Nerma Crnovrsanin, Sarah Zumsande, Ingmar Florin Rompen, Sabine Schiefer, Sarah Zimmer, Wenjun Hu, Johanna Arnscheidt, Fritz Brinkmann, Thomas Longerich, Georg Martin Haag, Thomas Schmidt, Mohammed Al-Saeedi, Leila Sisic, Henrik Nienhüser
{"title":"基于病理亚型的β受体阻滞剂对胃癌患者新辅助化疗预后的影响：一项回顾性队列研究","authors":"Nerma Crnovrsanin, Sarah Zumsande, Ingmar Florin Rompen, Sabine Schiefer, Sarah Zimmer, Wenjun Hu, Johanna Arnscheidt, Fritz Brinkmann, Thomas Longerich, Georg Martin Haag, Thomas Schmidt, Mohammed Al-Saeedi, Leila Sisic, Henrik Nienhüser","doi":"10.1245/s10434-025-17233-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Preclinical studies suggest that β-blockers (BBs), traditionally used for cardiovascular diseases, may improve cancer outcomes. This study assessed the effect of BB intake on oncological outcomes and response to chemotherapy in gastric cancer (GC) patients and the influence of ß2-adrenergic receptor (ADRB2) expression on local tumor innervation.</p><p><strong>Methods: </strong>We retrospectively analyzed the BB intake of 361 patients who underwent surgery with curative intent for GC after neoadjuvant chemotherapy at the University Hospital of Heidelberg. Resection specimens were analyzed and immunohistochemical stainings were performed to evaluate ADRB2 expression and neuronal markers (protein gene product 9 [PGP.9]). Survival rates were estimated using Kaplan-Meier curves, and multivariable Cox regression analysis was performed to control for confounding variables.</p><p><strong>Results: </strong>In patients with diffuse GC (DGC), BB users demonstrated improved overall survival (OS) and significantly improved recurrence-free survival (RFS) compared with non-users (median OS: not reached vs. 34 months [p = 0.072]; median RFS: not reached vs. 16 months [p = 0.031]). BB intake emerged as an independent prognostic factor in multivariable analysis for this subgroup (OS: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.17-0.76; RFS: HR 0.41, 95% CI 0.20-0.87). In contrast, BB use was associated with worse OS in intestinal subtype GC (median OS: 30 months vs. not reached; p = 0.044), an effect that diminished after adjusting for cardiovascular risk profiles. Higher ADRB2 expression was associated with less lymph node involvement in the DGC subtype (p = 0.030).</p><p><strong>Conclusion: </strong>This study suggests a differential impact of BB use on GC subtypes and underscores the importance of considering cancer subtypes and patient comorbidities when evaluating the potential benefits of BBs in cancer therapy.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":"5142-5153"},"PeriodicalIF":3.4000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129865/pdf/","citationCount":"0","resultStr":"{\"title\":\"β-Blockers Influence Oncological Outcomes in Gastric Cancer Patients Treated with Neoadjuvant Chemotherapy Based on the Pathological Subtype: A Retrospective Cohort Study.\",\"authors\":\"Nerma Crnovrsanin, Sarah Zumsande, Ingmar Florin Rompen, Sabine Schiefer, Sarah Zimmer, Wenjun Hu, Johanna Arnscheidt, Fritz Brinkmann, Thomas Longerich, Georg Martin Haag, Thomas Schmidt, Mohammed Al-Saeedi, Leila Sisic, Henrik Nienhüser\",\"doi\":\"10.1245/s10434-025-17233-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Preclinical studies suggest that β-blockers (BBs), traditionally used for cardiovascular diseases, may improve cancer outcomes. This study assessed the effect of BB intake on oncological outcomes and response to chemotherapy in gastric cancer (GC) patients and the influence of ß2-adrenergic receptor (ADRB2) expression on local tumor innervation.</p><p><strong>Methods: </strong>We retrospectively analyzed the BB intake of 361 patients who underwent surgery with curative intent for GC after neoadjuvant chemotherapy at the University Hospital of Heidelberg. Resection specimens were analyzed and immunohistochemical stainings were performed to evaluate ADRB2 expression and neuronal markers (protein gene product 9 [PGP.9]). Survival rates were estimated using Kaplan-Meier curves, and multivariable Cox regression analysis was performed to control for confounding variables.</p><p><strong>Results: </strong>In patients with diffuse GC (DGC), BB users demonstrated improved overall survival (OS) and significantly improved recurrence-free survival (RFS) compared with non-users (median OS: not reached vs. 34 months [p = 0.072]; median RFS: not reached vs. 16 months [p = 0.031]). BB intake emerged as an independent prognostic factor in multivariable analysis for this subgroup (OS: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.17-0.76; RFS: HR 0.41, 95% CI 0.20-0.87). In contrast, BB use was associated with worse OS in intestinal subtype GC (median OS: 30 months vs. not reached; p = 0.044), an effect that diminished after adjusting for cardiovascular risk profiles. Higher ADRB2 expression was associated with less lymph node involvement in the DGC subtype (p = 0.030).</p><p><strong>Conclusion: </strong>This study suggests a differential impact of BB use on GC subtypes and underscores the importance of considering cancer subtypes and patient comorbidities when evaluating the potential benefits of BBs in cancer therapy.</p>\",\"PeriodicalId\":8229,\"journal\":{\"name\":\"Annals of Surgical Oncology\",\"volume\":\" \",\"pages\":\"5142-5153\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129865/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Surgical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1245/s10434-025-17233-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Surgical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1245/s10434-025-17233-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/25 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
β-Blockers Influence Oncological Outcomes in Gastric Cancer Patients Treated with Neoadjuvant Chemotherapy Based on the Pathological Subtype: A Retrospective Cohort Study.
Introduction: Preclinical studies suggest that β-blockers (BBs), traditionally used for cardiovascular diseases, may improve cancer outcomes. This study assessed the effect of BB intake on oncological outcomes and response to chemotherapy in gastric cancer (GC) patients and the influence of ß2-adrenergic receptor (ADRB2) expression on local tumor innervation.
Methods: We retrospectively analyzed the BB intake of 361 patients who underwent surgery with curative intent for GC after neoadjuvant chemotherapy at the University Hospital of Heidelberg. Resection specimens were analyzed and immunohistochemical stainings were performed to evaluate ADRB2 expression and neuronal markers (protein gene product 9 [PGP.9]). Survival rates were estimated using Kaplan-Meier curves, and multivariable Cox regression analysis was performed to control for confounding variables.
Results: In patients with diffuse GC (DGC), BB users demonstrated improved overall survival (OS) and significantly improved recurrence-free survival (RFS) compared with non-users (median OS: not reached vs. 34 months [p = 0.072]; median RFS: not reached vs. 16 months [p = 0.031]). BB intake emerged as an independent prognostic factor in multivariable analysis for this subgroup (OS: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.17-0.76; RFS: HR 0.41, 95% CI 0.20-0.87). In contrast, BB use was associated with worse OS in intestinal subtype GC (median OS: 30 months vs. not reached; p = 0.044), an effect that diminished after adjusting for cardiovascular risk profiles. Higher ADRB2 expression was associated with less lymph node involvement in the DGC subtype (p = 0.030).
Conclusion: This study suggests a differential impact of BB use on GC subtypes and underscores the importance of considering cancer subtypes and patient comorbidities when evaluating the potential benefits of BBs in cancer therapy.
期刊介绍：
The Annals of Surgical Oncology is the official journal of The Society of Surgical Oncology and is published for the Society by Springer. The Annals publishes original and educational manuscripts about oncology for surgeons from all specialities in academic and community settings.
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