At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, once again, only a small number of presentations focused primarily on surgery. Nevertheless, surgical questions could be seen to be becoming increasingly important within perioperative multimodal treatment concepts. The most relevant contributions were secondary analyses of the phase III KEYNOTE-689 and NIVOPOSTOP trials. These data showed that, despite a higher rate of documented R0 resection and a lower frequency of pathological high-risk features after neoadjuvant immunotherapy, no reduction in the extent of resection could yet be justified and that oncologically indicated neck dissection should not be limited when postoperative immunotherapy was planned. Randomised data on adjuvant radiotherapy after adequately performed surgery for pT1-2 pN0 oral cavity cancer further emphasised the importance of clearly defined surgical quality criteria. New data on mandibular, laryngeal and pharyngeal preservation after neoadjuvant treatment reported high rates of R0 resection and organ preservation. However, small cohorts, the absence of control groups and insufficiently standardised indications for surgery preclude changes in clinical practice. Histological analyses demonstrated heterogeneous regression patterns with residual tumour islands after neoadjuvant immunotherapy and argued against reducing surgical margins solely based on radiological response. Ongoing randomised trials of neck dissection, sentinel lymph node biopsy and salvage surgery were still recruiting.

In adolescent girls and young women (AGYW), cervical cancer screening is not recommended as it offers little benefit and may cause harm. We describe temporal trends in cervical cancer overscreening among AGYW and examine its potential clinical drivers over time.

Using 2011-2023 National Survey of Family Growth on AGYW aged 15-20 years (n = 5,375), we examined temporal trends in the prevalence of cervical cancer overscreening, defined as receipt of a Papanicolaou test or human papillomavirus test in the past 12 months as part of a routine exam. We estimated risk ratios (RRs) and differences (RD) for potential clinical drivers of overscreening, including past guideline indications (e.g., sexual history, human immunodeficiency virus [HIV] testing) and cooccurring clinical situations (e.g., sexually transmitted infection [STI] testing).

From 2011 to 2023, the prevalence of cervical cancer overscreening declined from 22.1% to 4.5%. For a history of sexual intercourse, both the RR [95% confidence interval] (4.25 [1.62, 6.89]) and RD (24.37 [16.24, 32.50]%) decreased over time, but the RD remained statistically significant in 2022-2023 (5.89 [0.93, 10.66]). For HIV testing, neither the RR (1.16 [0.37, 1.96]) nor RD (1.83 [-6.54, 10.20]) were statistically significant in 2022-2023. For STI testing, however, the RD increased from 10.47 (-1.43, 22.37)% in 2011-2013 to 27.63 (6.63, 48.64)% in 2022-2023.

Cervical cancer overscreening among AGYW declined substantially since 2011. However, overscreening remains more prevalent among AGYW with a history of sexual intercourse and STI testing, underscoring the need to ensure evidence-based cervical cancer screening for AGYW.

Cuproptosis is a type of cell death that depends on the energy production process inside cells, and it is important in cancer treatment. This study aimed to identify cuproptosis-associated genes in triple-negative breast cancer (TNBC) and reveal regulatory pathways. We applied weighted gene co-expression network analysis to screen gene expression data from TNBC patients. Cuproptosis-associated genes were identified at the intersection of the co-expression modules and the cuproptosis gene dataset. G protein-coupled receptor 68 (GPR68) was identified as a cuproptosis-associated gene that is highly expressed in TNBC cells. Knockdown of GPR68 inhibited TNBC cell growth, migration, and invasion. The knockdown of GPR68 enhanced cuproptosis in TNBC cells when stimulated with ES-Cu, leading to an accumulation of cellular copper. This effect was reversed by the copper chelator tetrathiomolybdate. Correlation analysis verified that GPR68 regulates glutaminase (GLS) expression in TNBC cells. GLS knockdown reversed the promoted role of GPR68 in TNBC progression and the inhibitory role of GPR68 in TNBC cell cuproptosis. We further investigated the role of GPR68 in TNBC through pathway enrichment analysis, which revealed significant enrichment in the mitogen-activated protein kinase (MAPK) signaling pathway. GPR68 overexpression increased the levels of ERK phosphorylation. The ERK signaling pathway inhibitor, Trametinib, blocked the effects of GPR68 on TNBC progression and cuproptosis. GPR68 knockdown hindered TNBC development and induced cell cuproptosis by regulating the MEK/ERK signaling pathway, which is linked to GLS. This study provides new insights into developing cuproptosis targets for TNBC treatment.

