Clinical & Experimental Metastasis最新文献

{"title":"Nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil for metastatic pancreatic ductal adenocarcinoma following gemcitabine-based therapy. A systematic review and meta-analysis of randomized controlled trials.","authors":"Elsa Vitale, Alessandro Rizzo, Lorenza Maistrello, Angela Monica Sciacovelli, Raffaele De Luca, Anna Albano, Annarita Fanizzi, Raffaella Massafra, Claudio Lotesoriere, Gennaro Gadaleta-Caldarola, Salvatore Pisconti, Oronzo Brunetti","doi":"10.1007/s10585-026-10401-5","DOIUrl":"10.1007/s10585-026-10401-5","url":null,"abstract":"<p><p>INTRODUCTION: Pancreatic cancer has a poor prognosis. The present systematic review and meta-analysis evaluated progression free survival (PFS) and overall survival (OS) after gemcitabine-based therapy nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil for metastatic pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: The present systematic review and meta-analysis was registered in PROSPERO with id no. CRD42024608206. A systematic literature review was performed according to the PRISMA checklist, consulting Embase, PubMed, Scopus, and Web of Science databases. RESULTS: Screened studies considered median values for PFS and Hazard Ratio for OS. Heterogeneity among the selected studies was statistically significant both for PFS (P < 0.001; tau2 = 0.72; I2 = 98.67%) and OS (P = 0.010; tau2 = 0.24; I2 = 87.76%). Data indicated that PFS median values were longer in the experimental group than in the control one (Z = 4.46; P < 0.001). The results for OS showing no statistically significant difference between groups (HR = 0.79; P = 0.45). CONCLUSION: The present findings confirmed the outcomes improvements provided by nal-IRI for PDAC patients; however, our results should be interpreted cautiously. More data regarding the role of performance status, patient population, the line of treatment, and the role of eventual sequencing various regimens are awaited.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580665","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":"Encapsulated histopathological growth pattern of colorectal liver metastases predicts prolonged survival after repeat liver resection for recurrence.","authors":"Naoki Matsuyama, Takanori Konishi, Tsukasa Takayashiki, Shigetsugu Takano, Daisuke Suzuki, Nozomu Sakai, Isamu Hosokawa, Takashi Mishima, Hitoe Nishino, Kensuke Suzuki, Shinichiro Nakada, Masayuki Ohtsuka","doi":"10.1007/s10585-026-10403-3","DOIUrl":"10.1007/s10585-026-10403-3","url":null,"abstract":"<p><p>The encapsulated histopathological growth pattern (HGP) of colorectal liver metastases (CRLMs) has been reported as a favorable prognostic factor. However, its prognostic relevance in patients undergoing treatment for recurrence after liver resection remains unclear. This study aimed to evaluate the impact of encapsulated HGP on time to surgical failure (TSF) following liver resection, and to assess whether encapsulated HGP at initial resection is associated with outcomes after repeat resection for recurrence. We retrospectively analyzed 272 patients who underwent initial liver resection for CRLMs. HGPs were classified and their associations with postoperative outcomes were examined. 61 patients were classified as having encapsulated HGP. Patients with encapsulated HGP had significantly longer TSF after liver resection than those with non-encapsulated HGP (p < 0.01). Multivariate analysis identified encapsulated HGP as an independent factor for improved TSF (Hazard ratio: 0.35, p < 0.01). Recurrence occurred less frequently in encapsulated HGP than in non-encapsulated HGP (63.9% vs 79.2%, p = 0.02). In addition, patients with encapsulated HGP had a lower incidence of multi-organ recurrence and a higher repeat resection rate for recurrence (64.1% vs 45.6%, p < 0.01). Among patients with repeat liver resection for recurrent CRLMs, post-recurrence survival was significantly longer in encapsulated HGP than in non-encapsulated HGP (p = 0.01) and encapsulated HGP at initial resection was identified as an independent factor of favorable survival after repeat liver resection (Hazard ratio: 0.09, p = 0.04). Encapsulated HGP was associated with improved TSF following liver resection for CRLMs. HGPs at initial resection may predict survival after repeat liver resection for recurrent CRLMs.