Clinical & Experimental Metastasis最新文献

{"title":"Modeling the role of urokinase-type plasminogen activator, uPA, and circulating cancer-associated fibroblasts (cCAFs) in breast cancer cell extravasation.","authors":"Angela Spartz, Susan Schmidt, Fazila Mohamed, Benjamin Troness, Carol A Lange, Dorraya El-Ashry","doi":"10.1007/s10585-026-10411-3","DOIUrl":"10.1007/s10585-026-10411-3","url":null,"abstract":"<p><p>Circulating Cancer-Associated Fibroblasts (cCAFs) have been identified in circulating tumor cell clusters from all stages of disease progression in breast cancer patients. We have shown that CAFs promote lung metastases in the mouse tail vein model when they are clustered with triple negative breast cancer (TNBC) MDA-MB231 cells. Following on this observation, we saw that MDA-MB231-luciferase labeled cells persist at higher levels when present in CAF23/MDA-MB231 co-clusters compared to MDA-MB231 mono-clusters within the first 3 days after tail vein injection. This prompted us to investigate whether CAFs aid cancer cell extravasation from capillary venules into the lung parenchyma, which would impart better survival and faster seeding of metastases. Ex vivo lung extravasation assays showed that within the first 8-24 h after tail vein injection, more cells from CAF23/MDA-MB231 co-clusters extravasated than cells from MDA-MB231 mono-clusters. Using in vitro endothelial binding assays, we determined that CAF/TNBC co-clusters bind to HUVEC endothelial cells better than TNBC mono-clusters. Single-Cell RNA sequencing identified several genes in the fibrinolysis pathway whose expression increases in TNBC cells when they are clustered with CAFs. One of these genes is PLAU, which encodes the urokinase-type plasminogen activator, uPA. siRNA knockdown of PLAU decreased in vitro TNBC-endothelial cell interactions and ex vivo extravasation of MDA-MB231 mono-clusters, revealing a potential role for CAF-induced factors expressed in TNBC cells, such as uPA/PLAU, in breast cancer cell extravasation. Our data helps to define the role of CAFs in breast cancer extravasation and highlights the importance of our previous work showing that CAFs promote tumor cell dissemination and metastasis.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of breast cancer dormancy in bone metastasis.","authors":"Maria L Price, Jiabao Zhou, Christine L Le Maitre, Lewis A Quayle, Penelope D Ottewell","doi":"10.1007/s10585-026-10412-2","DOIUrl":"10.1007/s10585-026-10412-2","url":null,"abstract":"<p><p>Bone metastasis remains a serious threat to breast cancer patients. This condition arises from the outgrowth of previously dormant tumour cells in this site. Dormant tumour cells are almost impossible to detect in human patents, and these cells acquire \"stem like\" characteristics rendering them resistant to current cancer therapies. Furthermore, the development of therapies to target this population has proved challenging. The bone marrow is a particularly permissive environment for tumour cell dissemination and dormancy, but the mechanisms regulating this process remain to be completely elucidated. Expansion of our understanding of the mechanisms underlying tumour dormancy is critical to the development of targeted therapies and thus, the prevention, or treatment, of metastatic disease. This review aims to explore mechanisms of tumour dormancy in bone, in detail, focusing specifically on breast cancer dormancy. In addition to subsequent discussion of traditional and new, state of the art, methods of studying dormancy to aid further research efforts.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13233890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Expression of Concern: Hypermethylation-mediated inactivation of miR-124 predicts poor prognosis and promotes tumor growth at least partially through targeting EZH2/H3K27me3 in ESCC.","authors":"Ziqiang Tian, Zhenhua Li, Yonggang Zhu, Lingjiao Meng, Fei Liu, Meixiang Sang, Guiying Wang","doi":"10.1007/s10585-026-10408-y","DOIUrl":"https://doi.org/10.1007/s10585-026-10408-y","url":null,"abstract":"","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local control and dose selection for lung cancer brain metastases treated with radiosurgery: an artificial intelligence model.","authors":"Jheremy S Reyes, Alexandros Bouras, Constantinos G Hadjipanayis, Ajay Niranjan, L Dade Lunsford","doi":"10.1007/s10585-026-10409-x","DOIUrl":"10.1007/s10585-026-10409-x","url":null,"abstract":"<p><p>Clinical and radiological outcomes after Stereotactic radiosurgery (SRS) for lung cancer brain metastases are heterogeneous, and prescription dose selection is often guided by experience rather than individual patient and tumor specific features. A data-driven approach that links dose to quantitative local control and adverse effect predictions could improve planning and follow-up strategies. We performed a retrospective single-center cohort study of lung cancer brain metastases treated with GKRS at the University of Pittsburgh Medical Center (2014-2024). Using routinely available clinical, tumor, and