Kenrick Ng

Background This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow‐up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non‐users were those who had not used any statins. PCa‐related mortality was …

Patients with cancer have elevated cardiovascular risks compared to those without cancer. As cancer incidence increases and cancer-related mortality decreases, cardiovascular diseases in patients with a history of cancer will become increasingly important. This in turn is reflected by the exponentially increasing amount of cardio-oncology research in recent years. This narrative review aims to summarize the key existing literature in several main areas of cardio-oncology, including the epidemiology, natural history, prevention, management, and determinants of the cardiovascular health of patients with cancer, and identify relevant gaps in evidence for further research.

Dee, Ng, Shamash, and Nguyen respond to the work of Potosky et al, highlighting the importance of global quality of life in prostate cancer care. Factors such as companionship and spirituality must be considered in providing equitable and whole-person care.

Temporal trends in guideline-recommended cardiometabolic testing completeness before initiating immune checkpoint inhibitors: A cohort study Temporal trends in guideline-recommended cardiometabolic testing completeness before initiating immune checkpoint inhibitors: A cohort study J Intern Med. 2024 Mar;295(3):375-378. doi: 10.1111/joim.13754. Epub 2023 Nov 27. Authors Jeffrey Shi Kai Chan 1 , Oscar Hou In Chou 1 , Teddy Tai Loy Lee 1 , Yan Hiu Athena Lee 1 , Raymond Ngai Chiu Chan 1 , Edward Christopher Dee 2 , Kenrick Ng 3 , Tong Liu 4 , Gary Tse 4 5 6 Affiliations 1 Cardio-Oncology Research Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China. 2 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 3 Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, …

512Background: Testicular germ cell tumors (tGCTs) are rare but are highly curable, resulting in a large cohort of long-term survivors. The primary aim of most follow-up programs after initial treatment is to detect recurrence, which emphasizes regular imaging and measurement of serum tumor markers. Most relapses occur in the first two years after treatment. However, many of these patients also experience survivorship issues beyond the two-year timepoint which are underrecognized in the clinical setting and underreported in clinical literature. Methods: We retrospectively reviewed clinical documentation across a cohort of tGCT patients in St Bartholomew’s Hospital who received adjuvant treatment (n=171), treatment for metastatic cancer (n=325) and those who underwent surveillance only (n=225) from 2011 and 2021. Only patients with a minimum follow-up of 5 years were included. Data was collected between …

ObjectivesTo estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.MethodsSystematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsIn 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi …

BackgroundDespite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations.MethodsPatients with localized prostate adenocarcinoma diagnosed from 2004–2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease.ResultsIn our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16–1.21, p < 0.001). Additionally …

Background This study aims to examine the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with prostate cancer (PCa). Methods This study identified diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 retrospectively, with follow‐up until September 2021. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥180 days of concurrent metformin use and ADT, while non‐users had no concurrent metformin use and ADT or never used metformin. The primary outcome was PCa‐related mortality. The secondary outcome was all‐cause mortality. The study used inverse probability treatment weighting to …

At presentation, approximately 25% of patients will have muscle-invasive bladder cancer (MIBC), and patients with non-MIBC may subsequently progress to MIBC. Prognosis is dependent on TNM stage (Table 12.1) and pelvic lymph node status. The disease requires a multi-disciplinary approach, encompassing surgeon, oncologist, radiologist, pathologist and cancer specialist nurse.

IntroductionThe success in the management of germ cell tumors has encouraged researchers to pay more attention on long-term side effects and other survivorship issues. The de-escalation of treatment is intended to reduce side effects but must be balanced against any compromise of efficacy. Cisplatin-based therapy is the cornerstone of treatment for germ cell tumors. However, they can result in acute and long-term side effects, including ototoxicity, neurotoxicity, nephrotoxicity, and increased risk of second malignancies.Areas coveredThis review discusses approaches of de-escalation including biomarker-directed treatment using microRNAs, surveillance for immature teratoma, the use of carboplatin monotherapy for seminoma, and the option of non-cisplatin-based approaches in relapsed germ cell tumors.Expert opinionWhile the results with the current standard options in terms of cancer control are very good …

BackgroundWhile the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients.MethodsAdult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE …

