Citations

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.

The FAITH! (Fostering African-American Improvement in Total Health) Cardiovascular Health and Wellness Program is more than a decade-long community-based participatory research initiative aimed at addressing cardiovascular health disparities among African-Americans in Minnesota. Founded in 2013, the program employs a culturally tailored, community-driven approach by partnering with African-American faith communities to promote cardiovascular health through education, digital health tools, and multilevel interventions targeting the social determinants of health. Grounded in community-based participatory research principles, FAITH! prioritizes equitable academic-community partnerships, co-learning, community capacity building, and shared ownership in all aspects of research and implementation. The program’s exemplary innovations include the NIH-funded FAITH! Trial, a randomized clinical trial, testing a mobile health intervention (the FAITH! App) co-created with the African-American community, and the Techquity by FAITH! study. Techquity by FAITH! evaluates the effectiveness of a culturally relevant, community-informed mHealth intervention supported by a Digital Health Advocate network to improve overall cardiovascular health and digital health literacy. During its evolution, FAITH! has addressed emergent public health crises, including the COVID-19 pandemic, by adapting programming to provide emergency preparedness resources, health education, and vaccine outreach. Key outcomes include sustainable church-based health ministries, increased research participation, and successful translation of research into practice. The program has also contributed to research workforce development by mentoring and training diverse early-career scholars and community leaders in community-based participatory research and cardiovascular health equity research. Lessons learned highlight the transformative impact of community-based participatory research in building trust, facilitating culturally relevant dissemination, and sustaining health equity initiatives. The FAITH! model demonstrates a scalable, community-led strategy for advancing cardiovascular health in underserved populations and provides a blueprint for future initiatives aiming to reduce racial health disparities.

PURPOSE The likelihood of finding a human leukocyte antigen (HLA)–matched unrelated donor (MUD) for hematopoietic cell transplantation can be predicted using a donor search prognosis score. Patients without a MUD may use alternative donors (haploidentical related, mismatched unrelated, or umbilical cord blood). METHODS This multicenter biological assignment trial was conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1702). Eligibility criteria were broad to mirror clinical practice. The primary end point was 2-year survival from evaluability and compared between those Very Likely (>90%) and Very Unlikely (<10%) to find a MUD. All other patients, Less Likely to find a MUD, were enrolled in an observational arm. Transplant outcomes were compared for all three groups. RESULTS A total of 1,751 evaluable patients at 47 centers were Very Likely (54.7%), Less Likely (29.5%), and Very Unlikely (15.8%) to identify a MUD. Survival did not differ in univariate (hazard ratio [HR], 1.00 [95% CI, 0.82 to 1.21]; P = .98) or multivariate (HR, 1.07 [95% CI, 0.86 to 1.33]; P = .56) analyses between the Very Unlikely and Very Likely groups, measured through 2 years from the beginning of a search for a MUD or alternative donor. Of the transplanted patients (n = 1,179), MUD was used for 94% of the Very Likely, 38% of Less Likely, and 9% of Very Unlikely patients. Multivariate analyses showed no differences in relapse, treatment-related mortality, disease-free survival, and acute and chronic graft-versus-host diseases for the three search prognosis groups after transplantation. CONCLUSION Using a donor search prognosis strategy to prioritize an alternative donor for patients Very Unlikely to find a MUD resulted in survival and transplant outcomes that were not statistically different compared with those Very Likely to find a MUD.

PURPOSE Testing for germline BRCA1 and/or BRCA2 mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2–negative (HER2–) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline BRCA1 and/or BRCA2 (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited. METHODS Deidentified patient data from adults diagnosed with HER2– mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor–positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018. RESULTS Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]). CONCLUSION Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2– mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.

OBJECTIVE The principal tenet of minimally invasive neurosurgery is to limit approach-related tissue trauma, and a major assumption is that shorter incisions and smaller openings, in addition to protecting the brain, also have some perceptible benefits for the patient. This study tests the assumption of patient benefit and tries to define its significance. METHODS Procedures that fit the inclusion criteria of minimally invasive transcranial "keyhole" surgery were sought in the principal investigator’s archives. Each case was then paired with a classic procedure performed within the study time frame by the two senior authors, matched for pathology, size, location, and complexity. These pairs were then compared using a statistical tool (i.e., the Wilcoxon signed-rank test) designed for matched samples. Differences in estimated blood loss, duration of surgery, and length of hospital stay were examined. The narcotic needs during hospitalization were also examined as morphine milligram equivalent (MME). RESULTS Ninety patients were included in this study, evenly split between the minimally invasive surgery (MIS) and classic cohorts. Comparison of the 45 pairs showed no significant difference in estimated blood loss, though the operative times favored the MIS cohort significantly (mean ± SEM 310 ± 17 minutes vs 383 ± 24 minutes, p = 0.02). The length of stay was shorter for MIS, but the difference reached statistical significance only when cases with complications were excluded. The most important finding was that significantly less narcotic was needed during hospitalization in the MIS cohort (83 ± 15 MME vs 257 ± 47 MME). CONCLUSIONS The large difference in narcotic needs points to enhanced recovery from MIS techniques. While the difference in operative time did not lead to significantly shorter hospital stays, data suggest that minimally invasive technique may benefit the patient during recovery. This inspires further investigations to define the potentially positive impact on hospital and healthcare systems.

