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ABSTRACT Objective This study compared the effects of phentermine‐topiramate‐ER (mid‐dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). Methods We conducted a 12‐month, randomized, double‐blind, placebo‐controlled trial at a single tertiary academic center in the United States (June 2020–June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m 2 ) were enrolled in the DELI program, consisting of in‐person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth‐enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine‐topiramate‐ER ( n = 42) or placebo ( n = 38) in addition to the DELI. Results At 3 months, the phentermine‐topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference −6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference −9.48 kg; p < 0.001). Participants receiving phentermine‐topiramate‐ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline ( p = 0.004). Conclusions Phentermine‐topiramate‐ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. Trial Registration ClinicalTrials.gov : NCT04408586

PURPOSE Lack of race- and age-diversity in clinical trials adversely affects generalizability of trial results and equity of trial access. Research on barriers to representative accrual has focused on patient-level factors. We aimed to define site-level factors affecting the diversity of accrual to a multicenter clinical trial. METHODS Alliance 191901 (GETSET) is a national randomized controlled trial testing interventions to promote breast cancer endocrine therapy adherence, which oversamples Black women and those under age 50 years at 30% thresholds. A secondary study objective is to examine site-level factors associated with accrual of Black and younger participants. At 50% accrual to the parent study, we performed prespecified analyses of association between site characteristics (region, neighborhood racial composition, Alliance membership type, number of recent accruals to cooperative research group trials) and the proportion of Black patients and younger patients accrued. We also examined trajectories of accrual over time for race- and age-specified subgroups. RESULTS The analysis included 124 sites. Among 590 participants, 9.7% were Black, and 22.4% were age <50 years. Neither site type nor historical accrual volume was associated with Black participant recruitment. Southern sites recruited higher proportions of Black participants (19.0% v 7.3% for West, P < .001). Neighborhood racial composition was positively associated with recruitment of Black participants (16.2% at sites from highest Black composition v 1.4% in lowest, P < .01). Recruitment trajectories of Black participants were slower than target rates, whereas those among non-Black participants were faster. CONCLUSION Neighborhood composition and geographic region were predictors of proportions of Black participants accrued to A191901 sites, but site type and historical accrual volume were not. When trials must limit site selection, identifying sites based on neighborhood composition and geography may be an appropriate tool for increasing trial diversity.

Objectives To estimate the proportion and correlates of self-reported financial difficulty among patients with multiple myeloma (MM) or chronic lymphocytic leukaemia (CLL). Setting Sixty-six US community and minority oncology practices affiliated with the National Cancer Institute Community Oncology Research Programme (NCORP). Participants A total of 521 patients (=18 years) with MM or CLL consented and 416 responded to a survey (completion rate=79.8%). Respondents had a MM diagnosis (74.0%), an associate degree or higher (53.4%), were White (89.2%), insured (100%) and treated with clinician-administered drugs (68.0%). Study design Observational, theoretical model and protocol-based patient survey administered between May 2019 and June 2020. Primary and secondary outcome measures Financial difficulty was assessed using a single-item measure, the EORTC QLQC30: Has your physical condition or medical treatment caused you financial difficulties in the past year? and using an any-or-none composite measure of 22 items assessing financial difficulty, worries and the use of cost-coping strategies. Multivariable logistic regression models assessed the association of financial difficulty with diagnosis, socioeconomic and treatment characteristics. Results About 16.8% reported experiencing financial difficulty using the single-item measure and 60.3% using the composite measure. Most frequently endorsed items in the composite measure were financial worry about having to pay large medical bills related to cancer and difficulty paying medical bills. Financial difficulty using the single-item measure was associated with having MM vs CLL (adjusted OR (aOR), 0.34; 95% CI, 0.13 to 0.84; p=0.02), having insurance other than Medicare (aOR, 2.53; 95% CI, 1.37 to 4.66; p=0.003), being non-White (aOR, 2.21; 95% CI, 1.04 to 4.72; p=0.04) and having a high school education or below (aOR, 0.36; 95% CI, 0.21 to 0.64; p=0.001). Financial difficulty using the composite measure was associated with having a high school education or below (aOR, 0.62; 95% CI, 0.41 to 0.94; p=0.03). Conclusions US patients with MM and CLL report financial difficulty, especially those with low socio-economic status. Interventions are needed to mitigate patients financial difficulty. Trial registration number NCT03870633 .

Abstract Prevention trials in oncology are some of the most important cancer clinical trials that can be designed, implemented, analyzed, and interpreted. They are pivotal in the goal of stopping the development of cancer before it starts. Prevention trials are unique in that they not only have some of the same requirements and challenges as treatment trials but also have challenges that may make their design more complex. This paper aims to discuss some types of prevention trials and highlight their most common design challenges, including large sample size requirements, slow accrual rates with long accrual duration, extended follow-up periods with trial adherence issues and missing data, endpoints that require extended follow-up or have a high level of confounding, and problems with optimizing study design. This article provides real study examples and suggestions for designing prevention clinical trials while mitigating the known issues they face.