BackgroundAlthough androgen deprivation therapy (ADT) is associated with cardiovascular risks, the extent and temporal trends of cardiovascular burden amongst patients with prostate cancer receiving ADT are unclear.MethodsThis retrospective cohort study analyzed adults with PCa receiving ADT between 1993–2021 in Hong Kong, with follow-up until 31/9/2021 for the primary outcome of major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, and heart failure), and the secondary outcome of mortality. Patients were stratified into four groups by the year of ADT initiation for comparisons.ResultsAltogether, 13,537 patients were included (mean age 75.5 ± 8.5 years old; mean follow-up 4.7 ± 4.3 years). More recent recipients of ADT had more cardiovascular risk factors and used more cardiovascular or antidiabetic medications. More recent recipients of …

This article was co-authored by a patient’s relative describing their experiences of receiving a diagnosis and subsequent clinical management of a rare form of prostate cancer, neuroendocrine prostate cancer (NEPC). The difficulty of receiving this diagnosis, particularly as this was terminal with no options for systemic treatment, and experiences throughout this process are detailed. The relative’s questions regarding the care of her partner, NEPC and clinical management are answered. The treating physician’s perspective regarding clinical management is enclosed. Prostate cancer remains one of the most common cancer diagnoses, with small-cell carcinoma (SCC) of the prostate representing 0.5–2% of these. Prostatic SCC frequently develops in patients previously treated for prostate adenocarcinoma, more rarely arising de novo. Diagnosis and management present clinical challenges owing to its rarity …

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred …

Introduction Head and neck cancer is the eighth most common cancer in the UK. Current standard of care treatment for patients with recurrent/metastatic squamous cell head and neck carcinoma (HNSCC) is platinum-based chemotherapy combined with the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, cetuximab. However, most patients will have poor median overall survival (OS) of 6–9 months despite treatment. HNSCC tumours exhibit an immune landscape poised to respond to immunotherapeutic approaches, with most tumours expressing the immunosuppressive receptor programmed death-ligand 1 (PD-L1). We undertook the current study to determine the safety and efficacy of avelumab, a monoclonal antibody targeting the interaction between PD-L1 and its receptor on cytotoxic T-cells, in combination with cetuximab. Methods and analysis This is a multi-centre, single-arm dose de …

Background/Aims Concerns have been raised about the risk of malignancy with Janus kinase inhibitors (JAKi) following the ORAL Surveillance study, which reported an increased incidence of malignancy with tofacitinib compared with Tumor Necrosis Factor-α inhibitors (TNFi) in people with rheumatoid arthritis (RA) aged over 50 years who had additional cardiovascular risk factors. Our objective was to estimate the risk of malignancy for all licenced JAKi across disease indications, compared with TNFi, methotrexate (MTX), and placebo. Methods A systematic search of electronic databases (Medline, EMBASE, Cochrane) was performed to identify Phase 2/3/4 RCTs and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) in adults with RA, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic …

Southeast Asia has a population of over 680 million people—approximately half the population of India and twice the population of the United States—and is a region marked by rich and complex histories and cultures, dynamic growth, and unique and evolving health challenges. 1 Despite the momentum of economic development, health inequalities persist. These inequities have been aggravated since the COVID-19 pandemic, which pushed millions further into poverty, possibly exacerbating health disparities, especially among populations who suffer vulnerabilities. 2 Particularly salient are the challenges associated with providing adequate care for people with cancer, a leading cause of morbidity and mortality in the region. 1, 2 Cancer incidence and mortality in the region are projected to rise in the coming decades, given population growth and rapidly changing socioeconomic and geopolitical factors, as well as …

Background Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new‐onset overall cancer and pre‐specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium‐glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I. Methods This population‐based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong. Results This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all‐cause mortality (HR: 0.92; 95% CI: 0.84–0.99; p= 0.04 …

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population‐based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0‐81.5] years old; median follow‐up 3.3 [1.5‐6.7] years). Compared to those …

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients. Objective This real-world study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients. Design, setting and participants: This was a retrospective population-based cohort study of prospectively recorded data on type-2 diabetes mellitus (T2DM) male patients prescribed either SGLT2I or DPP4I between January 1st 2015 and December 31st 2020 from Hong Kong. Methods The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed and multivariable Cox regression was applied to compare the risk. A three-arm sensitivity analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted. Results This study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n=17120; DPP4I: n=25009). After matching, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). SGLT2I use was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) after adjustments than DPP4I. The results remained consistent in the sensitivity analysis. SGLT2I reduced the risks of prostate cancer prominently amongst patients who were older (age >65), patients with 2nd and 3rd quartile of HbA1c, concurrent metformin uses, and concurrent …

