NCI Community Oncology Research Program Research Articles

CTNI-24. WF-1801: SINGLE ARM PILOT STUDY OF RAMIPRIL FOR PREVENTION OF RADIATION-INDUCED COGNITIVE DECLINE IN GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIOTHERAPY

Abstract BACKGROUND Patients with glioblastoma (GBM) experience cognitive decline after chemoradiation. Radiation therapy (RT) to the brain creates chronic inflammation believed to contribute to cognitive decline. Ramipril counteracts neuroinflammatory changes in pre-clinical models when given during RT. METHODS This prospective single arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base assessed feasibility, tolerability, and potential efficacy of using ramipril in patients with GBM. Eligibility and treatment paradigms mirrored NRG/RTOG 0825 allowing for outcomes from the placebo arm to be used for comparison. Participants took ramipril during 6 weeks of chemoradiation with temozolomide and for 3 months after RT. Patients completed cognitive testing (HVLT-R, TMT, and COWA) and patient-reported outcomes at baseline, RT completion, and 1 and 4 months after RT. Co-primary endpoints were retention rate (compliance with 75% doses and completion of cognitive testing) and change in cognitive composite score 1 month after RT. RESULTS 75 participants were accrued between 3/25/2019 and 11/14/23: 65% were male, 89% White, median age 63 years. The NRG/RTOG 0825 placebo cohort (n=247) was younger (median 57, p<0.0001) with more White participants (95%, p=0.04). The overall retention rate in WF-1801 was 48% (one-sided 95% CI: 38%-100%); 61% completed >=75% of doses; 57% completed cognitive testing at all time points. The median (range) change in cognitive composite score 1 month after RT was 0.01 (-82.6, 13.0) reflecting an improvement from baseline. However, this was not significantly different from the NRG/RTOG 0825 placebo group median of 0.10 (-48.2, 8.6); p=0.49. CONCLUSION The overall retention rate fell short of our pre-specified endpoint of > 65%; however, medication compliance was high and well-tolerated in retained patients. Future investigations could identify patient subsets who may benefit more from concurrent ramipril. WF-1801 (NCT03475186) funded by UG1CA189824. NRG/RTOG-0825 (NCT00884741) funded by U10CA180868 and U10CA021661.

Testing the effectiveness of a virtual sustained tobacco treatment: Initial reporting of findings from the EAQ171CD randomized clinical trial conducted by ECOG-ACRIN within the NCI Community Oncology Research Program (NCORP).

376 Background: Persistent smoking among patients diagnosed with cancer is associated with adverse clinical outcomes, yet clinical guidelines for tobacco use interventions have not been integrated into community oncology settings. We conducted a trial of a virtual sustained tobacco treatment intervention across community oncology settings nationally. Methods: This randomized clinical trial, conducted through ECOG-ACRIN, compared the effectiveness of sustained telehealth counseling plus medication (Virtual Sustained Treatment; VST) to referral to the NCI quitline (Enhanced Usual Care; EUC) in assisting recently diagnosed cancer patients to quit smoking. The VST group received up to 11 synchronous telehealth sessions (4 weekly, 4 biweekly, 3 monthly) of motivational counseling and up to 12-weeks of free NRT patch and/or lozenge. Eligibility criteria included adults within 4 months of a new cancer diagnosis, cigarette use in the past 30 days, English/Spanish speaking, and access to an internet-enabled device. The primary outcome is 6-month self-reported 7-day point prevalence abstinence. Results: From 08/2019 to 12/2022, 306 patients were randomized from 30 NCORP Community Sites and 7 Minority/Underserved NCORP sites. Participants were 70.9% female; 86.3% White; 8.8% Black; and 2.9% Hispanic; median age 57 years; 25.5% completed a college degree; 50.3% stages 0-2; 46.4% had non-smoking-related tumors. Median cigarettes per day was 12.0; 72.2% (n = 221/306) smoked within 30 minutes of waking; 49.0% (n = 150/306) were in precontemplation/contemplation stage of readiness to quit. 73.8% (222/301) and 72.2% (210/291) completed the 3 and 6-month outcome assessments. Classifying missing smoking status as smokers, 6-month abstinence rates were 28.4% (42/148) in the VST group vs. 14.7% (21/143) in the EUC group (p<.005). For secondary outcomes, there were no significant differences when adjusted for multiple comparisons (α = 0.0025); abstinence at 3-months was 24.7% (38/154) in the VST group vs. 15.0% (22/147) in the EUC group (p=.035); continuous abstinence at 6 months was 18.9% (28/148) in the VST vs 9.1% (13/143) in the EUC (p=.016). 80.8% (126/156) of individuals randomized to VST participated in counseling; of those, 59.5% (75/126) completed at least 6 sessions, 46.0% (58/126) completed at least one monthly booster session, and 85.7% (108/126) were dispensed 4 weeks of NRT. Conclusions: Among recently diagnosed cancer patients, sustained remotely delivered telehealth counseling and free NRT produced a significantly higher 6-month quit rate than a quitline referral. Findings support adopting a policy of widespread sustained tobacco treatment and implementation of tobacco treatment into community oncology care settings nationwide. Clinical trial information: NCT03808818 .

