Feature-specific quantile normalization and feature-specific mean-variance normalization deliver robust bi-directional classification and feature selection performance between microarray and RNAseq data.

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 effects of TGF-ß1 and IFN-α2b on decorin, decorin isoforms and type I collagen in hypertrophic scar dermal fibroblasts.

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-ß1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-ß1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-ß1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-ß1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-ß1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-ß1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-ß1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.

Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

BACKGROUND: Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). OBJECTIVES: To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. METHODS: A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. RESULTS: Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. CONCLUSION: Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

Incidence of Nonmelanoma Skin Cancers in Alberta, Canada, From 2007 to 2018.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting Caucasian populations and has been seeing steady increases in incidence globally for decades. Our previous study (from Alberta, Canada) had shown a plateau in the incidence rates for NMSC. This contrasts with data from other regions within Canada and throughout the world that indicated a continued increase in incidence rates of NMSCs. OBJECTIVES: The objective of this study was to provide an update on the trends in incidence of NMSC in Alberta, Canada, from 2007 to 2018. METHODS: A retrospective analysis of patients from Alberta diagnosed with NMSC from 2007 to 2018 inclusive was conducted with data retrieved from Alberta Cancer Registry. Sex-, age-, anatomical location-, NMSC subtype-, stage-specific incidence rates and trends were examined. RESULTS: From 2007 to 2018, overall incidence rates of NMSC increased by 36%. Invasive squamous cell carcinoma (SCC) and in situ SCC demonstrated the most significant increase, invasive SCC [annual percentage change (APC) 3.48, P = .014] and in situ SCC (APC 5.61, P = .0001). In addition, we were able to determine that females had the most significant increases in NMSC incidence rates from 2007 to 2018 particularly invasive SCC (APC 3.03, P = <.0001) and in situ SCC (APC 5.08, P = <.0001). CONCLUSIONS: After initial levelling of NMSC incidence in Alberta in the early part of 21st century, the incidence of NMSC continues to increase over the past decade. The reasons for this change are not clear and likely multifactorial.

Elevated LAMTOR4 Expression Is Associated with Lethal Prostate Cancer and Its Knockdown Decreases Cell Proliferation, Invasion, and Migration In Vitro.

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 ß 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.

Disparities in prostate cancer screening, diagnoses, management, and outcomes between Indigenous and non-Indigenous men in a universal health care system.

BACKGROUND: Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought. METHODS: An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals. RESULTS: Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50-70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25-65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2-4.2; p < .01) than non-Indigenous men. CONCLUSIONS: Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.

Effect of transversus abdominis plane block on postoperative outcomes in gynecologic oncology patients managed on an Enhanced Recovery After Surgery pathway.

OBJECTIVES: To characterize the effect of transversus abdominis plane (TAP) blocks on post-operative outcomes in patients undergoing laparotomy for gynecologic malignancy. METHODS: This retrospective cohort study assessed patients undergoing laparotomy in 2016-2017 and 2020 in Alberta, Canada. The primary outcome was opioid consumption in oral morphine milligram equivalent (MME). Secondary outcomes included maximum pain scores, length of stay, and patient-controlled analgesia (PCA) use. Outcomes were compared using t-test with subgroup analysis by NSAID use. Multivariate regression modelling was performed for potential confounders. RESULTS: Data was collected on 956 patients; 828 received a TAP block, 128 did not. Opioid use in the first 24 h was lower in the TAP block group (35.9 mg MME vs 44.5 mg MME, p = 0.0294), without any increase in pain scores, this did not remain significant after regression analysis. Patients with TAP blocks had significant reduced mean length of stay (3.2 days vs. 5.0 days, p < 0.0001), and PCA use (19.9% vs. 56.25%, p < 0.0001). On subgroup analysis of patients that did not receive NSAIDs (n = 160), mean opioid use was decreased in those patients with TAP blocks compared to those without TAP blocks in the first 24 h (36.1 mg vs. 61.2 mg, p = 0.0017), and at 24 to 48 h (16.3 mg vs. 51.0 mg, p < 0.0001). CONCLUSIONS: Surgeon-administered TAP blocks were associated with decreased length of stay and post-operative opioid use in patients not receiving scheduled NSAIDs. This decrease in opioid use was not associated with any increase in average or maximum pain scores.

Patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms.

OBJECTIVE: To evaluate the patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms (NENs). METHODS: Linked administrative databases from the province of Alberta, Canada, were examined, and patients diagnosed with digestive NENs from 2004 to 2019 were reviewed. Incidents of emergency department visits in the 3 months before histological diagnosis were reviewed. Multivariable logistic regression analyses were used to examine factors associated with at least one emergency department (ED) visit as well as factors associated with more than one ED visit. The impact of pre-diagnosis ED visits on overall survival was further assessed in a multivariable Cox regression model, which included (in addition to ED visits), age at diagnosis, sex, histology, Charlson comorbidity index, and stage. RESULTS: A total of 2120 patients were considered eligible for the study, and they were included in the analysis (including 1041 patients (49.1%) with at least one ED visit in the 3 months before diagnosis). The following factors were associated with a higher likelihood of an ED visit prior to diagnosis: younger age (OR with increasing age: 0.983; 95% CI: 0.977-0.989), higher comorbidity index (OR: 1.332; 95% CI: 1.215-1.460), female sex (OR: 1.292; 95% CI: 1.084-1.540), and stage IV (OR: 1.515; 95% CI: 1.106-2.075). Likewise, the following factors were associated with more than one ED visit within 3 months before diagnosis: younger age (OR with increasing age: 0.985; 95% CI: 0.979-0.992), higher comorbidity index (OR: 1.280; 95% CI: 1.167-1.405), and female sex (OR: 1.516; 95% CI: 1.230-1.868). Using multivariable Cox regression modeling, the following factors were associated with worse overall survival (higher risk of death): older age (HR: 1.050; 95% CI: 1.043-1.056), higher comorbidity index (HR: 1.280; 95% CI: 1.209-1.356), stage IV (HR: 3.163; 95% CI: 2.562-3.905), neuroendocrine carcinoma histology (HR: 1.645; 95% CI: 1.350-2.003), pre-diagnosis ED visit (HR: 1.784; 95% CI: 1.529-2.083). CONCLUSION: Almost one-half of patients with NENs visit the ED within 3 months before diagnosis. ED visits were associated with younger age, female sex, advanced disease, and higher comorbidity. Moreover, pre-diagnosis ED visit(s) were associated with worse overall survival in the current cohort.

Prevalence of palliative radiotherapy abstracts presented at the annual scientific meetings of the Canadian Association of Radiation Oncology: 2003-2021.

PURPOSE: Approximately half of all radiotherapy (RT) is delivered with palliative intent. Clinical research in palliative RT aims to manage symptoms, improve quality of life (QoL), evaluate supportive care, and determine optimal dose-fractionation schedules. Our aim was to describe the prevalence of palliative research at the Canadian Association of Radiation Oncology (CARO) Annual Scientific Meeting (ASM) over time and compare this analysis to previously published work which evaluated the years 1992-2002. METHODS: Published abstracts (2003-2021) were independently reviewed by two authors who categorized each as curative-intent; palliative-intent; pertaining to both populations; or neither. Abstracts were considered palliative if they described incurable malignancy and interventions primarily for symptom control or QoL. Type of study, primary, site treated, and symptoms palliated were recorded. Descriptive and summary statistics were calculated including one-way ANOVA test for trend. RESULTS: Three hundred thirty-nine out of 4566 abstracts (7.4%, range 2.4-13.9% per year) were classified as palliative. 7.7% (26/339) described phase I-III trials. The main primary site was the lung (39/339) and the most common metastatic site was the bone (34.2%). QoL, symptom and toxicity outcomes were reported in 31.6% (107/339), 37.8% (128/339) and 17.7% (60/339), respectively. The most common symptom investigated was pain (38/339). The proportion of abstracts classified as curative, palliative or reporting toxicity endpoints demonstrated significant change over time (all p<0.0001). CONCLUSION: While proportion of palliative themed abstracts has increased with time, there remains a significant gap before equivalence with the prevalence of palliative RT in clinical practice is achieved.

Prescribing practices of oncology pharmacists working in ambulatory cancer centers in Alberta.