BackgroundDipeptidyl peptidase-4 inhibitors (DPP4I) may be associated with higher risks of acute pancreatitis and pancreatic cancer. This study compared the risks of acute pancreatitis and pancreatic cancer between sodium glucose cotransporter 2 inhibitors (SGLT2I) and DPP4I users.MethodsThis was a retrospective population-based cohort study of patients with type-2 diabetes mellitus on either SGLT2I or DPP4I between January 1st, 2015, and December 31st 2020 in Hong Kong. The primary outcome was new-onset acute pancreatitis and pancreatic cancer. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regressions were applied to identify significant predictors.ResultsThis cohort included 31609 Type 2 Diabetes Mellitus patients (median age: 67.4 years old [SD: 12.5]; 53.36% males). 6479 patients (20.49%) used SGLT2I, and …

Background Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. Methods Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. Results In total, 1,284 metformin users and 687 non‐users were studied. Over 8,045 person‐years, 9,049 …

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients.MethodsThis real-world study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients. This was a retrospective population-based cohort study of prospectively recorded data on type-2 diabetes mellitus (T2DM) male patients prescribed either SGLT2I or DPP4I between January 1 st 2015 and December 31 st 2020 from Hong Kong. The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1: 1 ratio) using the nearest neighbour search was performed and multivariable Cox regression was applied to compare the risk. A three-arm sensitivity analysis including the glucagon …

Background Immune checkpoint inhibitors (ICIs) have become a common treatment for many types of cancer. However, the effects of ICIs on HF hospitalisations (HFH) remained unexplored. This self-controlled case series (SCCS) thus explored possible associations between ICIs and HFH.Methods Data were acquired from the Clinical Data Analysis and Reporting System (CDARS), a prospective population-based database of all patients attending public healthcare facilities in Hong Kong with linked, governmental mortality data.Patients with cancer who received any ICI (programmed cell death protein-1 inhibitors [PD1i], PD ligand-1 inhibitors [PDL1i], or cytotoxic T-lymphocyte associated protein-4 inhibitors [CTLA4i]) in Hong Kong within 1/1/2014-31/12/2020 were included. Those without HFH (identified using International Classification of Diseases, Ninth revision [ICD-9] codes [428.0-428.9, 402.01, 402.11, and …

Objective This population‐based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)‐related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Methods Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa‐related mortality. Results Altogether, 4126 patients (median follow‐up 3.1[interquartile range 1.4–6.0] years) were included. A J‐shaped association was observed between baseline UA level and PCa‐related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above‐mean baseline UA levels (hazard ratio (HR) per standard deviation‐increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with …

Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognised to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify chemotherapy-induced Thioredoxin Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), through CD48 ligation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that loss of TXNIP/GDF15 axis functionality is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial stress drives local immune remodelling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

IntroductionHead and neck cancer is the eighth most common cancer in the UK. Current standard of care treatment for patients with recurrent/metastatic squamous cell head and neck carcinoma (HNSCC) is platinum-based chemotherapy combined with the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, cetuximab. However, most patients will have poor median overall survival (OS) of 6–9 months despite treatment. HNSCC tumours exhibit an immune landscape poised to respond to immunotherapeutic approaches, with most tumours expressing the immunosuppressive receptor programmed death-ligand 1 (PD-L1). We undertook the current study to determine the safety and efficacy of avelumab, a monoclonal antibody targeting the interaction between PD-L1 and its receptor on cytotoxic T-cells, in combination with cetuximab.Methods and analysisThis is a multi-centre, single-arm dose de …

Background Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new‐onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between‐class and ‐sex differences remain unexplored. Methods This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD‐1i) and programmed death ligand 1 inhibitors (PD‐L1i) were compared, alongside between‐sex comparison. When comparing PD‐1i against PD‐L1i, patients with the use of other ICIs or both PD‐1i and PD‐L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between‐group covariate imbalances. Results Altogether, 3375 patients were analyzed (65.2 …

