Frontiers in Oncology最新文献

Locally advanced solid tumors, characterized by complex involvement or encasement of major vascular structures, present a significant challenge in curative oncology. Achieving microscopically negative margins often mandates extensive surgical procedures, collectively termed Oncovascular Surgery (OVS). While OVS successfully addresses the anatomical barrier to resection, the resulting surgical trauma is intrinsically linked to an acute systemic release of pro-angiogenic factors, frequently correlating with accelerated tumor recurrence and metastatic potential. Novel Vascular Targeting Agents (VTAs) offer critical pharmacological control over the tumor vasculature. These agents are categorized primarily into Anti-Angiogenic Agents (AIAs), which inhibit new vessel growth, and Vascular Disrupting Agents (VDAs), which induce rapid collapse of established tumor blood vessels. The clinical integration of mechanical clearance (OVS) with strategic pharmacological control (VTA administration) is highly complex, demanding precise timing and toxicity management. This review synthesizes the molecular mechanisms underpinning VTA function and selectivity, details the technical necessity and consequences of OVS, and critically evaluates the biological interface including mechanisms of resistance and the systemic post-surgical angiogenic surge to establish a unified translational strategy for synergistic combination regimens.

Objectives: To investigate the feasibility analysis of predicting the pathological differentiation grade of breast invasive ductal carcinoma based on DCE-MRI imaging histology.

Methodology: 198 patients with breast invasive ductal carcinoma who underwent preoperative enhanced MRI were retrospectively collected from January 2019 to October 2024.According to Nottingham histologic grading, 108 cases were divided into a high-grade group and 90 cases into an intermediate-low-grade group, which were randomly divided into 148 cases of the training group and 50 cases of the validation group according to a 3:1 ratio. The 3D slicer software was applied to extract the image histological features of the region of interest, and five models, namely, decision tree, Gaussian plain Bayes, logistic regression, random forest, and AdaBoost, were constructed by filtering the features with intragroup correlation coefficients and the minimum absolute contraction and selection operators. Compare the area under the work characteristic curve of subjects in the validation group and select the best model. The performance of the best model validation group was evaluated, the clinical usability of the best model was examined using decision curves, and the accuracy of the predictive model was visualized using calibration curves.

Results: After rigorous stability and redundancy screening, 22 key radiomics features were selected from DCE-MRI images. Multiple machine learning models trained based on these features were evaluated for their predictive performance on the validation set. The logistic regression model achieved the highest AUC value of 0.795 (95% confidence interval: 0.664-0.927), outperforming other models such as random forest (AUC = 0.700), Gaussian naive Bayes (AUC = 0.700), AdaBoost (AUC = 0.718), and decision tree (AUC = 0.587). Consequently, the logistic regression model was ultimately selected as the optimal model.

Conclusion: The DCE-MRI radiomics model based on Logistic Regression can non-invasively and effectively predict the histological grade of IDC preoperatively, offering valuable potential for supporting individualized clinical decision-making.

Introduction: Smoking is the primary risk factor for lung cancer, and 37% - 42% of patients with non-small-cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) mutation being smokers. Nevertheless, the specific impact of smoking on prognosis in patients with unresectable stage III ALK-positive NSCLC remains to be elucidated.

Method: This two-centric, retrospective cohort study included 48 patients with unresectable stage III ALK-positive NSCLC. Gene ontology (GO) enrichment analysis was conducted on data from 25 patients who underwent NGS. We further performed Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to validate these findings, using the GSE31852 dataset (n = 34) patients from the Gene Expression Omnibus (GEO) database.

Results: In these 48 patients, the median age was 55.2 (range, 33-80) years; approximately half of the patients were men (50.0%) and smokers (45.8%); 62.5% patients had IIIB stage disease; 33.3% patients initially received chemoradiation therapy (CRT). After a median follow-up of 49.02 (interquartile range [IQR], 35.84 - 62.03) months, CRT significantly improved the locoregional-free survival (LRFS, P = 0.012). Univariate and multivariate Cox regression analysis suggested that smoking was independent prognostic factors for poorer OS (univariate HR = 3.01, P = 0.049; multivariate HR = 3.92, P = 0.023). Compared with never-smokers, smokers exhibited a significantly inferior 5-year OS (51.9% vs. 78.9%, Log-rank P = 0.038). GO analysis revealed distinct biological processes and cell components between never-smokers and smokers. Validation in the GSE31852 dataset subsequently confirmed these findings and further highlighted the significant differences in immune cell regulation, including immune cell infiltration, differentiation, and interactions between never-smokers and smokers.

