Liu, M

Abstract Objectives Right ventricular (RV) failure occurring after left ventricular assist device (LVAD) implantation is associated with increased mortality. Purpose We sought to determine whether RV strain by echocardiography predicts outcomes following LVAD. Methods Consecutive patients who underwent continuous flow LVAD placement at our clinic between February 2007 and October 2018 were included. Patients with complex congenital heart disease and arrhythmogenic right ventricular cardiomyopathy were excluded. Baseline characteristics, pre-operative hemodynamic catheterization (1 week) transthoracic echocardiography (1 month) measurements were obtained from the medical record. Speckle tracking RV free wall longitudinal 2D strain was measured using TomTec Imaging System. Univariate and multivariable analysis performed to identify predictors of mortality following LVAD. Results The study group was comprised of 323 patients (mean age 60.8±11.5, 79.9% male) of which 256 had adequate image quality for RV strain. RV strain was impaired in most patients (mean −11.7±3.47). RV strain of −8.1% was identified as predictive of poor outcomes. RV strain did not correlate with other measures of RV dysfunction including pulmonary artery pulsatility index (PAPi) and RVFAC. After adjusting for PAPi, RA pressure, and clinical cumulative risk scores (Matthews, Kormos and Lietz-Miller) impaired RV free wall longitudinal strain (OR: 1.14; 95% CI: 1.01–1.29, p=0.025), tricuspid regurgitation (by vena contracta width (TRvc) (OR: 1.19; 95% CI: 1.05–1.36, p=:0.0021) and smaller LVEDD (OR: 0.95; 95% CI: 0.92–0.99, p:0.023) predicted 30-day all-cause mortality and RV failure. Decreased RV free wall strain also predicted peri-operative mortality (22.58% vs. 4.89%, p=0.0003) and prolonged inotropic support (247.0.±277.4 vs. 122.8±139.3, p=0.024). Conclusions RV free wall strain is a non-invasive independent predictor of 30-day adverse outcomes (RV failure or all-cause mortality) Routine measurement of RV free strain may identify those patients at highest risk for early and long term mortality following LVAD. Funding Acknowledgement Type of funding source: None

Abstract Background: Patients with breast cancer (BC) and chest wall disease have limited treatment options. We hypothesize that checkpoint inhibition may be an effective treatment approach due to the inflammatory nature of chest wall infiltration, and the association of PD-1 expression with lymphocytic infiltration. Platinum chemotherapy may facilitate anti-tumor immunity in a synergistic manner, and clinical studies of the PD-1 inhibitor pembrolizumab with platinum combinations have been effective in the treatment of advanced lung cancer. In this study, we will evaluate the combination of carboplatin and pembrolizumab in BC patients with chest wall disease. Methods: This is a randomized phase II multicenter study in the TBCRC including patients with advanced, unresectable BC with hormone resistant or triple negative chest wall disease. Patients may have had prior surgery, prior chest wall radiation is not required, and other sites of distant metastases are allowed. Eighty-four patients at TBCRC sites will be randomized 2:1 to receive pembrolizumab and carboplatin (n=56, Arm A) or carboplatin alone (n=28, Arm B) until disease progression. Patients randomized to Arm B may cross-over following progression to pembrolizumab alone (Arm Bx). Patients in Arm A will be treated with pembrolizumab 200 mg IV and carboplatin AUC 5 IV every 3 weeks for at least 6 cycles followed by maintenance pembrolizumab 200 mg IV every 3 weeks if stable or responding disease. Patients in Arm B will be treated with carboplatin AUC 5 IV every 3 weeks until progression, then may cross-over to pembrolizumab 200 mg IV every 3 weeks alone (Arm Bx). An interim analysis for futility will be performed after 18 patients are enrolled into Arm B to allow early closure of that arm for lack of efficacy. The primary endpoint is disease control rate at 18 weeks of treatment; the study is powered to detect a 20% difference in disease control rates between arms (hazard ratio 0.52, α= 0.10, β= 0.20). Secondary endpoints include progression free survival, toxicity, and response based on PD-L1 expression and irRECIST. Exploratory endpoints include association of response with a number of biomarkers including tumor PD-L1 gene expression, tumor and peripheral blood immune composition and cytokine expression, peripheral T-cell PD-1 expression, circulating tumor DNA, circulating tumor cells, and tumor MYC genomic expression using tumor biopsy and peripheral blood testing before and after treatment. This study should be open to accrual by August of 2017. (NCT03095352) Citation Format: Vidula N, Goga A, Krummel M, Hwang J, Liu M, Park BH, Nanda R, Pohlmann P, Storniolo AM, Van Poznak C, Brufsky A, Abramson V, Wolff A, Rugo HS. TBCRC 044: A randomized phase II study of pembrolizumab in combination with carboplatin versus carboplatin alone in breast cancer patients with chest wall disease [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-03.