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Background: The management of advanced prostate cancer continues to evolve rapidly, particularly with the earlier use of survival-prolonging therapies in metastatic castration-sensitive prostate cancer (mCSPC). Though approved prior to the use of intensification therapy in mCSPC, taxane-based chemotherapies remain a relevant option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is little evidence determining the outcomes of taxane chemotherapies as the first subsequent taxane (FST) in mCRPC pts who received docetaxel intensification (DI) in mCSPC. The purpose of this study is to compare outcomes between the survival-prolonging taxanes, docetaxel and cabazitaxel as FST after DI. Methods: New patient consults seen at the Cross Cancer Institute from 1 July 2014 to 31 December 2020 were retrospectively reviewed. Pts were considered eligible if they received DI for mCSPC and then received either docetaxel or cabazitaxel in mCRPC. Variables of interest were collected from electronic medical records. The primary endpoint was ≥50% PSA response at 12 weeks relative to baseline for FST. Secondary endpoints included OS from mCSPC diagnosis, as well as PFS and OS from the FST start date. PSA responses were compared using the chi-squared test, and time-based endpoints were compared using the Kaplan–Meier method. Results: In total, 34 pts were identified: docetaxel = 22 and cabazitaxel = 12 as FST. 91.2% of pts (docetaxel 95.5% vs. cabazitaxel 83.3%) received FST in 2nd line mCRPC. The median age at diagnosis (63.1 vs. 67.1 yrs, p = 0.236) and the median time to CRPC (18.6 vs. 14.2 mos, p = 0.079) were similar for docetaxel and cabazitaxel, respectively. The median time to FST (24.1 vs. 34.6 mos, p = 0.036) and OS from mCSPC diagnosis (30.9 vs. 52.7 mos, p = 0.002) were significantly shorter for pts receiving cabazitaxel vs. docetaxel. PSA responses occurred in 40.9% of pts treated with docetaxel compared to 25.0% treated with cabazitaxel (p = 0.645). There was no significant difference in median PFS (2.7 vs. 3.5 mos, p = 0.727) or median OS (11.4 vs. 8.1 mos, p = 0.132) from the time of FST for pts treated with docetaxel vs. cabazitaxel, respectively. Conclusions: Both docetaxel and cabazitaxel demonstrated activity as FST after DI in mCSPC. Pts who received cabazitaxel had a shorter time to FST and OS from mCSPC. The reasons for this may reflect clinician preference for cabazitaxel in pts with aggressive or rapidly progressing disease. No difference was found in PSA response, PFS, or OS from FST with docetaxel compared to cabazitaxel. While limited by its retrospective nature and small sample size, this study suggests that docetaxel is active as FST despite treatment with DI in mCSPC.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13–0.68) and CN-ST (HR 0.68, CI 0.47–0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26–0.77) and CN-ST (HR 0.9, CI 0.68–1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

Abstract Background Cross-platform normalization seeks to minimize technological bias between microarray and RNAseq whole-transcriptome data. Incorporating multiple gene expression platforms permits external validation of experimental findings, and augments training sets for machine learning models. Here, we compare the performance of Feature Specific Quantile Normalization (FSQN) to a previously used but unvalidated and uncharacterized method we label as Feature Specific Mean Variance Normalization (FSMVN). We evaluate the performance of these methods for bidirectional normalization in the context of nested feature selection. Results FSQN and FSMVN provided clinically equivalent bidirectional model performance with and without feature selection for colon CMS and breast PAM50 classification. Using principal component analysis, we determine that these methods eliminate batch effects related to technological platforms. Without feature selection, no statistical difference was identified between the performance of FSQN and FSMVN of cross-platform data compared to within-platform distributions. Under optimal feature selection conditions, balanced accuracy was FSQN and FSMVN were statistically equivalent to the within-platform distribution performance in multivariable linear regression analysis. FSQN and FSMVN also provided similar performance to within-platform distributions as the number of selected genes used to create models decreases. Conclusions In the context of generating supervised machine learning classifiers for molecular subtypes, FSQN and FSMVN are equally effective. Under optimal modeling conditions, FSQN and FSMVN provide equivalent model accuracy performance on cross-platform normalization data compared to within-platform data. Using cross-platform data should still be approached with caution as subtle performance differences may exist depending on the classification problem, training, and testing distributions.

The PACIFIC trial led to a new standard of care for patients with locally advanced lung cancer, but real-world practice has demonstrated that immune checkpoint inhibitor (ICI) pneumonitis can lead to significant clinical complications. This study aimed to examine the clinical predictors, outcomes, and healthcare utilization data in patients who received consolidation durvalumab. Using the Alberta Immunotherapy Database, NSCLC patients who received durvalumab in Alberta, Canada, from January 2018 to December 2021 were retrospectively evaluated. We examined incidence and predictive values of severe pneumonitis, with overall survival (OS) and time-to-treatment failure (TTF) using exploratory multivariate analyses. Of 189 patients, 91% were ECOG 0–1 and 85% had a partial response from chemoradiation prior to durvalumab. Median TTF and OS were not reached; 1-year OS was 82%. An amount of 26% developed any grade of pneumonitis; 9% had ≥grade 3 pneumonitis. Male gender and a pre-existing autoimmune condition were associated with severe pneumonitis. V20 was associated with any grade of pneumonitis. Pneumonitis development was found to be an independent risk factor for worse OS (p = 0.038) and TTF (p = 0.007). Our results suggest clinical and dosimetric predictive factors of durvalumab-associated pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population.

Radiotherapy (RT) is often utilized for symptom control at the end of life. Palliative RT (pRT) may not be taken to completion by patients, thus decreasing clinical benefits and adversely impacting resource allocation. We determined rates of incomplete pRT and examined predictors of non-completion using an electronic questionnaire. Methods: A questionnaire was embedded within the RT electronic prescribing system for all five cancer centers of Alberta, Canada, between 2017 and 2020. Prescribing radiation oncologists (ROs) were tasked with completing the questionnaire. Treatment variables were collected for 2040 patients prescribed pRT. Details on pRT courses delivered and completed were used to determine rates of incomplete RT. Electronic medical records of a subset of 367 patients randomly selected from the 2040 patients were then analyzed to examine for association of non-completion of RT with patient, disease, and therapy-related factors. Results: Overall, 10% of patients did not complete pRT. The rate of single fractions prescribed as a proportion of all RT fractions increased from 18% (pre-2017: pre-study era) to 29% (2017–2020: study era) (p < 0.0001). After conducting multivariate analysis on the overall group, multiple lifetime malignancies (OR:0.64) or increasing the number of pRT fractions (OR:0.08–0.17) were associated with non-completion. Being selected for stereotactic RT (OR:3.75) or survival > 30 days post-RT prescription (OR:2.20–5.02) were associated with greater rates of RT completion. The ROs’ estimates of life expectancy at the time of RT prescription were not predictive of RT completion. In the multivariate analysis of the 367-patient subset, the presence of hepatic metastases (OR 2.59), survival 30–59 days (OR 6.61) and survival 90+ days (OR 8.18) post-RT prescription were associated with pRT completion. Only increasing pRT fractionation (OR:0.05–0.2) was associated with non-completion. Conclusion: One in ten patients prescribed pRT did not complete their treatment course. Decreasing pRT fractionation and improving prognostication in patients near the end of life may decrease rates of incomplete RT courses.