Conclusions: In patients with unresectable stage III ALK-positive NSCLC, CRT improved the disease control. Smokers exhibited a significantly poorer OS and DMFS, and may require more risk-adapted treatment strategies, such as the combination of CRT with upfront ALK TKIs. These findings suggest that smoking may adversely affect survival by modulating the tumor immune microenvironment.

Objective: This study aims to compare the effects of left and right thoracic approaches on patients undergoing esophagectomy.

Methods: A search was conducted across PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials, cohort studies, and non-randomized trials that evaluated the effects of the two approaches on patients with esophageal cancer up to March 19, 2025. Two reviewers independently screened the retrieved articles, extracted relevant data, and appraised the risk of bias. A meta-analysis was performed using Stata statistical software.

Results: A total of 21 studies were included. Compared with the left thoracic approach, the right approach had a longer surgical duration (mean difference [MD] = 77.51, 95% confidence interval [CI]: 53.19-101.84, P < 0.05), a higher number of lymph nodes removed (MD = 3.00, 95% CI: 0.30-5.69, P < 0.05), and a higher risk of anastomotic fistula (MD = 2.07, 95% CI: 1.49-2.88, P < 0.05), wound infection (MD = 1.68, 95% CI: 1.04-2.73, P < 0.05) and pulmonary complications (risk ratio = 1.39, 95% CI: 1.15-1.68, P < 0.01). There were no significant differences in the risk of chylothorax, postoperative hospital stays, long-term disease-free survival, or overall survival.

Conclusion: Esophagectomy through the right thoracic approach achieves more thorough lymph node dissection, but it is associated with an increased risk of longer surgical duration, anastomotic fistula, wound infection, and pulmonary complications.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251026319, identifier CRD420251026319.

Objective: To evaluate the necessity of postmastectomy radiotherapy (PMRT) in patients with T1-2N1M0 breast cancer who did not receive neoadjuvant therapy, by assessing its impact on locoregional recurrence (LRR) and overall survival (OS) in the context of contemporary systemic therapies. This meta-analysis aims to provide updated evidence on whether PMRT can be omitted in this specific population.

Methods: Statistical analysis was conducted using Review Manager version 5.4 software, as recommended by the Cochrane Collaboration. HR for LRR and OS were pooled between the PMRT and no-PMRT groups. A fixed-effects model was primarily used, with a random-effects model applied if heterogeneity (I² > 50%) was detected. Bias risk in the included studies was assessed using the Newcastle-Ottawa Scale, and publication bias was evaluated through funnel plot analysis.

Results: In patients with T1-2N1M0 breast cancer, PMRT significantly reduced the risk of LRR (pooled HR = 0.35, 95% CI: 0.23-0.53; p<0.001) and improved OS (pooled HR = 0.65, 95% CI: 0.61-0.69; p<0.001). Subgroup analyses showed consistent benefit for LRR reduction at 5 years (HR = 0.45, 95% CI: 0.35-0.56) and 10 years (HR = 0.33, 95% CI: 0.19-0.57; interaction p=0.33). For OS, a significant 5-year survival improvement was observed (HR = 0.63, 95% CI: 0.59-0.67; p<0.001), but the 10-year benefit was non-significant (HR = 0.80, 95% CI: 0.60-1.07; p=0.14).

Conclusions: This meta-analysis supports the use of postmastectomy radiotherapy in T1-2N1M0 breast cancer patients, demonstrating its significant reduction in LRR and improvement in OS. Future research should integrate molecular subtypes and dynamic risk models to optimize treatment decisions within contemporary systemic therapy frameworks, and prospective studies are needed to assess the long-term safety of PMRT omission in certain subgroups.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261287168, identifier CRD420261287168.

Introduction: Liquid-Liquid Phase Separation (LLPS), tumor microenvironment (TME), and long non-coding RNA (lncRNA) all have varying degrees of influence on the expression regulation of tumors. However, research on the association of these three in pancreatic cancer (PC) still requires further exploration. This study seeks to establish the relationships among these three themes through bioinformatics and to identify biomarkers that can predict the prognosis of PC patients.

Methods: Data sets from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) are obtained from the UCSC platform. lncRNAs associated with the LLPS and TME gene sets are screened, and model lncRNAs are identified through comprehensive analysis conducted with least absolute shrinkage and selection operator (LASSO) regression and cox proportional hazards (COX) regression. Additionally, the predictive efficacy of the model lncRNAs is validated through multiple databases and cohorts. Furthermore, the expression of the model lncRNAs is validated at a biological level.

