ACTOR: a latent Dirichlet model to compare expressed isoform proportions to a reference panel.

The relative proportion of RNA isoforms expressed for a given gene has been associated with disease states in cancer, retinal diseases, and neurological disorders. Examination of relative isoform proportions can help determine biological mechanisms, but such analyses often require a per-gene investigation of splicing patterns. Leveraging large public data sets produced by genomic consortia as a reference, one can compare splicing patterns in a data set of interest with those of a reference panel in which samples are divided into distinct groups, such as tissue of origin, or disease status. We propose A latent Dirichlet model to Compare expressed isoform proportions TO a Reference panel (ACTOR), a latent Dirichlet model with Dirichlet Multinomial observations to compare expressed isoform proportions in a data set to an independent reference panel. We use a variational Bayes procedure to estimate posterior distributions for the group membership of one or more samples. Using the Genotype-Tissue Expression project as a reference data set, we evaluate ACTOR on simulated and real RNA-seq data sets to determine tissue-type classifications of genes. ACTOR is publicly available as an R package at https://github.com/mccabes292/actor.

A prospective randomized trial of standard versus multimedia-supplemented counseling in patients undergoing endometrial cancer staging surgery.

OBJECTIVES: A patient's understanding of surgery is often limited, especially in the setting of complex oncologic procedures. The use of supplemental materials can improve patients' knowledge of their procedure and satisfaction with decision making. We sought to determine if a multimedia-supplemented approach in patients undergoing robotic endometrial cancer staging improves satisfaction with preoperative counseling. Secondary objectives were patient comprehension, physician satisfaction, and visit length. METHODS: From 2018 to 2019, patients were randomized to standard physician education (SPE) or multimedia-based education (MBE), which included watching two novel videos followed by focused physician counseling. Basic demographic information was collected. Patient satisfaction was assessed using the Client Satisfaction Questionnaire-8 (CSQ-8, a validated satisfaction survey, scored 8-32) and a global satisfaction score (GGS, 10-point scale). Physician satisfaction was assessed using a GGS. Comprehension was assessed with a study-specific 9-question survey at three time points. t-tests and linear mixed models were used to compare groups. RESULTS: Of the 75 patients included in the analysis, the majority were white (70%), 50-70 years old (72%), and had at least some college education (74%). The MBE group reported higher satisfaction on the CSQ-8 (31.69 vs 30.69, p < 0.01) and global satisfaction score (9.95 vs 9.74, p = 0.04). There was no difference in comprehension scores over time (p = 0.84) or between groups (p = 0.23). Visit lengths were significantly longer in the MBE group (90.36 vs 80.46 min, p = 0.04). CONCLUSIONS: Patients had high satisfaction and comprehension with both SPE and MBE. Multimedia education may be implemented in preoperative counseling based on provider preference and consideration should be made for further study of satisfaction, both patient and physician, and visit length after the initial implementation period.

Coronary Artery Calcifications and Cardiac Risk After Radiation Therapy for Stage III Lung Cancer.

PURPOSE: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. CONCLUSIONS: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.

A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium. METHODS: Randomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium. RESULTS: 61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition. CONCLUSION: High dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed. TRIAL REGISTRATION: Clinical Trials NCT03263442. FUNDING: Rising Tide Foundation for Clinical Cancer Research.

Feasibility and delivery of patient-reported outcomes in clinical practice among racially diverse bladder and prostate cancer patients.

OBJECTIVE: To assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time. SUBJECTS/PATIENTS AND METHODS: We recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy. Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time. RESULTS: Sixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046). CONCLUSIONS: Reported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care.