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480023","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":"Predictive factors of response in lung metastases treated by sbrt from colon rectal cancer.","authors":"Donatella Caivano, D Pezzulla, P Bonome, F Palmeri, C Scaringi, M Valeriani, D Musio, V de Sanctis, M F Osti","doi":"10.1007/s10585-026-10402-4","DOIUrl":"10.1007/s10585-026-10402-4","url":null,"abstract":"<p><strong>Purpose: </strong>To identify predictive factors of response in patients with lung metastases from primary colorectal cancer (CRC) treated with stereotactic body radiation therapy (SBRT). This retrospective, single-centre study included patients with histologically confirmed primary CRC, Karnofsky performance status > 60, and age > 18 years. Between 2008 and 2023, 149 lung metastases in 88 patients were treated with SBRT. Among the treated lesions, 23 were synchronous and 126 were metachronous. According to a simplified oligometastatic classification, 9 (6%) were synchronous, 57 (38%) oligorecurrent, 76 (51%) oligoprogressive, and 7 (5%) oligopersistent. Local control (LC) at 1 and 2 years was 76.8% and 64.0%, respectively. Time to polymetastatic conversion (tPMC) at 1 and 2 years was 76.0% and 73.0%. Progression-free survival (PFS) at 1 and 2 years was 76.0% and 73.0%. Overall survival (OS) at 1 and 2 years was 80.7% and 53.0%. On multivariate analysis (MVA), lesion diameter < 16 mm was the only statistically significant favorable prognostic factor for LC. No statistically significant prognostic factors were identified for tPMC or PFS on MVA. For OS, ECOG performance status 0 and female sex were the only statistically significant favorable prognostic factors on MVA. No toxicities ≥ grade 3 were reported. Outcomes and prognostic factors reported herein refer to the present single-centre cohort. In this cohort, SBRT was feasible and was associated with acceptable toxicity and encouraging local control in lung metastases from CRC. Further studies are needed to better define predictive factors and support tailored therapeutic strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479646","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":"LINC01996 suppresses non-small cell lung cancer proliferation and metastasis by orchestrating the miR-12115/CNRIP1/Ras signaling axis.","authors":"Yi Zhang, Xiaojing Li, Shanshan Liu, Qian Xue, Peize Meng, Xiaolu Ge, Qingnan Zhao, Haitao Ma","doi":"10.1007/s10585-026-10399-w","DOIUrl":"10.1007/s10585-026-10399-w","url":null,"abstract":"<p><p>Lung cancer is the most prevalent cancer and a major cause of cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been confirmed to be dysregulated in the progression of cancers. In this study, through RNA-next generation deep sequencing, we identified a new lncRNA (LINC01996), which was associated with prognosis of non-small cell lung cancer (NSCLC), downregulated in the NSCLC tissues and cell lines. We demonstrated that overexpressing LINC01996 inhibited NSCLC cell proliferation, EMT, and migration. Xenograft mouse models further validated the suppression role of LINC01996 in NSCLC progression and metastasis. By using differentially expressed genes in our RNA-next generation sequencing data, we discovered that LINC01996 was highly correlated with Cannabinoid receptor-interacting protein 1 (CNRIP1). Mechanistically, LINC01996 functions as a competitive endogenous RNA (ceRNA) by sponging miR-12115, thereby alleviating its repressive effect on CNRIP1 and leading to CNRIP1 upregulation. Overexpression of CNRIP1 ultimately inhibited Ras signaling pathway, leading to restrain of NSCLC proliferation and migration. In conclusion, LINC01996 can interact with miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate CNRIP1 positively and thus affect the proliferation and metastasis of NSCLC cells. LINC01996/miR-12115/CNRIP1/Ras signaling axis plays a suppressive role in NSCLC progression and metastasis, and could serve as potential diagnostic markers and therapeutic targets for NSCLC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472430","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":"Stereotactic ablative radiotherapy: an effective alternative for pancreatic metastases originating from renal cell carcinoma-experience from two European institutions.","authors":"Maria Ausilia Teriaca, Deesje Doppenberg, Tiziana Comito, Rodrigo Cartes, Lorenzo Lo Faro, Enrico Pozzo, Veronica Vernier, Ciro Franzese, Anna M E Bruynzeel, Marta