Results: A comprehensive analysis establishes an optimal combination consisting of 5 lncRNAs. The Kaplan-Meier curves and receiver operating characteristic (ROC) curves for each cohort demonstrates the effectiveness of the model lncRNAs characteristics. Additionally, the COX regression analysis of clinical characteristics and the analysis of mutation data further indicates the stability of the model lncRNAs. Furthermore, the expression levels of model lncRNAs in cell lines are consistent with the analysis results.

Conclusion: The model lncRNAs identified in this study, which are correlated with LLPS and TME, demonstrate significant potential as independent biomarkers for predicting the prognosis of PC patients.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a poor prognosis. Radical resection is the modality to cure patients with ICC. Thus, surgical quality is the key prognostic factor for survival. Textbook outcome (TO) is a multidimensional composite indicator reflecting surgical care quality. However, the association between neoadjuvant therapies-particularly those incorporating targeted and/or immunotherapeutic agents into chemotherapy regimens-and the attainment of TO in ICC remains unclear and warrants further investigation.

Materials and methods: This retrospective study analyzed 187 patients with ICC who underwent curative resection. TO was defined as the simultaneous achievement of R0 resection, with no perioperative blood transfusion, no postoperative complications, no mortality within 30 days, no unplanned readmission within 30 days, and a postoperative length of stay not exceeding the 75th percentile. Logistic regression was used to identify factors associated with TO, with further analysis focused on the role of neoadjuvant therapy. Cox regression was used to evaluate prognostic factors for overall survival (OS), and a prognostic nomogram incorporating TO was developed and validated.

Results: TO was achieved in 53 patients (28.3%), which was significantly associated with improved OS (p = 0.003) and recurrence-free survival (p < 0.001). Multivariable analysis identified neoadjuvant therapy [odds ratio (OR) = 2.687, p = 0.014], higher body mass index, higher albumin levels, lower carcinoembryonic antigen levels, and reduced blood loss as independent predictors of TO. Combination neoadjuvant regimens (chemotherapy plus targeted/immunotherapy; OR = 2.647, p = 0.009) were the primary contributors to this positive association. A nomogram integrating TO, lymph node metastasis, prothrombin time, and adjuvant therapy demonstrated excellent predictive accuracy for survival (1-year area under the curve = 0.891).

Conclusion: Achieving TO is associated with significantly improved survival in patients with ICC. Combined neoadjuvant therapy, including targeted or immunotherapy, is an independent positive predictor of TO, which challenges conventional perspectives. The proposed TO-integrated nomogram is a practical tool for prognostic prediction and surgical quality assessment.

Background: Mycosis Fungoides (MF) is a common subtype of primary cutaneous T-cell lymphoma (CTCL), a group of non-Hodgkin lymphomas. The clinical spectrum of MF ranges from isolated cutaneous lesions to widespread involvement of lymph nodes, blood, and skin, as seen in its aggressive variant, Sézary Syndrome (SS). Mogamulizumab, a defucosylated humanized IgG1-κ anti-CCR4 monoclonal antibody approved for relapsed/refractory MF/SS, has demonstrated a favorable safety and efficacy profile in multiple case series.

Methods: This retrospective, monocentric observational study analyzed data from 12 patients treated with Mogamulizumab between January 1, 2019, and December 31, 2024. We aim to evaluate the tolerability and clinical response to Mogamulizumab in patients with MF/SS.

Results: Of the 12 patients treated, 8 had MF and 4 had SS. The median follow-up time was 29.9 months (range 2.8-68.6 months). Four patients discontinued mogamulizumab: 3 due to disease progression and 1 due to the development of breast cancer. Adverse events included MAR in 4 patients (33%) and colitis in 1 patient (6%). The observed median PFS after mogamulizumab therapy was 5.4 months, and the observed ORR was 50%. For all 12 patients, the median time to response (TTR) was 129 days. The observed median overall survival (OS) was 11.5 months, with 1 reported death due to septic shock in a patient who underwent salvage allo-HSCT after mogamulizumab failure.

Conclusions: The results of this study reaffirm the efficacy of Mogamulizumab therapy for patients with Mycosis Fungoides and Sézary Syndrome in a real-world setting, which involves treatment decisions that must often consider patient heterogeneity, comorbidities, and prior lines of therapy.

[This corrects the article DOI: 10.3389/fonc.2025.1658621.].

[This corrects the article DOI: 10.3389/fonc.2025.1697550.].