Frontiers in Oncology最新文献

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.].

Objective: Although the fibrinogen-to-lymphocyte ratio (FLR) is an established prognostic biomarker in various solid tumors, its role in non-muscle-invasive bladder cancer (NMIBC) remains poorly defined. This study aimed not only to investigate the predictive value of preoperative FLR for overall survival (OS) in NMIBC patients undergoing transurethral resection of bladder tumor (TURBt), but also to develop and validate a novel FLR-based nomogram as a practical clinical tool.

Methods: This retrospective study enrolled 304 NMIBC patients who underwent TURBt at the Shijiazhuang People's Hospital between November 2013 and January 2024, with OS as the primary endpoint. The optimal prognostic cutoff for FLR was determined by maximizing the Youden index via receiver operating characteristic (ROC) curve analysis. Propensity score matching (1:2) was employed to balance baseline confounders. The dose-response relationship between continuous FLR and mortality risk was evaluated using restricted cubic splines (RCS), which confirmed a linear association. Subsequently, independent prognostic factors identified through Cox proportional hazards regression were integrated to construct a nomogram. The model's predictive accuracy and clinical utility were then comprehensively evaluated using the concordance index (C-index), calibration curves, time-dependent ROC curves, and decision curve analysis (DCA).

Results: The optimal FLR cutoff was identified as 2.91. Patients in the high-FLR group (FLR ≥ 2.91) exhibited significantly poorer OS (P < 0.001) and cancer-specific survival (CSS; P = 0.004). RCS analysis confirmed a significant positive linear association between increasing FLR levels and all-cause mortality risk. Critically, multivariate Cox regression validated FLR as an independent predictor for both OS (Hazard Ratio (HR): 1.520, 95% Confidence Interval (CI): 1.149-2.010) and CSS (HR: 1.536, 95% CI: 1.033-2.284). Integrating FLR into a baseline model improved the C-index for OS prediction from 0.739 to 0.772. The resulting nomogram demonstrated robust discrimination (C-index: 0.772), excellent calibration, and superior net clinical benefit in DCA.

Conclusion: Preoperative FLR is an independent predictor of overall survival in NMIBC, characterized by a robust linear dose-response relationship with mortality risk. This cost-effective biomarker, integrated into our validated nomogram, enhances risk stratification to guide personalized postoperative management.

Optimizing second-line therapy for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (mBC) in the Gulf Cooperation Council (GCC) is challenged by variations in diagnostic capacity, drug accessibility, comorbidities, and treatment pathways compared with other regions. While international guidelines provide an overarching evidence framework for breast cancer management, their practical application at the regional level often requires adaptation to local healthcare resources. There is an unmet need to optimize the treatment sequencing strategies for patients with HR+/HER2-negative mBC in the GCC region through expert guidance. Given this context, a virtual advisory board involving 10 oncologists from the GCC region was convened in November 2024. The panel aimed to review current evidence and develop pragmatic, implementable recommendations for second-line management. This consensus uniquely contextualizes global evidence for GCC-specific healthcare constraints, addressing gaps in diagnostic access, affordability, and real-world feasibility, while providing treatment recommendations that help clinicians refine therapeutic strategies and incorporate patient preferences for improved outcomes. The panel recommends early genomic testing (PIK3CA, AKT, BRCA, ESR1) to guide therapy, prioritizing targeted agents such as oral SERDs and PI3K/AKT inhibitors in second-line sequencing, cautious use of alpelisib in diabetic patients, and incorporating patient preferences through shared decision-making and multidisciplinary care.

Objectives: The detection of lung cancer at its early stages remains essential for better survival outcomes, but current diagnostic approaches show limited sensitivity and often suffer from poor generalizability and a lack of interpretability.

Methods: This retrospective study develops a machine-learning pipeline that integrates plasma metabolite measurements with pathways to derive a pathway-informed biomarker panel for lung cancer screening.

