Toxicity, disease management and outcome of treatment with immune checkpoint inhibitors by sex in patients with cancer and preexisting autoimmune disease.

Female sex is associated with a higher risk for autoimmune diseases (ADs) and immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs). While the safety of ICIs in AD cohorts has been reported, sex-segregated data on patient characteristics and outcomes are lacking. In the present study, the disease and treatment characteristics of 51 patients with cancer and preexisting AD (PAD) treated with ICIs at Bern University Hospital Cancer Center (Bern, Switzerland) between January 2017 and June 2021 were analyzed by sex. Rheumatic (n=12/27, 44.4%) and endocrine (n=11/24, 45.8%) PADs were most common among male and female patients, respectively. At the time of ICI initiation, 29.6% (n=8/27) of male and 20.8% (n=5/24) of female patients received immunosuppression for their PAD. Female patients were more likely to experience an irAE (58.3 vs. 48.1%), and less likely to encounter an exacerbation of their PAD (38.5 vs. 14.3%) compared with male patients. Multiple-site irAEs (46.2 vs. 21.4%), implication of an organ specialist for irAEs (100.0 vs. 57.1%) and use of additional immunosuppressive drugs (38.4 vs. 7.7%) were more common in male patients. IrAEs were resolved and ICIs were discontinued in 69.2% (n=9/13) and 71.4% (n=10/14) of the total male and female patients, respectively. Median progression-free survival was higher in male than female patients with irAEs (19.9 vs. 10.7 months) and without irAEs (4.4 vs. 1.8 months). The median overall survival time was higher in male than female patients with irAEs (not estimable vs. 22.5 months) and without irAEs (10.1 vs. 7.4 months). Taken together, these results suggested that sex-related differences existed regarding the clinical presentation of irAEs and treatment outcome

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry.

PURPOSE Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). METHODS A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. RESULTS A total of 3484 patients were diagnosed with non-advanced MIBC in 2018-2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. CONCLUSIONS Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes

Treatment Patterns and Use of Immune Checkpoint Inhibitors Among Patients with Metastatic Bladder Cancer in a Dutch Nationwide Cohort

Since 2017, two immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of metastatic urothelial carcinoma in Europe: pembrolizumab as second-line therapy and avelumab as maintenance therapy. Our aim was to describe the use of ICIs as first and later lines of treatment in patients with metastatic bladder cancer (mBC) in the Netherlands. We identified all patients diagnosed with primary mBC between 2018 and 2021 in the Netherlands from the Netherlands Cancer Registry (NCR). NCR data were supplemented with data from the Dutch nationwide Prospective Bladder Cancer Infrastructure (ProBCI) collected from medical files, with follow-up until death or end of data collection on January 1, 2023. A total of 1525 patients were diagnosed with primary mBC between 2018 and 2021 in the Netherlands. Of these, 34.7% received at least one line of systemic treatment with chemotherapy or ICI. After first-line platinum-based chemotherapy, 34.1% received second-line ICI and 3.9% received maintenance ICI. Among patients who completed or discontinued first-line cisplatin- or carboplatin-based chemotherapy after approval of maintenance ICI in the Netherlands, 40.7% and 19.7% received second-line ICI, and 9.3% and 14.1% received maintenance ICI, respectively. ICI use for mBC treatment has not increased considerably since their introduction in 2017. Future research should assess whether the introduction of maintenance avelumab (available since April 2021 in the Netherlands) has led to increases in the proportion of patients with mBC patients receiving systemic treatment and the proportion receiving ICI. Patient summary: We assessed the rate of immunotherapy use for patients with metastatic bladder cancer in the Netherlands. Since its introduction, immunotherapy has been used in a minority of patients, mostly as second-line treatment after platinum-based chemotherapy.</p

Hospital volume is associated with postoperative mortality after radical cystectomy for treatment of bladder cancer

Contains fulltext : 237666.pdf (Publisher’s version ) (Open Access)OBJECTIVE: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. PATIENTS AND METHODS: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. RESULTS: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. CONCLUSION: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered

Awareness of the impact of sex and gender in the disease risk and outcomes in hematology and medical oncology-a survey of Swiss clinicians.

BACKGROUND Although male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients. AIM To evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022. METHODS We collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate). RESULTS While most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research. CONCLUSION Our findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care

Cancer researchers’ perceptions of the importance of the sex of cell lines, animals, and human samples for cancer biology research

Sex differences in cancer risk and outcome are currently a topic of major interest in clinical oncology. It is however unknown to what extent cancer researchers consider sex as a biological variable for their research. We conducted an international survey among 1243 academic cancer researchers and collected both quantitative and qualitative data. Although most of the participants indicated that they were familiar with the concept of studying sex differences in cancer biology, they did not think it was important to investigate sex differences in every context of cancer research nor in all tumor types. This is in stark contrast to the current recommendations and guidelines and illustrates the need for increased awareness among cancer researchers regarding the potential impact of the sex of cell lines, animals, and human samples in their studies

Longitudinal multiple case study on effectiveness of network-based dementia care towards more integration, quality of care, and collaboration in primary care.