Background Medical research is important for professional advancement, and mentoring is a key means by which students and early‐career doctors can engage in research. Contrasting international research collaborations, research mentoring programmes are often geographically limited. As the COVID‐19 pandemic has led to increased use of online technology for classes and conferences, a virtual, international approach to medical research mentoring may be valuable. Approach We hereby describe our experience at the Cardiovascular Analytics Group, a virtual international medical research mentoring group established in 2015. We make use of virtual platforms in multi‐level mentoring with peer mentoring and emphasise active participation, early leadership, an open culture, accessible research support and a distributed research workflow. Evaluation With 63 active members from 14 different countries, the …

AimsGonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists.Materials and methodsPatients with PCa receiving GnRH agonists or antagonists during 2013–2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of …

BackgroundAndrogen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT.ObjectiveTo explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV.Design, setting, and participantsPCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021.Outcome measurements and statistical analysisThe outcome was MACEs (composite of heart failure …

Monoclonal antibody (Mab) treatments have significantly improved the quality and quantity of life, but are some of the most expensive treatments, resulting in some hesitance to introduce new Mab agents. A system for estimating the impact of Mab drugs in general would optimally inform health strategy and fully realise how a single scientific discovery can deliver health benefits. We evaluated such a method with several well-established Mab regimens. We selected five different Mab regimens in oncology and rheumatology in England. We carried out two systematic literature reviews and meta-analyses to assess health outcomes (Health assessment questionnaire-disability index for rheumatoid arthritis; overall mortality for melanoma) from realworld data, compared to the outcomes from randomised control trials (RCTs). We applied economic modelling to estimate the net monetary benefits for health outcomes for estimated patient population size for each Mab regimen. Meta-analyses of 27 eligible real-world data (RWD) sets and 26 randomised controlled trial (RCT) sets found close agreement between observed and expected health outcomes. A Markov model showed net positive monetary benefit in three Mab regimens and negative benefit in two regimens. However, because of limited access to NHS data, the economic model made several assumptions about the number of treated patients and the cost of treatment to the NHS, the accuracy of which may affect the estimation of net monetary benefit. RCT results reliably inform the real-world experience of Mab treatments. Calculation of net monetary benefit by the algorithm described provides a …

ObjectiveWe aim to describe and highlight the current use of immune checkpoint inhibitors (ICIs) in the muscle invasive bladder cancer (MIBC) treatment landscape, particularly focusing on the perioperative setting. We provide a comprehensive review of key trials of the use of ICI in the perioperative setting, discussing trial outcomes and limitations and reviewing the role of biomarkers.IntroductionICIs have recently been integrated into the treatment algorithm for metastatic urothelial carcinoma. More than 30 published studies have investigated the role of these agents in the radical treatment of MIBC. Some studies have demonstrated conflicting results, affecting widespread adoption in clinical practice.MethodsWe performed a narrative overview of the literature from databases including PubMed, MEDLINE, Embase, European society of Medical Oncology/American Society of Clinical Oncology Annual Proceedings …

Madam d Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, major classes of immune checkpoint inhibitors, are increasingly prescribed for different cancers. Data from Asian cohorts have been sparse [1], especially on the liver immune-related adverse effects [2]. We examined patients receiving PD-1 or PD-L1 inhibitors until 31 August 2020 in Hong Kong. The methods are detailed in Supplementary Methods. A list of PD-1 and PD-L1 drugs and ICD-9 codes are listed in Supplementary Tables S1 and S2, respectively. Propensity score matching between PD-1 and PD-L1 inhibitor users (1: 3) with nearest neighbour search strategy was carried out. Initially, 2426 cancer patients were identified (Supplementary Figure S1). After exclusion, 1735 patients were included (64.78% males, median age 63.5 years old; PD-1 inhibitors: n ¼ 1341, PD-L1 inhibitors: n ¼ 394)(Supplementary …