Scorsetti","doi":"10.1007/s10585-026-10400-6","DOIUrl":"10.1007/s10585-026-10400-6","url":null,"abstract":"<p><p>Pancreatic metastases from renal cell carcinoma (RCC) are associated with a favorable prognosis in oligometastatic disease. Stereotactic ablative radiotherapy (SABR) offers a non-invasive alternative to surgery. Given the limited data in literature, we report our experience using SABR in RCC patients presenting with pancreatic oligometastases. A retrospective analysis was conducted from 2017 to 2023 in two European institutions. SABR was delivered using Volumetric Modulated Arc Therapy or Magnetic Resonance-guided technique. Local control (LC), progression-free survival (PFS), overall survival (OS), toxicity and factors impacting on survival were explored. Thirty-three patients with 46 pancreatic metastases were included. Median time to pancreatic metastases development was 12 years from nephrectomy. Median size of lesions was 16 mm and SABR dose ranged between 35 and 45 Gy in 5–6 daily fractions. At median follow-up of 25 months, four patients experienced local progression. LC rates at 1, 2 and 5 years were 100%, 89% and 76%, respectively. Median time to best local response was 9 months, with partial/complete response in 58% of patients. The 1- and 5-year OS rates were 97% and 79%, respectively. Median PFS was 23 months. Size of pancreatic metastasis was significantly correlated with PFS. After SABR, median time to new therapy was 27 months. Overall, one patient had late G3 pancreatitis and no ≥G4 events were seen. In this analysis, the largest ever reported, SABR was a safe and effective treatment for pancreatic metastases from RCC, yielding a remarkable local control with minimal toxicities and delaying the subsequent systemic therapy.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456067","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":"Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.","authors":"Laurence Blavier, Andjela Crnjac, Yves A DeClerck","doi":"10.1007/s10585-026-10396-z","DOIUrl":"10.1007/s10585-026-10396-z","url":null,"abstract":"<p><p>Tumor-derived extracellular vesicles (TEVs) have been shown to actively contribute to the establishment of the pre-metastatic niche (PMN) through multiple mechanisms of action and the transfer of cargo material to host cells. Here, we report a review of 120 manuscripts published between January 2010 and April 2025 describing observations from in vivo experiments aimed at the examination of the contribution of TEVs to the PMN and the metastatic niche (MN). Whereas most of these publications reported observations made with models of exogenous administration of TEVs prepared in vitro, five publications used endogenous models of TEVs released by implanted tumors to track their fate and examine their role in the PMN. Breast and colon cancers and melanoma are the most common types studied, and lung, liver, bone, and lymph nodes are the most common sites of metastasis examined. Methods to isolate, characterize and label TEVs in exogenous models vary significantly with differential ultracentrifugation (DUC) being the most common method of isolation used, electron microscopy, nano tracking analysis (NTA) and western blotting being used for their characterization, and lipophilic dyes used for labeling. Immunodeficient and immunocompetent mice were used in the majority (94%) with some studies done in zebrafish. Single and multiple administrations of TEVs with doses ranging from 5 to 200 µg/mouse were reported. A review of the cells targeted by TEVs, the organs involved and the effects observed in the PMN and MN, led us to identify seven functional hallmarks: (1) Immune reprogramming, (2) Stromal cell activation, (3) Vascular permeability and angiogenesis, (4) Lymphatic remodeling and lymphangiogenesis, (5) Bone remodeling, (6) Extracellular matrix (ECM) remodeling and (7) Direct tumorigenicity. Altogether, these effects create an inflammatory and immunosuppressive microenvironment that favors tumor growth. Exogenous and endogenous models have both advantages and limitations and provide important complementary information. In both models, loss of function experiments aimed at determining whether TEVs are necessary for the formation of the PMN and MN represent an important challenge. Such experiments, however, will be critical to provide evidence that targeting TEVs could be a viable approach to inhibit or prevent metastasis in patients