Frontiers in Oncology最新文献

Radiation therapy (RT) is a cornerstone in the management of localized and locally advanced prostate cancer, traditionally delivered with a full bladder (FB) protocol to reduce radiation exposure to surrounding organs. However, consistent bladder filling is difficult to maintain, leading to workflow delays, anatomical inconsistencies, and variable toxicity outcomes. Recent evidence, including the ongoing RELIEF trial at Mayo Clinic, suggests that an empty bladder (EB) protocol provides comparable toxicity outcomes to FB while improving patient comfort and treatment consistency. To address the increased anatomical variability associated with EB protocols, we developed a deep learning (DL)-based dose prediction model tailored to EB patients. A conditional generative adversarial network (cGAN) with a modified 3D U-Net architecture was trained on 90 FB cases and fine-tuned on 20 EB cases stratified into stereotactic body radiotherapy (SBRT) and intensity-modulated radiotherapy (IMRT). Model performance was evaluated against clinical manual plans using mean absolute percentage error (MAPE) and dose-volume histogram (DVH) metrics. The EB Fine-tuning model(SBRT/IMRT) achieved superior accuracy compared with the general FB-trained model, with an average MAPE of 3.53 ± 0.40% versus 4.87 ± 0.86%. DVH analyses demonstrated improved agreement with manual plans for planning target volumes and organs at risk, with discrepancies consistently within 2.5 Gy or 3%. These results demonstrate that fine-tuning with EB-specific data enhances prediction accuracy and clinical relevance of the DL-based model. The proposed framework supports efficient EB treatment planning, provides reference dose distributions for quality assurance, and offers educational value to clinicians adopting EB protocols. By combining automation with clinical applicability, this approach facilitates broader adoption of EB radiotherapy in prostate cancer while improving workflow reproducibility and patient-centered care.

Background: Signaling pathways associated with spasmolytic polypeptide-expressing metaplasia (SPEM) pathogenesis play a critical role in disease development, particularly in gastric cancer precursor lesions. However, global research trends in signaling pathways in SPEM pathogenesis remain undetermined. This study aims to fill this gap by conducting a comprehensive bibliometric analysis to map the field, identify key insights, and guide future research directions.

Methods: Articles and reviews were retrieved from the Web of Science Core Collection up to June 8 2025. Bibliometric analysis and knowledge mapping were conducted via CiteSpace and VOSviewer.

Results: A total of 89 papers from 221 institutions, 719 authors, and 56 journals across 21 countries/regions were included. The number of publications is growing slowly. Gastroenterology led in publication and co-citation counts. The United States and China were at the top in terms of publication numbers. Goldenring JR emerged as the most co-cited and most published author. Key findings indicate limited collaboration despite a foundation of ten pivotal articles. Research elucidating gene-pathway interplay and cytokine roles in SPEM pathogenesis has consequently sharpened the focus on developing pharmacological agents that target these pathways, defining a pivotal new direction for combating gastric precancerous lesions.

Conclusion: By systematically reviewing signaling pathways in SPEM pathogenesis, this study provides critical guidance for future research strategic planning and collaboration. It highlights the urgent need for strengthened interdisciplinary and global partnerships to drive progress.

Background: Lymph node metastasis (LNM) of patients with cervical cancer (CC) is correlated with noticeably reduced five-year survival rate. but the role of conventional detection is limited for preoperative diagnosis of LNM. Therefore, we intended to develop a predictive model for LNM by integrating medical images, clinical data along with artificial intelligence-assisted method.

Methods: CC patients who underwent radical hysterectomy combined with pelvic lymphadenectomy between January 2013 and October 2024 were retrospectively enrolled in this study. For computed tomography (CT) and ultrasound (US) images, a pre-trained ResNet-18 model on large-scale samples was used to extract representative features, fine-tuned with random cropping data augmentation. For clinical indicators, after normalizing to the range [0,1], a multilayer perceptron block was applied to extract representative features. Then, contrastive learning and feature fusion methods were utilized to integrate similar messages. Finally, a multi-modal contrastive learning framework was developed by consolidating above two parts. The framework was estimated by accuracy, sensitivity, specificity and the area under the receiver operating characteristic curve (AUC).