Late endosomal/lysosomal adaptor, MAPK and mTOR, or LAMTOR, is a scaffold protein complex that senses nutrients and integrates growth factor signaling. The role of LAMTOR4 in tumorigenesis is still unknown. However, there is a considerable possibility that LAMTOR4 is directly involved in tumor cell proliferation and metastasis. In the current study, we investigated the protein expression of LAMTOR4 in a cohort of 314 men who were undergoing transurethral resection of prostate (TURP) consisting of incidental, advanced and castration-resistant cases. We also correlated the data with ERG and PTEN genomic status and clinicopathological features including Gleason score and patients’ outcome. Additionally, we performed in vitro experiments utilizing knockdown of LAMTOR4 in prostate cell lines, and we performed mRNA expression assessment using TCGA prostate adenocarcinoma (TCGA-PRAD) to explore the potential differentially expressed genes and pathways associated with LAMTOR4 overexpression in PCa patients. Our data indicate that high LAMTOR4 protein expression was significantly associated with poor overall survival (OS) (HR: 1.44, CI: 1.01–2.05, p = 0.047) and unfavorable cause-specific survival (CSS) (HR: 1.71, CI: 1.06–2.77, p = 0.028). Additionally, when high LAMTOR4 expression was combined with PTEN-negative cases (score 0), we found significantly poorer OS (HR: 2.22, CI: 1.37–3.59, p = 0.001) and CSS (HR: 3.46, CI: 1.86–6.46, p < 0.0001). Furthermore, ERG-positive cases with high LAMTOR4 exhibited lower OS (HR: 1.98, CI: 1.18–3.31, p = 0.01) and CSS (HR: 2.54, CI: 1.32–4.87, p = 0.005). In vitro assessment showed that knockdown of LAMTOR4 decreases PCa cell proliferation, migration, and invasion. Our data further showed that knockdown of LAMTOR4 in the LNCaP cell line significantly dysregulated the β catenin/mTOR pathway and tumorigenesis associated pathways. Inhibiting components of the mTOR pathway, including LAMTOR4, might offer a strategy to inhibit tumor progression and metastasis in prostate cancer.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010–2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with

SET-domain containing 2 (SETD2) is a histone methyltransferase and an epigenetic modifier with oncogenic functionality. In the current study, we investigated the potential prognostic role of SETD2 in prostate cancer. A cohort of 202 patients’ samples was assembled on tissue microarrays (TMAs) containing incidental, advanced, and castrate-resistant CRPCa cases. Our data showed significant elevated SETD2 expression in advanced and castrate-resistant disease (CRPCa) compared to incidental cases (2.53 ± 0.58 and 2.21 ± 0.63 vs. 1.9 ± 0.68; p < 0.001, respectively). Interestingly, the mean intensity of SETD2 expression in deceased vs. alive patients was also significantly different (2.31 ± 0.66 vs. 2 ± 0.68; p = 0.003, respectively). Overall, high SETD2 expression was found to be considered high risk and was significantly associated with poor prognosis and worse overall survival (OS) (HR 1.80; 95% CI: 1.28–2.53, p = 0.001) and lower cause specific survival (CSS) (HR 3.14; 95% CI: 1.94–5.08, p < 0.0001). Moreover, combining high-intensity SETD2 with PTEN loss resulted in lower OS (HR 2.12; 95% CI: 1.22–3.69, p = 0.008) and unfavorable CSS (HR 3.74; 95% CI: 1.67–8.34, p = 0.001). Additionally, high SETD2 intensity with ERG positive expression showed worse prognosis for both OS (HR 1.99, 95% CI 0.87–4.59; p = 0.015) and CSS (HR 2.14, 95% CI 0.98–4.68, p = 0.058). We also investigated the protein expression database TCPA, and our results showed that high SETD2 expression is associated with a poor prognosis. Finally, we performed TCGA PRAD gene set enrichment analysis (GSEA) data for SETD2 overexpression, and our data revealed a potential association with pathways involved in tumor progression such as the AMPK signaling pathway, the cAMP signaling pathway, and the PI3K-Akt signaling pathway, which are potentially associated with tumor progression, chemoresistance, and a poor prognosis.

Recent advances in our understanding of gastric cancer biology have prompted a shift towards more personalized therapy. However, results are based on population-based survival analyses, which evaluate the average survival effects of entire treatment groups or single prognostic variables. This study uses a personalized survival modelling approach called individual survival distributions (ISDs) with the multi-task logistic regression (MTLR) model to provide novel insight into personalized survival in gastric adenocarcinoma. We performed a pooled analysis using 1043 patients from a previously characterized database annotated with molecular subtypes from the Cancer Genome Atlas, Asian Cancer Research Group, and tumour microenvironment (TME) score. The MTLR model achieved a 5-fold cross-validated concordance index of 72.1 ± 3.3%. This model found that the TME score and chemotherapy had similar survival effects over the entire study time. The TME score provided the greatest survival benefit beyond a 5-year follow-up. Stage III and Stage IV disease contributed the greatest negative effect on survival. The MTLR model weights were significantly correlated with the Cox model coefficients (Pearson coefficient = 0.86, p < 0.0001). We illustrate how ISDs can accurately predict the survival time for each patient, which is especially relevant in cases of molecular subtype heterogeneity. This study provides evidence that the TME score is principally associated with long-term survival in gastric adenocarcinoma. Additional external validation and investigation into the clinical utility of this ISD model in gastric cancer is an area of future research.

PURPOSEStandard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011.METHODSWe included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts.RESULTSFour thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)–based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line.CONCLUSIONIn Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.

Introduction Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight.Methods and analysis Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile.Ethics and dissemination This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media.Trial registration number NCT03235804.

Abstract Background Postoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages compared to postoperative SRS, including less uncertainty in delineation of the intact tumor compared to the postoperative resection cavity, reduced rate of leptomeningeal dissemination postoperatively, and a lower risk of radiation necrosis. The recently published ASCO-SNO-ASTRO consensus statement provides no recommendation for the preferred sequencing of radiotherapy and surgery for patients receiving both treatments for their brain metastases. Methods This multicenter, randomized controlled trial aims to recruit 88 patients with resectable brain metastases over an estimated three-year period. Patients with ten or fewer brain metastases with at least one resectable, fulfilling inclusion criteria will be randomized to postoperative SRS (standard arm) or preoperative SRS (investigational arm) in a 1:1 ratio. Randomization will be stratified by age (

Abstract Background The legalization of Medical Assistance in Dying in Canada in 2016 provided new impetus for improving palliative care. This commitment to improvement included the development of a National Palliative Care Framework and Action Plan. The purpose of this study was to understand the progress made in palliative care since 2016 from the perspective of persons working and volunteering in palliative care and compare geographic differences. Methods A digital survey was developed from goals identified in Canada’s Palliative Care Framework and Action Plan and administered online using Qualtrics. Participants were recruited through national palliative care organizations. The survey included both quantitative survey items designed to evaluate improvements across 5 domains and 29 items and included open-ended questions about impacts, innovations, and ongoing challenges. Descriptive statistics were generated for survey domains, items, and demographic variables. Geographic differences were compared using Independent-Samples Kruskal–Wallis test. Qualitative data was analyzed inductively into themes. Results One hundred fifty surveys met inclusion criteria and were analysed. Overall, the most improvement was reported in palliative care education and the least improvement was reported in support for family caregivers. Items on which respondents reported the most improvement included healthcare provider education in palliative care, advance care planning, and use of technology. Items on which respondents reported the least improvement were respite for family caregivers, access to bereavement services, and in-home support for family caregivers. Notably, rural participants reported more statistically significant improvements in the domains of education, access, and research and data collection than their urban counterparts. However, rural participants reported less improvement in places to die when home is not preferable. The COVID-19 pandemic was a significant contributor to these perceived improvements and ongoing challenges. Conclusion Canada’s Framework and Action Plan sets out a roadmap for improving palliative care in Canada. Participants in this survey noted significant improvements in key areas, a notable accomplishment amidst the effects of the COVID-19 pandemic. Some improvements were a result of greater use of distance technology. Further leveraging these improvements will make an important contribution to solving some of the rural and remote palliative care issues that have arisen from Canada’s unique geography.