affected by cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372284","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":"Repurposing statins for choriocarcinoma: targeting the mevalonate pathway to disrupt mechanosignaling and overcome therapeutic resistance.","authors":"Ahmed Baker A Alshaikh, Hayder M Al-Kuraishy, Souzan Kafy, Ahmed M Abdelaziz, Gaber El-Saber Batiha","doi":"10.1007/s10585-026-10395-0","DOIUrl":"10.1007/s10585-026-10395-0","url":null,"abstract":"<p><p>Choriocarcinoma is a rare but highly aggressive gestational trophoblastic tumor, characterized by early vascular invasion and distant metastasis. While cure rates exceed 90% with chemotherapy, patients with high-risk, bulky, or chemoresistant disease have a poor prognosis. This review explores the repurposing of statins as a novel therapeutic strategy, hypothesizing that their inhibition of the mevalonate pathway critically disrupts the mechanosignaling networks that drive choriocarcinoma invasion and resistance. By depleting geranylgeranyl pyrophosphate (GGPP), statins inactivate Rho family GTPases, master regulators of cytoskeletal dynamics and cellular mechanics. In choriocarcinoma models, this step leads to the collapse of the actin cytoskeleton, abrogation of cell migration, and suppression of matrix metalloproteinase activity. Preclinical studies demonstrate that achievable concentrations of simvastatin and atorvastatin reduce proliferation, trigger apoptosis, lower β-hCG secretion, and inhibit tumor growth and metastasis, even in chemoresistant lines. GGPP, but not cholesterol, reverses these effects, confirming a prenylation-dependent mechanism. To build a translational rationale, we synthesize the epidemiology, risk factors, and pathophysiology of choriocarcinoma with statin pharmacology. The evidence suggests that statins attack a core vulnerability of this malignancy by impairing mechanotransduction, effectively reprogramming the tumor cell from an invasive to a static state. We argue for early-phase clinical trials of statins in high-risk or refractory choriocarcinoma, positioning them as a promising, low-toxicity adjunct that targets the biomechanical engines of disease progression.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324973","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":"Clinical utility of the ESTRO-EORTC classification in oligometastatic disease treated with stereotactic body radiotherapy: a single-institution retrospective study.","authors":"Masaaki Goto, Tetsuo Nonaka, Daiki Maruyama, Genki Ishii, Masatoshi Nakamura, Keiichiro Baba, Hazuki Nitta, Hideyuki Sakurai","doi":"10.1007/s10585-026-10398-x","DOIUrl":"10.1007/s10585-026-10398-x","url":null,"abstract":"<p><p>This study aimed to classify patients who underwent stereotactic body radiotherapy (SBRT) for oligometastatic disease (OMD) at our institution using the consensus classification proposed by the European Society for Radiotherapy and Oncology and the European Organization for Research and Treatment of Cancer (ESTRO–EORTC) and to evaluate clinical outcomes based on this classification. Patients diagnosed with extracranial OMD who underwent SBRT, regardless of the primary tumour site, between April 2020 and December 2022 were retrospectively analysed. Based on the ESTRO–EORTC classification, cases were categorised into three OMD states: de novo, repeat, and induced OMD. We assessed overall survival (OS), local recurrence (LR) rates, and treatment-related adverse events (AEs). A total of 60 patients with 70 lesions were included, with a median follow-up of 24 months. All lesions were successfully classified according to the ESTRO–EORTC classification: 37 as de novo, 20 as repeat, and 13 as induced OMD. SBRT was delivered using the CyberKnife® system, with a median dose of 35 Gy in five fractions. The median OS for all patients was 71 months. The 1- and 2-year LR rates were 7.6% and 12%, respectively. Among OMD states, induced OMD had the poorest OS (median: 41 months), compared with de novo OMD (not reached) and repeat OMD (71 months). Only one Grade ≥ 3 AE was observed. All SBRT-treated OMD cases at our institution were successfully classified using the ESTRO–EORTC system. The classification showed potential prognostic value, suggesting its utility for stratifying patients with OMD.