A nationwide double-blind phase III randomized clinical trial (RCT) of olanzapine vs. prochlorperazine for the treatment of refractory nausea in patients receiving moderately or highly emetogenic chemotherapy among NCI Community Oncology Research Program (NCORP) practices.

185 Background: Despite advances in antiemetics given during chemotherapy, nausea remains a clinically significant issue and greatly impairs quality of life (QOL). Current ASCO guidelines recommend olanzapine or prochlorperazine for refractory chemotherapy-induced nausea. However, there is a lack of direct empirical comparisons to establish their relative efficacy. Methods: The URCC NCORP Research Base and 21 NCORP practices enrolled 1,363 chemotherapy-naïve patients with breast cancer starting a high/moderate emetogenic chemotherapy regimen to this Phase III RCT (NCT03367572). Antiemetics were prescribed per ASCO guidelines. Screening occurred during Cycle 1, followed by randomization for Cycle 2. Those with ≥ moderate nausea (≥3 on a 1-7 scale) in Cycle 1 and willing to continue were randomized (1:1:1 ratio) into 3 arms (n=310): 1) ASCO regimen plus olanzapine (OLZ), 2) ASCO regimen plus prochlorperazine (PC), or 3) ASCO regimen plus placebo. Nausea was evaluated using a four-day home diary (4x daily), with the primary outcomes being changes in average (avg) and maximum (max) nausea. FACT-G measured QOL. Intent-to-treat primary analyses (ANOVA and Cohen’s Δ effect size) evaluated whether OLZ or PC improved nausea, testing between-arm differences in nausea change from Cycle 1 to 2 compared to placebo at a p=0.025 significance level corrected for 3 arms. Results: The median age was 50.7y, with 80.7% White/12.3% Black/5.8% Asian/4.2% Latino, and evenly distributed across groups. The change in avg nausea score was statistically significant for the OLZ (avg change = −1.07: Cohen’s Δ = 0.49) and PC arms (avg change = −0.94: Cohen’s Δ = 0.38) compared to the placebo (avg change = −0.50; p <0.001 vs OLZ, p = 0.01 vs PC). Similar but larger changes were noted for change in max nausea score in the OLZ (max change = −2.57: Cohen’s Δ = 0.86) and PC arms (max change = −2.01: Cohen’s Δ = 0.47) against the placebo (max change = −1.30; p <0.001 vs OLZ, p <0.01 vs PC). The OLZ arm had a clinically significant change in overall QOL from pre-chemo to Cycle 2 vs placebo (FACT-G mean difference = +4.91; p = 0.006) but the PC arm vs placebo did not (FACT-G mean difference = −0.87; p = 0.61). OLZ exhibited superiority over PC in terms of changes in max nausea (mean difference = −0.56; p = 0.023) and QOL (FACT-G mean difference = +5.80; p = 0.006), but not for avg nausea (mean difference = −0.13; p = 0.418). Conclusions: OLZ and PC, when added to ASCO guidelines, each significantly reduces refractory nausea. OLZ demonstrates superior max nausea control with clinically and statistically significant improvements in QOL. This study fills the gap in empirical comparisons and solidifies OLZ's position as a promising intervention for refractory nausea. Clinical trial information: NCT03367572 .

Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of a Presurgical Toolkit (OPTI-Surg)-Final Results of a Phase III Cluster Randomized Trial (Alliance A231601CD).

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. 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. 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. 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). 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.

