Clinical & Experimental Metastasis最新文献

{"title":"Time to metastasis as a prognostic factor in metastatic urothelial carcinoma: results from the ARON-2 study.","authors":"Renate Pichler, Gerald Klinglmair, Kirstin Binz, Enrique Grande, Alina Pirshtuk, Hideki Takeshita, Yüksel Ürün, Javier Molina-Cerrillo, Zin W Myint, Alfonso Gómez de Liaño, Augusto Mota, Alessia Salfi, Wataru Fukuokaya, Enrico Sammarco, Martin Angel, Jakub Kucharz, Deniz Tural, Ondřej Fiala, Alejo Rodriguez-Vida, Franco Morelli, Alexandr Poprach, Mobin Safi, Alvaro Pinto, Francesco Massari, Sebastiano Buti, Shilpa Gupta, Fernando Sabino Marques Monteiro, Andrey Soares, Nicola Battelli, Ravindran Kanesvaran, Matteo Santoni","doi":"10.1007/s10585-025-10382-x","DOIUrl":"10.1007/s10585-025-10382-x","url":null,"abstract":"<p><p>Metastatic urothelial carcinoma (mUC) may present with metastases at the time of initial diagnosis (synchronous) or develop them during follow-up (metachronous). The impact of the timing of metastasis on the outcome of mUC remains unclear. We aimed to evaluate overall survival (OS) stratified by time to metastasis (TTM) in patients receiving systemic therapy in different lines. Retrospective real-world data from the ARON-2 study were analyzed to compare patient outcomes according to TTM. Cohort 1 included 735 patients receiving first-line platinum-based chemotherapy, Cohort 2 included 1164 patients receiving second-line pembrolizumab, Cohort 3 included 588 patients receiving third-line enfortumab vedotin. TTM (synchronous vs. < 6 months, and ≥ 6 months) significantly influenced overall survival (OS) in Cohort 1 (19.2 vs. 22.3 vs. 27.4 months, p = 0.004) and Cohort 2 (14.6 vs. 15.4 vs. 21.2 months, p = 0.015), but not in Cohort 3. In the multivariable Cox analysis, TTM remained an independent prognostic parameter of poor OS in Cohort 1 (hazard ratio [HR]: 1.14, 95% confidence interval [CI] 1.02-1.27; p = 0.016) and Cohort 2 (HR: 1.12, 95% CI 1.02-1.22; p = 0.014). Our findings suggest that the TTM in mUC significantly influences OS in patients receiving first-line platinum-based chemotherapy and second-line pembrolizumab. The prognostic role of TTM should be considered in the future clinical trial designs.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 1","pages":"1"},"PeriodicalIF":3.7,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562867","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":"A radiomics-driven machine learning model for predicting bladder cancer prognosis identifies genes associated with radiomic features.","authors":"Xin Chang Zou, Bin Wang, Zhan Jiang Yu, Hai Chao Chao, Xiang Da Xu, Tao Zeng","doi":"10.1007/s10585-025-10383-w","DOIUrl":"10.1007/s10585-025-10383-w","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND AND PURPOSE: Bladder cancer (BC) exhibits pronounced tumor heterogeneity, which poses a persistent clinical challenge for accurate prognostic prediction and monitoring. This study aims to develop and validate an interpretable machine learning model that leverages radiomics features to predict BC outcomes, while also investigating associated genetic signatures and their relationship with tumor immunity. METHODS: RNA-seq data were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Clinicopathological parameters and radiomics features for bladder cancer (BC) cases were obtained from TCGA and The Cancer Imaging Archive (TCIA). Differentially expressed genes (DEGs) were identified from both TCGA and GEO datasets. Key radiomics features were selected through univariate Cox regression followed by LASSO-Cox regression, while independent clinicopathological prognostic factors were determined using univariate and multivariate Cox regression analyses. A support vector machine (SVM)-based prognostic model was developed by integrating clinicopathological and radiomics features. The performance of this model was evaluated against three other machine learning models using ROC curves, accuracy, precision, and F1-score. Feature importance scores were computed, and model interpretability was enhanced using SHapley Additive exPlanations (SHAP). Based on the feature importance coefficients derived from the SVM model, BC patients were classified into distinct risk groups. Subsequently, radiomics-associated DEGs were analyzed to pinpoint key genes linked to imaging phenotypes. These genes were subjected to functional annotation via Gene Ontology (GO), pathway enrichment analysis using KEGG, gene set enrichment analysis (GSEA), and immune infiltration analysis to investigate potential patterns of immune cell enrichment. RESULTS: After rigorous screening, 91 bladder cancer patients with high-quality enhanced CT images, complete clinicopathological data, and RNA sequencing profiles were included in the study. These patients were randomly allocated to a training set and a validation set at a 7:3 ratio to develop an