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Angiotensin inhibitors during neoadjuvant chemotherapy improve esophageal squamous cell carcinoma outcomes
Maohui Chen1,2,3,4, Yizhou Huang1,2,3,4, Felix Liu5
1Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Background:
The renin-angiotensin-aldosterone system (RAAS) is implicated in the initiation, progression, and therapeutic response of several solid malignancies. RAAS inhibitors (angiotensin system inhibitors) exhibit potential antitumor effects; however, their impact on patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant therapy remains scarce.
Objectives:
To investigate whether incidental ASI use during neoadjuvant treatment is associated with enhanced pathological response and survival outcomes in patients with ESCC.
Design:
A retrospective study.
Methods:
We retrospectively analyzed 391 ESCC patients who underwent neoadjuvant therapy followed by R0 resection between 2015 and 2022, stratified according to incidental use of ASIs during neoadjuvant chemotherapy (NAC). Baseline characteristics, major pathologic response (MPR), and long-term survival outcomes were compared. MPR rates were compared using the Chi-square test and multivariable logistic regression. Kaplan-Meier analysis was used to estimate overall survival (OS) and disease-free survival (DFS), and multivariable Cox proportional hazards models were applied to adjust for potential confounders. Sensitivity analyses were performed using propensity score matching (PSM).
Results:
Overall, 67 (17.1%) patients were administered ASIs. Compared with non-users, ASI users were older (p = 0.006) with a higher prevalence of hypertension (p < 0.001), while other characteristics were comparable. Overall, ASI use was significantly associated with improved OS (hazard ratio (HR) = 0.48, 95% confidence interval (CI): 0.29-0.79, p = 0.004) and DFS (HR = 0.56, 95% CI: 0.36-0.90, p = 0.015). The MPR rate was also higher in the ASI group (31.3% vs 17.0%, p = 0.007) and consistent with the results of the multivariable analysis (odds ratio = 2.19, 95% CI: 1.21-3.97, p = 0.010). After PSM, the survival benefit of ASI use remained significant for OS (HR = 0.38, p = 0.003) and DFS (HR = 0.54, p = 0.038).
Conclusion:
In ESCC patients receiving NAC, incidental ASI use correlated with better pathological response and improved long-term survival. RAAS inhibition shows promise as a perioperative therapeutic approach and warrants postoperative validation.
Insights
Incidental use of angiotensin system inhibitors (ASIs) during neoadjuvant chemotherapy improved pathological response and survival outcomes in patients with esophageal squamous cell carcinoma (ESCC). RAAS inhibition warrants further investigation as a perioperative therapy.
Area of Science:
- Oncology
- Pharmacology
- Cardiovascular Research
Background:
- The renin-angiotensin-aldosterone system (RAAS) plays a role in various cancers.
- RAAS inhibitors (ASIs) show potential antitumor effects, but their impact on esophageal squamous cell carcinoma (ESCC) during neoadjuvant therapy is understudied.
Purpose of the Study:
- To determine if incidental ASI use during neoadjuvant treatment enhances pathological response and survival in ESCC patients.
- To evaluate the association between ASI use and outcomes in ESCC.
Main Methods:
- Retrospective analysis of 391 ESCC patients undergoing neoadjuvant therapy and R0 resection.
- Comparison of baseline characteristics, major pathological response (MPR), overall survival (OS), and disease-free survival (DFS) between ASI users and non-users.
- Statistical analyses included Chi-square, logistic regression, Kaplan-Meier, Cox models, and propensity score matching (PSM).
Main Results:
- ASI use (17.1% of patients) was associated with significantly improved OS (HR=0.48) and DFS (HR=0.56).
- ASI users had a higher MPR rate (31.3% vs 17.0%, p=0.007) and improved survival post-PSM.
- ASI use was independently associated with better pathological response (OR=2.19).
Conclusions:
- Incidental ASI use during neoadjuvant chemotherapy correlates with better pathological response and long-term survival in ESCC patients.
- RAAS inhibition presents a promising perioperative therapeutic strategy for ESCC.
- Further postoperative validation studies are warranted.
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