Abstract Background Family carers of persons living with dementia who are residing in long term care (LTC), often experience significant changes in their roles and relationships which affects mental and physical health. Research has focused on describing the carers’ experience, but not on how they deal with these changes or their perceptions of support needs. The purpose of this study was to explore how family carers of persons living with dementia residing in LTC deal with significant changes and to understand how best to support these carers. Methods Eight face-to-face audio-recorded focus group interviews were conducted with 45 participants from September 2019 to January 2020, as part of a larger study aimed at guiding the adaptation of an online toolkit to support family carers of persons living with dementia residing in LTC. Applied thematic analysis was used to analyze the focus group data. Findings/results Carers dealt with the significant changes they experienced through the process of “building a new life” consisting of two sub-processes: a) building new relationships (with their family member, LTC staff and others outside of LTC), and b) finding space for themselves (sharing of care and finding balance). Understanding dementia, support from others (staff, family and friends), connecting with resources, and being included in care decisions helped carers build a new life. Conclusion The process of building a new life describes the ways that family carers deal with the life-altering changes they experienced when a family member is admitted to LTC. Carers may be supported in building their new life, by providing them with information about dementia and how to relate to staff and their family member living with dementia. The quality of care being provided and the LTC environment may also play an important role in how carers deal with the significant changes they experience.

Abstract Background The Serious Illness Care Program (SICP) increases quality of documentation about patients’ values and priorities, but it is not known whether patient characteristics and goals of care are associated with the elements documented. The purpose of this study was to explore for associations between the quantity and type of elements documented after SICP conversations with patient characteristics and goals of care order. Methods Documentation of SICP conversations by internal medicine physicians with hospitalized patients was evaluated in a retrospective chart review between March 2018 to December 2019. The conversations occurred after SICP implementation in a Tertiary Hospital, Medical teaching unit which uses “Goals of Care Designation” (GCD) medical orders to communicate a patient’s general intent, specific interventions, and preferred locations of care. A validated SICP codebook was used to determine the frequency of conversation elements documented for (1) Goals and Values; (2) Prognosis/illness understanding; (3) End-of-life care planning and (4) GCD/Life-sustaining treatment preferences. Univariate and multivariate generalized linear models were used to analyze associations between quantity of elements documented and patient characteristics (age, gender, frailty, language spoken and GCD). Results Of 175 SICP conversations documented, in the univariate analysis more goals and values were documented for patients who understand/speak English (0.89; 95% CI: 0.14 - 1.63) and more content was recorded for patients with a non-resuscitative GCD focus (“Medical”: 2.42; 95% CI: 1.51 – 3.33; “Comfort”: 1.06; 95% CI: 0.24 – 1.88) although not in all domains. In the multivariate analysis, controlling for age, gender, language and frailty, the association between content scores and GCD remained highly significant. Patients with a non-resuscitative GCD had higher total domain scores than those with a resuscitative GCD (“Medical”: 1.27 95% CI: 0.42–2.13; “Comfort”: 2.67, 95% CI:1.71–3.62). Conclusion The type of content documented by physicians after a SICP conversation is associated with the patient’s goals of care.

Abstract Background Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra‐cranial imaging for the screening of asymptomatic BM in mRCC. Aims To evaluate the potential utility of routine intra‐cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. Methods and Results The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi‐square tests, analysis of variance, and Kaplan–Meier method to characterize survival outcomes. A p‐value of 1) BM (75%) with no significant differences noted in number of BM or BM‐directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32–62) for patients with asymptomatic BM, and 39 months (95% CI: 29–48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18–42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10–21) in the symptomatic BM group (p = 0.04). Conclusions Given a substantial proportion of patients may present with asymptomatic BM, limiting intra‐cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra‐cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.

Cancer in all its forms of expression is a major cause of death. To identify the genomic reason behind cancer, discovery of biomarkers is needed. In this paper, genomic data of bladder cancer are examined for the purpose of biomarker discovery. Genomic biomarkers are indicators stemming from the study of the genome, either at a very low level based on the genome sequence itself, or more abstractly such as measuring the level of gene expression for different disease groups. The latter method is pivotal for this work, since the available datasets consist of RNA sequencing data, transformed to gene expression levels, as well as data on a multitude of clinical indicators. Based on this, various methods are utilized such as statistical modeling via logistic regression and regularization techniques (elastic-net), clustering, survival analysis through Kaplan–Meier curves, and heatmaps for the experiments leading to biomarker discovery. The experiments have led to the discovery of two gene signatures capable of predicting therapy response and disease progression with considerable accuracy for bladder cancer patients which correlates well with clinical indicators such as Therapy Response and T-Stage at surgery with Disease Progression in a time-to-event manner.

Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013–2019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm2/m2) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox’s proportional hazards models. Tissue changes varied widely (∆SMI: −17.8 to +7.3 cm2/m2, ∆ATI: −106.1 to +37.7 cm2/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (−3.2 cm2/m2, p < 0.001; −12.4 cm2/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (−1.6 cm2/m2, p = 0.013) and GEM/NAB with greater adipose loss (−11.2 cm2/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.

Potential oncogene cleavage and polyadenylation specific factor 4 (CPSF4) has been linked to several cancer types. However, little research has been conducted on its function in prostate cancer (PCa). In benign, incidental, advanced, and castrate resistant PCa (CRPCa) patient samples, protein expression of CPSF4 was examined on tissue microarray (TMAs) of 353 PCa patients using immunohistochemistry. Using the ‘The Cancer Genome Atlas’ Prostate Adenocarcinoma (TCGA PRAD) database, significant correlations were found between high CPSF4 expression and high-risk genomic abnormalities such as ERG-fusion, ETV1-fusion, and SPOP mutations. Gene Set Enrichment Analysis (GSEA) of CPSF4 revealed evidence for the increase in biological processes such as cellular proliferation and metastasis. We further examined the function of CPSF4 in vitro and confirmed CPSF4 clinical outcomes and its underlying mechanism. Our findings showed a substantial correlation between Gleason groups and CPSF4 protein expression. In vitro, CPSF4 knockdown reduced cell invasion and migration while also causing G1 and G2 arrest in PC3 cell lines. Our findings demonstrate that CPSF4 may be used as a possible biomarker in PCa and support its oncogenic function in cellular proliferation and metastasis.

Abstract Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT’s potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.

Background: Ataxia Telangiectasia Mutated (ATM) serine/threonine protein kinase is a known tumor suppressor, involved in DNA damage repair. It has prognostic and predictive therapeutic implications and is associated with aggressive prostate cancer (PCa). Objective: To investigate the prognostic value of ATM protein expression in PCa patients and assessed the combined value of ATM, ERG, and PTEN status. Design, setting, and participants: This study consisted of 303 patients with incidental, locally advanced, and castrate-resistant PCa by transurethral resection of the prostate (TURP). Outcome measurements and statistical analysis: TURP samples from 303 PCa patients were assessed by immunohistochemistry (IHC for ATM, ERG, and PTEN. Individual and combined marker status were correlated with International Society of Urological Pathology Gleason grade group, overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations: Decreased ATM expression (negative/weak intensity) occurred in 164/303 (54.1%) patients, and was associated with shorter OS and higher PCSM (p = 0.015 and p = 0.001, respectively). Negative/weak ATM expression was significantly associated with PCSM with a hazard ratio of 2.09 (95% confidence interval 1.34–3.27, p = 0.001). Assessment of Combined ATM/PTEN expression showed improved prognostic power to predict OS and PCSM, independent of Gleason grade groups. Conclusions: Decreased ATM protein expression is associated with poor outcomes in advanced PCa patients. Patients with combined low ATM/PTEN negative expression are at the highest risk for reduced OS and PCSM. Assessing the combined status of ATM/PTEN by IHC in PCa patients may aid in risk stratification relative to OS and PCSM. Moreover, since ATM plays an integral role in DNA damage response pathways, future studies will enhance our understanding of how outcomes of patients with altered ATM and PTEN expression can be improved further with poly-ADP ribose polymerase inhibitors (PARPi), combinations of PARPi and androgen receptor–targeted therapies, as well as platinum-based chemotherapies. Patient summary: Lower ATM intensity is associated with increased cancer-specific mortality in prostate cancer patients. Patients with lower ATM and PTEN negative expression showed decreased overall survival and increased cancer mortality compared with controls.

