Clinical & Experimental Metastasis最新文献

{"title":"m1A-regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19.","authors":"Shuyi Mi, Jie Hu, Wenwen Chen, Jingyu Chen, Zhipeng Xu, Meng Xue","doi":"10.1007/s10585-024-10323-0","DOIUrl":"10.1007/s10585-024-10323-0","url":null,"abstract":"<p><strong>Background: </strong>In recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC).</p><p><strong>Methods: </strong>We performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets. The role of DIAPH3 in the migration and invasion of CRC cells was evaluated using wound healing assay, Transwell assay and xenograft metastatic model. The downstream targets of DIAPH3 were screened using mass spectrometry. By co-transfecting DIAPH3 siRNA and a keratin 19 (KRT19) ectopic plasmid into CRC cells, the role of DIAPH3-KRT19 signaling axis was confirmed.</p><p><strong>Results: </strong>The mRNA level of DIAPH3 and its m1A modifications increased simultaneously in the CRC tissues. In addition, high DIAPH3 expression in CRC tissues is significantly associated with metastasis and progression to an advanced stage. After the knockdown of DIAPH3, the migration and invasion capabilities of CRC cells suffered a notable decline, which could be rescued by overexpressing KRT19. In addition, the proteasome inhibitor MG132 could block the degradation of KRT19 induced by DIAPH3 silencing.</p><p><strong>Conclusions: </strong>Our study reveals that DIAPH3 mRNA was modified in CRC cells by m1A methylation. Silencing DIAPH3 suppresses the migration and invasion of CRC cells, potentially through the proteasome-dependent degradation of downstream KRT19.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 2","pages":"10"},"PeriodicalIF":4.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022310","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":"Efficacy of radiotherapy in treating local recurrence concomitant with distant metastasis of nasopharyngeal carcinoma: a long-term retrospective multicenter study.","authors":"Lu Li, Mingyou Deng, Jianlan Ren, Wenjun Liao, Liangjian Zheng, Hui Ma, Jinyi Lang, Mei Feng, Yangkun Luo","doi":"10.1007/s10585-025-10329-2","DOIUrl":"https://doi.org/10.1007/s10585-025-10329-2","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with nasopharyngeal carcinoma (NPC) experiencing locoregional recurrence concomitant with distant metastases (rmNPC) after initial treatment represent a unique subgroup with significant management challenges. This study aimed to evaluate overall survival (OS) in rmNPC patients treated with systemic therapies with or without radiotherapy.</p><p><strong>Methods: </strong>This retrospective multicenter study included patients with locally recurrent and metastatic NPC from five hospitals. Kaplan-Meier analyses and log-rank tests were applied to assess survival outcomes based on recurrence and metastasis profiles, as well as treatment modalities. Independent prognostic factors affecting OS were identified using Cox regression models.</p><p><strong>Results: </strong>A total of 52 patients were analyzed, with a median follow-up duration of 68.3 months (range: 7-240 months). The median OS was 23.4 months (range: 11.1-35.6 months), and the 1-, 2-, 3-, 4-, and 5-year OS rates were 61.3%, 46.5%, 31.0%, 27.9%, and 10.5%, respectively. The treatment modality did not significantly affect OS overall (P = 0.071). Median OS was 10.8 months (95% CI, 7.7-13.9) for chemotherapy alone, 24.2 months (95% CI, 8.9-39.4) for chemotherapy combined with PD-1 inhibitors, and 47.1 months (95% CI, 10.2-84.0) for chemotherapy combined with radiotherapy. In patients with oligometastasis, radiotherapy significantly improved OS (50.1 vs. 24.1 months, P = 0.021), whereas no significant OS benefit was observed for radiotherapy in polymetastatic patients (8.6 vs. 14.8 months, P = 0.168). Similarly, radiotherapy extended OS in patients with one-organ metastases (50.1 vs. 24.1 months, P = 0.026), while no significant benefit was observed in those with multiple-organ metastases (8.6 vs. 11.0 months, P = 0.831).</p><p><strong>Conclusions: </strong>Radiotherapy, when combined with other treatment modalities, significantly improves OS in rmNPC patients with oligometastases or one-organ metastases.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 2","pages":"11"},"PeriodicalIF":4.