Citations

Background The decision to initially implant an implantable cardioverter-defibrillator (ICD) is informed by robust randomized controlled trials, but no such data exist to guide the decision to replace an ICD generator. In this study, we aimed to determine outcomes after ICD generator replacement. Methods All patients with ischemic or nonischemic cardiomyopathy who underwent ICD generator replacement from 2001 to 2011 at Mayo Clinic, MN, or Beth Israel Deaconess Medical Center, MA, were included. Outcomes included (1) appropriate therapy after generator replacement and (2) death before appropriate therapy after generator replacement. Cox proportional hazards modeling was used to determine the associations between patient characteristics and outcomes. Results In 1421 patients undergoing ICD generator replacement (mean±SD age 69.6±12.1 years, 81% male), appropriate therapy occurred after replacement in 435 patients (30.6%) over a mean follow-up of 2.7±2.6 years. Associated factors included lower left ventricular ejection fraction and history of appropriate therapy before generator replacement. Death before appropriate ICD therapy occurred in 336 (23.7%) patients. Older age, lower left ventricular ejection fraction, and noncardiac comorbidities, including diabetes mellitus, chronic lung disease, peripheral vascular disease, lower hemoglobin, and lower glomerular filtration rate, were associated with greater risk of death before appropriate therapy. A progressive increase in mortality was observed with aggregation of these noncardiac comorbidities. Conclusions The decision to replace the ICD should take into consideration not only left ventricular ejection fraction and history of ventricular arrhythmias, but also comorbid illnesses that may impact the duration and the quality of life.

11503 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell subtype commonly found in the peripheral blood of patients in all stages of solid malignancies and in a variety of cancer subtypes. However, while their biological association to cancer is being studied, their clinical utilization as it relates to cancer prognosis has not been evaluated. Methods: A two year prospective study was undertaken to evaluate the relationship of CAMLs and overall survival (OS) in 6 solid tumor types. The single blind multi-institutional study consisted of 269 stage I-IV patients; breast (n = 57), esophageal (n = 21), prostate (n = 43), pancreatic (n = 59), lung (n = 54), and renal cell (n = 35), in treatment (n = 134) and untreated baseline (n = 135). 7.5mL of whole blood was filtered by CellSieve microfiltration assay and CAMLs enumerated, as previously described. Patients were grouped by CAML number ( < 6 or ≥6) and by size ( < 49 or ≥50 µm) to evaluate hazard ratios (HR) by censored univariate & multivariate analysis. Results: CAMLs were identified in 93% of samples, averaging 8.2 CAMLs/7.5mL blood sample, and found in all 6 cancers at baseline and during treatment. Average CAML number was associated with disease stage and CAML positivity was 4.4 & 80% (Stage I), 4.7 & 93% (Stage II), 9.3 & 98% (Stage 3), 12.1 & 97% (Stage IV). Univariate analysis of patients (n = 269) stratified by ≥6 CAMLs had reduced OS (HR = 1.8, 95%CI 1.1-2.9, p = 0.03). Further, CAML size also had reduced OS in patients with ≥50 µm CAMLs (HR = 2.7, 95%CI 1.8-4.0, p < 0.0001). Conclusions: Our data suggests that in solid malignancies, CAML number and size appear to clinically correlate with OS in early and late stage disease. Given these results relating CAMLs with OS, further analysis is warranted to determine if CAMLs can serve as a clinically-relevant blood-based marker.

9090 Background: We identified factors associated with better OS for previously treated, PD-L1–expressing advanced NSCLC using data from KEYNOTE-010 (NCT01905657; Herbst et al. Lancet. 2016;387:1540-50), in which pembrolizumab had superior OS over docetaxel. Methods: 1033 patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel 75 mg/m2 Q3W. Response was assessed per RECIST v1.1 by independent central review. Multivariate analyses were performed using a Cox proportional hazards regression model on OS in the pembrolizumab arms. A set of variable selection methods was applied to 19 baseline demographic and disease characteristics, including smoking status, and identified 7 factors that contributed to OS. Data cut was September 30, 2016. Results: Adjusted hazard ratios (HRs) for the factors in the pembrolizumab arm from the model are shown in the Table. Updated OS with an additional 6 months of follow-up from this data lock for KEYNOTE-010 will be presented. Conclusions: While the overall result of KEYNOTE-010 revealed improved OS with pembrolizumab compared with docetaxel in previously treated patients with PD-L1–positive advanced NSCLC, exploratory, post hoc multivariate analyses showed that some laboratory and tumor characteristics such as nonsquamous histology, normal baseline lactate dehydrogenase (LDH), PD-L1 TPS ≥50%, and wild-type EGFR mutation status were associated with better OS among patients treated with pembrolizumab. Clinical trial information: NCT01905657. [Table: see text]