SVM-based model for estimating the 5-year overall survival (OS) in muscle-invasive bladder cancer. The model demonstrated robust predictive performance, with an area under the ROC curve (AUC) of 0.861, an accuracy of 0.889, a precision of 0.790, and an F1 score of 0.837. Decision curve analysis (DCA) confirmed the model’s significant net clinical benefit. Through integrated analyses of TCGA (n = 406) and GEO (n = 175) datasets, we identified 500 DEGs, which were refined to 240 radiomics-associated DEGs based on SVM-derived risk stratification. Immune infiltration analysis revealed that levels of NK cells, M0 macrophages, memory B cells, and activated dendritic cells were significantly higher in normal tissues compared to tumor tissues, indicating an immunologically favorable tumor microenvironment. Additionally,","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"63"},"PeriodicalIF":3.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511573","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":"Borderline decisions in brain-metastatic breast cancer: efficacy of multimodality treatments in breast cancer patients with very limited prognosis suffering from brain metastases.","authors":"Stephanie Bendrich, Marc Alexander Wilhelm Pietrkiewicz, Markus Anton Schirmer, Hanne Elisabeth Ammon, Leif Hendrik Dröge, Laura Anna Fischer, Carla Marie Zwerenz, Charlotta Friederike Pagel-Nozari, Stefan Rieken, Julia Gallwas, Manuel Guhlich, Sandra Donath","doi":"10.1007/s10585-025-10376-9","DOIUrl":"10.1007/s10585-025-10376-9","url":null,"abstract":"<p><p>Diagnosis of brain metastases (BM) has traditionally marked a turning point in treatment goals and prognosis of patients with breast cancer (BC). However, new systemic treatment options have both prevented the development and improved the prognosis of BC patients with BM. Stereotactic radiotherapy techniques (SRT) have widely replaced whole brain radiotherapy (WBRT) in patients with limited BM, yielding impressive survival at modest toxicity rates. However, based on established prognostic scores, many patients will not profit from modern SRT treatment concepts and, therefore, remain candidates for WBRT or best supportive care (BSC). Here, treatment decisions may be challenging. This study aims to describe clinical outcomes and explore potential prognostic factors in a single-center cohort of BC patients treated with WBRT comprising patients across the prognosis continuum reflecting everyday work routine. We retrospectively analyzed 108 patients diagnosed with BM who received WBRT between 2008 and 2020. The cohort included patients with a broad range of prognostic factors (≥ 60 years old, Karnofsky Performance Status [KPS] ≤ 70, >3 BM and a Graded Prognostic Assessment [GPA] score < 1 [anticipated life expectancy of < 4 months]), who were either treated with palliative WBRT alone or in case of focal symptoms attributed to individual location of metastasis with surgery, SRT, or WBRT + focal dose escalation (\"boost\"). Survival rates were estimated using the Kaplan-Meier method, and factors potentially affecting outcome were statistically assessed by the log-rank test. Uni- and multivariable Cox regression was used in survival analysis to estimate hazard ratios and to evaluate the influence of various variables on survival time. For all statistical procedures SPSS software (v. 26) was used. Median survival after diagnosis of BM was 4 months (95% CI 3-5 months). The most relevant negative prognostic factor within the group of GPA-classifiers was KPS (≤ 70), followed by the number of BM (>3). Metastasectomy displayed significantly improved survival in univariable analysis (log rank p = 0.008; Cox-Regression p = 0.018), but did not elicit as predictive for OS in multivariable analysis (p = 0.47). Furthermore, completion of the prescribed RT series had the strongest impact on OS in both univariable and multivariable Cox regression analyses (p < 0.00001) while delivery of a radiation boost in addition to WBRT exerted no significant benefit (Cox regression p = 0.358). Despite the continuous development of effective treatment strategies for BM, BC patients who are ineligible for innovative treatment modalities show poor survival rates. Following prognostic assessment may help to make treatment decisions. KPS and number of BM may be most important in this context. In our retrospective cohort surgical removal of BM and completion of RT series were associated with improved prognosis, while focal radiation dose escalation in addition to WBRT was not.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"62"},"PeriodicalIF":3.