Results: This work consisted of 127 CT images of patients with pathologically diagnosed cervical malignancies. After integrating clinical-imaging feature and artificial intelligence-assisted algorithm, the finally developed LNM predicting model achieved a high accuracy of 92.31% with an AUC of 0.88. Additionally, the model also displayed strong sensitivity (80.0%) and specificity (95.45%) in CC cohorts.

Conclusion: This study presented an efficient noninvasive and highly accurate diagnostic tool for LNM, which may significantly enhance surgical decision-making for lymph node dissection in CC patients with LNM.

For patients with certain types of unresectable locally advanced solid tumors, concurrent chemoradiotherapy (CCRT) is the standard treatment regimen. However, in clinical practice, specific patient populations such as the elderly, those with poor performance status (PS) scores, or those with significant underlying comorbidities often struggle to tolerate CCRT, resulting in unfavorable prognosis, and the clinical outcomes are even worse when accompanied by tumor bleeding. This paper reports three specific cases of locally advanced solid tumors (including one case each of lung cancer, esophageal cancer, and cervical cancer) with bleeding that could not tolerate concurrent chemotherapy. All cases received combined treatment of radiotherapy and drug-eluting bead transarterial chemoembolization (DEB-TACE). The results demonstrated that hemorrhagic symptoms were rapidly and effectively controlled in all patients, and all achieved long-term complete response (CR) after treatment. These findings suggest that the combination of radiotherapy and DEB-TACE may be a promising treatment strategy for such specific patients with hemorrhagic locally advanced solid tumors.

Introduction: Visceral crisis in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer poses a therapeutic challenge, traditionally managed with chemotherapy due to the urgency of organ dysfunction. However, recent evidence suggests that cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), in combination with endocrine therapy (ET), may offer rapid and effective disease control even in aggressive presentations.

Case presentation: We report the case of a 52-year-old premenopausal woman diagnosed with de novo HR+, HER2-negative metastatic lobular breast cancer presenting with severe anemia and thrombocytopenia secondary to diffuse bone marrow infiltration. The patient was initially managed with letrozole and goserelin, followed by the addition of ribociclib. Clinical and hematologic parameters improved rapidly, and the patient achieved a complete metabolic response after nine treatment cycles without significant toxicity.

Discussion: This case highlights bone marrow infiltration as a form of visceral crisis, reinforcing the heterogeneity of visceral crisis presentations beyond solid organ involvement. The rapid response and sustained disease control observed with CDK4/6i plus ET challenge the traditional paradigm favoring chemotherapy in such scenarios. Supporting evidence from RIGHT Choice, ABIGAIL, and recent case series further validates this therapeutic approach in carefully selected patients.

Conclusion: CDK4/6 inhibitors in combination with endocrine therapy may constitute an effective and well-tolerated alternative to chemotherapy in HR+/HER2- metastatic breast cancer presenting with visceral crisis, including hematologic compromise due to bone marrow involvement. This case underscores the need to reconsider current treatment algorithms to include targeted therapies as a viable and effective option in acute and life-threatening presentations of HR+/HER2- metastatic breast cancer.

Immunity during cancer progression involves critical responses that may be harnessed to augment anti-tumor cytotoxicity. A potent arm of immunity in cancer involves cytotoxic T cells (a key CD8+ T-lymphocyte subset): Anti-tumor responses by such cells optimally involve sensitization and acquired responses to tumor antigens by antigen presenting cells. Many tumor microenvironment (TME) biophysical and functional limitations in carcinomas limit robust achievement of this ideal cellular-immunologic pathway. This is especially challenging in lung carcinoma, on which we focus mechanistically and with an eye to therapeutic translation. Localization of tumor-sensitized and activated CD8+ T cells to tumor "nests" with efficient tumor cytolysis involves many challenging steps. Amplifying and sustaining such responses is also a unique challenge. The variety of homeostatic and immunosuppressive obstacles often becomes overwhelming. Measuring the state of this response during lung cancer progression is also challenging, making it difficult to mount (and/or predict) T-cytotoxic responses in the heterogeneous and dynamic carcinoma antigen landscape. We investigate these challenges herein, while examining strategies to boost T-cytotoxic immunity in lung cancer through novel and emerging immunotherapeutic approaches. Beyond current immune checkpoint blockade approaches that are relatively non-specific with respect to antigen recognition by the T-cell receptor, we highlight ongoing and translational vaccines, cell-therapies, antigen-presenting cell boosting approaches, T-cell therapies, and biophysical considerations with an eye to overcome key barriers of this powerful arm of anti-tumor immunity.