OBJECTIVE: To describe and quantify independent prescribing of oncology pharmacists working in adult, ambulatory cancer centers in Alberta, Canada. METHODS: A retrospective chart review of oncology pharmacists prescribing in the electronic health record, ARIA® was conducted. Prescriptions from January 1, 2018 to June 30, 2018 were analyzed. Descriptive statistics were used to quantify prescription volume and class of medications prescribed. A cross-sectional analysis was then performed on a random sample to determine the type of prescription intervention and evaluate pharmacist documentation. RESULTS: Over 6 months, 3474 prescriptions were ordered by 33 clinically deployed pharmacists. The median number of medications prescribed was 7 per month (interquartile range: 1.50-27.00; Range: 0.17-79.5). When prescribing was standardized by pharmacist's time clinically deployed, the median was 21.67 (interquartile range: 5.00-79.67; range: 0.67-216.67) prescriptions per month per full-time equivalent. The most prescribed class of medication was antiemetic (24.1%). From a sample of 346 prescriptions, 172 (50%) were new medications initiated, 160 (46%) were the continuation of existing prescriptions and 14 (4%) were prescription dosage adjustments. Adherence to the specified documentation standards was 47%. CONCLUSIONS: Oncology pharmacists utilize their independent prescribing to initiate and continue supportive care medications for cancer patients. The prescribing volume varied greatly among pharmacists. Opportunities exist to further engage pharmacist prescribing.

Pharmacists' practices and views regarding management of sexual health in patients with cancer.

INTRODUCTION: Sexual health issues associated with cancer can significantly impact patients' psychosocial well-being and overall quality of life. These issues are frequently medication-related, placing pharmacists in an opportune position to manage sexual health concerns in patients with cancer. Currently, no literature exists exploring pharmacists' practices related to the management of sexual health in oncology patients. METHODS: An anonymous, descriptive, cross-sectional, web-based survey was conducted to elicit pharmacists' views and practices regarding managing sexual health in oncology patients. Pharmacists practicing in Canada who provide care to adult malignant hematology or oncology patients were eligible to participate. The survey was disseminated through the Canadian Association of Pharmacy in Oncology and through informal oncology pharmacy practitioner networks. RESULTS: Of the 102 pharmacists who participated, 96 completed the survey in its entirety. Most respondents were female, practiced in Alberta, and primarily saw oncology patients in outpatient cancer facilities. Although 85% of participants felt pharmacists should be involved in giving patients an opportunity to discuss sexual health, only 8% reported managing sexual health in at least 50% of their oncology patients. The most commonly agreed upon barriers to this were presence of family members and friends at appointments, lack of knowledge or training, limited time, and the belief that sexual health is not applicable to all oncology patients. CONCLUSIONS: This study explored pharmacists' views and practices regarding managing sexual health in patients with cancer. Several barriers were identified, which may aid in future development of resources to assist pharmacists in routinely addressing sexual health in oncology patients.

A prospective Canadian gastroesophageal cancer database: What have we learned?

BACKGROUND: Minimal literature exists on outcomes for Canadian patients with gastroesophageal adenocarcinoma (GEA). The objective of our study was to establish a prospective clinical database to evaluate demographic characteristics, presentation and outcomes of patients with GEA. METHODS: Patients diagnosed with GEA were recruited from Jan. 30, 2017, to Aug. 30, 2020. Data collected included demographic characteristics, presentation, treatment and survival. A multivariable model for overall survival in patients treated with curative intent was created using sex, lymph node status, resection margin status, age and tumour location as variables. RESULTS: A total of 122 patients with adenocarcinoma of the stomach or gastroesophageal junction were included. Median age was 65 years (interquartile range [IQR] 59-74), 70% of patients were male and 26% were born outside of Canada. Median follow-up time was 14.5 (IQR 8.0-31.0) months. Following staging computed tomography scanning, 88% of patients were deemed to have potentially resectable disease. Eighty-one (76%) received staging laparoscopy and 74 (61%) were treated with curativeintent surgery. Forty-six (62%) patients had nodal metastases. The median number of nodes harvested was 22 (IQR 18-30). The R0 resection margin rate was 82%. The 3-year overall survival for patients who received curative-intent treatment was 63% and 38% for all patients. On multivariable analysis, female sex (hazard ratio [HR] 3.88, p = 0.01), positive nodal status (HR 3.58, p = 0.02), positive margins (HR 3.11, p = 0.03) and tumour location (HR 3.00, p = 0.03) were associated with decreased overall survival. CONCLUSION: Many of the patients with GEA in this study presented with advanced disease, and only 61% were offered curative-intent surgery. A prospective multicentre national GEA database is now being established.

Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.

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.

Glycyl-tRNA Synthetase (GARS) Expression Is Associated with Prostate Cancer Progression and Its Inhibition Decreases Migration, and Invasion In Vitro.

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.

Downregulation of BUD31 Promotes Prostate Cancer Cell Proliferation and Migration via Activation of p-AKT and Vimentin In Vitro.

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.

Do Radiation Oncology Residents Have a Preferred Radiation Treatment Planning Review Format?

In an era of increasing virtual communication, we aimed to investigate current formats used by radiation oncology residents for reviewing radiation treatment plans with attendings, preferences for formats, and reasons contributing to preferences. Residents enrolled in Canadian radiation oncology programs received questionnaires examining training level, typical review formats, preferred format, and reasons for preference. Analysis excluded PGY-1s due to insufficient exposure. Fifty-two residents participated. National response rate was 55%. Overall, hybrid review was the most used format (77%). Virtual review was the most preferred format (44%). Preference for virtual review was most common among junior residents (57%), while in-person review was most preferred by senior residents (45.4%). Few residents typically use their preferred format (35%). Reasons for preference varied between groups in convenience (p < 0.01), interactivity (p < 0.01), and teaching quality (p = 0.04). The persistence of e-learning suggests that virtual treatment planning education will continue to some degree. Junior residents prefer virtual review, while a clearly preferred review format was less apparent among senior residents. Preferences are multifactorial, and the trends seen in reasons for preference between formats may reflect advantages inherent to each. Progress is still needed in optimizing treatment planning education, as suggested by few residents using their preferred format. Residents and staff should collectively decide which educational format for treatment planning best meets educational needs.

Design and Implementation of a Multidisciplinary High-Fidelity Simulation Course for the Management of Malignant Spinal Cord Compression.

High-fidelity simulation (HFS) training is suited to high-stakes, uncommon situations such as malignant spinal cord compression (MSCC), allowing for rare hands-on practice. This pilot study was created as the first of its kind to examine educational outcomes of a radiation therapist (RTT)-led multidisciplinary radiation oncology (RO) emergency simulation course. A multidisciplinary course design team composed of RO residents, radiation oncologists, RTT course instructors, and medical physicists created a high-fidelity MSCC simulation course using collaboratively developed learning goals. Fifteen learners including RO residents, senior RTT students, and a medical physics (MP) resident participated in a live, RTT-facilitated simulation. Participants completed anonymized pre- and post-simulation standard interdisciplinary education perception (IEP) scales and a course evaluation assessing educational outcomes. Standard IEP questionnaire results showed highly favorable perceptions of respondents' own specialty and other allied specialties, with mean total pre-simulation scores of 91.76 and post-simulation scores of 94.23. The course evaluation assessed 10 learning objective domains, with significant improvements seen in self-rated post-course knowledge in 9 domains. Pre-course evaluations showed that 6/15 participants agreed or strongly agreed that they felt comfortable in their knowledge of all included domains; after course completion, 14/15 participants agreed or strongly agreed they felt comfortable in all domains. Collaboratively designed and led HFS courses are not only viable but can be an effective means of improving learning outcomes for RO residents, RTT students, and MP residents.

Ability of Anthropometric Measurements to Predict Metabolic Health among Patients in Alberta: A Cross-sectional Study in Primary Care.

