The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Reduced confounding by impaired ventilatory function with oxygen uptake efficiency slope and VE/VCO2 slope rather than peak oxygen consumption to assess exercise physiology in suspected heart failure.

Heart failure and ventilatory disease often coexist; both create abnormalities in cardiopulmonary exercise test measurements. The authors evaluated the relative dependency of a well-recognized index of heart failure, peak oxygen consumption (VO(2)), and 2 newer indices, the minute ventilation (VE)/carbon dioxide production (VCO(2)) slope and oxygen uptake efficiency slope (OUES), on standard markers of impaired cardiac and ventilatory function. One hundred twenty-four patients (median age, 65.8; range, 22.6-84.9), with functional limitation from clinical heart failure were exercised. Peak VO(2) was 17.14 ± 7.58 mL/kg/min, VE/VCO(2) slope 50.1 ± 20.1, OUES 1.46 ± 0.68 L/min, and forced expiratory volume in 1 second (FEV(1) ) 1.88 ± 0.75 L. Peak VO(2) is substantially more sensitive to FEV(1) than ejection fraction (4.0 mL/kg/min difference between above- and below-median FEV(1) and 1.5 mL/kg/min between above- and below-median ejection fraction). OUES does not share this peculiar excess sensitivity to FEV(1) (0.12 L/min difference between above- and below-median FEV(1) and 0.01 L/min between above- and below-median ejection fraction). VE/VCO(2) slope has a borderline effect by FEV(1) (7.07 difference between above- and below-median FEV(1) and 2.07 between above- and below-median ejection fraction). Although widely used as a marker of heart failure severity, peak VO(2) is very sensitive to spirometry status and is indeed more affected by FEV(1) than by ejection fraction. OUES in contrast does not show this preferential sensitivity to impaired FEV(1).

Usefulness of a Z-score of E' versus raw E' velocities to detect left ventricular dysfunction in patients with mitral or aortic regurgitation or dilated cardiomyopathy.

Despite their potential as a sensitive measure of ventricular performance, tissue Doppler velocities vary with normal aging. This is inconvenient for nonspecialists to interpret and makes it difficult to use as an entry criterion for clinical studies. The age-adjusted tissue Doppler Z-scores might avoid these disadvantages and be more discriminant for myocardial impairment than the raw velocities. We conducted a meta-regression of studies reporting age-specific normal tissue Doppler velocities to determine a consensus formula for Z-scores (8 studies, 1,867 patients) that we then tested in an independent study at our institution. We next compared the Z-scores head-to-head with the raw velocities for their ability to distinguish a fresh set of 81 healthy subjects from groups in whom subtle ventricular dysfunction might be expected, including 50 patients with dilated cardiomyopathy, 50 with aortic regurgitation, and 50 with mitral regurgitation. The discriminant capacity, assessed by the area under the receiver operating characteristic curves, was higher for the Z-scores than for the raw velocities in each patient group. At the septal angle of the mitral annulus: dilated cardiomyopathy 0.95 versus 0.92 (p = 0.03), aortic regurgitation 0.83 versus 0.78 (p = 0.02), mitral regurgitation 0.85 versus 0.81 (p = 0.04). At the lateral angle: dilated cardiomyopathy 0.94 versus 0.88 (p = 0.005), aortic regurgitation 0.92 versus 0.83 (p = 0.001), mitral regurgitation 0.87 versus 0.85 (p = 0.31). In conclusion, the Z-scores of the tissue Doppler velocities were better than the raw velocities at detecting myocardial impairment in valvular or heart muscle disease. The calculation needs only the raw velocity and patient age. Tissue Doppler Z-scores could be used to create a novel, more sensitive, definition of ventricular dysfunction and might make it easier for nonspecialists to interpret the reports.