Financial needs and opioid use among head and neck cancer (HNC) survivors: Baseline findings from the HN-STAR trial (WF-1805CD).

365 Background: HNC survivors often experience post-treatment pain. Given known disparities in pain management and opioid use in the non-cancer population, we explored sociodemographic predictors of opioid use in HNC survivors enrolled in the HN-STAR trial (NCT04208490, funding: American Cancer Society and UG1CA189824). Methods: Survivors of HNC (stages I-III) who completed therapy 6-24 months prior and had no evidence of disease were enrolled throughout the NCI Community Oncology Research Program (NCORP). Survivors were randomized to a clinical informatics intervention or usual care. Baseline surveys elicited recent prescription opioid use in the prior week (yes/no). Blinded to arm assignment, we conducted bivariate analyses of recent opioid use and the following sociodemographic predictors: age, gender, marital status, race and ethnicity (non-white/Latinx vs all others), highest level of education, and being able to meet daily financial needs in the prior 4 weeks. We conducted stepwise multivariable logistic regression to evaluate the association of these factors on opioid use. Results: Among 254 survivors (mean age 63, 74% male, 25% non-white/non-Latinx, 13% reporting financial need) at 25 oncology practices, 14% (n=35) reported recent opioid use. In bivariate analyses, survivors who reported financial needs were more likely to have used opioids (odds ratio [OR] 4.35, 95% confidence interval [CI] 1.85-10.20, p<.001). In stepwise multivariable analyses, only having financial needs remained in the final model (Table). Conclusions: In a national sample of post-treatment HNC survivors during a subacute survivorship period (6-24 months after treatment completion), 1 in 7 survivors reported using opioids in the past week – more than twice the annual rate of opioid receipt in the general adult population. Several demographic factors related to opioid use were examined and not associated with recent opioid use among HNC survivors. Findings suggest that financial concerns may be a barrier to non-narcotic pain management (e.g., cognitive behavioral approaches, physical therapy) – or simply that unmet financial needs are associated with lower quality of pain management. Attention should focus on equitable pain management in this population. Clinical trial information: NCT04208490 . Predictors of opioid use in past week. Bivariate Models Estimate (standard error) p-value Age (years) -.01 (.02) .52 OR (95% CI) p-value Female .98 (.41, 2.16) .97 Latinx/non-white .71 (.27, 1.63) .45 Married .56 (.27, 1.18) .13 Some college or more .62 (.30, 1.30) .20 Had financial needs 4.35 (1.85,10.20) <.001 Final model OR (95% CI) p-value Had financial needs 4.35 (1.85,10.20) <.001

Baseline characteristics of parents enrolled in ACCL20N1CD: Financial distress during treatment for pediatric acute lymphoblastic leukemia (ALL) in the US.

220 Background: Personal costs of childhood cancer can contribute to disparities in health outcomes. The purpose of ACCL20N1CD is to examine trajectories of parental costs and the associated financial distress, cost coping behaviors, and household material hardships (HMH) during treatment for pediatric ALL. Objective is to report baseline characteristics of the parents and their households. Methods: The study used a prospective cohort design with repeated measures. Setting was Children’s Oncology Group (COG) practices at National Cancer Institute Community Oncology Research Program (NCORP) institutions. Parents who use English or Spanish, and have children newly diagnosed with ALL treated at COG NCORP practices were eligible. Parents were asked to complete surveys at 3 time points, including baseline (T1; during induction and <7 days after planned induction remission evaluation). Surveys included items about (a) parent socio‐economic status, financial distress measured by 8-item Personal Wellness Scale (PFWS), and cost coping behaviors, and (b) HMH. Factors related to high PFWS scores were evaluated by logistic regression. Results: Of 104 evaluable parents, most were female (83.7%), white (65.4%), non-Hispanic (48.1%), partnered (79.8%), > high school diploma (93.3%), used English (84.6%), worked full (48.1%) or part (5.8%) time, and paid for their child’s care with public insurance (57.7%). Median household income=$50,000 (Inter-Quartile Range/IQR 20,000-100,000) for 4 (IQR 4-5) people. Not including wages lost due to caregiving, out of pocket payments for medical care + other ALL-related costs in the prior month >15% of monthly income for 51.9% of households, which is considered financially catastrophic. 24.0% of households lacked food stability; 21% had housing insecurity. Conclusions: At baseline, sizeable proportions of parents exhibit high out of pocket costs, high financial distress level, and multiple cost coping behaviors with implications for future health and individual and household quality of life.