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257804","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 novel multimodal combining radiomics and tumor-stroma ratio (TSR) improves diagnosis of gastric cancer peritoneal metastasis.","authors":"Lin Zhong, Ting Lin, Dong Hou, Hongyun Huang, Shihai Zhou, Yu Lin, Yue Yu, Liangquan Liu, Jing Luo, Fanghai Han, Lang Xie","doi":"10.1007/s10585-026-10393-2","DOIUrl":"10.1007/s10585-026-10393-2","url":null,"abstract":"<p><p>Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer (GC), frequently leading to severe complications and a significantly poor prognosis. Prompt and early diagnosis of PM in GC is crucial. However, diagnostic laparoscopy and CT scans, while being the primary methods for identifying PM in GC, have notable limitations, such as being invasive and having low sensitivity. Therefore, developing a diagnostic model for PM in GC based on routine examination results holds substantial importance. In this retrospective study, we enrolled 813 patients from two medical centers and developed a robust diagnostic model by integrating various routine examination results, including CT scans, endoscopy, pathology, and hematological tests. To further explore the potential significance of various examination results, we conducted radiomic analysis of CT images, analyzed histopathological results via the Tumor-Stroma Ratio (TSR), and examined hematological results through parameters such as the Prognostic Nutritional Index (PNI), Neutrophil to Lymphocyte Ratio (NLR), and Albumin to Globulin Ratio (AGR). A novel diagnostic model, incorporating CA125, CA724, Borrmann classification, radiomics features, and the TSR, was successfully constructed. This model demonstrated strong performance in diagnosing synchronous PM (AUC = 0.874) and predicting metachronous (AUC = 0.784) PM in GC. To facilitate clinical application, a nomogram was constructed. Consequently, the study presents a novel and comprehensive diagnostic model for PM in GC patients, offering significant promise for clinical applicability based on routine examination results.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 2","pages":"13"},"PeriodicalIF":3.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225626","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":"Gamma knife radiosurgery for cerebellar brain metastases: clinical outcomes and artificial intelligence-based predictive modeling.","authors":"Jheremy S Reyes, Alexandros Bouras, Constantinos G Hadjipanayis, L Dade Lunsford, Ajay Niranjan","doi":"10.1007/s10585-026-10394-1","DOIUrl":"10.1007/s10585-026-10394-1","url":null,"abstract":"<p><p>Cerebellar brain metastases pose unique management challenges due to the risk of rapid neurological deterioration. Resection is often considered for large posterior fossa tumors. Gamma Knife radiosurgery (GKRS) is an established treatment for intracranial metastases, yet data dedicated to posterior fossa tumors remain limited. We retrospectively analyzed 490 patients harboring 1296 cerebellar metastases treated with GKRS between 2014 and 2024. Demographic, tumor, and dosimetry variables were collected. Overall survival (OS), local control (LC), and treatment-related toxicity were evaluated. Subgroup analyses examined tumors ≥ 10 cc. In parallel, a feedforward neural network (FNN) was developed to predict the appropriate prescription dose expected to result in the best OS, and LC for a specific patient. Across the cohort, LC was 82.5%, median OS was 10.2 months. Immunotherapy significantly improved OS (13.5 vs. 8.1 months, p < 0.001) and LC (89.4% vs. 78.1%, p = 0.012). Tumors ≥ 10 cc (n = 72) achieved outcomes comparable to smaller tumors, with OS of 11.1 months, LC of 80.6%, and minimal toxicity. Immunotherapy further improved survival and LC in this subgroup. Tumor progression was managed with repeat SRS for 10%, resection for 5%, and WBRT for 2% tumors. The FNN achieved strong predictive performance (R2 = 0.81 for dose, R2 = 0.77 for OS, AUC = 0.83 for LC), demonstrating feasibility of artificial intelligence for radiosurgical planning. GKRS provides safe and effective treatment for cerebellar metastases, including large tumors. This is the first study to integrate an FNN for outcome prediction in Gamma Knife radiosurgery, establishing a foundation for personalized, data-driven neurosurgery.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 1","pages":"12"},"PeriodicalIF":3.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118214","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}