dosimetric variables, we trained a tumor-level Random Survival Forest to predict Local Control and Dose Selection for Lung Cancer Brain Metastases after GKRS treatment. Internal validation used leakage-resistant patient-level grouped cross-validation. Performance was assessed using Harrell's concordance index (C-index) and integrated Brier score (IBS). A connected dose-sweep decision layer evaluated predicted local control across a clinically feasible margin dose grid and selected the dose associated with the most favorable predicted profile at prespecified horizons. The survival model demonstrated good internal performance (C-index 0.83; IBS 0.15). A baseline dose imitation model predicted historical margin dose with low error (OOF MAE 1.59 Gy). The integrated decision layer generated individualized local control trajectories and returned horizon-specific local control probabilities and model-based prescription dose recommendations. An Artificial Intelligence framework integrating time-to-event prediction with outcome-linked dose sweeping can provide individualized GKRS decision support for lung cancer brain metastases by delivering quantitative local control forecasts and model-based dose recommendations.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating single-cell analysis and digital pathology for risk stratification in pancreatic cancer.","authors":"Wenhao Bao, Kaiming Leng, Xiaodan Xia, Jingyu Chang, Pengchao Ying, Shaohai Luan, Qihua Yuan","doi":"10.1007/s10585-026-10410-4","DOIUrl":"10.1007/s10585-026-10410-4","url":null,"abstract":"<p><p>Early liver metastasis is a major factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Single-cell RNA sequencing (scRNA-seq) can analyze the heterogeneity between the primary tumor and metastatic lesions, but its wide clinical application is limited by costs, tissue requirements, and analytical complexity. In contrast, H&E-stained sections are more commonly available. However, it is not clear whether the risk signals derived from images can truly reflect the biological characteristics related to metastasis. We integrated the single-cell RNA sequencing data (GSE154778) of primary and metastatic pancreatic ductal adenocarcinoma (PDAC) with TCGA transcriptome, clinical pathological, and H&E image data. The copy number pattern based on InferCNV was used to distinguish malignant ductal cells with high copy numbers from ductal cells with low copy numbers. Differential expression and LASSO screening identified a transfer-related feature consisting of four genes (ARHGAP18, ASPH, EIF4EBP1, LY6D), and this feature was subsequently associated with image-derived features extracted through a dual-stream pathomics pipeline. The reproducibility of transcriptional levels in prognosis was evaluated in six independent GEO PDAC subgroups, and the locked pathological model was further tested on an external CPTAC subset using frozen cutoff values from TCGA. Pseudotime analysis suggested that a subset of metastatic malignant ductal cells occupied a progenitor-like transcriptional state. Cell-cell communication analysis indicated reduced antigen-presentation/prostaglandin-related signaling and relative enrichment of MIF- and laminin-associated pathways in metastases. The pathology model retained prognostic stratification in the internal TCGA validation split, although discrimination was lower than in training. Across six external GEO cohorts analyzed with cohort-specific optimal cutoffs, LY6D showed significant adverse survival associations in four cohorts, ARHGAP18 and ASPH in three cohorts each, and EIF4EBP1 in one cohort. In the external CPTAC cohort, the locked pathomics score also remained prognostic (HR 1.60, 95% CI 1.11-2.30; log-rank P = 0.011), with 12-, 24-, and 36-month time-dependent AUCs of 0.635, 0.617, and 0.639. This study presents an integrative genotype-to-phenotype workflow linking scRNA-seq-derived metastatic features to routine pathology images. External transcript-level validation and supportive CPTAC pathomics evaluation strengthen the findings, but larger independent validation studies and mechanistic experiments remain necessary before any clinical translation.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix and stromal cues cooperatively regulate dormancy-like states of prostate cancer in a dual-niche metastatic model.","authors":"Bo Han, Zhi Yang, Shuqing Zhao, Gangning Liang, Ba Xuan Hoang","doi":"10.1007/s10585-026-10405-1","DOIUrl":"10.1007/s10585-026-10405-1","url":null,"abstract":"<p><p>Prostate cancer (PCa) exhibits a strong tropism for bone, where interactions with the bone microenvironment critically influence metastatic progression and therapeutic resistance. However, the complexity of tumor-bone interactions remains difficult to model in conventional systems. Here, we developed an engineered dual-niche platform that recapitulates both primary tumor and bone metastatic microenvironments using tunable extracellular matrix mechanics, bone matrix-derived soluble factors (BMSFs), and bone marrow stromal cells (BMSCs). Within the primary