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022290","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":"Metastatic sites and clinical outcomes in renal cell carcinoma patients receiving immune-based combinations: the MOUSEION-08 study.","authors":"Alessandro Rizzo, Fernando Sabino Marques Monteiro, Veronica Mollica, Oronzo Brunetti, Elsa Vitale, Angela Monica Sciacovelli, Andrey Soares, Francesco Massari, Matteo Santoni","doi":"10.1007/s10585-024-10327-w","DOIUrl":"10.1007/s10585-024-10327-w","url":null,"abstract":"<p><p>Immune-based combinations have significantly improved the treatment of metastatic renal cell carcinoma (mRCC); however, immunotherapy has reported varying degrees of efficacy across different metastatic sites, with liver and bone metastases traditionally considered more challenging to treat. In MOUSEION-08 study, we aimed to investigate the association between lung, liver, and bone metastases and clinical outcomes such as Overall Survival (OS) and Progression- Free Survival (PFS) in mRCC patients receiving immune-based combinations. The present systematic review and study-level meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PFS and OS were measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). The protocol was registered with PROSPERO, Registration number: CRD42024581488. Our search resulted in the identification of 2364 potentially relevant reports, which were subsequently restricted to three. The pooled HRs for OS and PFS in patients with lung metastases receiving immune-based combinations versus sunitinib were 0.61 (95% CI, 0.51-0.72) and 0.47 (95% CI, 0.38-0.59), respectively. In patients with liver metastases, the pooled HRs for OS and PFS were 0.56 (95% CI, 0.42-0.75) and 0.48 (95% CI, 0.34-0.67), while the pooled HRs for OS and PFS in patients with bone metastases were 0.64 (95% CI, 0.49-0.84) and 0.36 (95% CI, 0.27-0.49), respectively. According to our findings, the analyses reported similar HRs for OS and PFS, something that further underlines the role of immune-based combinations in this setting, regardless of metastatic sites, such as lung, liver, and bone metastases. Ongoing research and clinical trials are destined to refine and improve immunotherapeutic strategies for mRCC, aiming to enhance efficacy across all metastatic sites and to define predictive biomarkers.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"9"},"PeriodicalIF":4.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909283","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":"Establishing patient-derived tumor organoids of bone metastasis from lung adenocarcinoma reveals the transcriptomic changes underlying denosumab treatment.","authors":"Xianglin Hu, Huajian Wu, Kewen Hu, Yani Kang, Guoqiang Hua, Mo Cheng, Wangjun Yan, Wending Huang","doi":"10.1007/s10585-024-10321-2","DOIUrl":"10.1007/s10585-024-10321-2","url":null,"abstract":"<p><p>Patient-derived tumor organoids (PDTOs) models have been widely used to investigate the response of primary cancer tissues to anti-cancer agents. Nonetheless, only few case study tried to establish PDTOs and test treatment response based on bone metastasis (BoM) tissues. Fresh BoM tissues were obtained from lung cancer (LC) patients who underwent spinal metastatic tumor surgery for PDTOs culture. Morphology of LC-BoM-PDTOs were characterized during the process: they were high-efficient in self-assembly and regeneration, forming mature 3D-multicellular structures in 2-3 weeks. To be more specific, organoids of BoM derived from patients with EGFR mutation tended to be follicular conglomeration and resembled \"a bunch of grapes\", while organoids of BoM derived from patients without driver gene mutation were featured with full sphere and \"a ripe sunflower\". PDTOs of BoM retained good consistencies of HE morphology and immunohistochemical markers expression with their parental BoM tissues. Down-regulation of receptor activator of nuclear factor kappa-B ligand (RANKL) expression in LC-BoM-PDTOs after in vitro DMAb intervention was associated with earlier clinical ossification efficacy of DMAb on BoM (median time: 5 vs. 8 months, P = 0.049). Accordingly, BoM-PDTOs can be expected to be a preferred model for predicting treatment response of bone metastatic tumors, considering its high-efficient expansion and good biological consistency with parental bone tumor tissues.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"8"},"PeriodicalIF":4.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909282","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":"Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.","authors":"Kimberly J Jasmer, Vinit C Shanbhag, Kevin Muñoz Forti, Lucas T Woods, Nikita S Gudekar, Gary A Weisman, Michael J Petris","doi":"10.1007/s10585-024-10325-y","DOIUrl":"10.1007/s10585-024-10325-y","url":null,"abstract":"<p><p>Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck. In this study, we demonstrated that elevated LOX expression correlates with decreased overall survival and shorter median time to first progression in patients with lung cancer. Previous studies have demonstrated that LOX secreted from tumors is critical for pre-metastatic niche formation by promoting ECM remodeling and the recruitment of immune cells and endothelial precursors. Here, we demonstrated that ablation of the LOX gene in Lewis lung carcinoma (LLC) cells diminishes tumor growth and metastasis compared to wild-type LLC cells in a syngeneic mouse model. Although the role of tumor-derived LOX in tumor formation and metastasis is well established, little is known regarding the possible contribution of LOX produced by the parenchymal tissue of metastatic organs. Thus, this report describes our findings that host-derived LOX produced by the lung contributes to the pulmonary metastasis of LLC cells in mice. The suppression of pulmonary lysyl oxidase expression reduces the metastatic potential of Lewis Lung Carcinoma cells in mice, revealing a previously unknown influence of LOX expression in the parenchymal tissue of metastatic target organs on the seeding of tumor cells.