Abstract Background Patients in Alberta, Canada are referred to the United States (US) for proton treatment. The Alberta Ministry of Health pays for the proton treatment and the cost of flights to and from the United States. This study aimed to determine the out-of-pocket expenses incurred by patients or patients’ families. Methods An electronic survey was sent to 59 patients treated with proton therapy between January 2008 and September 2019. Survey questions asked about expenses related to travel to the US and those incurred while staying in the US, reimbursement of expenses, and whether any time away from work was paid or unpaid leave. Results Seventeen respondents (response rate, 29%) reported expenses of flights for family members (mean, CAD 1886; range CAD 0–5627), passports/visas and other travel costs (mean, CAD 124; range CAD 0–546), accommodation during travel to the US (mean, CAD 50; range CAD 0–563), food during travel to the US (mean, CAD 89; range CAD 0–338), accommodation in the US (rented home/apartment mean, CAD 7394; range CAD 3075-13,305; hotel mean, CAD 4730; range CAD 3564-5895; other accommodation mean CAD 2660; range CAD 0–13,842), transportation in the US (car mean, CAD 2760; range CAD 0–7649; bus/subway mean, CAD 413; range CAD 246–580), and food in the US (mean, CAD 2443; range 0–6921). Expenses were partially reimbursed or covered by not-for-profit organizations or government agencies for some patients (35%). Patients missed a mean of 59 days of work; accompanying family members missed an average of 34 days. For 29% this time away from work was paid, but unpaid for 71% of respondents. Conclusions Multiple factors contributed to the expenses incurred including age of the patient, number of accompanying individuals, available accommodation, mode of transportation within the US, and whether the patient qualified for financial support. Added to this burden is the potential loss of wages for time away from work. The study showed a large variation in indirect costs for each family and supports actively seeking more opportunities for financial support for families with children with cancer.

Purpose: With the integration of immunotherapy (IO) agents in the management of metastatic renal cell carcinoma (mRCC), there has been interest in the combined use with radiation therapy (RT). However, real world data are limited. The purpose of this study was to evaluate outcomes in patients with mRCC receiving both RT and IO compared with IO alone. Methods and Materials: Data were collected from Canadian Kidney Cancer Information System from January 2011 to September 2019 across 14 academic centers. Patients with mRCC who received IO as first- or second-line therapy were included. RT was categorized as radical dose or palliative dose. Kaplan-Meier estimates were reported for overall survival (OS) and time to treatment failure. Cox proportional hazard models were used adjusted for age and International Metastatic RCC Database Consortium risk categories. Results: In total, 505 patients were included in the study: 179 received RT + IO and 326 received IO alone. Two-year OS for the RT + IO group was 55.0% compared with 66.4% in the IO alone cohort (adjusted hazard ratio [aHR], 1.38; P = .07). At 2 years, 12.2% of the RT + IO patients remained on therapy versus 30.9% in the IO alone group (aHR, 1.30; P = .02). For patients receiving first-line therapy, 2-year OS in the RT + IO group was 56.4% versus 78.4% in the IO alone arm, though this difference was not statistically significant (aHR, 1.23; P = .56). For patients receiving radical dose and palliative dose, 2-year OS was 57.0% and 53.9%, respectively (aHR, 0.86; P = .63). Conclusions: In this descriptive analysis, more than one-third of patients with mRCC received RT and demonstrated inferior outcomes compared with IO alone. Potential explanations include greater presence of adverse metastatic sites in those receiving RT. Prospective clinical trials evaluating potential benefits of RT in an IO era remain an important need.

Background: There is an urgent need for community-based interventions that can be scaled up to meet the growing demand for palliative care. The purpose of this study was to scale out a volunteer navigation intervention called Nav-CARE by replicating the program in multiple contexts and evaluating feasibility, acceptability, sustainability, and impact. Methods: This was a scale-out implementation and mixed-method evaluation study. Nav-CARE was implemented in 12 hospice and 3 nonhospice community-based organizations spanning five provinces in Canada. Volunteers visited clients in the home approximately every 2 weeks for 1 year with some modifications required by the COVID-19 public health restrictions. Qualitative evaluation data were collected from key informants ( n = 26), clients/family caregivers ( n = 57), and volunteers ( n = 86) using semistructured interviews. Quantitative evaluation data included volunteer self-efficacy, satisfaction, and quality of life, and client engagement and quality of life. Findings: Successful implementation was influenced by organizational capacity, stable and engaged leadership, a targeted client population, and skillful messaging. Recruitment of clients was the most significant barrier to implementation. Clients reported statistically significant improvements in feeling they had someone to turn to, knowing the services available to help them in their community, being involved in things that were important to them, and having confidence in taking care of their illness. Improvements in clients’ quality of life were reported in the qualitative data, although no statistically significant gains were reported on the quality of life measure. Volunteers reported good self-efficacy and satisfaction in their role. Conclusion: The feasibility, acceptability, and sustainability of the program were largely dependent on strong intraorganizational leadership. Volunteers reported that their involvement in Nav-CARE enabled them to engage in ongoing learning and have a meaningful and relational role with clients. Clients and families described the positive impact of a volunteer on their engagement and quality of life.

Among men, prostate cancer (PCa) is the second most frequently diagnosed cancer subtype and has demonstrated a high degree of prevalence globally. BUD31, also known as Functional Spliceosome-Associated Protein 17, is a protein that works at the level of the spliceosome; it is functionally implicated in pre-mRNA splicing as well as processing, while also acting as a transcriptional regulator of androgen receptor (AR) target genes. Clinically, the expression of BUD31 and its functions in the development and progression of PCa is yet to be elucidated. The BUD31 expression was assessed using IHC in a tissue microarray (TMA) constructed from a cohort of 284 patient samples. In addition, we analyzed the prostate adenocarcinoma (TCGAPRAD-) database. Finally, we used PCa cell lines to knockdown BUD31 to study the underlying mechanisms in vitro.Assesment of BUD31 protein expression revealed lower expression in incidental and advanced PCa, and significantly lower expression was observed in patients diagnosed with castrate-resistant prostate cancer. Additionally, bioinformatic analysis and GSEA revealed that BUD31 increased processes related to cancer cell migration and proliferation. In vitro results made evident that BUD31 knockdown in PC3 cells led to an increase in the G2 cell population, indicating a more active and proliferative state. Additionally, an investigation of metastatic processes revealed that knockdown of BUD31 significantly enhanced the ability of PC3 cells to migrate and invade. Our in vitro results showed BUD31 knockdown promotes cell proliferation and migration of prostate cancer cells via activation of p-AKT and vimentin. These results support the clinical data, where low expression of BUD31 was correlated to more advanced stages of PCa.

Glycyl-tRNA synthetase (GARS) is a potential oncogene associated with poor overall survival in various cancers. However, its role in prostate cancer (PCa) has not been investigated. Protein expression of GARS was investigated in benign, incidental, advanced, and castrate-resistant PCa (CRPC) patient samples. We also investigated the role of GARS in vitro and validated GARS clinical outcomes and its underlying mechanism, utilizing The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. Our data revealed a significant association between GARS protein expression and Gleason groups. Knockdown of GARS in PC3 cell lines attenuated cell migration and invasion and resulted in early apoptosis signs and cellular arrest in S phase. Bioinformatically, higher GARS expression was observed in TCGA PRAD cohort, and there was significant association with higher Gleason groups, pathological stage, and lymph nodes metastasis. High GARS expression was also significantly correlated with high-risk genomic aberrations such as PTEN, TP53, FXA1, IDH1, SPOP mutations, and ERG, ETV1, and ETV4 gene fusions. Gene Set Enrichment Analysis (GSEA) of GARS through the TCGA PRAD database provided evidence for upregulation of biological processes such as cellular proliferation. Our findings support the oncogenic role of GARS involved in cellular proliferation and poor clinical outcome and provide further evidence for its use as a potential biomarker in PCa.