tumor-like niche, increasing matrix stiffness suppressed LNCaP-C4-2B cell proliferation while promoting cell dissemination. In contrast, BMSFs exerted a dual effect by inhibiting tumor proliferation while inducing osteomimetic differentiation through upregulation of Runx2 and Cbfa1. In vivo, BMSFs elicited inflammatory and vascular responses associated with suppressed tumor expansion. Notably, BMSCs primed with bone matrix factors markedly enhanced PCa cell proliferation and migration in vitro and accelerated tumor formation in vivo, revealing a stromal-driven pro-tumorigenic mechanism. Together, these findings uncover a functional dichotomy within the bone microenvironment, in which bone matrix-derived factors promote tumor adaptation and dormancy, while stromal components drive tumor expansion. This engineered dual-niche model provides a versatile platform to dissect microenvironment-specific mechanisms and may inform strategies targeting bone metastatic progression in prostate cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All-site radiotherapy for metastatic ewing's sarcoma: a short-term analysis of feasibility, response, and safety.","authors":"YuanYou Yang, Lu Xie, Xin Sun, Jie Xu, Gang Ren","doi":"10.1007/s10585-026-10406-0","DOIUrl":"10.1007/s10585-026-10406-0","url":null,"abstract":"<p><strong>Background: </strong>Metastatic Ewing sarcoma (EWS) has a poor prognosis. While metastasis-directed therapy benefits oligometastatic disease, the role of comprehensive all-site radiotherapy in widespread disease remains underexplored. This study aimed to preliminarily assess its short-term efficacy and safety.</p><p><strong>Methods: </strong>This retrospective analysis included 21 consecutive metastatic EWS patients treated with helical tomotherapy (Aug 2024-Jun 2025). All known metastases and unresected primary tumors received radiotherapy (45-55 Gy in 20 fractions for most sites; 12-45 Gy for lung/pleural metastases). Concurrent systemic therapies included chemotherapy, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), or combinations. Primary endpoints were local objective response rate (ORR, RECIST 1.1) at 2 months post-radiotherapy and acute toxicity (CTCAE 5.0). Systemic therapy subgroup analyses were exploratory.</p><p><strong>Results: </strong>Median follow-up was 6 months (range 2-11). Among 77 target lesions, ORR was 61.0% (CR 48.1%), and disease control rate (DCR) was 97.4%. Soft tissue lesions had a significantly higher CR rate than bone metastases (78.3% vs 3.2%, p < 0.001), potentially influenced by RECIST 1.1 limitations and treatment heterogeneity. Median progression-free survival (PFS) was 6.0 months (95% CI: 2.30-9.70), and median overall survival (OS) was 8.0 months (95% CI: 6.69-9.31). Combination systemic therapy was associated with improved PFS (HR 3.94, 95%CI 1.32-11.78; p = 0.014), with chemotherapy-based regimens yielding the best PFS (8.5 months). TKI-containing regimens were linked to shorter PFS (4.0 vs 8.5 months, p = 0.048) due to selection bias. Acute toxicity was manageable, with grade 3 thrombocytopenia (19.0%) and pneumonitis (4.7%) resolving with treatment.</p><p><strong>Conclusion: </strong>All-site radiotherapy achieves promising short-term local control with manageable toxicity in metastatic EWS, demonstrating feasibility and a lesion site-specific response warranting further investigation. Systemic therapy, particularly chemotherapy, correlates with improved PFS. Given high systemic progression rates, long-term outcomes may benefit from integration with more effective systemic therapies, supporting future prospective trials.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXM1 expression is induced by the brain microenvironment and supports CRC brain metastatic adaptation.","authors":"Fayhaa Khair, Inbal Greenberg, Sivan Fuchs, Guy Shapira, Asia Zubkov, Noam Shomron, Michal Raz, Ido Wolf, Tami Rubinek","doi":"10.1007/s10585-026-10397-y","DOIUrl":"10.1007/s10585-026-10397-y","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading cause of cancer-related mortality in the Western world. While brain metastasis (BMs) are relatively uncommon in CRC, they represent the fourth most frequent cause of BMs overall, and their occurrence is increasingly recognized as a complication in advanced CRC, associated with poor prognosis and limited treatment options. The brain microenvironment presents unique metabolic challenges, including low oxygen levels and restricted lipid availability. In order to survive in this hostile environment, CRC cells must acquire metabolic adaptations allowing them to survive and proliferate. To identify key drivers that enable CRC cells to metastasize to and survive within the brain, we conducted a transcriptomic screen of CRC BMs and compared it to liver metastasis (LMs). FOXM1, a transcription factor critical for tumor progression, was identified among the upregulated genes, and these results were validated by immunohistochemistry. To study the role of the brain microenvironment in mediating FOXM1 expression, we examined FOXM1 expression in CRC cell lines grown in either astrocyte-conditioned media (A-CM) or hepatocyte-conditioned media (H-CM). We observed a marked upregulation of FOXM1 following exposure to A-CM. Moreover, using an intracranial CRC BMs mouse model, a significant FOXM1 overexpression was observed. In accordance with the importance of fatty acid metabolism in BMs, our study revealed a significant correlation between FOXM1 and fatty acid synthase (FASN) in the CRC BMs, in agreement with public databases. These findings suggest that FOXM1 plays a key role in CRC BMs progression and may serve as a promising therapeutic target in this challenging disease setting.