Dataset Information

Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

ABSTRACT: Introduction: Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC. Methods: This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absence (NSBB) of beta-1 selectivity of BB, exposure duration, and multimorbidity], oncological (stage and anticancer treatment regimen), and biological (renal and liver function) data were collected. The endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for survival outcomes associated with BB exposure were estimated using Cox regression model and propensity score (PS) methods. Results: Forty-one patients (22.5%) were exposed to BB. A total of 104 patients progressed (57.1%) to PDAC and 139 (76.4%) patients died at the end of follow-up (median, 320 days; IQR, 438.75 days). When compared to the non-exposed group, there was no increase in survival outcomes associated with BB use (OS: HR = 1.38, 95% CI = 0.80-2.39, p = 0.25; PFS: adjusted HR = 0.95, 95% CI = 0.48-1.88, p = 0.88). Similar results were obtained using the PS method. Compared to no BB usage, SBB use was associated with a significant decrease in OS (HR = 1.80, 95% CI = 1.16-2.80, p < 10^-2). Conclusion: BB exposure was not associated with improved PDAC survival outcomes. Beta-1-selectivity was not independently associated with any differences.

SUBMITTER: Le Bozec A

PROVIDER: S-EPMC10235451 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

Le Bozec Antoine A Brugel Mathias M Djerada Zoubir Z Ayad Marya M Perrier Marine M Carlier Claire C Botsen Damien D Nazeyrollas Pierre P Bouché Olivier O Slimano Florian F

Frontiers in pharmacology 20230519

<b>Introduction:</b> Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC. <b>Methods:</b> This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absenc ...[more]

PMID: 37274119

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Project description:Assessing the perioperative outcomes of pancreaticoduodenectomy (PD) based solely on individual complications is not comprehensive, and the association between perioperative outcomes and the long-term prognosis of individuals diagnosed with pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Our study is designed to evaluate the impact of a novel composite indicator, textbook outcomes (TO), on the long-term prognosis of patients undergoing PD for PDAC. This study conducted a retrospective analysis of 139 patients who underwent PD for pathologically confirmed PDAC at our hospital between January 2018 and December 2021. After applying exclusion criteria, a total of 111 patients were included in the subsequent analysis. These patients were categorized into two groups: the non-TO group (n=42) and the TO group (n=69). The Kaplan-Meier survival curve was employed to describe the relationship between TO and disease-free survival (DFS) and overall survival (OS). Cox regression was employed to assess the impact of achieving TO on long-term survival. Logistic regression was employed to investigate the risk factors affecting the achievement of TO. Out of the 111 PDAC patients, 69 (62.2%) achieved TO following PD. The achievement of TO significantly improved the OS of PDAC patients [P=0.03; hazard ratio (HR) =0.60; 95% confidence interval (CI): 0.37-0.83]. Cox regression analysis indicated that achieving TO was a protective factor for OS (P=0.04; HR =4.08; 95% CI: 1.07-15.61). Logistic regression analysis indicated that high amylase in drainage fluid on the third day after surgery (>1,300 U/L) was detrimental to achieve TO [odds ratio (OR) =0.10; 95% CI: 0.02-0.58; P=0.01], longer surgery durations (≥6.25 hours) was detrimental to achieve TO (OR =0.19; 95% CI: 0.06-0.54; P=0.002), and soft pancreatic texture was detrimental to achieve TO (OR =0.31; 95% CI: 0.10-0.93, P=0.04). Achievement of TO significantly improves the OS of PDAC patients and has the potential to serve as a robust prognostic indicator. Looking ahead, it is highly necessary for TO to become a standard surgical quality control measure in hospitals.

Project description:BackgroundClinical trials investigating the effects of beta-blockers (BBs) on cancer are underway. Evidence from preclinical research suggests that BBs could serve as anticancer agents and immune boosters. There is conflicting evidence regarding the effect of BB use on clinical outcomes in patients with breast cancer.ObjectivesThe study aimed to determine whether BB use is associated with progression-free survival (PFS) and overall survival (OS) in patients receiving anti-human epidermal growth factor receptor 2 (HER2) treatment for advanced breast cancer.DesignRetrospective hospital-based study.MethodsThe participants enrolled were breast cancer patients with advanced HER2-positive status who initiated trastuzumab monotherapy or concomitant therapy with trastuzumab and any dose of BB. The patients were enrolled between January 2012 and May 2021 and divided into three groups based on whether they received a BB or not in the therapeutic regimen: BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+. PFS and OS were the primary and secondary endpoints, respectively.ResultsThe estimated median PFS in the BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+ groups was 51.93, 21.50, and 20.77 months, respectively. The corresponding OS was 56.70, 29.10, and 27.17 months. The intergroup differences in these durations were significant. Both PFS [adjusted hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.56-3.12; p < 0.001]) and OS (adjusted HR: 2.46, 95% CI: 1.69-3.57; p < 0.001) were worse when BBs were used.ConclusionOur study provides important evidence that BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. Nevertheless, despite the study's results, cardiovascular disease (CVD) should be appropriately treated in patients with HER2-positive advanced breast cancer. Other types of drugs can be used to treat CVD, but BB use should be avoided. Large real-world database and prospective studies should be conducted to validate the results of this study.

Project description:ImportanceChemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood.ObjectiveTo investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy.Design, setting, and participantsThis prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018.ExposuresThe chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center.Main outcomes and measuresRates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival.ResultsOf 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy.Conclusions and relevanceThis pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.

Project description:Previous studies have suggested that β-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p < 0.01). In multivariable analysis, beta-blockers usage was not associated with improved survival (Hazard Ratio (HR) 1.04, 95%, Confidence Interval (CI) 0.98-1.1, p = 0.2). When patients were stratified by conditions with indications for beta-blocker usage, such as hypertension, coronary artery disease and cardiac arrhythmia, differences in survival were insignificant compared to non-users in all groups (p > 0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p > 0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8-0.9, p < 0.01). Beta-blocker usage before diagnosis does not confer a survival advantage in patients with PDAC, though continuous use before and after diagnosis did confer a survival advantage. Prospective studies into the mechanism for this advantage are needed.

Dataset Information

Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

Publications

Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

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