Abstract The intracluster correlation coefficient (ICC) measures the correlation of observations within clusters and is a key parameter for power and sample size calculations for cluster randomized trials (CRTs). To facilitate the design of future CRTs within the National Cancer Institute Community Oncology Research Program (NCORP), all studies from the NCORP website were reviewed to identify completed CRTs. ICCs for primary and secondary outcomes (when available) were ascertained from these trials and summarized in this article as a resource for future trial development. Although ICCs are relatively small for many outcome cluster combinations, that is not always the case, so consideration should always be given to the specific outcome of interest, trial design, and type of cluster when estimating an ICC to facilitate trial development.

Abstract Cancer care delivery research trials conducted within the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) routinely implement interventions at the practice or provider level, necessitating the use of cluster randomized controlled trials (cRCTs). The intervention delivery requires cluster-level randomization instead of participant-level, affecting sample size calculation and statistical analyses to incorporate correlation between participants within a practice. Practical challenges exist in the conduct of these cRCTs due to unique trial network infrastructures, including the possibility of unequal participant accrual totals and rates and staggered study initiation by clusters, potentially with differences between randomized arms. Execution of cRCT designs can be complex, ie, if some clusters do not accrue participants, unintended cluster-level crossover occurs, how best to identify appropriate cluster-level stratification, timing of randomization, and multilevel eligibility criteria considerations. This article shares lessons learned with potential mitigation strategies from 3 NCORP cRCTs.

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.

Abstract Purpose: Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong androgen-deprivation therapy–free survival or progression-free survival (PFS) in patients with metachronous oligometastatic castration-sensitive prostate cancer (omCSPC). Although most patients with omCSPC have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating prostate-specific membrane antigen-positive (PSMA+) extracellular vesicles (EV) and PSA in a biomarker correlative study using blood samples from three independent patient cohorts. Experimental Design: Plasma samples from 46 patients with omCSPC on the ORIOLE trial and 127 patients with omCSPC on the STOMP trial protocol treated with SABR were included in the study. Pre-SABR PSMA+EV levels (EV/mL) were measured by nanoscale flow cytometry. Kaplan–Meier curves and logistic regression models were used to determine the association of PSMA+EV and PSA levels with clinical outcomes. Results: In the pooled cohorts, the median biochemical PFS were 26.1 and 15.0 months (P = 0.005), and the median radiographic PFS were 36.0 and 25.0 months (P = 0.003) for PSMA+EV-low and -high groups, respectively. The combination of pre-SABR low levels of both PSMA+EV and PSA was associated with a lower risk of radiographic progression (HR, 0.34, 95% confidence interval, 0.18–0.58; P = 0.0002). In the ORIOLE cohort, which included both an SABR arm and an observation arm, low PSMA+EV was predictive of benefit from SABR (P = 0.012). Conclusions: PSMA+EV is a novel prognostic and predictive biomarker of radiographically occult tumor burden in omCSPC. PSMA+EV may inform clinical decisions about identifying patients who will achieve a durable benefit from consolidative SABR alone.

Abstract Patient-reported outcomes (PROs) are often collected in cancer clinical trials. Data obtained from trials with PROs are essential in evaluating participant experiences relating to symptoms, financial toxicity, or health-related quality of life. Although most features of clinical trial design, implementation, and analyses apply to trials with PROs, several considerations are unique. In this paper, we focus on specific issues such as selection of the tool, timing and frequency of assessments, and data collection methods. We discuss how the estimand framework can be used in connection with PROs, properties of common estimation methods, and handling of missing outcomes. With a plethora of literature available, we aim to summarize best practices and pragmatic approaches to the design and analysis of the studies incorporating PROs.

Objective: To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery. Background: Frailty is common in older adults. It increases the risk of poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown. Methods: Thoracic, gastrointestinal, and urologic oncological surgery practices within the National Cancer Institute Community Oncology Research Program (NCORP) were randomized 1:1:1 to usual care (UC), OPTI-Surg, or OPTI-Surg with an implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients 70 years old or above undergoing curative intent surgery were eligible. The primary outcome was 8 weeks postoperative function (kcal/wk). The key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined. Results: From July 2019 to September 2022, 325 patients were enrolled in 29 practices. One hundred ninety-nine (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ in total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function (P=0.53). UC and OPTI-Surg patients did not significantly differ in postoperative complications (25.6% UC, 35.3% OPTI-Surg, P=0.5). Conclusions: Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared with UC. Future analysis will explore practice-level factors associated with toolkit implementation and the differences between the coaching and noncoaching arms.