Our multitarget docking analysis identified Quercetin-3-O-Phosphate as the top compound, a quercetin derivative found in fruits and vegetables such as onions, apples, berries, broccoli, and citrus. The compound showed docking and MM/GBSA scores ranging from -5.835 to -11.627 Kcal/mol and -14.28 to -47.07 Kcal/mol, respectively, and the key interacting residues with their counts include 10ASP, 9LEU, 9LYS, 7ALA, 7ARG, 7TYR, 6GLN, 5ASN, 5GLU, 5ILE, and 5VAL. We also performed and analysed DFT and pharmacokinetics in detail, which supported its further evaluation as it met all the required criteria. We conducted a 5 ns WaterMap simulation, which confirmed the interactions and highlighted key hydration sites that support the complex's stability. A 100 ns MD simulation using the TIP3P water model showed minimal deviation and fluctuations, indicating stable interactions and the trajectories used for MM/GBSA calculations, assessing binding free, which reinforced the stability of the complexes and helped rank the best candidates. All results indicate that Quercetin-3-O-Phosphate holds strong potential for lung cancer treatment, though experimental validation is needed for clinical confirmation.

Metastasis is a major determinant of treatment failure and mortality in thyroid cancer, yet the interplay between malignant evolution and the immune microenvironment remains poorly characterized. Immunotherapy offers promise, but its efficacy requires a deeper understanding of tumor-associated immune infiltration and checkpoint regulation. In this study, we constructed a high-resolution transcriptomic atlas of the thyroid cancer ecosystem by analyzing 55,005 single cells from paired primary tumors and lymph node metastases. By integrating chromosomal copy number variation (CNV) inference with consensus nonnegative matrix factorization (cNMF), we deciphered the intrinsic heterogeneity of malignant epithelial cells, revealing distinct transcriptional programs and developmental trajectories driving the metastatic cascade. The metastatic niche exhibited significant reprogramming of the immunosuppressive landscape, characterized by the enrichment of FOXP3⁺ regulatory T (Treg) cells, LAMP3⁺ dendritic cells (DCs), and CCL18⁺ M2-like macrophages. Notably, while canonical checkpoints PD-1 and PD-L1/2 showed minimal expression, ligand-receptor interaction analysis identified the LAG3-LGALS3 axes as dominant immune evasion pathways mediating the crosstalk between CD8⁺ T cells and the tumor stroma. In conclusion, this study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche. By uncovering the specific role of LAMP3⁺ DCs and identifying LAG3/TIGIT as critical alternative checkpoints, our findings challenge the utility of conventional PD-1 blockade in this context and provide a robust molecular rationale for developing next-generation immunotherapeutic strategies tailored to thyroid cancer. Although limited by a modest sample size, these findings provide a foundation for further investigation of the metastatic immune landscape in thyroid cancer.

With fifteen agents now FDA-approved and indications expanding into earlier treatment lines, antibody-drug conjugates (ADCs) represent a rapidly growing class of targeted cancer therapeutics. Despite their selective mechanism of action, infectious complications are clinically significant and have been flagged as a disproportionate safety signal in post-marketing surveillance. This review characterizes the infection risk profiles of all fifteen FDA-approved ADCs through systematic extraction of prescribing information and pivotal trial safety data, and examines the pathophysiological mechanisms, antigen-specific clinical patterns, and evidence-based prophylaxis strategies applicable to this class.

Calicheamicin-based agents carry the highest infection burden, with grade ≥ 3 infection rates exceeding 30-47% and near-universal severe neutropenia. CD30- and CD79b-targeting vedotin conjugates are associated with opportunistic infections-including progressive multifocal leukoencephalopathy and Pneumocystis jirovecii pneumonia-through mechanisms beyond myelosuppression, particularly T-cell immune surveillance disruption and bystander-effect lymphotoxicity. Solid tumor ADCs demonstrate lower overall infection rates with distinct organ-specific patterns: genitourinary infections predominate with Nectin-4- and Tissue Factor-directed agents, whereas pulmonary events characterize HER2- and c-Met-targeted conjugates. Linker cleavability, drug-to-antibody ratio, and payload metabolism are identified as key pharmacological determinants of myelosuppressive and infectious risk. Infectious complications of ADC therapy are clinically significant but heterogeneous, with risk profiles primarily determined by target antigen, immunologic context, and concurrent treatment. These findings support the growing adoption of a combined prevention strategy incorporating disease-based risk stratification and drug-directed infection prophylaxis.

The pathogenesis of radiation pneumonitis (RP) is complex, involving multiple genetic and molecular factors. Single-nucleotide polymorphisms (SNPs) at specific microRNA gene loci can influence miRNA expression, even affect disease progression. Genotype distribution of rs1347093 in RP and non-RP groups was analyzed, and the underlying mechanism was explored in human pulmonary microvascular endothelial cells (HPMECs). TaqMan SNP genotyping assay was used to complete the genotyping in 545 subjects with lung cancer, of whom 260 had RP and 285 did not. HPMECs were exposed to 15 Gy of X-rays to mimic RP in vitro. mRNA levels were measured via RT-qPCR, while cell apoptosis was assessed via flow cytometry assay. Targeting relationship between the miRNA and the gene was ensured via dual luciferase reporter and RIP assay. The composition ratio of rs1347093 CA genotype carriers in RP group exhibited a significant increase in relation to the non-RP group. The risk of developing pneumonia was 1.827 times higher among CA carriers than CC genotype carriers. Rs1347093 CA/AA genotype remained significantly positively associated with RP risk after controlling for confounding factors. The expression of miR-216a-5p in RP patients exhibited genotype-specific expression patterns, with a significant decrease detected in CA/AA genotype carriers. In HPMECs, miR-216a-5p overexpression attenuated X-ray-mediated apoptosis and ICAM-1 release by targeting and sequestering TGFβR2. Rs1347093 may be a potential genetic marker for susceptibility to RP. It may affect the inflammatory imbalance in RP patients by regulating miR-216a-5p expression.

Germline pathogenic variants (PVs) in POT1, one of the shelterin complex genes, correlate with tumor predisposition, primarily with melanoma, hematologic malignancies, sarcoma, papillary thyroid carcinoma and glioma. Breast cancer (BC) risk has not been shown to be elevated. We analyzed BC occurrence and features in a cohort of 29 female PV heterozygotes, of whom 13/29 (45%) were diagnosed with BC. Data regarding genetic, clinical, pathologic, treatment, and outcome characteristics were extracted. Patients in our cohort harbored three different POT1 PVs; The c.233T > C Ashkenazi founder PV occurred in 11/13 (84.6%). Median age at first BC diagnosis was 54 years (range 44-72); no patient was diagnosed before the age of 40. Pathological subtypes varied; invasive ductal carcinoma was the most common. All primary tumors were estrogen receptor positive; one was HER2-enriched; no triple-negative cancers were observed. Stage at diagnosis varied: 6 of 10 tumors with known staging were stage 0 or I, and one patient presented with metastatic disease. Treatment approaches were diverse as clinically appropriate. After a median follow-up of 110 months, three second BC events occurred, with no BC-related mortality. Personal and family history of other malignancies were frequent. This is the first dedicated report describing BC phenotypes in POT1 PV heterozygotes. Our findings suggest that enhanced BC surveillance may be warranted in this population. Larger cohorts are needed to further characterize the clinicopathological features of BC in POT1 carriers, to define lifetime BC risk and determine whether BC-specific screening recommendations should be established for this group.