Exploring the reliability and validity of clinically-relevant outcome measures for chemotherapy-induced peripheral neuropathy.

To explore the reliability and validity of clinically-relevant outcome measures for balance (i.e., The Short Physical Performance Battery [SPPB] - Balance Subscale) and sensation (i.e., monofilament threshold testing) for use in clinical trials of chemotherapy-induced peripheral neuropathy (CIPN). Adult, post-treatment cancer survivors (N = 142) who had reported ≥ 4/10 CIPN symptom severity following neurotoxic chemotherapy were recruited from six National Cancer Institute Community Oncology Research Program (NCORP) sites associated with the University of Rochester Cancer Center NCORP Research Base. Participants completed the monofilament threshold test at the screening and baseline time points (i.e., one week apart), while the Quality of Life Questionnaire-CIPN20, Treatment-Induced Neuropathy Assessment Scale, and SPPB - Balance Subscale were completed at baseline. Test-retest reliability of the monofilament threshold testing scores was assessed using the Intraclass Correlation Coefficient (ICC). The convergent validity among monofilament threshold testing, SPPB - Balance Subscale, and CIPN patient-reported outcome (PRO) scores at baseline was assessed using Spearman's correlation. Ceiling effects were observed for SPPB-Balance Subscale scores as 113 (79.6%) respondents reported the highest score. Agreement between the screening and baseline monofilament threshold testing scores was moderate (ICC = 0.65). Monofilament threshold testing (rs Range: 0.14 - 0.21) and SPPB Balance Subscale scores (rs Range: -0.36 - -0.22) showed largely low correlations with all PRO measures. Monofilament threshold testing demonstrated moderate test-retest reliability, but low convergent validity with CIPN PROs, while the SPPB - Balance Subscale demonstrated low convergent validity with CIPN PROs and ceiling effects (i.e., highest possible score) among post-treatment cancer survivors with CIPN. Future research is needed to identify promising measures of balance and sensation loss for use in clinical trials that complement CIPN PROs to aid in the identification of clinically relevant treatments for CIPN. NCT04367490 [April 29, 2020].

Self-Reported Financial Difficulties Among Patients with Multiple Myeloma and Chronic Lymphocytic Leukemia Treated at U.S. Community Oncology Clinics (Alliance A231602CD).

To estimate the proportion and correlates of self-reported financial difficulty among patients with multiple myeloma (MM) or chronic lymphocytic leukemia (CLL). 23 U.S. community and minority oncology practice sites affiliated with the National Cancer Institute Community Oncology Research Program (NCORP). 521 patients (≥18 years) with MM or CLL were 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%). Observational, prospective, protocol-based survey administered in 2019-2020. Financial difficulty was assessed using a single-item standard 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 between financial difficulty, diagnosis, and socioeconomic and treatment characteristics. 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 versus CLL (adjusted odds ratio [aOR], 0.34; 95% CI, 0.13-0.84; P=.02), having insurance other than Medicare (aOR, 2.53; 95% CI, 1.37-4.66; P=.003), being non-White (aOR, 2.21; 95% CI, 1.04-4.72; P=.04), and having a high school education or below (aOR, 0.36; 95% CI, 0.21-0.64; P=.001). Financial difficulty using the composite measure was associated with having a high school education or below (aOR, 0.62; 95% CI, 0.41-0.94; P=.03). U.S. patients with blood cancer report financial difficulty, especially those with low socio-economic status. Evidence-based and targeted interventions are needed.