Background: Serine-arginine protein kinase 1 (SRPK1) has been implicated in prostate cancer (PCa) progression. However, its prognostic value and association with ERG and PTEN expression, two of the most common genetic alterations, have not been explored fully. Objective: We assessed the prognostic value of SRPK1 in association with ERG and PTEN in a cohort of patients managed nonsurgically by androgen deprivation therapy (ADT) for advanced disease. Design, setting, and participants: The study cohort consisted of men diagnosed with PCa by transurethral resection of the prostate (TURP; n = 480). The patients were divided into three main groups: incidental (patients with Gleason score [GS] ≤7 with no prior ADT), advanced (patients with GS ≥8 with no prior ADT), and castrate-resistant PCa (patients with prior ADT). Outcome measurements and statistical analysis: A total of 480 TURP samples were assessed by immunohistochemistry for SRPK1, ERG, and PTEN, and results were correlated with Gleason grade group (GG), overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations: High SRPK1 expression was noted in 105/455 (23%) available patient cores. Expression of SRPK1 was associated with Gleason grade grouping (p

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19–99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.

Introduction Breast cancer-related lymphoedema (BCRL) is a chronic swelling in the arm on the side of the breast cancer surgery, affecting one in five women. Recent studies in BCRL have demonstrated that resistance exercise can improve symptoms and quality of life without worsening lymphoedema. No studies have explored whether combining the principles of progressive resistance exercise training with therapeutic strategies of compression therapy and the decongestive lymphatic exercise sequence are beneficial in reducing arm lymphoedema volume. The aim of this three-arm, provincial randomised controlled trial is to determine the efficacy of a 12-week decongestive progressive resistance exercise (DRE) programme in combination with the one of two types of compression garments compared with standard care.Methods and analysis Sixty women with BCRL will be recruited and randomly assigned to one of the following three groups: (1) Standard care, (2) DRE with use of a daytime compression garment during exercise and (3) DRE with use of an adjustable compression wrap during exercise. The primary outcome is the percentage reduction in arm lymphoedema volume. Secondary outcomes include bioimpedance analysis, muscular strength, shoulder range of motion, physical activity level and health-related quality of life. Exploratory outcomes include evaluating changes in arm tissue composition using MRI and examining outcomes between the two DRE experimental groups. The primary analysis will compare changes between the groups from baseline to week 12 reflecting the end of the randomised control trial period.Ethics and dissemination The trial has received ethics approval from the Health Research Ethics Board of Alberta: Cancer Committee. The study results will be disseminated through scientific peer-reviewed publications, and presented at national and international conferences, and other media portals. The programme protocol will be shared with healthcare professionals and patient groups through clinical workshops and webinars.Trial registration number NCT05022823.Protocol version 12 November 2021.Issue date 26 April 2021.

Abstract Background Volunteer navigation is an innovative way to help older persons get connected to resources in their community that they may not know about or have difficulty accessing. Nav-CARE is an intervention in which volunteers, who are trained in navigation, provide services for older persons living at home with chronic illness to improve their quality of life. The goal of this study was to evaluate the impact of Nav-CARE on volunteers, older persons, and family participating across eight Canadian sites. Methods Nav-CARE was implemented using a knowledge translation approach in eight sites using a 12- or 18-month intervention period. A mixed method evaluation was used to understand the outcomes upon older person engagement; volunteer self-efficacy; and older person, family, and volunteer quality of life and satisfaction with the intervention. Results Older persons and family were highly satisfied with the intervention, citing benefits of social connection and support, help with negotiating the social aspects of healthcare, access to cost-effective resources, and family respite. They were less satisfied with the practical help available for transportation and errands. Older persons self-reported knowledge of the services available to them and confidence in making decisions about their healthcare showed statistically significant improvements (P

Abstract Background When a family member resides in long term care facility (LTC), family carers continue caregiving and have been found to have decreases in mental health. The aim of My Tools 4 Care – In Care (an online intervention) is to support carers of persons living with dementia residing in LTC through transitions and increase their self-efficacy, hope, social support and mental health. This article comprises the protocol for a study to evaluate My Tools 4 Care-In Care (MT4C-In Care) by asking the following research questions: 1) Is there a 2 month (immediately post-intervention) and 4 month (2 months post-intervention) increase in mental health, general self-efficacy, social support and hope, and decrease in grief and loneliness, in carers of a person living with dementia residing in LTC using MT4C-In CARE compared to an educational control group? 2) Do carers of persons living with dementia residing in LTC perceive My Tools 4 Care- In Care helps them with the transitions they experience? Methods This study is a single blinded pragmatic mixed methods randomized controlled trial. Approximately 280 family carers of older persons (65 years of age and older) with dementia residing in LTC will be recruited for this study. Data will be collected at three time points: baseline, 2 month, and 4 months. Based on the feasibility study, we hypothesize that participants using MT4C-In Care will report significant increases in hope, general self-efficacy, social support and mental health quality of life, and significant decreases in grief and loneliness from baseline, as compared to an educational control group. To determine differences between groups and over time, generalized estimating equations analysis will be used. Qualitative descriptive analysis will be used to further evaluate MT4C-In Care and if it supports carers through transitions. Discussion Data collection will begin in four Canadian provinces (Alberta, Manitoba, Ontario and Saskatchewan) in February 2020 and is expected to be completed in June 2021. The results will inform policy and practice as MT4C-In Care can be revised for local contexts and posted on websites such as those hosted by the Alzheimer Society of Canada. Trial registration NCT04226872 ClinicalTrials.gov Registered 09 January 2020 Protocol Version #2 Feb 19, 2020.

Abstract Background Body composition is minimally investigated in an immunotherapy era. Specific body composition signals such as myosteatosis may reflect aspects of patients' immunology and thereby their ability to respond to immunotherapies. Ipilimumab is a key checkpoint inhibitor in metastatic melanoma. As an antibody, it may also be more accurately dosed using body composition parameters rather than weight alone. This retrospective study aimed to investigate body composition‐based dosing and outcomes. Methods Pretreatment computed tomography images from metastatic melanoma, ipilimumab‐treated patients from 2009 to 2014 were used to measure myosteatosis [skeletal muscle radiographic density or SMD, in Hounsfield units (HU)] and surface area (cm2) as previously described. Cut point analysis determined whether a level of ipilimumab dose and myosteatosis demonstrated differences in progression‐free (PFS) and overall survival (OS). Secondary endpoints included objective response rates and toxicities. Results Of 121 identified, 97 patients were evaluable. Baseline demographics included 56 years median age, 60% male participants, and 23.7% with BRAF mutations. SMD analysis identified cut‐offs of SMD < 42 in those with BMI < 25 kg/m2 and 2.03 mg/cm2 are prognostic of poorer melanoma outcomes post ipilimumab. SMD may identify patients with flawed immunology and predict who may better respond to such therapy. Ipilimumab dosing by skeletal muscle index stands in contrast to weight‐based dosing and may demonstrate a more accurate method of antibody dosing.

An inadequate supply of fresh tissue is a major limitation of three-dimensional patient-derived gastric organoid research. We propose that tissue procurement for organoid culture could be increased by developing a cold storage shipment protocol for fresh surgical tissues. Sixty stomach specimens from C57BL/6J mice were resected, of which forty-five were stored in Hank’s Balanced Salt (HBSS), University of Wisconsin (UW), or Histidine-Tryptophan-Ketoglutarate (HTK) solutions for subsequent organoid culture. Stomachs were dissociated and processed into gastric organoids as fresh tissue or after transport at 4 °C for 24 or 48 h. All gastric organoid cultures were established and maintained for 10 passages. Cold storage for 24 or 48 h did not significantly affect organoid viability. Although cold storage was associated with decreased organoid growth rate, there were no differences in viability, cytotoxic dose response, or LGR5 and TROY stem cell gene expression compared to organoids prepared from fresh tissue. As a proof of concept, six human gastric cancer organoids were established after 24 or 48 h of storage. Patient-derived gastric organoids from mouse and human gastric tissue can be established after 48 h of cold ischemia. Our method, which only requires ice packs, standard shipping containers, and HBSS is feasible and reliable. This method does not affect the reliability of downstream dose–response assays and maintains organoid viability for at least 10 passages. The shipment of fresh tissue for organoid procurement could serve to enhance multicenter collaboration and achieve more elaborate or controlled organoid experimentation.

