Search

Simple Summary: Roughly 430,000 new cases of renal cell carcinoma (RCC) occurred worldwide in 2022, and about one-third of RCC cases are diagnosed at an advanced stage of disease (aRCC). When patients with aRCC fail first-line treatment, they commonly receive one of the recommended second-line treatments, i.e., axitinib, cabozantinib, lenvatinib plus everolimus, pazopanib, sunitinib, or tivozanib. Axitinib is a second-generation tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor tyrosine kinases 1, 2, and 3. It has been available since 2011 for the treatment of aRCC after the failure of prior therapy with sunitinib or cytokines. The aim of our research was to understand how axitinib compares with other treatment options considering data from clinical trials and observational studies that reflect real-world clinical practice. Therefore, we conducted a systematic literature review to summarise evidence on commonly used and recommended treatments in aRCC after the failure of prior therapy with sunitinib or cytokines. Background: We conducted a systematic literature review (SLR) to identify clinical evidence on treatments in advanced renal cell carcinoma (aRCC) after the failure of prior therapy with cytokines, tyrosine kinase inhibitors, or immune checkpoint inhibitors. Herein, we summarise the evidence for axitinib in aRCC after the failure of prior therapy with cytokines or sunitinib. Methods: This SLR was registered with PROSPERO (CRD42023492931) and followed the 2020 PRISMA statement and the Cochrane guidelines. Comprehensive searches were conducted in MEDLINE and Embase as well as for conference proceedings. Study eligibility was defined according to population, intervention, comparator, outcome, and study design. Results: Of 1252 titles/abstracts screened, 266 peer-reviewed publications were reviewed, of which 182 were included. In addition, 28 conference abstracts were eligible. Data on axitinib were reported in 55 publications, of which 16 provided efficacy and/or safety outcomes on axitinib after therapy with sunitinib or cytokines. In these patients, median progression-free and overall survival ranged between 5.5 and 8.7 months and 11.0 and 69.5 months, respectively. Conclusions: Axitinib is commonly used in clinical practice and has a well-characterised safety and efficacy profile in the treatment of patients with aRCC after the failure of prior therapy with sunitinib or cytokines. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials show improved progression‐free survival (PFS) and overall survival (OS) in first‐line metastatic renal cell carcinoma (mRCC) patients with immunotherapy containing systemic anti‐cancer therapies (SACT). However, in the favourable international metastatic renal cell cancer database consortium (IMDC) group there is no trial evidence for OS benefit despite clear PFS improvement when comparing anti‐VEGF tyrosine kinase inhibitor (TKI) monotherapy and (immunotherapy and TKI) IO/TKI combinations. Objective: To assess the impact of first‐line SACT choice on the clinical outcomes of PFS and OS in mRCC. To evaluate this impact of initial SACT for allcomers and the favourable IMDC group. Methods: A multicentre retrospective review of patients who started SACT for mRCC (01/01/2018–30/06/2021) at 17 UK NHS trusts. Patient demographics and IMDC group were analysed. Survival data were compared using Kaplan–Meier curves, and the statistical significance of differences in outcome between the groups was assessed with the log‐rank test. Univariable and multivariable Cox proportional hazard modelling estimate the hazard ratios (HRs) for survival outcomes associated with IMDC and treatment subtype. Results: One thousand three hundred and nineteen patients were identified with a median age of 64. 294 (22.3%), 695 (52.7%) and 321 (24.3%) were IMDC group favourable, intermediate and poor, respectively. 311 (23.6%), 197 (14.9%) and 778 (59%) patients received checkpoint inhibitor and anti‐CTLA4 monoclonal antibody (IO/IO), IO/TKI and TKI first‐line SACT across all IMDC groups. Significant PFS improvement favouring IO/TKI versus TKI was demonstrated in allcomers HR = 0.61. In the favourable risk group, Log rank testing demonstrated a significant benefit for IO/TKI over TKI for PFS (HR = 0.60, 95% CI [0.39, 0.91]) and OS (HR = 0.42, 95% CI [0.18, 0.99]). Conclusion: In this real‐world evidence cohort, we have shown OS and PFS benefit with IO/TKI versus TKI in the favourable IMDC risk group. This has not been previously reported from trial outcomes and would support use of front‐line IO/TKI in mRCC favourable risk patients. [ABSTRACT FROM AUTHOR]

