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-adren...

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Hauptverfasser: Crnovrsanin, Nerma (VerfasserIn) , Zumsande, Sarah (VerfasserIn) , Rompen, Ingmar F. (VerfasserIn) , Schiefer, Sabine (VerfasserIn) , Zimmer, Sarah (VerfasserIn) , Hu, Wenjun (VerfasserIn) , Arnscheidt, Johanna (VerfasserIn) , Brinkmann, Fritz (VerfasserIn) , Longerich, Thomas (VerfasserIn) , Haag, Georg Martin (VerfasserIn) , Schmidt, Thomas (VerfasserIn) , Saeedi, Mohammed al (VerfasserIn) , Peters, Leila (VerfasserIn) , Nienhüser, Henrik (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 25 March 2025
In: Annals of surgical oncology
Year: 2025, Jahrgang: 32, Heft: 7, Pages: 5142-5153
ISSN:1534-4681
DOI:10.1245/s10434-025-17233-9
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1245/s10434-025-17233-9
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Verfasserangaben:Nerma Crnovrsanin, MD, Sarah Zumsande, Ingmar Florin Rompen, MD, Sabine Schiefer, MD, Sarah Zimmer, M.Sc., Wenjun Hu, Johanna Arnscheidt, MD, Fritz Brinkmann, MD, Thomas Longerich, MD, Georg Martin Haag, MD, Thomas Schmidt, MD, PhD, Mohammed Al-Saeedi, MD, Leila Sisic, MD, and Henrik Nienhüser, MD

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520 |a 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. 
650 4 |a Adenocarcinoma 
650 4 |a Adrenergic beta-Antagonists 
650 4 |a Adult 
650 4 |a Aged 
650 4 |a Antineoplastic Combined Chemotherapy Protocols 
650 4 |a Beta-blocker 
650 4 |a Chemotherapy, Adjuvant 
650 4 |a Diffuse gastric cancer 
650 4 |a Female 
650 4 |a Follow-Up Studies 
650 4 |a Gastric adenocarcinoma 
650 4 |a Gastric neoplasm 
650 4 |a Humans 
650 4 |a Male 
650 4 |a Middle Aged 
650 4 |a Neoadjuvant Therapy 
650 4 |a Neoplasm Recurrence, Local 
650 4 |a Prognosis 
650 4 |a QuPath 
650 4 |a Receptors, Adrenergic, beta-2 
650 4 |a Retrospective Studies 
650 4 |a Stomach Neoplasms 
650 4 |a Survival Rate 
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