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12559089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376669","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":"Defining the Tumor-Bone axis: the role of extracellular vesicles in a crucial exchange route for breast cancer development and progression.","authors":"Carlos D Coronado-Alvarado, Humberto Astiazaran-Garcia","doi":"10.1007/s10585-025-10377-8","DOIUrl":"10.1007/s10585-025-10377-8","url":null,"abstract":"<p><p>Bone disorders frequently manifest as long-term outcomes of breast cancer. Consequently, the relationship between breast cancer and bone metabolism is often studied at advanced stages of the disease. Emerging evidence suggests that bidirectional communication between mammary and bone tissues begins much earlier. In this context, extracellular vesicles (EVs) have been recognized as key mediators of intercellular communication, with emerging evidence supporting their role in breast cancer progression and the regulation of bone metabolism. This review examines bone imbalances occurring throughout the course of breast cancer, the pathophysiological mechanisms behind them, and the role of EVs in their development. From this integrated perspective, we propose the concept of Tumor-Bone Axis, a continuous and dynamic crosstalk between breast cancer and bone cells that supports tumor progression and bone complications. This axis regulates distinct metabolic states governing the activity of breast cancer cells and the balance in bone remodeling, enabling cellular reprogramming events during malignant transformation, immunoediting, tumor growth, and metastasis formation. Additionally, the impact of antineoplastic treatments on this axis may underlie chemoresistance, relapse, or therapy-induced metastasis. While multiple mediators are involved-including cell-to-cell contact, cell migration, osteoimmune interactions, hormones, soluble factors, and nutrients-EVs appear to be critical, especially through their role in exchanging epigenetic regulators of central signaling pathways in these cellular reprogramming events. Understanding the temporal and functional dynamics of the Tumor-Bone Axis and the extracellular vesicular traffic within it could reveal novel diagnostic biomarkers and therapeutic strategies for both breast cancer and its bone-related manifestations.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"59"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307061","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":"Differentiation grade is highly concordant between matched primary and metastatic colorectal cancer.","authors":"Camilla M Reehorst, Jennifer K Mooi, Charles J Uy, Kristen A Needham, Sarah Ellis, Ian Y Luk, Laura J Jenkins, Rebecca Nightingale, Fiona Chionh, Andreas Behren, Niall C Tebbutt, David S Williams, John M Mariadason","doi":"10.1007/s10585-025-10380-z","DOIUrl":"10.1007/s10585-025-10380-z","url":null,"abstract":"<p><p>Differentiation grade of colorectal cancers (CRC) is histologically defined by the proportion of the tumour which retains the glandular architecture of the normal colon. Poorly differentiated CRCs display loss of glandular architecture and canonical markers of colonic differentiation and are associated with increased metastatic capacity and poorer prognosis. It is currently unclear whether poorly differentiated cells within a heterogeneous primary tumour are more likely to establish metastases and if this cellular trait is conserved in the secondary tumours, or whether metastasis is largely stochastic, with most cells in the primary tumour harboring metastatic potential. To explore this, we examined the concordance in histological grade, expression of markers of colonic differentiation, and epithelial to mesenchymal transition (EMT) in 67 matched primary and metastatic CRCs. Tumour differentiation grade was scored categorically, and expression of differentiation and EMT markers were scored as continuous variables. In matched primary-metastatic pairs, tumour grade was concordant in 88% of cases (59/67 pairs), irrespective of the site of metastasis. In tumour pairs with discordant grade (n = 8), tumour grade was higher in the metastatic lesion in 6/8 (75%) cases. Consistent with the histological concordance, expression of the key driver of colonic differentiation (CDX2); colonic lineage-specific markers (VIL1, MUC2, SYN and CHG); and the markers of epithelial-to-mesenchymal transition (E-Cadherin and Vimentin) were highly concordant between matched primary and metastatic lesions. Finally, no staining of the squamous lineage marker Cytokeratin5/6 was observed in either primary or metastatic tumours. Tumour grade assessed histologically or using expression of markers of colonic differentiation or epithelial to mesenchymal transition was largely concordant between primary and metastatic CRC. These findings complement previously reported genomic similarities between primary and metastatic lesions and demonstrate that the histological grade of a primary tumour can in most cases inform the differentiation grade of associated metastatic lesions.