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.

Challenging presentations of germ cell tumours in routine clinical practice.

Testicular cancer is the most common malignancy in young men. We discuss four cases of germ cell tumours (GCTs) presenting to general practitioners and physicians where there were notable preventable delays in the diagnosis and management. This diagnostic delay is associated with a more advanced stage of disease, and subsequent increased treatment-related morbidity and decreased survival. Our series highlights the variety of ways in which GCTs may present and we discuss the importance of prompt diagnosis through a thorough history and examination, early measurement of serum tumour markers and appropriate multidisciplinary team discussion. GCTs are highly curable cancers in the majority of patients and delays in management can, therefore, have devastating consequences.

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies.

OBJECTIVE: The level of hippocampal atrophy in dementia with Lewy bodies (DLB) is typically less than that observed in Alzheimer's disease (AD). However, it is not known how the cognitive phenotype of DLB is influenced by hippocampal atrophy or the atrophy of adjacent medial temporal lobe structures. METHODS: Dementia with Lewy bodies (n = 65), AD (n = 76) and control (n = 63) participants underwent 3T magnetic resonance imaging and cognitive Cambridge Cognitive Examination and Mini-Mental State Examination (CAMCOG and MMSE) assessments. Hippocampal volume, and parahippocampal, entorhinal and temporal pole cortical thickness, was compared between groups. Regression models were used to investigate whether hippocampal volume and cortical thickness associated with global cognition and cognitive subdomains. RESULTS: Dementia with Lewy bodies, AD and control participants showed significantly different hippocampal, parahippocampal and entorhinal cortical thinning, where atrophy was greatest in AD and intermediate in DLB. Temporal pole thickness was reduced in DLB and AD compared with control participants. In DLB, but not AD, hippocampal volume associated with total CAMCOG, CAMCOG memory and MMSE scores. In DLB, parahippocampal, entorhinal and temporal pole thickness associated with total CAMCOG and CAMCOG memory scores, parahippocampal thickness associated with MMSE scores, and entorhinal thickness associated with CAMCOG executive function scores. CONCLUSIONS: In this large sample, these results are in agreement with other studies indicating that hippocampal atrophy is less severe in DLB than AD. Hippocampal atrophy and medial temporal lobe cortical thickness were associated with the severity of cognitive symptoms, suggesting that atrophy in these structures, as a potential proxy of AD pathology, may partly mediate specific DLB cognitive symptoms. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

The relationship between real world ambulatory activity and falls in incident Parkinson's disease: influence of classification scheme.

INTRODUCTION: Few studies have categorized falls in early Parkinson's disease (PD) and little is known about falls incidence and evolution. Fall incidence and frequency are reported to be 'U' shaped with respect to disease severity and may be influenced by time spent engaged in ambulatory activity. METHODS: Twelve months prospective falls in an incident PD cohort (n = 111) were reported and the relationship between falls and ambulatory activity was examined in a subgroup (n = 83). Fall events were collected using standardised protocols and were categorized by fall frequency (non-faller, single fall, recurrent falls) and also by a novel classification based on pre-fall event: (1) engaged in advanced activity; (2) ambulation; and (3) transition. Non-parametric statistics compared groups in both classifications. RESULTS: At baseline 23 (20.7%) of the cohort had fallen, increasing to 41 (36.9%) participants over 12 months. Total time spent walking was significantly lower for transition fallers compared with non-fallers and ambulation fallers (p = 0.041), who also had significantly increased disease severity. There were no significant relationships when fallers were categorized by frequency. We present an inverted U curve model depicting the relationship between falls and activity over time in PD, and propose that at this stage transition and ambulation fallers occupy different places on the curve. CONCLUSIONS: Falls are more common than recognised in newly-diagnosed PD. Daily activity is reduced even in early disease for people who fall during transitions. Classification methods that take pre-fall event into account may be useful to understand the heterogeneity of this complex problem.

MicroRNAs in gastrointestinal malignancy: a tool in cancer prevention?

Gastrointestinal malignancies are a major cause of morbidity and mortality worldwide. Most cases are diagnosed at an advanced stage and, as such, 5-year survival rates are poor. MicroRNAs (miRNAs) are short, noncoding RNAs that negatively regulate gene expression at a post-transcriptional level. It is now evident that miRNAs are essential for normal physiological functioning, and aberrant miRNA expression is a hallmark of human cancers, including gastrointestinal cancers. Initially seen as a very promising source of breakthroughs in cancer management, there has been little translation of miRNA science from the bench to the bedside. This review will summarize the role of miRNAs in the pathogenesis of gastrointestinal malignancies. Further, it will serve to highlight the potential role of miRNAs in cancer prevention: namely their use as biomarkers and as targets for chemoprevention.