No abstract

The use of biomarkers in medicine has become essential in clinical practice in order to help with diagnosis, prognostication and prediction of treatment response. Since Alexander Breslow’s original report on “melanoma and prognostic values of thickness”, providing the first biomarker for melanoma, many promising new biomarkers have followed. These include serum markers, such as lactate dehydrogenase and S100 calcium-binding protein B. However, as our understanding of the DNA mutational profile progresses, new gene targets and proteins have been identified. These include point mutations, such as mutations of the BRAF gene and tumour suppressor gene tP53. At present, only a small number of the available biomarkers are being utilised, but this may soon change as more studies are published. The aim of this article is to provide a comprehensive review of melanoma biomarkers and their utility for current and, potentially, future clinical practice.

Prostate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations in DDR genes have been found in both primary and metastatic prostate cancer. Among these, BRCA mutations have been found to be especially clinically relevant with a role for germline or somatic testing. Prostate cancer with DDR defects may be sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors which target proteins in a process called PARylation. Initially they were used to target BRCA-mutated tumor cells in a process of synthetic lethality. However, recent studies have found potential for PARP inhibitors in a variety of other genetic settings. In this review, we explore the mechanisms of DNA repair, potential for genomic analysis of prostate cancer and therapeutics of PARP inhibitors along with their safety profile.

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

Non-epithelial ovarian cancers (NEOC) are a group of uncommon malignancies that mainly includes germ cell tumours (GCT), sex cord-stromal tumours (SCST), and some extremely rare tumours, such as small cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. The aetiology and molecular origins of each sub-group of NEOC require further investigation, and our understanding on the genetic changes should be optimised. In this article, we provide an update on the clinical presentation, pathology, genetics, treatment and survival of the main histological subtypes of the GCT and the SCST, as well as of ovarian small cell carcinomas. We also discuss miRNA expression profiles of NEOC and report the currently active clinical trials that include NEOC.

Epithelial ovarian cancer (EOC) is one of the cancers most influenced by hereditary factors. A fourth to a fifth of unselected EOC patients carry pathogenic variants (PVs) in a number of genes, the majority of which encode for proteins involved in DNA mismatch repair (MMR) pathways. PVs in BRCA1 and BRCA2 genes are responsible for a substantial fraction of hereditary EOC. In addition, PV genes involved in the MMR pathway account for 10–15% of hereditary EOC. The identification of women with homologous recombination (HR)-deficient EOCs has significant clinical implications, concerning chemotherapy regimen planning and development as well as the use of targeted therapies such as poly(ADP-ribose) polymerase (PARP) inhibitors. With several genes involved, the complexity of genetic testing increases. In this context, next-generation sequencing (NGS) allows testing for multiple genes simultaneously with a rapid turnaround time. In this review, we discuss the EOC risk assessment in the era of NGS.

The COVID-19 pandemic has undoubtedly affected all national healthcare systems at different levels. In countries heavily hit by the pandemic, it was reported that healthcare workers were asked to work long hours, had increased workload, were faced with difficult decisions, and that the resources were stretched. As such, the COVID-19 pandemic would create the perfect storm for burnout in healthcare workers. Within this context, we conducted a survey in a district general hospital in Southeast England. We focused on doctors in training, in different specialties. This survey included parts of the Maslach Burnout Inventory for healthcare professionals, along with other relevant questions, such as the financial impact and seeking of psychological support. The results showed moderate levels of emotional exhaustion, but high levels of personal satisfaction, a positive impact on doctors finances and very low levels of seeking support.

Introduction: Malignant spinal cord compression (MSCC) is one of the most devastating complications of cancer. This event requires rapid decision-making on the part of several specialists, given the risk of permanent spinal cord injury or death. The goals of treatment in spinal metastases are pain control and improvement of neurological function. There can be challenges in delivering prompt diagnosis and treatment in a secondary care setting. We have reflected on the experience of managing MSCC in a district general setting. Aim: Our retrospective audit identified 53 patients with suspected MSCC who entered the relevant pathway from April 2017 to March 2018 at Medway, United Kingdom (UK). Our audit standards were set out by Medway Maritime Hospital and Maidstone and Tunbridge Wells NHS Trust MSCC working group members, using a combination of published evidence and best practice. Results: The patients with suspected MSCC were 53 and 29 of them (54.7%) had confirmed MSCC. The most common malignancies within the confirmed MSCC were lung (11 patients, 37.9%), breast (5 patients 17.2%), and renal (3 patients, 10.3%), followed by prostate, myeloma and carcinoma of unknown primary (2 patients (6.9%) each), as well as pancreatic, colorectal, lymphoma and, bladder (1 patient (3.4%) each). A magnetic resonance imaging (MRI) scan was performed in 48 patients (90.5%); the majority (31 patients, 64.6%) underwent the MRI within the first 24 h, whereas 3 patients had the investigation between 24 and 72 h from the admission. Among the 29 patients with confirmed MSCC, 6 (20.6%) were treated with surgical decompression, while 20 (69%) received radiotherapy (RT) and 3 (10.3%) best supportive care, respectively. Median time to surgery was 5 days (ranged between 2 and 8 days), whereas for RT 44.4 h (ranged between 24 and 72 h). Finally, all 3 patients that decided on symptom control were referred to a palliative care team within the first 24 h following the MRI scan. Conclusions: MSCC is frequently presented outside tertiary care. This may cause subsequent delays in investigation, diagnosis, and treatment, which can be improved by following a fast track referral pathway.