Abstract Background High-protein diets and total diet replacements are becoming increasingly popular for weight regulation; however, further research is needed to elucidate their impact on the physiology of body weight regulation. The aim of this inpatient metabolic balance study is to compare the impact of a high-protein total diet replacement versus a control diet (North American) on energy expenditure, macronutrient oxidation rates and balances, metabolic blood markers and appetite sensations in healthy adults. Methods Two randomized, controlled, cross-over clinical trials conducted separately in men and women will be conducted. In each trial, participants will be allocated to two isocaloric arms: a) Control diet: 55% carbohydrate, 15% protein, and 30% fat; b) High-protein total diet replacement: 35% of carbohydrate, 40% protein, and 25% fat. They will receive the prescribed diets for 32 h while inside the whole-body calorimetry unit. Diets will be designed to ensure participants are in energy balance. The following physiological changes will be compared between groups: energy expenditure, macronutrient oxidation rates and balances, metabolic blood markers, and appetite sensations. Body composition will be assessed at baseline using dual-energy X-ray absorptiometry. Discussion This will be the first inpatient metabolic balance study examining the impact of a high-protein total diet replacement on energy metabolism, metabolic blood markers and appetite sensations in healthy young adults (of both sexes) using a whole-body calorimetry unit. Results of this clinical trial can ultimately be used to develop strategies to optimize high-protein diet interventions and weight management. Trial registration ClinicalTrials.gov Identifiers: NCT02811276 (registered on 16 June 2016) and NCT03565510 (registered on 11 June 2018). Protocol version NCT02811276: version 10 (2 March 2018); NCT03565510: version 3 (28 September 2018).

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p p = 0.002) and cause-specific survival (CSS) (HR: 2.012, CI 1.29–3.13, p = 0.002) using univariate analysis. When compared to each sub-molecular type. High CDK2AP1/PTEN-loss, abnormal AR or p53 expression showed even worse association to poorer OS and CCS and remained significant when adjusted for GG. Our data indicates that CDK2AP1 directly binds to p53 using the Co-Immunoprecipitation (Co-IP) technique, which was validated using molecular docking tools. This suggests that these two proteins have a significant association through several binding features and correlates with our observed clinical data. In conclusion, our results indicated that the CDK2AP1 overexpression is associate with worse OS and CSS when combined with certain PCa molecular subtypes; interaction between p53 stands out as the most prominent candidate which directly interacts with CDK2AP1.

Background: The 2016 wildfires in Fort McMurray (Alberta, Canada) led to a massive displacement of 88,000 people and destroyed 2,400 homes. Although no direct human fatality resulted, many individuals feared for their lives or those of their loved ones.Objectives: (1) To estimate the prevalence of post-traumatic stress, major depressive, insomnia, generalized anxiety, and substance use disorders in the adult population of Fort McMurray 1 year after the evacuation; (2) To identify pre-, peri-, and post-disaster correlates of mental health disorders.Methods: A phone survey using random digit sampling was used to survey evacuees. A total of 1,510 evacuees (response rate = 40.2%, 55.5% women, mean age = 44.11, SD = 12.69) were interviewed between May 9th and July 28th, 2017. Five validated scales were administered: the PTSD Symptoms Checklist (PCL-5), the Insomnia Severity Index (ISI), the depression and anxiety subscales of the Patient Health Questionnaire (PHQ-9, GAD-7), and the CAGE Substance Abuse Screening Tool.Results: One year after the wildfires, 38% had a probable diagnosis of either post-traumatic stress, major depressive, insomnia, generalized anxiety, or substance use disorder, or a combination of these. Insomnia disorder was the most common, with an estimated prevalence of 28.5%. Post-traumatic stress, major depressive and generalized anxiety disorders were almost equally prevalent, with ~15% each. The estimated prevalence of substance use disorder was 7.9%. For all five mental health disorders, having a mental health condition prior to the fires was a significant risk factor, as well as having experienced financial stress or strain due to the economic decline already present in Fort McMurray. Five post-disaster consequences were significant predictors of four of the five disorders: decrease in work, decrease in social life, poorer current health status, increase in drug and alcohol use, and higher level of stress experienced since the fires.Conclusion: One year after the fires, more than one third of the evacuees had clinically significant psychological symptoms, including those of insomnia, post-traumatic stress, depression, anxiety, and substance use. This study helped identify individuals more at risk for mental health issues after a natural disaster and could guide post-disaster psychosocial support strategies.

Background: Natural disasters happen in an increased frequency, and telemental health interventions could offer easily accessible help to reduce mental health symptoms experienced by survivors. However, there are very few programs offered to natural disaster survivors, and no research exists on therapists’ experiences with providing blended interventions for natural disaster survivors. Aims: Our qualitative case study aims to describe psychologists’ experiences with an online, therapist-assisted blended intervention for survivors of the Fort McMurray wildfires in Alberta, Canada. Method: The RESILIENT intervention was developed in the frames of a randomized controlled trial to promote resilience after the Fort McMurray wildfires by providing survivors free access to a 12-module, therapist-assisted intervention, aiming to improve post-traumatic stress, insomnia, and depression symptoms. A focus group design was used to collect data from the therapists, and emerging common themes were identified by thematic analysis. Results: Therapists felt they could build strong alliances and communicate emotions and empathy effectively, although the lack of nonverbal cues posed some challenges. The intervention, according to participating therapists, was less suitable for participants in high-stress situations and in case of discrepancy between client expectations and the intervention content. Moreover, the therapists perceived specific interventions as easy-to-use or as more challenging based on their complexity and on the therapist support needed for executing them. Client engagement in the program emerged as an underlying theme that had fundamental impact on alliance, communication, and ultimately, treatment efficiency. Therapist training and supervision was perceived as crucial for the success of the program delivery. Conclusions: Our findings provided several implications for the optimalization of blended interventions for natural disaster survivors from our therapists’ perspective.

Background: Chronic pain is a common and distressing symptom reported by patients with chronic kidney disease (CKD). Clinical practice and research in this area do not appear to be advancing sufficiently to address the issue of chronic pain management in patients with CKD. Objectives: To determine the prevalence and severity of chronic pain in patients with CKD. Design: Systematic review and meta-analysis. Setting: Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity. Patients: Adults with glomerular filtration rate (GFR) category 3 to 5 CKD including dialysis patients and those managed conservatively without dialysis. Measurements: Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of pain, and severity of pain. Methods: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library, last searched on February 3, 2020. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of overall chronic pain, musculoskeletal pain, bone/joint pain, muscle pain/soreness, and neuropathic pain and the I 2 statistic was computed to measure heterogeneity. Random effects models were used to account for variations in study design and sample populations and a double arcsine transformation was used in the model calculations to account for potential overweighting of studies reporting either very high or very low prevalence measurements. Pain severity scores were calibrated to a score out of 10, to compare across studies. Weighted mean severity scores and 95% confidence intervals were reported. Results: Sixty-eight studies representing 16 558 patients from 26 countries were included. The mean prevalence of chronic pain in hemodialysis patients was 60.5%, and the mean prevalence of moderate or severe pain was 43.6%. Although limited, pain prevalence data for peritoneal dialysis patients (35.9%), those managed conservatively without dialysis (59.8%), those following withdrawal of dialysis (39.2%), and patients with earlier GFR category of CKD (61.2%) suggest similarly high prevalence rates. Limitations: Studies lacked a consistent approach to defining the chronicity and nature of pain. There was also variability in the measures used to determine pain severity, limiting the ability to compare findings across populations. Furthermore, most studies reported mean severity scores for the entire cohort, rather than reporting the prevalence (numerator and denominator) for each of the pain severity categories (mild, moderate, and severe). Mean severity scores for a population do not allow for “responder analyses” nor allow for an understanding of clinically relevant pain. Conclusions: Chronic pain is common and often severe across diverse CKD populations providing a strong imperative to establish chronic pain management as a clinical and research priority. Future research needs to move toward a better understanding of the determinants of chronic pain and to evaluating the effectiveness of pain management strategies with particular attention to the patient outcomes such as overall symptom burden, physical function, and quality of life. The current variability in the outcome measures used to assess pain limits the ability to pool data or make comparisons among studies, which will hinder future evaluations of the efficacy and effectiveness of treatments. Recommendations for measuring and reporting pain in future CKD studies are provided. Trial registration: PROSPERO Registration number CRD42020166965