The identification of genetic variants in melanoma has enabled the development of targeted therapies. Under the National Institute for Health and Care Excellence (NICE) guidance, patients with BRAF V600E variant are eligible for BRAF and MEK inhibitor therapy. For those with advanced or highly symptomatic disease, a rapid response to treatment is often seen. Current practice relies on tissue biopsy to perform immunohistochemistry (IHC) or next generation sequencing (NGS) to identify these variants; however, this can take up to 2 weeks. In patients with widespread disease, rapid initiation of treatment can be lifesaving. We describe a case in which hotspot circulating tumour DNA (ctDNA) analysis confirmed BRAF variant 6 days prior to biopsy results. This was utilised to expedite treatment initiation and symptomatically, the patient had initial improvement within a few days. This article demonstrates the potential value of ctDNA analysis and the need for further research into this as an alternative to NGS for patients with rapidly progressive disease. [ABSTRACT FROM AUTHOR]

Background Palliative care went through a significant evolution in the 20th century, but the 19th century has been seen my some scholars as the real turning point toward the more modern concept of hospices and palliative care. Methods To investigate some examples of earlier uses of the word 'palliative', a literature search was conducted within the earliest available BMJ archive sections, the years 1840 to 1842. This provided a glimpse into how the word was used in the medical literature in Victorian times, mid-nineteenth century. Results Search results brought up a number of case reports, and the word was employed to describe medicines ('use of palliatives') as well as passive, non-active treatment approaches, probably best described as a watch-and-wait strategy. Of note is that the first recorded use of the word in the archives is by a surgeon. Conclusions Some doctors associated the word palliative with there not being any prospect for cure and only for the relief of symptoms and greater comfort of the patient. There were, however, early reflections on whether palliative treatments may in some cases increase the length of patients' lives. [ABSTRACT FROM AUTHOR]

This is a case of a 45-year-old woman, with known alcoholic liver disease who presented with a large right-sided pleural effusion. A pleural tap was performed followed by insertion of an intercostal drain. 7 litres were drained over 4 h and only 300 ml of 20% albumin were administered with the patient becoming acutely short of breath and requiring admission to the intensive treatment unit due to the development of the known and recognised complication of re-expansion pulmonary oedema. The patient required continuous positive airway pressure in an intensive care setting but made a good recovery. It is important to consider re-expansion pulmonary oedema in patients who become acutely short of breath during drainage of pleural fluid or air. Steps should be made to ensure that drainage of large volumes of fluid are performed in a controlled manner to avoid this preventable complication. [ABSTRACT FROM AUTHOR]

The authors present a case of an 84-year-old patient who presented to the emergency department with sudden onset abdominal pain radiating to the neck. The patient's medication included warfarin, and alendronate, which was started by the general practitioner 2 days prior to presentation. Initial systemic examination and investigations, including chest x-ray, were unremarkable. Within 24 h of presentation the patient developed bilateral pneumonia with effusions. Due to continued clinical deterioration over the next 48 h, a CT thorax was performed that showed evidence of large oesophageal perforation with mediastinitis and gas in the mediastinum. The patient was treated with an expandable metal stent, bilateral chest drains, broad spectrum antibiotics, antifungals and total parenteral nutrition. Over a period of 8 weeks the patient made an excellent recovery. This rare case illustrates the importance of vigilance for the life-threatening complication of oesophageal perforation with alendronate treatment. [ABSTRACT FROM AUTHOR]