Artificial intelligence-assisted virtual screening enables identification of chemically diverse bioactive small molecules. We targeted transglutaminase 2 (TG2), a multifunctional protein associated with mesenchymal-like features in breast cancer. Approximately 10 million compounds were screened against the catalytic site of open TG2 using the AtomNet structure-based deep-learning model. The top 30,000 candidates underwent physicochemical and structural filtering, diversity clustering, and manual selection, yielding 84 compounds for experimental evaluation. Fourteen induced apoptosis in MCF-7, eight retained activity in MDA-MB-436, and three in MDA-MB-231 cells, also reducing transamidase activity in cellular lysates. Chemical-space and fingerprint analyses placed C10, C12, and G11 outside the principal clusters of known active TG2 inhibitors, identifying structurally differentiated, nonpeptidic scaffolds. Docking into open and intermediate TG2 conformations consistently ranked G11 as the most favorable candidate, with predicted binding near the catalytic core. In a 5-(biotinamido)pentylamine (5-BAP-based assay, G11 inhibited purified recombinant human TG2 with an IC₅₀ of 7.64 ± 2.87 μM, while an independent dimethyl casein-dansyl cadaverine assay confirmed concentration-dependent inhibition and yielded an estimated K_i of 44 ± 11 μM, assuming competitive inhibition with respect to the substrate. Finally, G11 did not significantly affect the viability of HEK293 cells, which express negligible or very low levels of TG2.

Primary Burkitt lymphoma (BL) of the maxillary sinus is rare, particularly in immunocompetent adults, and only a few cases have been reported in the literature. Its clinical presentation may mimic benign conditions, such as chronic rhinosinusitis or neuropathic facial pain, potentially resulting in diagnostic delay. We present the case of a 38-year-old male with a five-month history of isolated left-sided facial pain. Comprehensive clinical, radiological, and histopathological evaluation established the diagnosis of BL, and the patient subsequently received systemic chemotherapy. This case highlights the importance of considering BL in the differential diagnosis of persistent or atypical sinonasal symptoms, particularly those unresponsive to empirical treatment. Prompt biopsy and histopathological and immunohistochemical evaluation are essential for establishing the diagnosis and initiating appropriate treatment without delay.

Unsupervised anomaly detection in histopathological images has been widely explored using reconstruction-based approaches that measure reconstruction errors, yet these methods often fail to capture subtle, semantic-level pathological variations due to the inherent heterogeneity of tissue textures. To address this limitation, this study presents RareCode, a vector quantization-based framework that extends the detection paradigm beyond pixel-level reconstruction to incorporate semantic-level codebook activation analysis. The core innovation is Codebook Activation Rarity (CAR) scoring, which profiles the activation frequency of each codebook entry during training on exclusively normal samples and flags infrequent activations as anomaly indicators at inference time, thereby complementing reconstruction errors with semantic-level discrimination. Building upon this single-scale CAR mechanism, a Multi-scale Hierarchical Codebook (MHC) module is further introduced, employing codebooks of varying sizes with learnable fusion weights to capture pathological patterns spanning from coarse tissue-level structures to fine cellular-level details. Leveraging the multi-scale design, hierarchical anomaly heatmaps are generated at each codebook granularity, providing pathologists with interpretable, multi-dimensional visual localization cues indicating both where and at what structural level anomalies occur. Five-fold cross-validation on a clinically annotated colorectal cancer histopathological image dataset obtained from Shenzhen People's Hospital demonstrates that RareCode achieves an area under the curve (AUC) of 96.82%, outperforming baseline methods. Per-class analysis showed stronger performance for cancer detection (AUC = 99.44%, specificity = 94.21%) than for inflammation detection (AUC = 94.30%, specificity = 60.44%). These findings suggest that CAR analysis may offer a promising unsupervised approach for histopathological anomaly detection, potentially aiding clinical pre-screening in colorectal cancer diagnosis.