Background: Colorectal cancer (CRC), currently the second leading cause of cancer-related mortality worldwide, poses a significant burden on public health. This study systematically analyzes the temporal trends in CRC disease burden based on Global Burden of Disease (GBD) data from 1990 to 2021, aiming to provide robust evidence for epidemiological research, disease prevention, and the formulation of public health policies.

Methods: This study analyzed CRC incidence, mortality, and disability-adjusted life years (DALYs) using GBD1990-2021 data. Temporal trends were evaluated via estimated annual percentage changes (EAPC), with Pearson correlation assessing Socio-demographic Index (SDI) associations. Projections of global CRC epidemiology through 2035 were developed to inform public health strategies.

Results: In 2021, global CRC accounted for 2,194,143 incident cases, 1,044,072 deaths, and 24,401,100 DALYs. CRC remains a major public health challenge worldwide. From 1990 to 2021, age-standardized incidence rates (ASIR) increased (EAPC = 0.15, 95% CI: 0.12-0.19), while mortality (EAPC=-0.81, -0.84 to -0.77) and DALY rates (EAPC=-0.83, -0.87 to -0.80) declined significantly. Notable socioeconomic gradients were observed across the spectrum of regions. Geographic disparities were prominent: high-SDI regions had the highest ASIR (40.525, 37.445-42.447 per 100,000), whereas high-middle-SDI regions showed peak mortality (15.709, 14.144-17.25) and DALY rates (338.225, 316.751-354.913). Males and individuals aged >85 years experienced disproportionate burden increases. By 2035, the global burden of CRC is projected to maintain its current upward trajectory.

Conclusions: Globally, CRC's ASIR has gradually increased, while age-standardized death rate (ASDR) and DALY rates have declined significantly, reflecting an overall reduction in disease burden. Regions with higher SDI, male predominance, and aging populations contribute most to rising CRC cases. Despite progress in mortality reduction, CRC prevention and control will continue to pose significant public health challenges in the coming years.

Background: Glioma is the most common primary brain tumor, and the WHO 4 glioma, glioblastoma (GB), is a malignant tumor with high invasiveness and mortality. Tumor-associated macrophages (TAMs), as the main immune cells in glioma, play an important role in the growth, invasiveness, immune escape, and drug resistance. The M2 phenotype of macrophages, but not the M1 phenotype, promotes glioma development. Recent studies have shown that sphingosine kinase 2 (SPHK2) is positively associated with TAM infiltration and glioma proliferation. SPHK2-deficient tumors showed impaired growth and failed to polarize macrophages toward an M2 phenotype.

Objective: Our aim was to reveal whether SPHK2 affects exosome microRNA (miRNA) release from glioma cells and which miRNAs regulated by SPHK2 could mediate the polarization of macrophages around glioma cells.

Methods: SPHK2 knockdown of the human glioma cell line U373 was performed using short hairpin RNA (shRNA) lentiviruses. Exosome miRNAs were isolated and evaluated using RNA sequencing (RNA-seq). Gene Ontology (GO) analysis was carried out to determine the function of exosome miRNAs targeting genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to view the pathways of these genes.

Results: We successfully isolated exosomes from the U373-HK and U373-SH glioma cell lines. We found 12 exosome miRNAs differentially expressed between U373-HK and U373-SH cells. The heatmap showed two upregulated and 10 downregulated miRNAs in glioma cells with SPHK2 knockdown. There were 12 miRNAs targeting genes assigned to 118 GO terms, including 53 biological processes, 30 cellular components, and 35 molecular function terms. KEGG mapping further clustered several signaling pathways, such as "Wnt signaling," "p53 signaling," "proteoglycans in cancer," and "cell cycle." "Wnt signaling" was identified as the most significantly enriched pathway in the KEGG analysis. A total of 17 genes were enriched in this pathway.

Conclusions: The present study elucidates that SPHK2 promoted the release of 10 exosome miRNAs, but inhibited the release of two miRNAs. The KEGG data indicated that these miRNAs targeted several important genes of Wnt signaling. This study provides not only a genomic resource for further studies but also novel insights into uncovering the molecular mechanism of SPHK2 regulating M2 TAM polarization.