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"61"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307064","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":"Postoperative stereotactic radiotherapy for brain metastases: results from a single-center retrospective analysis.","authors":"E K M Lam, D K C Leung, V H F Lee, B B T Taw, L F Li, G Ho, H C W Choi, B M F Cheung, J S C Cheung, Y P Ng, M Y Luk, K K Yuen","doi":"10.1007/s10585-025-10379-6","DOIUrl":"10.1007/s10585-025-10379-6","url":null,"abstract":"<p><p>To evaluate outcomes and prognostic factors in patients with resected brain metastases treated with postoperative SRS/SRT, and to develop a novel overall survival (OS) prognostic model. We retrospectively analyzed 70 patients (72 lesions) treated with postoperative SRS/SRT from July 2017 to May 2024. Outcomes included in-field and out-field intracranial progression-free survival (PFS), OS, and incidence of radionecrosis. Prognostic factors were identified using Cox regression. Recursive Partitioning Analysis (RPA) was used to construct an OS model. Median follow-up was 15.1 months. In-field PFS was 96.2% and 90.2%; Out-field PFS was 69.3% and 64.4% at 1 and 2 years respectively. Prior cranial radiotherapy was associated with worse out-field PFS. OS rates were 67.5% at 1 year, 46.7% at 2 years. ECOG performance status, time from surgery to radiotherapy of ≤ 56 days and biologically effective dose using α/ß of 10 (BED₁₀) ≥ 51 Gy were significant OS predictors. Radionecrosis occurred in 7 patients (10%) with median onset at 25.0 months. The novel RPA model stratified patients into 3 groups: RPA-I (ECOG < 2 & BED₁₀ ≥ 51 Gy; median OS 43.4 months, 95% CI 22.3 months-Not reached), RPA-II (ECOG < 2 & BED₁₀ < 51 Gy; median OS 11.9 months, 95% CI 3 months-19.2 months) and RPA-III (ECOG ≥ 2 regardless of BED₁₀ delivered; median OS 4.1 months, 95% CI 1.2 months - 22.0 months) (p < 0.001). RPA-II and RPA-III had higher death risk compared with RPA-I. This model outperformed existing models after bootstrapping validation. Postoperative SRS/SRT is effective for brain metastases. Appropriate patient selection, timely initiation and sufficient radiation dose improve outcomes. Our novel RPA model offers promising prognostic stratification for guiding treatment decisions.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"60"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307038","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":"Adhesion to aggression: unravelling sLe^a and sLe^x in cancer metastasis.","authors":"Prasanna H Megalamani, Anne Harduin-Lepers, J Manasa, Maruti J Gurav, Ashwini S Sanji, Vishwanath B Chachadi","doi":"10.1007/s10585-025-10378-7","DOIUrl":"10.1007/s10585-025-10378-7","url":null,"abstract":"<p><p>The sialylated Lewis antigens sLe^a and sLe^x are terminal glycans that are crucial for adhesive and signalling functions during cancer metastasis. As high affinity ligands for E-, P-, and L-selectins, these epitopes allow tumor cells to arrest, evade immune cells and extravasate in the vascular microenvironment, mimicking leukocyte trafficking. This review provides a detailed analysis of sLe^a/x biosynthesis, structure, function and their role in metastatic progression. We focus on the differential roles of glycoprotein versus glycolipid associated sLe^a/x, their glycosyltransferase mediated synthesis and the spatial trafficking mechanisms that govern their surface expression. We also highlight the carrier scaffolds and glyco-enzyme hierarchies that present the ligand across different cancers, mucins, integrins and glycosphingolipids. A section is dedicated to how exosome bound sLe^a/x primes pre-metastatic niche and immune modulation, a new perspective on glycan mediated systemic signaling. We also compile validated tumor specific profiles of sLe^a/x across several cancer types, linking structural expression to metastatic phenotypes. Additionally, we discuss emerging strategies targeting sLe^a/x pathways from glycosylation inhibitors to selectin blocking therapeutics and the translational challenges and opportunities. Overall, this synthesis shows the importance of sLe^a and sLe^x in metastasis and lays the foundation for their use as biomarkers and therapeutic targets in precision oncology.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"58"},"PeriodicalIF":3.