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox processes in the treatment of advanced skin cancers.","authors":"Celine Gergele, Julia Berner, Sander Bekeschus","doi":"10.1007/s10585-026-10404-2","DOIUrl":"10.1007/s10585-026-10404-2","url":null,"abstract":"<p><p>Reactive oxygen and nitrogen species (ROS/RNS) are central regulators of cellular processes, governing signaling, metabolism, and stress responses. The source of reactive species, together with the capacity of antioxidant networks, determines whether redox signals support cell survival or provoke cytotoxicity. Dysregulation of redox homeostasis promotes genomic instability, metabolic reprogramming, immune evasion, and therapy resistance, thereby contributing to tumor initiation and progression. Tumors further adapt their metabolism and antioxidant defenses, which changes their sensitivity to oxidative stress. Consequently, redox biology emerges as a highly promising target for intervention. This review focuses on topical ROS‑based strategies for advanced skin cancer, offering an overview of fundamental redox principles and evaluating both conventional topical agents (e.g., 5‑fluorouracil and imiquimod) and direct ROS-producing modalities (e.g., photodynamic therapy and medical gas plasma). Topical ROS‑based interventions can impose defined oxidative stress on tumors, combining direct tumoricidal activity with immunogenic effects. While standard agents rely primarily on antiproliferative or immune‑stimulatory mechanisms, pro‑oxidant therapies intentionally generate ROS/RNS to induce tumor cell death and stimulate antitumor immunity. They therefore may synergize with drugs that impair antioxidant defenses or sensitize cells to ferroptosis. Advanced cutaneous malignancies are suited to topical redox interventions because their surface accessibility permits localized treatment that addresses unmet therapeutic needs. To translate these opportunities, harmonized delivery and dosimetry, validated biomarkers for tumor redox phenotypes, and prospective trials integrating pharmacodynamic and safety endpoints are required to guide patient selection and combination strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic resonance-guided stereotactic body radiotherapy (MRIgSBRT) for nodal disease in oligometastatic setting: a single-institution study.","authors":"Giuditta Chiloiro, Giulia Panza, Angela Romano, Rosa Autorino, Ciro Mazzarella, Gabriele Turco, Marco Valerio Antonelli, Matteo Nardini, Simone Raggio, Lorenzo Placidi, Maria Antonietta Gambacorta, Luca Boldrini","doi":"10.1007/s10585-026-10407-z","DOIUrl":"10.1007/s10585-026-10407-z","url":null,"abstract":"<p><p>We evaluated the feasibility and clinical outcomes of MRIgSBRT for nodal recurrence in the oligometastatic disease (OMD) setting, focusing on per-lesion outcomes and prognostic factors. We collected clinical and dosimetric data from a retrospective single-center cohort of patients treated with a 0.35 T MRIgSBRT for nodal recurrences. Endpoints included the 1-year progression-free survival (PFS), local progression-free survival (LPFS), and 3-year overall survival (OS) rate from recurrence. Per-lesion Kaplan-Meier and Cox regression assessed clinical, dosimetric, and technical predictors. 71 patients received nodal MRIgSBRT, with a total of 115 treated metastatic lesions. Local control was high: LPFS 95.5% at 12 months and 94.0% at 24/36 months. OS was favorable (100% at 12 months, 97.2% at 24 months, 95.3% at 36 months). Systemic progression drove most events: PFS 52.6% at 12 months and 24.4% at 24 months; median 12.4 months. No clinically relevant acute or late toxicity was observed. On multivariable analysis, BED₁₀ ≥ 70 Gy was independently associated with improved OS. Multiple metastases increased the risk of local failure in univariate analysis (UVA) (HR 6.30, p = 0.027). MRIgSBRT represents a safe and viable treatment option in nodal oligometastatic setting. It provides excellent and durable local control with minimal toxicity. As distant progression remains the main challenge, careful selection in low-burden disease, dose escalation to BED₁₀ ≥ 70 Gy, and thoughtful integration with systemic therapy emerge as key levers to optimize outcomes. Further prospective studies are needed to assess OMD long-term survival and quality of life and to evaluate possible further treatment optimization strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}