RESUMO
To determine Labyrinthin (LAB) expression in non-small-cell lung cancer (NSCLC), we immunostained and scored for LAB immunohistochemistry (IHC) expression on sections of tissue microarrays (TMAs) prepared from 256 archival tissue blocks of NSCLC. Propensity-score-weighted Kaplan-Meier curves and weighted Cox models were used to associate LAB expression with overall survival. LAB mRNA expression was assessed in The Cancer Genome Atlas (TCGA) and correlated with clinical phenotype and outcome. Positive LAB IHC expression (>5% of tumor cells) was detected in 208/256 (81.3%) of NSCLC samples, and found in both lung adenocarcinomas (LUAD) and lung squamous cell cancer (LUSC). LAB positivity was associated with poor overall survival (HR = 3.56, 95% CI: 2.3-5.4; p < 0.0001) and high tumor differentiation grade or metastasis compared with negative LAB expression. Univariant and multivariate survival analyses demonstrated LAB expression as an independent prognostic factor for NSCLC patients. LAB RNA expression in TCGA-LUAD was higher in primary and advanced-stage tumors than in normal tissue, and was associated with poorer overall survival. No significant differences or associations were found with LAB RNA expression in TCGA-LUSC. The LAB IHC assay is being used to identify candidate cancer patients for the first-in-human phase I trial evaluating the LAB vaccines (UCDCC#296, NCT051013560).
RESUMO
BACKGROUND: Days at home (DAH) quantifies time spent at home after a medical event but has not been fully evaluated for TAVR. We sought to compare 1- and 5-year DAH (DAH365, DAH1825) among high-risk patients participating in a randomized trial of transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR). METHODS: We linked data from the U.S. CoreValve High Risk Trial to Medicare Fee-for-Service claims in 456 patients with 450 (234 TAVR/216 SAVR) and 427 (222 TAVR/205 SAVR) analyzed at 1 and 5 years. DAH was calculated as the number of days alive and spent outside of a hospital, skilled nursing facility, rehabilitation, long-term acute care hospital, emergency department, or observation stay. RESULTS: Mean DAH365 was higher in patients who underwent TAVR compared with SAVR (295.1 ± 106.9 vs 267.8 ± 122.3, difference in days 27.2 [95% CI 6.0, 48.5], P = .01). Compared with SAVR, TAVR patients had a shorter index length of stay (LOS) (7.4 ± 4.5 vs 12.5 ± 9.0, difference in days -5.1 [-6.5, -3.8], P < .001). The largest contributions to decreased DAH365 were mortality days and total facility days after discharge from the index hospitalization (mortality days-TAVR: 34.7 ± 93.1 vs SAVR: 48.0 ± 108.8, difference in days -13.3 [95% CI -32.1, 5.5], P = .17; total facility days-TAVR: 27.9 ± 47.4 vs SAVR: 36.7 ± 48.9, difference in days -8.8 [95% CI -17.8, 0.1], P = .05). Mean DAH1825 was numerically but not statistically significantly higher in TAVR (TAVR: 1154.2 ± 659.0 vs SAVR: 1067.6 ± 697.3, difference in days 86.6 [95% CI -42.3, 215.6], P = .19). Landmark analysis showed no difference in DAH from years 1 to 5 (TAVR: 1040.4 ± 477.5 vs SAVR: 1022.9 ± 489.3, P = .74). CONCLUSIONS: In the U.S. CoreValve High Risk Trial linked to Medicare, high-risk patients undergoing TAVR spend an average of 27 additional DAH compared with SAVR in the first year after the procedure due to a shorter index LOS and the additive effect of fewer but nonsignificantly different mortality and total facility days after discharge from the index hospitalization compared with SAVR. After the first year, both groups spend a similar number of DAH. These results describe the postprocedural course of high-risk patients from a patient-centered perspective, which may guide expectations regarding longitudinal health care needs and inform shared decision-making.