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BACKGROUND End-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PURPOSE To clarify the clinical implications of ADPAF in adults. METHODS AND RESULTS The study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSE

BackgroundNo adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. MethodsWe conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. ResultsThe median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P

Human epidermal growth factor receptor 2 (HER2)-targeted agents are effective treatment for patients with HER2-positive breast cancer. However, the lack of survival benefit in HER2-negative patients as well as the toxic effects and high cost of these drugs highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel one-step, fully automated in-situ hybridization (Auto-RISH) method developed to facilitate hybridization. This method takes advantage of the non-contact mixing effect of an alternating current electric field. Eighteen specimens from patients diagnosed with primary breast cancer identified immunohistochemically as HER2 (2+) or (3+) were used. The specimens were all tested using DISH with an automated slide stainer (DISH-ASS), fluorescence in-situ hybridization, and Auto-RISH. With RISH the HER2 test was completed within 6 h, as compared to 20-22 h needed for the standard protocol. We found 88.8% agreement between standard DISH-ASS and Auto-RISH based on the status of the HER2 signals, and both methods stained nearly all samples from HER2-IHC 3+ patients equally well. These findings suggest Auto-RISH could potentially serve as an automated clinical tool for prompt determination of HER2 status in breast cancer samples.

LBA4001Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46?0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9?12.4), 11.8 (7.1?27.4), and 5.7 (4.4?8.7) mo and for all randomized pts: 8.2 (6.9?9.7), 11.1 (8.3?14.0), and 7.1 (5.7?8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153.OS (tumor cell PD-L1 ≥ 1%)NIVO + chemoN = 158NIVO + IPIN = 158ChemoN = 157Median OS, mo (95% CI)15.4 (11.9?19.5)13.7 (11.2?17.0)9.1 (7.7?10.0)HR vs chemo (CI; P value)0.54 (99.5% CI 0.37?0.80;P < 0.0001)0.64 (98.6% CI 0.46?0.90;P = 0.001)?OS (all randomized pts)N = 321N = 325N = 324Median OS, mo (95% CI)13.2 (11.1?15.7)12.8 (11.3?15.5)10.7 (9.4?11.9)HR vs chemo (CI; P value)0.74 (99.1% CI 0.58?0.96;P = 0.0021)0.78 (98.2% CI 0.62?0.98;P = 0.011)?Safety: treatment-related events ?(all treated pts), n (%)N = 310N = 322N = 304Any grade/grade 3?4297 (96)/147 (47)256 (80)/102 (32)275 (90)/108 (36)Leading to discontinuationa106 (34)57 (18)59 (19)Deaths5 (2)5 (2)4 (1)aDue to any component of the regimen.