Low molecular weight heparin (LMWH) is the standard of care for treating cancer-associated thrombosis (CAT), although new evidence for direct oral anticoagulants (DOACs) supports use in specific cancer populations. In this retrospective review at a specialty CAT clinic from 2016 to 2019, we report the use of anticoagulants (LMWH, DOACs, warfarin, anticoagulant class change) in the acute and chronic phases of CAT and compare use before/after publication of the Hokusai-VTE Cancer trial. Death, venous thromboembolism (VTE) recurrence and bleeding was also reported. Of the 221 included, median age was 69 years, with 57.5% having metastatic disease. In the acute phase, 80.1% were prescribed LMWH, 4.1% DOAC, and 14.5% had an anticoagulant class change (LMWH to DOAC; 78.1%). In the chronic phase, 35.8% were prescribed LMWH, 11.3% DOAC, and 42.9% had an anticoagulant class change (LMWH to DOAC; 90.1%). Use of DOACs in the acute and chronic phase prior to the Hokusai-VTE trial was 1.0% and 2.0%, respectively, and following publication was 6.8% and 19.6%. Death occurred for 22.6% patients, recurrent VTE in 7.2%, and bleeding in 5.0%. DOAC use is increasing with time; real-world data may help to guide optimization of the care of complex patients.

Sarcopenic obesity is associated with several negative health outcomes. However, the prevalence of this condition – and the relationship to physical performance parameters – varies across definitions. The aim of this cross-sectional investigation was to describe the prevalence of sarcopenic obesity using different published definitions and their relationship with handgrip strength and walking speed in older Canadian adults. Individuals aged 65+ in the Canadian Longitudinal Study on Aging (n = 11,803; 49.6% male, 50.4% female) were included. Body composition was measured using dual X-ray absorptiometry. Sarcopenic obesity was defined using 29 definitions. Low handgrip strength was identified as < 27 kg in males and < 16 kg in females and poor physical performance was defined as gait speed ≤ 0.8 m/s. The prevalence of sarcopenic obesity ranged from 0.1 to 85.3% in males, and from 0 to 80.4% in females. Sarcopenic obesity was frequently associated with low handgrip strength (p < 0.05) in both males (14/17 definitions, 82.4%) and females (21/29 definitions, 72.4%). In very few definitions, sarcopenic obesity was associated with slow gait speed (males: 1/17 definitions [6.7%]; females: 2/29 [6.9%]). In conclusion, the prevalence of sarcopenic obesity varied greatly according to definitions and sarcopenic obesity was frequently associated with low handgrip strength.

Human cytomegalovirus (HCMV) infects 40–70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0–100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes. HCMV gB DNA was detected in 18.4% of 136 breast tumors while 62.8% of 94 breast cancer patients were seropositive for HCMV. mRNA for the HCMV immediate early gene was not detected in any sample, suggesting viral latency in breast tumors. HCMV seropositivity was positively correlated with age, body mass index and menopause. Patients who were HCMV seropositive or had HCMV DNA in their tumors were 5.61 (CI 1.77–15.67, p = 0.003) or 5.27 (CI 1.09–28.75, p = 0.039) times more likely to develop Stage IV metastatic tumors, respectively. Patients with HCMV DNA in tumors experienced reduced relapse-free survival (p = 0.042). Being both seropositive with HCMV DNA-positive tumors was associated with vascular involvement and metastasis. We conclude that determining the seropositivity for HCMV and detection of HCMV gB DNA in the breast tumors could identify breast cancer patients more likely to develop metastatic cancer and warrant special treatment.

Introduction: Nav-CARE (Navigation: Connecting, Accessing, Resourcing and Engaging) is an evidence-based program that was implemented over 1 year in a rural community in western Canada. Nav-CARE uses volunteers who are trained in navigation to facilitate access to resources and provide social support to older persons living in the community with serious illness such as cancer, congestive heart failure and chronic obstructive pulmonary disease. Following implementation in which Nav-CARE was found to be feasible, acceptable and have positive outcomes, Nav-CARE was integrated into the local community-based hospice society program. Two years after a successful implementation, it continued to be sustainable in this same rural community. The purpose of this study was to explore the key factors that facilitated the sustainability of Nav-CARE in a rural hospice society. Methods: A qualitative single case study design was used with data from several sources collected at different times: (a) pre-implementation, (b) Nav-CARE program implementation (1-year time period), (c) immediately after implementation and (d) 6 months to 2 years after implementation). Data included individual interviews with community stakeholders (n=9), the study volunteer coordinator (n=1), hospice society coordinator (n=1) and Nav-CARE volunteers (n=9). It also included meeting notes of volunteer debriefing sessions and meetings with stakeholders planning for sustainability of Nav-CARE that were held during the 1-year implementation. Data were organized using the i-PARIHS (integrated Promoting Action on Research Implementation in Health Services) framework (a well known implementation framework). Data were analyzed using Yin's qualitative case study approach. Results: The findings from this case study suggested that key factors in facilitating sustainability of a rural community intervention (Nav-CARE) were the organizational context (inner context) and facilitation (facilitator and facilitation processes). Additionally, the inner context included the fit of Nav-CARE with the organization's priorities, the absorptive capacity of the organization, and organizational structure and mechanisms to integrate Nav-CARE into current programs. The hospice society was well established and supported by the rural community. The role of the facilitator and the planned facilitation processes (training of volunteer navigators, ongoing support and planning events) were key factors in the sustainability of the Nav-CARE program. The findings found that the formal role of the facilitator in the implementation and sustainability of Nav-CARE in this rural community required skills and knowledge, as well as ongoing mentorship. As well, the facilitation process for Nav-CARE included formal sustainability planning meetings involving stakeholders. Conclusion: Using the i-PARIHS framework and a case study approach, key factors for facilitating sustainability were identified. The role of the facilitator, the facilitation processes and the characteristics of the organizational context were important for the sustainability of Nav-CARE. Future research is needed to understand how to assess and enhance an organization's sustainability capacity and the impact of additional facilitator training and mentoring. This study provides a foundation for future research and adds to the discussion of the issue of sustainability of evidence-based interventions in rural community settings.

ARPC1B (Actin Related Protein 2/3 Complex Subunit 1B) has been found to be involved in platelet abnormalities of immune-mediated inflammatory disease and eosinophilia. However, its role in prostate cancer (PCa) has not been established. We characterized the role of ARPC1B in PCa invasion and metastasis and investigated its prognosis using in vitro cellular models and PCa clinical data. Higher immunohistochemistry (IHC) expressions of ARPC1B were observed in localized and castrate resistant PCa (CRPC) vs. benign prostate tissue (p < 0.01). Additionally, 47% of patients with grade group 5 (GG) showed high ARPC1B expression vs. other GG patients. Assessing ARPC1B expression in association with two of the common genetic aberrations in PCa (ERG and PTEN) showed significant association to overall and cause-specific survival for combined assessment of ARPC1B and PTEN, and ARPC1B and ERG. Knockdown of ARPC1B impaired the migration and invasion of PC3 and DU145 PCa cells via downregulation of Aurora A kinase (AURKA) and resulted in the arrest of the cells in the G2/M checkpoint of the cell cycle. Additionally, higher ARPC1B expression was observed in stable PC3-ERG cells compared to normal PC3, supporting the association between ERG and ARPC1B. Our findings implicate the role of ARPC1B in PCa invasion and metastasis in association with ERG and further support its prognostic value as a biomarker in association with ERG and PTEN in identifying aggressive phenotypes of PCa cancer.