INTRODUCTION:This study aimed to provide insight into the merits of DementiaNet, a network-based primary care innovation for community-dwelling dementia patients. METHODS:Longitudinal mixed methods multiple case study including 13 networks of primary care professionals as cases. Data collection comprised continuously-kept logs; yearly network maturity score (range 0-24), yearly quality of care assessment (quality indicators, 0-100), and in-depth interviews. RESULTS:Networks consisted of median nine professionals (range 5-22) covering medical, care and welfare disciplines. Their follow-up was 1-2 years. Average yearly increase was 2.03 (95%-CI:1.20-2.96) on network maturity and 8.45 (95%-CI:2.80-14.69) on quality indicator score. High primary care practice involvement and strong leadership proved essential in the transition towards more mature networks with better quality of care. DISCUSSION:Progress towards more mature networks favored quality of care improvements. DementiaNet appeared to be effective to realize transition towards network-based care, enhance multidisciplinary collaboration, and improve quality of dementia care

Ethnic minority status as social determinant for COVID-19 infection, hospitalisation, severity, ICU admission and deaths in the early phase of the pandemic: A meta-analysis

Introduction Early literature on the COVID-19 pandemic indicated striking ethnic inequalities in SARS-CoV-2-related outcomes. This systematic review and meta-analysis aimed to describe the presence and magnitude of associations between ethnic groups and COVID-19-related outcomes. Methods PubMed and Embase were searched from December 2019 through September 2020. Studies reporting extractable data (ie, crude numbers, and unadjusted or adjusted risk/ORs) by ethnic group on any of the five studied outcomes: confirmed COVID-19 infection in the general population, hospitalisation among infected patients, and disease severity, intensive care unit (ICU) admission and mortality among hospitalised patients with SARS-CoV-2 infection, were included using standardised electronic data extraction forms. We pooled data from published studies using random-effects meta-analysis. Results 58 studies were included from seven countries in four continents, mostly retrospective cohort studies, covering a total of almost 10 million individuals from the first wave until the summer of 2020. The risk of diagnosed SARS-CoV-2 infection was higher in most ethnic minority groups than their White counterparts in North American and Europe with the differences remaining in the US ethnic minorities after adjustment for confounders and explanatory factors. Among people with confirmed infection, African-Americans and Hispanic-Americans were also more likely than White-Americans to be hospitalised with SARS-CoV-2 infection. No increased risk of COVID-19 outcomes (ie, severe disease, ICU admission and death) was found among ethnic minority patients once hospitalised, except for a higher risk of death among ethnic minorities in Brazil. Conclusion The risk of SARS-CoV-2 diagnosis was higher in most ethnic minorities, but once hospitalised, no clear inequalities exist in COVID-19 outcomes except for the high risk of death in ethnic minorities in Brazil. The findings highlight the necessity to tackle disparities in social determinants of health, preventative opportunities and delay in healthcare use. Ethnic minorities should specifically be considered in policies mitigating negative impacts of the pandemic. PROSPERO registration number CRD42020180085

Prospective bladder cancer infrastructure for experimental and observational research on bladder cancer: Study protocol for the 'trials within cohorts' study ProBCI

Introduction A better understanding of the molecular profile of bladder tumours, the identification of novel therapeutic targets, and introduction of new drugs and has renewed research interest in the field of bladder cancer. We describe the design and setup of a Dutch Prospective Bladder Cancer Infrastructure (ProBCI) as a means to stimulate and accelerate clinically meaningful experimental and observational research. Methods and analysis ProBCI entails an open cohort of patients with bladder cancer in which the trials within cohorts (TwiCs) design can be embedded. Physicians in participating hospitals prospectively recruit invasive (≥T1) patients with bladder cancer on primary diagnosis for inclusion into the study. Extensive clinical data are collected and updated every 4 months, along with patient-reported outcomes and biomaterials. Informed consent includes participation in TwiCs studies and renewed contact for future studies. Consent for participation in questionnaires and molecular analyses that may yield incidental findings is optional. Ethics and dissemination The Dutch ProBCI is a unique effort to construct a nation-wide cohort of patients with bladder cancer including clinical data, patient-reported outcomes and biomaterial, to facilitate observational and experimental research. Data and materials are available for other research groups on request through www.probci.nl. Ethics approval was obtained from METC Utrecht (reference: NL70207.041.19). Trial registration number NCT04503577

Overall Survival of Patients Receiving Cisplatin or Carboplatin for Primary Metastatic Urothelial Carcinoma of the Bladder: A Contemporary Dutch Nationwide Cohort Study

Background: Cisplatin is preferred to carboplatin when treating metastatic urothelial carcinoma of the bladder (mUCB), despite its greater toxicity. Randomised studies underpinning this have been performed in noncontemporary populations with limitations in sample sizes and analyses, affecting their validity in current clinical practice. Objective: To estimate overall survival (OS) and assess the benefit of cisplatin-based regimens over carboplatin-based regimens in a contemporary cohort of patients with mUCB. Design, setting, and participants: A nationwide retrospective cohort study was conducted in patients diagnosed with de novo mUCB in the Netherlands between 2016 and 2019, who underwent first-line treatment with cisplatin- or carboplatin-based chemotherapy, based on the data from the Netherlands Cancer Registry. Outcome measurements and statistical analysis: A propensity model for receiving cisplatin-based chemotherapy based on age, sex, age-adjusted Charlson Comorbidity Index, renal function, performance status, serum haemoglobin, and the presence of visceral and bone metastases was used to produce inverse probability weighting (IPW) per patient. Unadjusted and IPW-adjusted Kaplan-Meier OS curves of both chemotherapy groups were compared by restricted mean survival time (RMST). Results and limitations: Of the 1041 patients with mUCB, 359 received either cisplatin (n = 170; 47%) or carboplatin (n = 189; 53%) as first line. The cisplatin group was younger, had fewer comorbidities, and had better performance status and renal function. The median OS in the cisplatin and carboplatin groups was 13.1 and 11.5 mo, respectively. After IPW adjustment, prognostic factors were balanced between the two chemotherapy groups (standardised differences <0.1), and differences in RMST were <2.0 mo and not statistically significant up to 24 mo. Conclusions: After accounting for all known prognostic factors, we found no significant survival benefit for cisplatin over carboplatin as first-line chemotherapy in mUCB. Patient summary: In this study, we compared the survival benefits of cisplatin- and carboplatin-based chemotherapy for patients with metastatic bladder cancer