BackgroundThe association between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are currently unknown.MethodsThis was a retrospective population-based cohort study including type-2 diabetes mellitus (T2DM) patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. Patients with concurrent DPP4I and SGLT2I usage were excluded. The primary outcomes were NAFLD and HCC. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Univariable and multivariable Cox regression was applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed.ResultsThis cohort included 62699 patients with T2DM, amongst which 22154 patients were on SGLT2I and 40545 patients were on DPP4I. After matching (44308 patients), 1090 patients developed new-onset NAFLD (Incidence: 4.6; 95% Confidence interval [CI]: 4.3-4.9) and 187 patients developed HCC (Incidence: 0.8; 95% CI: 0.7-0.9). Overall, SGLT2I was associated with lower risks of NAFLD (Hazard ratio [HR]: 0.39; 95% CI: 0.34-0.46), and HCC (HR: 0.46; 95% CI: 0.29-0.72) compared to DPP4I after adjustments. SGLT2I was also associated with lower risks of cancer-related mortality (HR: 0.29; 95% CI: 0.23-0.37) and all-cause mortality (HR: 0.28; 95% CI: 0.25-0.31). However, amongst patients with …

ObjectivesDespite their proven efficacy for treating lung cancer, the cardiovascular risks associated with programmed cell death protein 1 (PD-1) inhibitors and their combinations with chemotherapy (chemo-immunotherapy) are unclear. This study aimed to investigate these associations.Materials and methodsThis retrospective cohort study included Hong Kong patients with lung cancer receiving PD-1 inhibitors during 2013–2021. Patients with non-concurrent use of PD-1 inhibitors and chemotherapy, any use of tyrosine kinase inhibitors or other immunotherapy agents, and those with prior stroke, heart failure, or myocardial infarction were excluded. PD-1 inhibitors and chemo-immunotherapy were compared for major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, heart failure, stroke, and myocardial infarction. All patients were followed up until the end of 2021. Inverse probability of …

417Background: Following relapse from first line chemotherapy, 30-60% of patients with germ cell tumors (GCTs) can be salvaged with further chemotherapy. Oxaliplatin-based therapies may offer reduced toxicity. Methods: Eligible patients with GCTs who progressed following cisplatin-based chemotherapy were recruited into this single-arm, phase II clinical trial (NCT01782339). Participants were recruited from six centers and received four 21-day cycles of: Actinomycin D 1mg/m2, high dose Methotrexate 5-8g/m2 day 1, Paclitaxel 80mg/m2 days 1, 8 and 15, Oxaliplatin 85mg/m2 days 4 and 8 with Pegfilgrastim support. Participants underwent an FDG-PET scan at baseline, prior to cycle 2 and on completion of treatment. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Results: 44 patients received at least one …

Role of immunotherapy in early muscle invasive urothelial or bladder cancer — University of Hertfordshire (Research Profiles) Skip to main navigation Skip to search Skip to main content University of Hertfordshire (Research Profiles) Home University of Hertfordshire (Research Profiles) Logo Home Researchers Research output Projects Research units Search by expertise, name or affiliation Role of immunotherapy in early muscle invasive urothelial or bladder cancer Saachi Chhaya, Isabella Watts, Kenrick Ng, Rami Mustapha, Thomas Powles, Anand Sharma, Nikhil Vasdev Centre for Health Services and Clinical Research Basic and Clinical Science Unit Extracellular Vesicle Research Unit School of Life and Medical Sciences Department of Clinical, Pharmaceutical and Biological Science Research output: Contribution to journal › Article › peer-review Overview Fingerprint Original language English Journal BJUI …

Context Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. Objective The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. Methods This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. Results This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up …

Funding Acknowledgements Type of funding sources: None. OnBehalf Cardioovascular Analytics Group Background Medical research is critical to professional advancement, and mentoring is an important means of early research engagement in medical training. In contrast to international research collaborations, research mentoring programs are often locally limited. With the COVID-19 pandemic causing drifts to virtual classes and conferences, virtual international medical research mentoring may be viable. We hereby describe our experience with a virtual, international mentorship group for cardiovascular research. Methods Our virtual international research mentorship group has been running since 2015. The group focuses on risk stratification and outcomes research in cardiovascular medicine and epidemiology. Mentees from any …

Background: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). Methods: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation …

Background Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin‐releasing hormone (GnRH) agonist use duration and cardiovascular risks. Methods This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999–2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing‐risk regression using the Fine‐Gray subdistribution model was used, with mortality from any cause as the competing event. Results In total, 4038 patients were analyzed (median age 74 …