Results: Using 800 plasma samples from the Cooperative Human Tissue Network biobank (586 cancer, 214 controls) with 166 metabolites and 60 derived pathways, we identified a subset of 41 predictors (9 pathways, 26 metabolites, 6 demographic variables) through an ensemble selection framework. Several models were tested with the Support Vector Machines (SVM) model, achieving the best results. The model delivered an overall 97% accuracy with a ROC AUC of 0.97 on this subset. After eliminating pathway-related metabolites from the initial dataset, feature selection reduced the number of variables from 170 to 41, retaining biological relevance and minimizing overfitting. The glutaminolysis and tryptophan metabolism pathway analysis yielded the most enhanced biological indicators.

Conclusions: This noninvasive, interpretable approach using plasma panel could facilitate cost-effective, early-stage lung cancer screening for at high-risk population cohort, with strong translational potential in clinical settings. Future work should focus on multi-center validation, prospective validation, assessing potential longitudinal biomarker stability, and integration with other omics data to further advance precision oncology, ultimately improving early detection and patient outcomes in lung cancer management.

Non-small-cell lung cancer (NSCLC) is a leading cause of morbidity and mortality globally, due in large part to the development of NSCLC-associated brain metastases (L-BM). Upon initial presentation, 11-26% of patients with NSCLC will have L-BM, while half of patients with NSCLC will develop L-BM over the course of their disease. The emergence of PD-1/PD-L1 immunotherapy and targeted therapies for EGFR, ALK, and ROS1 mutations has transformed the treatment landscape and improved outcomes for select patient populations. CNS progression remains a major challenge due to therapy resistance, the blood-brain barrier (BBB), and the unique molecular and transcriptomic adaptations exhibited by NSCLC brain metastases which differs markedly from primary lung tumors. In this review, we examine the molecular drivers of CNS metastasis, oncogenic signaling-targeted therapies, and next-generation CNS drug-delivery strategies including intraventricular or intranasal administration, focused ultrasound, nanocarriers, and efflux transporter modulation. Furthermore, we provide a comprehensive update on recent and ongoing preclinical and clinical studies, highlighting novel CNS-penetrant agents with demonstrated intracranial efficacy. Understanding these mechanisms and refining targeted approaches are critical to improving CNS disease control, survival outcomes, and quality of life for NSCLC patients with brain involvement.

Introduction: Head-to-head comparative evidence of the relative efficacies of atezolizumab plus bevacizumab (Atezo+Bev) and tremelimumab plus durvalumab (Treme+Dur) as first-line therapies for advanced hepatocellular carcinoma (HCC) remains limited. Thus, in the present study, we compared the real-world efficacy and safety of these two modalities using a target trial emulation approach.

Methods: Using the TriNetX Research Network, we identified adults (≥20 years) with HCC (ICD-10 C22.0) who initiated first-line Atezo+Bev or Treme+Dur (November 2022- November 2024). Propensity score matching (1:1) was used to balance the baseline characteristics. The primary outcome measure was overall survival (OS). Secondary outcomes included 1- or 2-year OS and organ-specific immune-related adverse events (irAEs) within 12 months, based on pre-specified ICD-10 definitions.

Results: After matching, 640 patients were included in each group. Residual imbalance persisted in hepatic reserve markers (albumin, international normalized ratio, and platelet count; standardized mean differences >0.1). One-year OS was numerically higher in the Atezo+Bev group than in the Treme+Dur group (61% vs 55%; hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.665-0.976; p = 0.027). Two-year OS (HR, 0.864; 95% CI, 0.723-1.031; p = 0.105) and overall OS showed no significant differences (median: 19.4 vs 19.0 months [591 vs 578 days]; HR, 0.886; 95% CI, 0.743-1.057; p = 0.179). Most irAEs were similar; however, the time-to-first hepatic irAEs favored Atezo+Bev (HR, 0.678; 95% CI, 0.487-0.943; p = 0.020). Notably, respiratory irAEs occurred significantly earlier in the Treme+Dur group than in the Atezo+Bev group (mean onset: 2.4 vs 3.2 days; p = 0.031).

Conclusions: In this real-world target trial emulation, Atezo+Bev and Treme+Dur demonstrated broadly comparable long-term OS rates when used as first-line therapies for HCC. While baseline hepatic reserve plays an important role, the treatment regimen itself may contribute to earlier onset of hepatic and respiratory irAE. Careful monitoring for early-onset hepatic dysfunction and respiratory irAEs may be warranted in patients treated with Treme+Dur combination therapy.