Prostate cancer is the second most frequent cancer in men, with increasing prevalence due to an ageing population. Advanced prostate cancer is diagnosed in up to 20% of patients, and, therefore, it ...is important to understand evolving mechanisms of progression. Significant morbidity and mortality can occur in advanced prostate cancer where treatment options are intrinsically related to lipid metabolism. Dysfunctional lipid metabolism has long been known to have a relationship to prostate cancer development; however, only recently have studies attempted to elucidate the exact mechanism relating genetic abnormalities and lipid metabolic pathways. Contemporary research has established the pathways leading to prostate cancer development, including dysregulated lipid metabolism-associated de novo lipogenesis through steroid hormone biogenesis and β-oxidation of fatty acids. These pathways, in relation to treatment, have formed potential novel targets for management of advanced prostate cancer via androgen deprivation. We review basic lipid metabolism pathways and their relation to hypogonadism, and further explore prostate cancer development with a cellular emphasis.
A primary variant of social media, online support groups (OSG) extend beyond the standard definition to incorporate a dimension of advice, support and guidance for patients. OSG are complementary, ...yet significant adjunct to patient journeys. Machine learning and natural language processing techniques can be applied to these large volumes of unstructured text discussions accumulated in OSG for intelligent extraction of patient-reported demographics, behaviours, decisions, treatment, side effects and expressions of emotions. New insights from the fusion and synthesis of such diverse patient-reported information, as expressed throughout the patient journey from diagnosis to treatment and recovery, can contribute towards informed decision-making on personalized healthcare delivery and the development of healthcare policy guidelines.
We have designed and developed an artificial intelligence based analytics framework using machine learning and natural language processing techniques for intelligent analysis and automated aggregation of patient information and interaction trajectories in online support groups. Alongside the social interactions aspect, patient behaviours, decisions, demographics, clinical factors, emotions, as subsequently expressed over time, are extracted and analysed. More specifically, we utilised this platform to investigate the impact of online social influences on the intimate decision scenario of selecting a treatment type, recovery after treatment, side effects and emotions expressed over time, using prostate cancer as a model. Results manifest the three major decision-making behaviours among patients, Paternalistic group, Autonomous group and Shared group. Furthermore, each group demonstrated diverse behaviours in post-decision discussions on clinical outcomes, advice and expressions of emotion during the twelve months following treatment. Over time, the transition of patients from information and emotional support seeking behaviours to providers of information and emotional support to other patients was also observed.
Findings from this study are a rigorous indication of the expectations of social media empowered patients, their potential for individualised decision-making, clinical and emotional needs. The increasing popularity of OSG further confirms that it is timely for clinicians to consider patient voices as expressed in OSG. We have successfully demonstrated that the proposed platform can be utilised to investigate, analyse and derive actionable insights from patient-reported information on prostate cancer, in support of patient focused healthcare delivery. The platform can be extended and applied just as effectively to any other medical condition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epigenetics is a growing field and in bladder cancer, it is of particular interest in advanced or metastatic disease. As opposed to genetic mutations in which the nucleotide sequence itself is ...altered, epigenetic alterations refer to changes to the genome that do not involve nucleotides. This is of great interest in cancer research because epigenetic alterations are reversible, making them a promising target for pharmacological agents. While chemoimmunotherapy is the mainstay for metastatic disease, there are few alternatives for patients who have progressed on first- or second-line treatment. By targeting reversible epigenetic alterations, novel epigenetic therapies are important potential treatment options for these patients. A search of clinical registries was performed in order to identify and collate epigenetic therapies currently in human trials. A literature search was also performed to identify therapies that are currently in preclinical stages, whether this be in vivo or in vitro models. Twenty-five clinical trials were identified that investigated the use of epigenetic inhibitors in patients with bladder cancer, often in combination with another agent, such as platinum-based chemotherapy or pembrolizumab. The main classes of epigenetic inhibitors studied include DNA-methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and histone methyltransferase (HMT) inhibitors. At present, no phase 3 clinical trials have been registered. Few trials have published results, though DNMT inhibitors have shown the most promise thus far. Many patients with advanced or metastatic bladder cancer have limited treatment options, particularly when first- or second-line chemoimmunotherapy fails. Epigenetic alterations, which are common in bladder cancer, are potential targets for drug therapies, and these epigenetic agents are already in use for many cancers. While they have shown promise in pre-clinical trials for bladder cancer, more research is needed to assess their benefit in clinical settings.
Androgen deprivation therapy (ADT) is still a mainstay of treatment for advanced prostate cancer. Continuous ADT causes considerable patient morbidity including sexual dysfunction, poor mood and ...physical capacity, changes in body composition and health-care-related costs. Intermittent ADT has been used as an approach to ADT monotherapy to limit morbidity by enabling cyclical recovery of serum testosterone levels. To date, a number of well-performed randomized controlled trials and meta-analyses have demonstrated statistically insignificant differences in oncological outcomes between intermittent and continuous ADT monotherapy. Sexual outcomes, morbidity profiles and cost-savings favour intermittent therapy in most randomized trials, but the benefit for clinical practice is unclear. Despite the growing body of evidence, the optimal administration regime for ADT has not been clearly established and incorporation of adjunctive upfront treatments such as chemotherapy and novel anti-androgen agents has further hampered progress. Recommendations by authoritative urological and oncological societies regarding the use of intermittent ADT are limited. The potential benefits of reduced morbidity for a particular patient must be considered in light of the possible oncological outcomes. Although the oncological changes associated with intermittent ADT are controversial, intermittent ADT does seem to provide symptomatic benefit in patients compared with continuous ADT. However, careful selection of suitable patients is crucial.
Purpose
Contemporary, original research should be utilised to inform guidelines in urology relating to the COVID-19 pandemic. This comprehensive review aimed to: identify all up-to-date original ...publications relating to urology and COVID-19, characterise where publications were from, and outline what topics were investigated.
Methods
This review utilised a search strategy that assessed five electronic databases, additional grey literature, and global trial registries. All current published, in-press, and pre-print manuscripts were included. Eligible studies were required to be original research articles of any study design, reporting on COVID-19 or urology, in any of study population, intervention, comparison, or outcomes. Included studies were reported in a narrative synthesis format. Data were summarised according to primary reported outcome topic. A world heatmap was generated to represent where included studies originated from.
Results
Of the 6617 search results, 48 studies met final inclusion criteria, including 8 pre-prints and 7 ongoing studies from online registries. These studies originated from ten countries according to first author affiliation. Most studies originated from China (
n
= 13), followed by Italy (
n
= 12) and USA (
n
= 11). Topics of the study included pathophysiological, administrative, and clinical fields: translational (
n
= 14), COVID-19-related outcomes (
n
= 5), urology training (
n
= 4), telemedicine (
n
= 7), equipment and safety (
n
= 2), urology in general (
n
= 4), uro-oncology (
n
= 3), urolithiasis (
n
= 1), and kidney transplantation (
n
= 8).
Conclusion
This review has outlined available original research relevant to COVID-19 and urology from the international community. This summary may serve as a guide for future research priorities in this area.
Objective
To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess ...oncological and functional outcomes.
Materials and Methods
This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time‐to‐event outcomes were described using the Kaplan–Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size.
Results
Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow‐up was 24 months. Treatment‐related grade 1–2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4–5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001).
Conclusion
The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune‐mediated response and warrants further investigation.
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