PURPOSEWe identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors.METHODSWe assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors.RESULTSAmong 980,889 men (median age 66 years), all AANHPI …

Background: With known anticancer properties, statins have the potential to be an adjuvant cancer therapy, but their associations with mortality in prostate cancer (PCa) remain debatable. This study investigated the associations between statin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian patients with PCa.Methods: Adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified, with follow-up until September 2021. Patients with< 180 days of medical castration without subsequent bilateral orchidectomy,< 180 days of concurrent statin use and ADT, or missing total cholesterol level at baseline were excluded. Statin users had≥ 180 days of concurrent statin and ADT use, while non-users were those without any statin use. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates.Results: 4920 patients were studied (2578 statin users and 2342 non-users; mean age 76.1±8.2 years). Over a mean follow-up of 4.2±3.3 years, statin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.56 [95% confidence interval 0.48, 0.65], p< 0.001) and all-cause mortality (0.57 [0.51, 0.63], p< 0.001) regardless of the type of ADT. The associations appeared stronger in patients without chemotherapy or antiandrogens use.Conclusions: Statin use concurrent with ADT was associated with lower risks of mortality in Asian patients with PCa, warranting further studies of its role in the treatment of …

BackgroundDipeptidyl peptidase-4 inhibitors (DPP-4I) have demonstrated survival benefit in patients with cancer, but their impact on patients with prostate cancer (PCa), especially with androgen deprivation therapy (ADT), is unclear. This study examined the impact of DPP-4I use on mortality risks in patients with type 2 diabetes (T2D) and PCa receiving ADT.MethodsAdults with T2D and PCa who received metformin and ADT attending public hospitals in Hong Kong between 1 January 2006 and 31 March 2021 were retrospectively identified. Patients with< 6 months of chemical castration without bilateral orchidectomy,< 6 months of concurrent DPP-4I and ADT use, or missing baseline HbA1c were excluded. DPP-4I users had≥ 6 months of concurrent DPP-4I and ADT use, while non-users never had DPP-4I use. Included patients were followed-up until 30 September 2021. The endpoints were PCa-specific mortality and all-cause mortality. Inverse probability treatment weighting was used to balance covariates.ResultsIn total, 1465 patients (286 DPP-4I users and 1179 non-users; mean age 76.0±7.9 years old) were analyzed. Over a mean follow-up of 4.0±3.0 years, DPP-4I users had lower risks of PCa-specific mortality (weighted hazard ratio (wHR) 0.40 [95% confidence interval (CI) 0.26–0.59], p< 0.001) and all-cause mortality (wHR 0.59 [95% CI 0.48–0.73], p< 0.001). Such associations were independent of diabetic control. Moreover, the association between DPP-4I use and risks of PCa-specific mortality was independent of chemotherapy or androgen receptor signaling inhibitor use.ConclusionsDPP-4I use is associated with decreased …

Background: Advanced head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict progression-free survival (PFS) with a multivariate risk prediction model. Methods: Experimental covariates were derived from blood samples of 56 HNSCC patients which were prospectively obtained within a Phase 2 clinical trial (NCT02633800) at baseline and after the first treatment cycle of combined platinum-based chemotherapy with cetuximab treatment. Clinical and experimental covariates were selected by Bayesian multivariate regression to form risk scores to predict PFS.Results: A ‘baseline’and a ‘combined’risk prediction model were generated, each of which featuring clinical and experimental covariates. The baseline risk signature has three covariates and was strongly driven by baseline percentage of CD33+CD14+HLADRhigh monocytes. The combined signature has six covariates, also featuring baseline CD33+CD14+HLADRhigh monocytes but is strongly driven by on-treatment relative change of CD8+ central memory T cells percentages. The combined model has a higher predictive power than the baseline model and was successfully validated to predict therapeutic response in an independent cohort of nine patients from an additional

ROS1 rearrangements are a known oncogenic driver in 1–2% of patients with non-small cell lung cancer. ROS1 fusions pair its kinase domain with an array of partners promoting constitutive ROS1 kinase activitation. Fluorescence in situ hybridization (FISH) is considered the gold standard method for diagnosing ROS1 rearrangements, although next generation sequencing (NGS) is rapidly gaining a role. Crizotinib was the first targeted therapy licensed for patients with NSCLC harboring ROS1 fusions, demonstrating high response rates and survival benefit in trials, but with limited intracranial efficacy. Resistance to crizotinib inevitably develops in all patients. A new generation of tyrosine kinase inhibitors are currently being developed to circumvent resistance to crizotinib.

Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer …

BackgroundMetformin is associated with lower risks of developing prostate cancer (PCa), but its association with mortality in PCa is unclear. This study examined the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with PCa.MethodsDiabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified. Patients with< 6 months of medical castration without subsequent bilateral orchidectomy,< 6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had≥ 6 months of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. Included patients were followed up until September 2021. The primary outcome was PCa-related …

Androgen deprivation therapy (ADT), which pharmacologically or surgically suppresses androgen activity, is a key treatment for prostate cancer (PCa). 1 However, it is associated with increased cardiovascular risks, including elevated risks of cardiovascular mortality, myocardial infarction and stroke. 2, 3 Nonetheless, prior studies have focussed on the first occurrence of adverse cardiovascular events, 2, 4, 5 and the burden of cardiovascular hospitalizations in patients with PCa receiving ADT has remained unexplored. Similarly, the long-term burden of cardiovascular mortality amongst ADT users has been underexplored. 6, 7 Given the adverse cardiovascular effects of ADT, it is important to better understand the long-term burden of cardiovascular mortality and hospitalizations in these patients. Henceforth, this study aimed to describe the long-term burden of cardiovascular mortality and hospitalizations in patients with PCa receiving ADT. This prospective cohort study was approved by The Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number 2022.051), and was conducted according to the Declaration of Helsinki. Reporting of the study conforms to broad EQUATOR guidelines. 8 Since only deidentified data were used, the need for individual consent was waived.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α …

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan–Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen’s kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594–0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays. Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade. Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated. Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the …

The COVID-19 pandemic has resulted in a substantial increase in waiting times for cystoscopies, prompting concerns of delayed diagnoses and substandard surveillance of bladder cancer. Expanding the role of urinary biomarkers in diagnostic and surveillance pathways could be a strategy to address this problem, and several novel biomarkers have shown promise for this purpose.

We propose a novel pipeline for the analysis of imaging mass cytometry data, comparing an unbiased approach, representing the actual gold standard, with a novel biased method. We made use of both synthetic/ controlled datasets as well as two datasets obtained from FFPE sections of follicular lymphoma, and head and neck patients, stained with a 14 and 29-markers panels respectively. The novel pipeline, denominated RUNIMC, has been completely developed in R and contained in a single package. The novelty resides in the ease with which multi-class random forest classifier can be used to classify image features, making the pathologist’s and expert classification pivotal, and the use of a random forest regression approach that permits a better detection of cell boundaries, and alleviates the necessity of relying on a perfect nuclear staining.

The STAMPEDE and CHAARTED trials established docetaxel as first-line treatment alongside androgen deprivation therapy (ADT) in patients with metastatic hormonesensitive prostate cancer (mHSPC). However, this treatment regimen is associated with a considerable risk of febrile neutropenia (FN). The CHAARTED trial reported FN rates of 6%[1] whereas STAMPEDE demonstrated an FN rate of 15%[2]. Both were significantly higher than the rate of 3% exhibited in the castrate-resistant setting [3]. Real-world studies have demonstrated FN occurrences up to 30%[4–6], prompting calls to use granulocyte colony stimulating factor (GCSF) as primary FN prophylaxis; which is costly and associated with a range of side effects. We investigated the effectiveness of prophylactic fluoroquinolones as primary FN prophylaxis in mHSPC. We concurrently explored the contribution of maintenance prednisolone to FN, as …

Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.