Purpose: This study compared anthropometric and body fat percent (BF%) equations in relation to measures of metabolic health.Methods: BF% calculations (Bergman, Fels, and Woolcott) and anthropometric measurements were used to determine obesity among a sample of patients attending primary care in Alberta, Canada. Anthropometric variables included body mass index (BMI), waist circumference, waist:hip ratio, waist:height ratio, and calculated BF%. Metabolic Z-score was computed as the average of the individual Z-scores of triglycerides, total cholesterol, and fasting glucose and the number of standard deviations from the sample mean.Results: Five hundred and fourteen individuals were included (41.2% male, age: 53 ± 16y, BMI: 27.4 ± 5.7 kg/m2). BMI ≥ 30 kg/m2 detected the smallest number of participants (n = 137) as having obesity, while Woolcott BF% equation categorized the largest number of participants as having obesity (n = 369). No anthropometric or BF% calculation predicted metabolic Z-score in males (all p ≥ 0.05). In females, age-adjusted waist:height ratio had the highest prediction power (R2 = 0.204, p < 0.001), followed by age-adjusted waist circumference (R2 = 0.200, p < 0.001) and age-adjusted BMI (R2 = 0.178, p < 0.001).Conclusions: This study did not find evidence that BF% equations more strongly predicted metabolic Z-scores than other anthropometric values. In fact, all anthropometric and BF% variables were weakly related to metabolic health parameters, with apparent sex differences.

Nighttime compression supports improved self-management of breast cancer-related lymphedema: A multicenter randomized controlled trial.

BACKGROUND: Lymphedema is a prevalent long-term effect of breast cancer treatment associated with reduced quality of life. This study examined the efficacy of nighttime compression as a self-management strategy for women with chronic breast cancer-related lymphedema. METHODS: Th authors conducted a parallel 3-arm, multicenter, randomized trial. Women were recruited from 3 centers in Canada and randomized to group 1 (daytime compression garment alone [standard care]), group 2 (daytime compression garment plus nighttime compression bandaging), or group 3 (daytime compression garment plus the use of a nighttime compression system garment). The primary outcome was the change in excess arm volume from the baseline to 12 weeks. Participants from all groups used a nighttime compression system garment from weeks 13 to 24. RESULTS: One hundred twenty women were enrolled, 118 completed the randomized trial, and 114 completed the 24-week follow-up. The rates of adherence to nighttime compression were 95% ± 15% and 96% ± 11% in the compression bandaging and nighttime compression system groups, respectively. After the intervention, the addition of nighttime compression was found to be superior to standard care for both absolute milliliter reductions (P = .006) and percentage reductions (P = .002) in excess arm lymphedema volume. Significant within-group changes were seen for quality of life across all groups; however, no between-group differences were found (P > .05). CONCLUSIONS: The trial demonstrated a significant improvement in arm lymphedema volume from the addition of nighttime compression whether through the application of compression bandaging or through the use of a nighttime compression system garment. LAY SUMMARY: Lymphedema is swelling that occurs in the arm on the side of the surgery for breast cancer. Lymphedema occurs in approximately 21% of women. Lymphedema tends to worsen over time and can result in recurrent infections in the arm, functional impairment, and pain. Currently, treatment consists of intensive treatments to reduce the swelling followed by regular use of a compression sleeve during the day. This study examined and found a benefit from the addition of nighttime compression (whether through self-applied compression bandaging or through the use of a nighttime compression system garment) to the use of a daytime compression sleeve.

A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases.

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 (< 60 versus ≥60 years), histology (melanoma/renal cell carcinoma/sarcoma versus other), and number of metastases (one versus 2-10). In the standard arm, postoperative SRS will be delivered within 3 weeks of surgery, and all unresected metastases will receive primary SRS. In the investigational arm, enrolled patients will receive SRS of all brain metastases followed by surgery of resectable metastases within one week of SRS. In either arm, single fraction or hypofractionated SRS in three or five fractions is permitted. The primary endpoint is to assess local control at 12 months in both arms. Secondary endpoints include local control at other time points, regional/distant brain recurrence rates, leptomeningeal recurrence rates, overall survival, neurocognitive outcomes, and adverse radiation events including radiation necrosis rates in both arms. DISCUSSION: This trial addresses the unanswered question of the optimal sequencing of surgery and SRS in the management of patients with resectable brain metastases. No randomized data comparing preoperative and postoperative SRS for patients with brain metastases has been published to date. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04474925; registered on July 17, 2020. Protocol version 1.0 (January 31, 2020). SPONSOR: Alberta Health Services, Edmonton, Canada (Samir Patel, MD).