Abstract Background Following institutionalization of a relative with Alzheimer disease and related dementias (ADRD), family carers continue to provide care. They must learn to negotiate with staff and navigate the system all of which can affect their mental health. A web-based intervention, My Tools 4 Care-In Care (MT4C-In Care) was developed by the research team to aid carers through the transitions experienced when their relative/friend with ADRD resides in a long-term care (LTC) facility. The purpose of this study was to evaluate MT4C-In Care for feasibility, acceptability, ease of use, and satisfaction, along with its potential to help decrease carer’s feelings of grief and improve their hope, general self-efficacy, and health-related quality of life. Methods The study was a mixed-methods single-arm repeated measures feasibility study. Participants accessed MT4C-In Care over a 2-month period. Data were collected at baseline and 1 and 2 months. Using a checklist, participants evaluated MT4C-In Care for ease of use, feasibility, acceptability, and satisfaction. Measures were also used to assess the effectiveness of the MT4C-In Care in improving hope (Herth Hope Index), general self-efficacy (GSES), loss and grief (NDRGEI), and health-related quality of life (SF12v2) of participants. Qualitative data were collected at 2 months and informed quantitative findings. Results The majority of the 37 participants were female (65%; 24/37), married (73%; 27/37), and had a mean age of 63.24 years (SD = 11.68). Participants reported that MT4C-In Care was easy to use, feasible, and acceptable. Repeated measures ANOVA identified a statistically significant increase over time in participants hope scores (p = 0.03) and a significant decrease in grief (

Background: Digital rectal examination (DRE) is considered an important part of the physical examination. However, it is unclear how many patients have a DRE performed at the primary care level in the work-up of rectal cancer, and if the absence of a DRE causes a delay to consultation with a specialist. Methods: A retrospective patient questionnaire was sent to 1000 consecutive patients with stage II or stage III rectal cancer. The questionnaire asked patients to recall if they had a DRE performed by their general practitioner (GP) when they first presented with symptoms or a positive FIT test. Demographic data, staging data, and time to consultation with a specialist were also collected. Results: A thousand surveys were mailed out, and a total of 262 patients responded. Of the respondents, 46.2% did not recall undergoing a digital rectal examination by their primary care provider. Women were less likely to undergo a DRE than men (28.6% vs. 44.3%, p = 0.019). While there was a trend towards longer times to specialist consultation in patients who did not undergo a DRE (27.0 vs. 12.2 weeks), this was not statistically significant (p = 0.121). Conclusion: A significant proportion of patients who are FIT positive or have symptomatic rectal bleeding do not recall having a DRE by their primary care provider. Barriers may include lack of comfort with performing DRE or lack of time. Clearer guidelines and more support for GP’s may increase uptake of DRE.

Purpose: Patients with left-sided breast cancer (LSBC) are at increased risk of cardiac morbidity from adjuvant breast radiation therapy (ABRT). Breath-hold (BH) techniques substantially reduce the radiation received by heart during radiation therapy for LSBC. However, a subset of patients with LSBC are ineligible for BH techniques due to an inability to breath-hold or because of other comorbidities. To reduce radiation to the heart, we routinely use a custom-made breast shell for the treatment of patients with LSBC who are ineligible for BH techniques. This study evaluates the dosimetric impact of using a breast shell for patients with LSBC undergoing ABRT. Methods and materials: Sixteen consecutive patients with LSBC who failed BH and underwent ABRT using a breast shell during the period of 2014 to 2016 were identified. Treatment was planned using field-in-field tangents with a prescribed dose of 42.5 Gy in 16 fractions. Comparisons between plans with and without a shell were made for each patient using a paired t test to quantify the sparing of organs at risk (OARs) and target coverage. Results: There was no statistically significant difference in the planning target volume of breast coverage. A statistically significant improvement was observed in sparing the heart, left ventricle (LV), and ipsilateral lung (P-value

Abstract Background Family carers of older persons with Alzheimer’s’ disease and related dementia (ADRD) and multiple chronic conditions (MCC) experience significant, complex, and distressing transitions such as changes to their environment, roles and relationships, physical health, and mental health. An online intervention (My Tools 4 Care) was developed for family carers of persons with ADRD and MCC living at home, with the aim of supporting these carers through transitions and increasing their self-efficacy, hope, and health related quality of life (HRQoL). This study will evaluate My Tools 4 Care (MT4C) by asking the following research questions: 1. Does use of MT4C result in a 3 month (immediately post intervention) and 6-month (3 months after intervention) increase in HRQoL, self-efficacy, and hope, in carers of persons with ADRD and MCC compared to an educational control group? 2. Does use of MT4C help carers of community-dwelling older adults with ADRD and MCC deal with significant changes they experience as carers? and 3. Are the effects/benefits of the MT4C intervention achieved at no additional cost compared to an educational control group? Methods/Design Using a pragmatic mixed methods randomized controlled trial design, 180 family carers of community dwelling older persons (65 years of age and older) with ADRD and MCC will participate in the study. Data will be collected from the intervention and an educational control group at four time points: baseline, 1 month, 3 and 6 months. We expect to find that family carers using MT4C will show greater improvement in hope, self-efficacy and HRQoL, at no additional cost from a societal perspective, compared to those in the educational control group. General estimating equations will be used to determine differences between groups and over time. Discussion Data collection began in Ontario and Alberta Canada in June 2015 and is expected to be completed in June 2017. The results will inform policy and practice as MT4C can be easily revised for local contexts and is scalable in terms of posting on websites such as those hosted by the Alzheimer Society. Trial registration ClinicalTrials.gov Identifier: NCT02428387

Purpose: Whole brain radiation therapy (WBRT) remains the standard of care for patients with multiple brain metastases, but more than half of treated patients will develop intracranial progression. Because there is no clear consensus on the optimal therapeutic approach, a prognostic index would be helpful to guide treatment options at progression. We explored whether the recursive partitioning analysis (RPA) score prior to repeat WBRT is predictive of survival. Methods and materials: This multi-institutional pooled analysis included patients with 2 or more brain metastases from any solid primary tumor that was treated with 2 courses of WBRT. Information on demographics, disease characteristics, and intervals between courses was collected. RPA class was abstracted or retrospectively assigned, and descriptive statistics calculated. Median survival (MS) was determined using the Kaplan-Meier method and compared using log rank tests. Univariate and multivariate analyses were performed via Cox regression analysis. Results: For 205 patients, the median age was 55 years (range, 25-83 years), 68% were female, 40.5% had non-small cell lung cancer, and 31.2% had small cell lung cancer. Prior to the second WBRT, 4.9% of patients were RPA class 1, 36.6% were RPA2, and 58.5% were RPA3, with an MS of 7.5 months (95% confidence interval [CI], 4.7-10.3), 5.2 months (95% CI, 3.7-6.7 months), and 2.9 months (95% CI, 2.2-2.9 months), respectively (P = .001). On univariate and multivariate analyses, a Karnofsky Performance Status of

The transition experience of male spouses of women with breast cancer is largely unknown. Ninety-one open-ended surveys of male spouses were analyzed using thematic analysis to understand the transition experience of this population when their partners were diagnosed and treated for breast cancer. While 10 participants indicated they experienced no changes, the majority experienced changes to their roles and relationships, their mental health, and their share of household work. Spouses took on a supportive role. They adjusted to the changes they faced by proactively becoming aware of their situation, fostering a positive approach, and being actively involved in their partners’ experiences. Implications for nurses entail recognizing the role of the spouse, as well as facilitating access to reliable information and support networks.