Frontiers in Oncology最新文献

Lung cancer remains one of the malignancies with the highest incidence and mortality rates worldwide, and its treatment continues to pose significant challenges. Metabolic reprogramming, as one of the hallmarks of cancer, supports the abnormal growth, proliferation, invasion, and drug resistance of cancer cells by altering glucose, lipid, and amino acid metabolic pathways, providing both energy and biosynthetic precursors. It has thus become a critical focus in lung cancer research. Circular RNAs (CircRNAs), owing to their unique closed-loop structure and high stability, play important roles in regulating tumor metabolism and progression. This review systematically summarizes the molecular mechanisms through which CircRNAs drive metabolic reprogramming in lung cancer, including the regulation of key metabolic enzymes, influence on metabolism-related signaling pathways, remodeling of the tumor microenvironment, and mediation of epigenetic modifications. Furthermore, CircRNAs demonstrate great potential in clinical applications for lung cancer, not only as biomarkers for early diagnosis and prognostic evaluation but also as promising therapeutic targets. Leveraging their stability and low immunogenicity, the development of CircRNA-based vaccines and targeted delivery systems has opened new avenues for lung cancer immunotherapy. However, challenges remain in the synthesis of CircRNAs, understanding their in vivo metabolism, and achieving multi-target synergistic interventions, which warrant further investigation. This review provides a theoretical foundation for in-depth exploration of the metabolic regulatory network in lung cancer and the development of precise therapeutic strategies, while also highlighting the broad prospects of CircRNAs in translational medicine. We conducted a literature search across databases including PubMed up to 2025, focusing on keywords related to circRNA, lung cancer, and metabolic reprogramming. Ultimately, 161 relevant references were included in this narrative review.

Introduction: This study aimed to comprehensively analyze the dosimetric parameters, plan complexity, gamma passing rates (GPRs), and most importantly, the beam-on time (BOT) of stereotactic body radiotherapy (SBRT) for small-volume inoperable early-stage centrally-located non-small-cell lung cancer (NSCLC) at a radiotherapy center. The analysis was based on both single-arc (SA) and dual-arc (DA) VMAT techniques under the deep inspiration breath hold (DIBH) scenario.

Methods: We retrospectively selected 24 cases of small-volume inoperable early-stage centrally-located NSCLC treated with SBRT under the DIBH scenario at our institution between March 2021 and June 2024. The redesigned SA-VMAT plans (SA plans) adopted the same prescription dose of 50 Gy/5 fractions and flattening-filter free (FFF) beam as the original DA-VMAT plans (DA plans). The 2-group plans (i.e., the SA and DA plans) were normalized to cover 95% of the planning target volume (PTV) and 99% of the gross tumor volume (GTV) by the prescription dose. The evaluation factors included PTV parameters (D_98%, D_2%, HI, CI, and R_50%), organs at risk (OARs), plan complexity (segments and MUs), GPRs, and BOT.

Results: The SA technique consistently yielded superior plans. Among the PTV parameters, the SA plans were superior to the DA plans in D_98%, D_2%, and HI (all p < 0.05), whereas the CI and R_50% of the 2-group plans were comparable (all p > 0.05), and the SA plans had an increase in the ipsilateral PBT D_max (p < 0.05). Otherwise, the differences between other OARs were insignificant (all p > 0.05). The SA plans had reduced complexity, with mean segments and mean MUs decreasing by 18.82% and 8.15%, respectively (all p < 0.001); the GPRs did not differ significantly under the three acquisition parameters (all p > 0.05). The mean BOT was reduced by 19.70% in SA plans (p < 0.001).

Discussion: The SA plans significantly shortened the BOT while maintaining comparable plan quality, thereby improving comfort for patients with small-volume inoperable early-stage centrally located NSCLC under the DIBH scenario. Future studies should accumulate more patient data to evaluate the long-term clinical outcomes of SA plans.

Alterations involving the mitogen-activated protein kinase (MAPK) pathway are central drivers of pediatric and adult low-grade gliomas (LGGs), with BRAF fusions representing a dominant oncogenic mechanism in pilocytic astrocytoma. While KIAA1549::BRAF remains the most prevalent fusion, an expanding repertoire of alternative fusion partners continues to refine the molecular landscape of MAPK-driven gliomas and has important therapeutic implications. Here, we report a previously unrecognized ASAP1::BRAF fusion identified in a young adult with a World Health Organization grade 1 temporal lobe pilocytic astrocytoma, highlighting both its biological plausibility and potential relevance for targeted therapy. A 31-year-old female presented with new-onset seizures and underwent gross total resection of a well-circumscribed, partially cystic left temporal lobe tumor. Histopathological and immunohistochemical findings were consistent with pilocytic astrocytoma, demonstrating low proliferative activity and absence of high-grade features. Comprehensive molecular profiling using RNA-based next-generation sequencing revealed an in-frame ASAP1 exon 29::BRAF exon 9 fusion, preserving the intact C-terminal BRAF kinase domain while eliminating N-terminal regulatory regions. No additional pathogenic variants were detected. To substantiate the structural authenticity of the fusion, deep learning-based breakpoint validation using FusionAI was performed, yielding a high fusion probability score and supporting a bona fide genomic rearrangement rather than an RNA-sequencing artifact. Genomic feature annotation demonstrated enrichment of repetitive elements, regulatory regions, and chromatin accessibility features flanking the breakpoint, consistent with known mechanisms of fusion gene formation. Functionally, the ASAP1::BRAF fusion is predicted to emphasize constitutive MAPK pathway activation via dimer-dependent BRAF signaling, analogous to canonical BRAF fusions and mechanistically distinct from BRAF V600E mutations. Clinically, BRAF fusion-driven tumors are typically resistant to first-generation BRAF inhibitors but may be sensitive to MEK inhibitors or emerging type II RAF inhibitors that effectively target RAF dimers. Although no adjuvant therapy was required following complete resection, documentation of this fusion provides a rational framework for future molecularly guided treatment should disease recurrence occur. This case expands the spectrum of oncogenic BRAF fusion partners in LGG and underscores the importance of integrated RNA-based diagnostics and computational validation in precision neuro-oncology.

Primary intracranial myxofibrosarcoma (MFS) is an exceedingly rare mesenchymal malignancy, with only a few cases reported. We report a 34-year-old male with a right frontal lobe MFS who subsequently developed two non-contiguous recurrences in the right temporal and left frontal lobes. Histopathological examination revealed a stepwise progression from low- to intermediate- to high-grade disease, accompanied by progressively increasing Ki-67 labeling indices. Notably, the pattern of spatially separate recurrences suggests the possibility of cerebrospinal fluid-mediated dissemination. This case highlights the aggressive and heterogeneous nature of intracranial MFS and underscores the importance of long-term, comprehensive follow-up to detect recurrences, particularly at non-contiguous sites.

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.

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.

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.

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.