A brain metastasis liquid biopsy: Where are we now?

Brain metastases remain a challenging and feared complication for patients with cancer and research in this area has lagged behind research into metastases to other organs. Due to their location and the risks associated with neurosurgical biopsies, the biology underpinning brain metastases response to treatment and evolution over time remains poorly understood. Liquid biopsies are proposed to overcome many of the limitations present with tissue biopsies, providing a better representation of tumor heterogeneity, facilitating repeated sampling, and providing a noninvasive assessment of tumor biology. Several different liquid biopsy approaches have been investigated including circulating tumor cells, circulating tumor DNA, extracellular vesicles, and tumor-educated platelets; however, these have generally been less effective in assessing brain metastases compared to metastases to other organs requiring improved techniques to investigate these approaches, studies combining different liquid biopsy approaches and/or novel liquid biopsy approaches. Through this review, we highlight the current state of the art and define key unanswered questions related to brain metastases liquid biopsies.

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.

Contrast Clearance Analysis (CCA) to Assess Viable Tumour following Stereotactic Radiosurgery (SRS) to Brain Metastasis in Non-Small Cell Lung Cancer (NSCLC).

BACKGROUND AND OBJECTIVE: Brain metastases are common in lung cancer and increasingly treated using targeted radiotherapy techniques such as stereotactic radiosurgery (SRS). Using MRI, post-SRS changes may be difficult to distinguish from progressive brain metastasis. Contrast clearance analysis (CCA) uses T1-weighted MRI images to assess the clearance of gadolinium and can be thus used to assess vascularity and active tumours. DESIGN AND METHODS: We retrospectively assessed CCAs in 62 patients with non-small cell lung cancer (NSCLC) undergoing 104 CCA scans in a single centre. RESULTS: The initial CCA suggested the aetiology of equivocal changes on standard MRI in 80.6% of patients. In all patients whose initial CCA showed post-SRS changes and who underwent serial CCAs, the initial diagnosis was upheld with the serial imaging. In only two cases of a presumed progressive tumour on the initial CCA, subsequent treatment for radionecrosis was instigated; a retrospective review and re-evaluation of the CCAs show that progression was reported where a thin rim of rapid contrast clearance was seen, and this finding has been subsequently recognised as a feature of post-treatment change on CCAs. The lack of concordance with CCA findings in those who underwent surgical resection was also found to be due to the over-reporting of the thin blue rim as disease in the early cases of CCA use and, in three cases, potentially related to timelines longer than 7 days prior to surgery, both factors being unknown during the early implementation phase of CCA at our centre but subsequently learned. CONCLUSIONS: Our single-centre experience shows CCA to be feasible and useful in patients with NSCLC in cases of diagnostic uncertainty in MRI. It has helped guide treatment in the majority of patients, with subsequent outcomes following the implementation of the treatment based on the results, suggesting correct classification. Recommendations from our experience of the implementation include the careful consideration of the thin rim of the rapid contrast clearance and the timing of the CCA prior to surgery for suspected brain metastasis progression.

A comprehensive hospital agile preparedness (CHAPs) tool for pandemic preparedness, based on the COVID-19 experience.

COVID-19 presents an unprecedented challenge to hospitals and the systems in which they operate. The primary exponential surge of COVID-19 cases is arguably the most devastating event a hospital will face. In some countries, these surges during the initial outbreak of the disease have resulted in hospitals suffering from significant resource strain, leading to excess patient mortality and negatively impacting staff wellbeing. As experience builds in managing these surges, it has become evident that agile, tailored planning tools are required. The comprehensive hospital agile preparedness (CHAPs) tool provides clinical planners with six key domains to consider that frequently create resource strain during COVID-19; it also allows local planners to identify issues unique to their hospital, system or region. Although this tool has been developed from COVID-19 experiences, it has potential to be modified for a variety of pandemic scenarios according to transmission modes, rates and critical care resource requirements.

Guillain-Barré syndrome complicated by takotsubo cardiomyopathy: an under-recognised association.

A 41-year-old woman was admitted with progressive paraesthesia and weakness and was diagnosed with Guillain-Barré syndrome. Following an initial period of recovery with intravenous immunoglobulin treatment, she developed acute chest pain associated with electrocardiographic changes. Investigations excluded acute coronary syndrome and instead confirmed a diagnosis of takotsubo cardiomyopathy, which was treated medically. The patient made an excellent neurological and cardiac recovery. Here we discuss the rarely described association between these two conditions and suggest that patients admitted with Guillain-Barré syndrome may benefit from routine screening with echocardiography.

Hypoplasia of the inferior vena cava in a young man presenting with extensive deep venous thrombosis.

We present a case of a 34-year-old man with extensive deep venous thrombosis (DVT) who was found to have multiple abnormalities of venous anatomy, notably hypoplasia of the inferior vena cava with azygous continuation. DVT has an annual incidence of around 1 in 1000 people in the UK. Many cases will have readily identifiable risk factors, such as underlying malignancy, immobility or thrombophilia, but at times, these might not be so straightforward and unexpected contributing factors may be found. Although relatively uncommon in the general population, congenital venous abnormalities have been found at higher incidence in young adults presenting with spontaneous DVT and should therefore remain a consideration when classical risk factors are absent.