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"7"},"PeriodicalIF":4.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876337","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":"Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study.","authors":"Alexander Fabian, Daniel Buergy, Fabian Weykamp, Juliane Hörner-Rieber, Denise Bernhardt, Judit Boda-Heggemann, Montserrat Pazos, Nora Mehrhof, David Kaul, Alicia S Bicu, Eugenia Vlaskou Badra, Susanne Rogers, Stefan Janssen, Hossein Hemmatazad, Katharina Hintelmann, Eleni Gkika, Tim Lange, Konstantinos Ferentinos, Heiko Karle, Thomas Brunner, Andrea Wittig, Marciana Nona-Duma, Oliver Blanck, David Krug","doi":"10.1007/s10585-024-10326-x","DOIUrl":"10.1007/s10585-024-10326-x","url":null,"abstract":"<p><p>Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site. Outcomes included local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Cumulative incidence analysis was used for LR, Kaplan-Meier estimates for PFS and OS. Covariables included patient, disease, and SRT characteristics. We performed univariable and multivariable analyses (MVA). Among 444 patients, 751 metastases were treated with SRT. Of these, 73% were intracranial and 27% extracranial lesions. Oligometastatic disease (OMD) was present in 66% of the patients. LR after two years occurred significantly more often in intracranial (25%) versus extracranial lesions (7%). In MVA of patients with OMD treated for intracranial sites, higher performance status was significantly associated with longer PFS. Further, higher performance status, biologic subtype (HR-pos./HER2-pos.), and MDT to all sites were significantly associated with longer OS. In MVA of oligometastatic patients treated for extracranial sites, biologic subtype (HR-neg./HER2-pos.) and synchronous metastasis were associated with significantly longer PFS, whereas higher grading was associated with significantly shorter PFS. Moreover, biologic subtype (HR-neg./HER2-neg.) was associated with significantly shorter OS. In conclusion, the role of MDT for breast cancer may vary per clinical scenario. Patients with OMD treated for intracranial lesions who had MDT to all sites showed superior OS. Our results should be validated prospectively.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"6"},"PeriodicalIF":4.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871640","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":"Current preclinical models of brain metastasis.","authors":"Zacharie Drouin, Flavie Lévesque, Korina Mouzakitis, Marilyne Labrie","doi":"10.1007/s10585-024-10318-x","DOIUrl":"10.1007/s10585-024-10318-x","url":null,"abstract":"<p><p>Brain metastases (BMs) represent the most prevalent intracranial malignancy within the adult. They are identified in up to 20% of patients with solid tumors and this percentage varies between tumor types and age. Due to the selective permeability of the blood-brain barrier, most anticancer drugs can't reach significant concentrations in the brain, representing a major obstacle to the patients' survival. Furthermore, intra- and inter-patient heterogeneity and the unique brain microenvironment add a layer of complexity to the clinical management of BMs. In the perspective of finding new therapeutic approaches and better understanding the molecular mechanisms involved in brain metastasis, the use of appropriate preclinical models is essential. Here, we review current in vivo, in vitro and ex vivo models for the study of brain metastasis while outlining their advantages and limitations.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"5"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853205","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":"Stereotactic ablative radiotherapy for pulmonary metastasis from sarcoma: a retrospective comparison with metastasectomy.","authors":"Youngju Song, Yeon Joo Kim, Sehoon Choi, Jae Kwang Yun, Jin-Hee Ahn, Jeong Eun Kim, Jong Seok Lee, Wanlim Kim, Kyung-Hyun Do, Hye Won Chung, Geun Dong Lee, Si Yeol Song","doi":"10.1007/s10585-024-10320-3","DOIUrl":"10.1007/s10585-024-10320-3","url":null,"abstract":"<p><p>Recent studies report excellent local control (LC) and favorable toxicities of stereotactic ablative radiotherapy (SABR) for pulmonary metastasis (PM) from