e12502 Background: In March 2022, the United States Food and Drug Administration approved olaparib as adjuvant treatment (tx) for patients with germline BRCA1/2 pathogenic or likely pathogenic variants and HER2-negative eBC at high risk of recurrence who have been treated with neo-adjuvant or adjuvant chemotherapy. Approval was based on results from the OlympiA trial which demonstrated a significant increase in invasive-disease free survival [hazard ratio, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001] and overall survival [hazard ratio, 0.68; 99% CI, 0.47-0.97; P=0.009] with olaparib vs placebo. To date, there has been limited real-world data for eBC on olaparib utilization patterns and characteristics of olaparib users. Methods: This retrospective analysis using closed claims from KHM included adult pts with HER2-negative eBC receiving first olaparib prescription (index date) from March 11, 2022 to Nov 30, 2023. Continuous medical and pharmacy enrollment of ≥12 months pre-index and ≥30 days post-index was required. Pt characteristics were summarized descriptively, and Kaplan-Meier (KM) analysis was conducted for time-to-event utilization outcomes. Outcomes were evaluated for pts overall and stratified by hormone receptor (HR) status and race/ethnicity. Non-persistence was defined as minimum of 2 consecutive missed prescription fills. Medication possession ratio (MPR) was calculated as the sum of days of olaparib supply, divided by the total number of days from olaparib initiation to the last claim plus days of olaparib supply in the last claim. Results: We identified 176 pts with HER2-negative eBC who received olaparib. Median age was 44 years, and the majority (66.5%) had commercial insurance. KM-calculated median persistence on olaparib was 11 months (95% CI: 9.2-12.2); overall, adherence measured by MPR ≥80% was 74.2% by month 6 of olaparib use; adherence is higher among Caucasian than non-Caucasian pts (Table). While the majority of HR+/HER2- pts (77.9%, N=53/68) took olaparib concurrently with other (88.7% hormonal) adjuvant tx, most TNBC pts (70.4%, N=76/108) received olaparib alone. Among TNBC pts who took olaparib concurrently with other adjuvant tx (N=32/108), 81.3% received olaparib combined with immunotherapy. Conclusions: Our study provides evidence of favorable persistence and adherence to adjuvant olaparib in a real-world setting and data on utilization of olaparib concurrently with other tx. Recent approvals of other adjuvant tx for HER2- high-risk eBC warrants further research on the efficacy of olaparib used alone, versus olaparib combined or sequenced with other treatments. Olaparib MPR ≥80% by follow-up time points between Caucasians and non-Caucasians. Cohorts 30 days 60 days 180 days 365 days Caucasians (N=70) 92.5% 71.7% 80.6% 90.9% Non-Caucasians(N=55) 88.7% 66.7% 70.0% 50.0%

Background: Cognitive change is an important factor in understanding dementia. Estimating effects of exposures on cognitive change requires choosing an analytical timescale, typically time on study or current age. There is limited consensus regarding timescale choice in epidemiologic cognitive aging research. Methods: Using a coordinated analytic approach in 10 cohorts of older adults, we evaluated whether estimated effects of two exposures on memory change differed depending on timescale (time on study or current age). We modeled effects of apolipoprotein-E (APOE) ε4 genotype (a time-invariant exposure) and diabetes (a potentially time-varying/acquired exposure evaluated at baseline) using mixed-effects models with linear and nonlinear time specifications for both timescales. Results: Among APOE ε4 carriers, model-estimated memory scores at baseline (time on study timescale) or at each cohort’s median baseline age (current age timescale) were lower, and the average rate of decline was faster than among APOE ε4 noncarriers. Model-estimated memory scores at baseline or at median baseline age were generally similar across baseline diabetes status, with variability across cohorts in the diabetes-memory change association. In some cohorts, trends in diabetes-memory change associations differed in direction across timescales. Conclusions: Timescale was largely inconsequential for estimated effects of APOE genotype, but yielded differences in estimated diabetes effects, raising questions about the appropriate scale. The current age scale may be problematic because diabetes was measured heterogeneously in age across individuals, a common issue in aging cohorts. Our work demonstrates approaches to evaluate alternative timescales, including in multicohort analyses, and highlights potential implications for estimated exposure effects on cognitive change.

Abstract Purpose: The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings. Experimental Design: In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types. Results: Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P &lt; 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44–0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity. Conclusions: Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.