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307115","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":"Dosimetric comparison of fractionated gamma knife icon and cyber ​​knife radiosurgery treatment plans in patients with intracranial metastatic tumors.","authors":"Esil Kara, Özlem Dagli","doi":"10.1007/s10585-025-10373-y","DOIUrl":"10.1007/s10585-025-10373-y","url":null,"abstract":"<p><p>This study aims to compare the dosimetric performance of GammaKnife ICON and CyberKnife S7 radiosurgery systems in the treatment of single brain metastases using a fractionated stereotactic schedule. Fifteen patients with single brain metastases were retrospectively and consecutively included. For each patient, treatment plans were generated using both GammaKnife ICON and CyberKnife S7 systems, delivering a total dose of 27 Gy in three fractions. Dosimetric parameters including Paddick Conformity Index (PCI), Gradient Index (GI), Heterogeneity Index (HI), beam-on time (BOT), and doses to organs at risk (OARs) were compared across modalities and stratified by target volume. GammaKnife plans showed significantly higher PCI (0.862 vs. 0.825; p < 0.05) and lower HI (1.94 vs. 2.09; p < 0.05), indicating superior dose conformity and acceptable heterogeneity. GI was lower for GammaKnife, though not statistically significant. BOT was significantly shorter for GammaKnife (14.2 vs. 34.3 min; p < 0.05). Brainstem doses were significantly lower in GammaKnife plans, especially for lesions close to critical structures. Volume-based subgroup analysis confirmed that GammaKnife consistently delivered more conformal and steep dose distributions across all tumor sizes. GammaKnife ICON demonstrates dosimetric superiority in conformity, gradient sharpness, and treatment efficiency. These advantages may translate into improved clinical outcomes, such as enhanced local control, reduced toxicity, and increased patient comfort through shorter treatment sessions and better motion management. Gamma Knife, CyberKnife, Brain Metastasis, Radiosurgery.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 6","pages":"57"},"PeriodicalIF":3.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250310","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":"The abscopal effect in metastatic lung cancer: a retrospective analysis of combined radiotherapy and immunotherapy.","authors":"David Alexander Ziegler, Markus Ambold, Markus Anton Schirmer, Leif Hendrik Dröge, Sonia Ziegler, Benedikt Kieslich, Laura Anna Fischer, Sandra Donath, Jona Bensberg, Martin Leu, Manuel Guhlich, Lisa Antonia von Diest, Friederike Braulke, Alexander von Hammerstein-Equord, Stefan Andreas, Stefan Rieken, Achim Rittmeyer, Rami El Shafie","doi":"10.1007/s10585-025-10375-w","DOIUrl":"10.1007/s10585-025-10375-w","url":null,"abstract":"<p><strong>Background: </strong>The abscopal effect (AbE) refers to the regression of non-irradiated tumors following localized radiotherapy (RT), suggesting a systemic immune-mediated response. The combination of RT with immunotherapy (IO) has been proposed to enhance the AbE by overcoming RT-induced immunosuppressive mechanisms, but robust evidence, specifically in non-small cell lung cancer (NSCLC), is lacking. This study aimed to determine the prevalence of the AbE and its association with progression-free survival (PFS) and overall survival (OS) in metastatic lung cancer patients receiving RT and IO.</p><p><strong>Materials and methods: </strong>We analyzed consecutive metastatic lung cancer patients who received IO at a certified lung cancer center in Germany between 2009 and 2021. Inclusion required RT to at least one lesion and at least one measurable non-irradiated lesion. The AbE was defined as radiological regression of a non-irradiated lesion following RT. PFS and OS were analyzed using Kaplan-Meier estimates and Cox regression models. Factors influencing survival, such as RT site selection and IO duration, were assessed in univariable and multivariable analyses.</p><p><strong>Results: </strong>A total of 72 patients were included. The AbE was observed in 9.3% (n = 7). While the AbE was significantly associated with prolonged PFS (HR = 0.41, 95% CI: 0.19-0.92, p  = 0.03), it did not significantly impact OS (HR = 0.70, 95% CI: 0.30-1.64, p  = 0.41). In contrast, RT to the primary tumor (HR = 0.16, p = 0.004) and longer IO duration (HR = 0.83, p = 0.001) were strong predictors of improved OS.</p><p><strong>Conclusion: </strong>While the AbE remains an intriguing phenomenon, its occurrence was rare and not significantly associated with OS. Strategic RT site selection and optimized treatment sequencing were more strongly linked to improved survival outcomes, highlighting the need for refined radioimmunotherapy strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"56"},"PeriodicalIF":3.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148161","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":"Correction: Associations amongst genes, molecules, cells, and organs in breast cancer metastasis.","authors":"S David Nathanson, Lothar C Dieterich, Xiang H-F Zhang, Dhananjay A Chitale, Lajos Pusztai, Emma Reynaud, Yi-Hsuan Wu, Alejandro Ríos-Hoyo","doi":"10.1007/s10585-025-10371-0","DOIUrl":"10.1007/s10585-025-10371-0","url":null,"abstract":"","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 5","pages":"55"},"PeriodicalIF":3.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084883","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}