BACKGROUND: Bleomycin, Etoposide and Cisplatin (BEP) chemotherapy is the conventional treatment regimen for patients with germ cell tumours. The regimen is highly emetogenic and immunosuppressive. High dose steroids are often prescribed with this regimen as antiemetic prophylaxis but may have adverse effects in the context of immunosuppression. OBJECTIVE: To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving BEP chemotherapy. DESIGN, SETTING, PARTICIPANTS AND STATISTICAL ANALYSIS: Records from 108 patients who received BEP in St Bartholomew's Hospital, London were divided into two groups by antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and Group 2 (treated 2014-2017) were given a steroid-sparing protocol, i.e. using olanzapine. Outcomes include incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions due to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided Chi-squared tests. RESULTS AND LIMITATIONS: Baseline characteristics were balanced in age, gender, histology, and proportion of IGCCCG poor-risk patients. The incidence of neutropenia of any grade (Group 1, 96.2%, Group 2, 98.1%) was comparable although Group 2 had more patients with severe neutropenia (77.7%, G1 vs 88.8%, G2). There was a significant difference in FN Incidence (22%, G1 vs 7.5%, in G2, p=0.030 …

PurposeSeveral studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen.MethodsIndividual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status …

AimThis narrative review aims to describe established and emerging urinary biomarkers in the diagnosis and surveillance of non-muscle invasive bladder cancer. It provides a comprehensive account of classical, FDA-approved protein biomarkers and discusses their limitations. Further, we discuss the role that epigenetic, genetic, and exosomal markers can play to enhance sensitivity and specificity of the available tests.BackgroundThe initial diagnosis and surveillance of bladder cancer involves a combination of cystoscopy, upper urinary tract imaging, and urine cytology. Despite high specificity, cytology is limited by low sensitivity. There are currently 6 urinary assays approved by the FDA to enhance diagnosis and surveillance of bladder cancer. While these have improved diagnosis and surveillance when combined with cytology, these tests are still not sufficiently sensitive and false positives often occur in benign …

Tertiary lymphoid structures: conduits for tumor cell dissemination — King's College London Skip to main navigation Skip to search Skip to main content King's College London Home King's College London Logo Home Profiles Research units Research output Projects Student theses Activities Datasets Impacts Prizes Search by expertise, name or affiliation Tertiary lymphoid structures: conduits for tumor cell dissemination Rami Mustapha, Kenrick Ng, James Monypenny of Pitmilly, Tony Ng * * Corresponding author for this work Comprehensive Cancer Centre Cell Imaging UCL University College London UCL Hospitals NHS Foundation Trust Research output: Contribution to journal › Review article › peer-review Overview Original language English Journal Frontiers in Molecular Biosciences Publication status Accepted/In press - 17 Aug 2021 Cite this APA Author BIBTEX Harvard Standard RIS Vancouver …

Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING …

The COVID-19 pandemic has resulted in a substantial increase in waiting times for cystoscopies, prompting concerns of delayed diagnoses and substandard surveillance of bladder cancer. Expanding the role of urinary biomarkers in diagnostic and surveillance pathways could be a strategy to address this problem, and several novel biomarkers have shown promise for this purpose.

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment …

This article is co-authored by a patient with metastatic hormone-sensitive prostate cancer who is receiving abiraterone and androgen deprivation therapy treatment in Manchester, UK. The patient relates his personal experiences struggling with the diagnosis, his experience with treatment and the physical, emotional and psychosexual impact on his life. After his diagnosis, the patient has become an outspoken advocate and fundraiser for prostate cancer awareness and wants to ensure that novel treatments with proven efficacy and tolerability, such as abiraterone, are available for all men in his condition. The specialist nursing and physician perspectives, provided by healthcare professionals based in London who are not directly involved in this patient’s care, were written in response to the challenges and concerns highlighted by this patient. The role of the specialist nurse as a key healthcare professional in the …

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double‐strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule‐targeted therapies and, in recent years, immunotherapy (IT). Cancer‐cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T‐cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic …

Purpose: To assess the benefits and risks of co-administering maintenance prednisolone with docetaxel and androgen-deprivation therapy (ADT) in hormone sensitive metastatic prostate cancer (HSMPC).Methods: Records from 159 patients with HSMPC who received first-line docetaxel across three major NHS Trusts in London–University College London Hospital, St Bartholomew’s Hospital and Barnet General Hospital–between January 2015 and February 2018 were collected and divided into two cohorts. Cohort A (n= 81) received up to six cycles of docetaxel 75 mg/m 2 Q3W+ ADT+ maintenance prednisolone 5 mg BD. Cohort B (n= 78) received a similar treatment regimen without steroids. Patients in cohort B also received prophylactic ciprofloxacin 500 mg BD between days 5 and 15 of each cycle of treatment. Statistical analyses were carried out using chi-squared tests.Results: The median follow-up times in …