Local recurrence after surgery remains a major clinical challenge in patients with T3 and T4 non-small cell lung cancer (NSCLC). To address the lack of a standardized preoperative imaging-based strategy for characterizing local recurrence, a computed tomography (CT)-based radiomic framework is presented to capture intratumoral and peritumoral heterogeneity and differentiate local recurrence from distant metastasis after R0 resection. The proposed protocol integrates radiomic features extracted from tumor and peritumoral regions on preoperative contrast-enhanced CT images. The application cohort comprised 103 patients with pathologically confirmed T3-T4, N0-2, M0 NSCLC who underwent surgery with R0 resection between January 2013 and December 2020. 33 developed local recurrence, and 70 developed distant metastasis. All preprocessing, feature selection, normalization, hyperparameter tuning, model fitting, and threshold determination were restricted to the training cohort. Tumor-only, peritumoral, and combined radiomic models were evaluated in a held-out validation cohort. Clinical characteristics, tumor location, preoperative laboratory parameters, and treatment information were collected. Tumor-specific and tumor-peritumoral combined radiomic representations were constructed and evaluated to characterize the behavior of the proposed framework. In the validation cohort, the peritumoral radiomic representation demonstrated improved discrimination compared with tumor-only features, while the combined tumor-peritumoral framework showed the most stable and consistent performance (AUC = 0.80). This protocol is a preliminary demonstration of a standardized CT radiomics workflow for differentiating postoperative failure patterns after R0 resection; multicenter external validation is required before clinical implementation.

Chordoma is a rare malignant bone tumor with an annual incidence of approximately 0.08 per 100,000 individuals according to the Surveillance, Epidemiology, and End Results (SEER) database, and intracranial chordoma accounts for approximately one-third of all chordoma cases. Its rarity has limited understanding of the disease, particularly of uncommon pathological subtypes, and no universal consensus has been established regarding pathological classification and optimal treatment strategies. Intracranial chordoma is also characterized by difficulty in achieving gross total resection, resistance to conventional radiotherapy and chemotherapy, and a high recurrence rate, which complicate clinical management. This narrative review synthesizes clinical studies and translational research addressing the pathological classification and treatment of intracranial chordoma, with emphasis on surgical approaches, radiotherapy, and targeted therapies. More detailed characterization of pathological subtypes, together with developments in neuroendoscopic surgery, proton beam therapy, carbon ion radiotherapy, and molecularly targeted treatment, has expanded the available approaches to disease classification and management. Evaluation of these developments provides an updated overview of current strategies and remaining challenges in the diagnosis and treatment of intracranial chordoma.

The incidence of colorectal cancer (CRC) has been on the rise in recent years. We explored the clinical significance and molecular mechanisms of miR-1298 in CRC. A total of 85 patients with CRC were enrolled. All gene levels were evaluated by RT-qPCR. In CRC cells, the levels of miR-1298 and bone morphogenetic protein 7 (BMP7) were regulated using cell transfection. The target of miR-1298 was predicted using bioinformatics analysis and was identified by the dual-luciferase reporter system. CRC cell function was assessed utilizing the CCK-8 assay, the Transwell assay, and flow cytometry. The correlation between miR-1298 and BMP7 in CRC tissues was analyzed utilizing Pearson's correlation. miR-1298 was substantially downregulated in CRC and was associated with malignant clinicopathological features. In CRC cells, miR-1298 suppressed proliferation, migration, and invasion, and elevated apoptosis. BMP7 was a downstream target of miR-1298 and was negatively correlated with miR-1298. Overexpression of BMP7 partially reversed the suppressive effect of miR-1298 on proliferation, migration, and invasion in CRC cells, as well as its promotion of apoptosis. miR-1298 was related to invasion and migration and may suppress the progression of CRC. BMP7 may be a potential functional mediator of miR-1298 in CRC.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly important cause of hepatocellular carcinoma (HCC). Fibrosis and cirrhosis remain the best-validated predictors of HCC, yet a substantial minority of MASLD-related tumors are diagnosed without cirrhosis. This narrative review evaluates what 'beyond fibrosis' should mean for risk assessment rather than treating fibrosis as dispensable. We first separate the proportion of HCC cases that are noncirrhotic from the much lower absolute incidence of HCC in the noncirrhotic MASLD population. We then synthesize human, animal, and in vitro evidence for lipotoxic and oxidative injury, insulin and insulin-like growth factor signaling, gut-liver communication, and immune remodeling. We distinguish plausible mechanistic drivers from clinical risk modifiers, future-risk biomarkers, early detection tests, and disease-modifying interventions. Current evidence supports fibrosis-centered, layered risk stratification using clinical factors and noninvasive fibrosis measures, whereas genetic, proteomic, microbial, and immune markers remain investigational. Resmetirom and semaglutide improve MASH histology in selected noncirrhotic patients with F2-F3 fibrosis; evidence for direct HCC prevention by metabolic drugs or bariatric surgery remains observational or absent. Routine surveillance is not justified for MASLD without advanced fibrosis, but individualized evaluation in F3 disease and prospective validation of multivariable risk models are priorities.