Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: a Kaplan-Meier-derived patient data meta-analysis.

PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

Impact of periprocedural myocardial injury after transcatheter aortic valve implantation on long-term mortality: a meta-analysis of Kaplan-Meier derived individual patient data.

Background: Periprocedural myocardial injury (PPMI) frequently occurs after transcatheter aortic valve implantation (TAVI), although its impact on long-term mortality is uncertain. Methods: We performed a pooled analysis of Kaplan-Meier-derived individual patient data to compare survival in patients with and without PPMI after TAVI. Flexible parametric models with B-splines and landmark analyses were used to determine PPMI prognostic value. Subgroup analyses for VARC-2, troponin, and creatine kinase-MB (CK-MB)-defined PPMI were also performed. Results: Eighteen observational studies comprising 10,094 subjects were included. PPMI was associated with lower overall survival (OS) after two years (HR = 1.46, 95% CI 1.30-1.65, p < 0.01). This was also observed when restricting the analysis to overall VARC-2-defined PPMI (HR = 1.23, 95% CI 1.07-1.40, p < 0.01). For VARC-2 PPMI criteria and VARC-2 troponin-only, higher mortality was restricted to the first 2 months after TAVI (HR = 1.64, 95% CI 1.31-2.07, p < 0.01; and HR = 1.32, 95% CI 1.05-1.67, p = 0.02, respectively), while for VARC-2 defined CK-MB-only the increase in mortality was confined to the first 30 days (HR = 7.44, 95% CI 4.76-11.66, p < 0.01). Conclusion: PPMI following TAVI was associated with lower overall survival compared with patients without PPMI. PPMI prognostic impact is restricted to the initial months after the procedure. The analyses were consistent for VARC-2 criteria and for both biomarkers, yet CK-MB was a stronger prognostic marker of mortality than troponin.

Angiotensin Receptor-Neprilysin Inhibitor Effects on Atherosclerotic Cardiovascular Disease Events: A Meta-Analysis of Randomized Controlled Trials.

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.