sarcoma. This study compared the LC and survival of SABR and metastasectomy for sarcoma PM. We analyzed the LC rates of 54 PMs treated with SABR between 2008 and 2022. For survival analysis, we compared 14 patients who received SABR as first-line treatment with 61 patients who underwent metastatectomy. For SABR-treated PMs, a median total dose of 55 Gy (range, 48-60) was administered over 3-10 fractions. Median follow-up for LC in SABR-treated PMs was 19.2 months (range, 0.8-124.0), and the 2-year LC rate was 92.2%. No patients experienced toxicities of grade 3 or higher. The median age of the patients in the survival analysis was 73 years (range, 42-83) in the SABR group and 54 years (range, 19-78) in the metastasectomy group (p < 0.001). PMs in the \"gray zone\" were more common in the SABR group (35.7%) than in the metastasectomy group (8.2%) (p = 0.029). The median follow-up for survival analysis was 44.8 months (interquartile range, 21.5-66.4). The 3-year rates of LC and overall survival were 92.3% and 57.3% in the SABR group and 89.2% and 75.9% in the metastasectomy group (p = 0.807, 0.224), respectively. The out-of-field intrapulmonary failure-free survival and extrapulmonary systemic failure-free survival rates at 3 years were not significantly different (p = 0.673, 0.386). SABR for sarcoma PM demonstrated excellent LC with acceptable toxicity. Survival rates of SABR were comparable to those of metastasectomy.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"2"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827545","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":"Multi-institutional study using sbrt to treat mediastinal and hilar lymphadenopathy.","authors":"D Caivano, D Pezzulla, P Bonome, C Ricciardi, P Zuccoli, M Rotondi, R C Sigillo, M Serio, F Giannetti, A Molinari, C Menichelli, M Valeriani, V De Sanctis, A Fanelli, M F Osti","doi":"10.1007/s10585-024-10324-z","DOIUrl":"10.1007/s10585-024-10324-z","url":null,"abstract":"<p><p>Mediastinal and hilar lymphadenopathy (MHL) is a common pattern of cancer spread, particularly in lung disease. Recently, there has been interest in the use of SBRT for MHL, especially in the oligometastatic setting. The goal is to improve local control (LC) and to achieve shorter treatment durations to minimize systemic treatment interruptions. The primary endpoint of this study was local control (LC). The secondary endpoints were distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) and predictive factors of response. This is a retrospective study. It analyses a group of patients treated with SBRT for MHL with different primary tumours and histologies. From November 2007 to June 2023, we treated 159 MHL in 128 patients. The primary most represented was lung cancer. A single fraction was used in 16% of cases and multiple fractions in 84% of cases. The medium BED 10 was 75.06 Gy (range: 37-120 Gy). Actuarial LC rates at 1, 2 and 5 years were 80.0%, 78.8% and 75.2%. The actuarial DMFS rates at 1, 2 and 5 years were 43.9%, 34.1% and 14.1%, respectively. Actuarial PFS rates at 1, 2 and 5 years were 37.2%, 23.9% and 8.3%, respectively. Actuarial OS rates at 1, 2 and 5 years were 68.8%, 52.7% and 26.9%, respectively. SBRT may be an option for the treatment of MHL. In addition, achieving a complete response is one of the most important predictors of our endpoints, in addition to tumour burden and volume.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"4"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827544","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":"Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis.","authors":"Alessandro Rizzo, Fernando Sabino Marques Monteiro, Veronica Mollica, Andrey Soares, Oronzo Brunetti, Angela Dalia Ricci, Francesco Massari, Matteo Santoni","doi":"10.1007/s10585-024-10322-1","DOIUrl":"10.1007/s10585-024-10322-1","url":null,"abstract":"<p><p>Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Overall Survival (OS) was measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). Our search resulted in the identification of 1429 potentially relevant reports, which were subsequently restricted to four following independent evaluation of three authors. The pooled HR for OS in RCC patients receiving early ToD versus late ToD dosing was 0.62 (95% Confidence Interval, 0.50-0.72; p < 0.001). According to our findings, a statistically significant improvement in terms of OS for mRCC patients receiving early ToD administration compared with late ToD dosing was observed, with a reduction of death by 38%. Well-designed, randomized clinical and translational trials are required to clarify this issue and to establish recommendations for personalized treatments according to ToD.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"42 1","pages":"3"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827531","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}