Financial Hardship Among Patients With Early-Stage Colorectal Cancer

The degree of cancer patients' financial hardship is dynamic and can change over time. To assess longitudinal changes in financial hardship among patients with early-stage colorectal cancer. In this prospective longitudinal cohort study, English-speaking adult patients with a new diagnosis of stage I to III colorectal cancer being treated with curative intent at National Cancer Institute (NCI) Community Oncology Research Program (NCORP) practices between May 2018 and July 2020 and who had not started chemotherapy and/or radiation were included. Data analysis was conducted from March to December 2023. Patients completed surveys at baseline as well as at 3, 6, 12, and 24 months after enrollment. Cost-related care nonadherence and material hardship, as adopted by Medical Expenditure Panel Survey, were measured. Factors associated with financial hardship were assessed using longitudinal multivariable logistic regression models with time interaction. A total of 451 patients completed baseline questions, with 217 (48.1%) completing the 24-month follow-up. Mean (SD) age was 61.0 (12.0) years (210 [46.6%] female; 33 [7.3%] Black, 380 [84.3%] White, and 33 [7.3%] American Indian or Alaska Native, Asian, multiracial, or Native Hawaiian or Other Pacific Islander individuals or those who did not report race or who had unknown race). Among 217 patients with data at baseline and 24 months, 19 (8.8%) reported cost-related care nonadherence at baseline vs 20 (9.2%) at 24 months (P = .84), and 125 (57.6%) reported material hardship at baseline vs 76 (35.0%) at 24 months (P < .001). In multivariable analysis, lower financial worry (odds ratio [OR], 0.90; 95% CI, 0.87-0.93), higher education (OR, 0.34; 95% CI, 0.15-0.77), and older age (OR, 0.94; 95% CI, 0.91-0.98) were associated with lower nonadherence. Receipt of chemotherapy was associated with higher material hardship (OR, 2.68; 95% CI, 1.15-6.29), while lower financial worry was associated with lower material hardship (OR, 0.83; 95% CI, 0.80-0.96). Over 24 months, female sex was associated with lower nonadherence (OR, 0.90; 95% CI, 0.85-0.96), while higher education was associated with higher nonadherence (OR, 1.09; 95% CI, 1.03-1.17). Being employed was associated with lower material hardship (OR, 0.85; 95% CI, 0.78-0.93), while receipt of care at safety-net hospitals was associated with higher hardship (OR, 1.09; 95% CI, 1.01-1.17). In patients with early-stage colorectal cancer, material hardship was more common than cost-related cancer care nonadherence and decreased over time, while nonadherence remained unchanged. Early and longitudinal financial screening and referral to intervention are recommended to mitigate financial hardship.

Recruitment of informal caregivers into community oncology research studies: results from the 2022 Landscape Assessment.

Understanding the experiences of community oncology practices in recruiting informal (unpaid/family) caregivers into research studies can inform strategies to improve caregiver enrollment. We used data from the 2022 National Cancer Institute Community Oncology Research Program (NCORP) Landscape Assessment to describe the experience of recruiting informal caregivers for research studies in community oncology practices. Among 258 practice groups, only one-third (30%, 78/258) reported prior experience recruiting informal caregivers for research studies. In multivariable logistic analyses, having a greater number of oncology providers (increase per 10 providers, adjusted odds ratio [AOR] 1.16, 95% CI 1.03-1.31) and having advanced practice providers (APPs) involved in research (AOR 2.17, 95% CI 1.05-4.48) were significantly associated with prior experience recruiting caregivers. In conclusion, many community oncology practices lack caregiver recruitment experience and may benefit from education, integration of APPs/caregiver stakeholders in research infrastructure, and/or other strategies to improve caregiver recruitment.

The National Cancer Institute Clinical Trials Planning Meeting to Address Gaps in Observational and Intervention Trials for Cancer-Related Cognitive Impairment.

Cancer-related cognitive impairment (CRCI) is a broad term encompassing subtle cognitive problems to more severe impairment. CRCI severity is influenced by host, disease, and treatment factors and affects patients prior to, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a Clinical Trial Planning Meeting (CTPM) to review the state of the science on CRCI and to develop both Phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system (CNS) disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of CRCI, members of the SxQOL SC, patient advocates, representatives from all seven NCI Community Oncology Research Program (NCORP) Research Bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacologic and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three CTPM working groups (longitudinal studies and pharmacologic and behavioral intervention trials) convened for one year to discuss and report on top priorities and to design studies. The CTPM experts concluded sufficient data exist to advance Phase II/Phase III trials utilizing selected pharmacologic and behavioral interventions for the treatment of CRCI in the non-CNS setting with recommendations included herein.

Changes in S100 calcium-binding protein β (S100β) and cognitive function from pre- to post-chemotherapy among women with breast cancer

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

The impact of non- and anthracycline-based chemotherapy on fatigue in breast cancer survivors: results from WF-97415

PurposeTo examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors.MethodsThis study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables.ResultsAmong 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point.ConclusionWomen with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

If you build it, they will come: Success of the EROS (Engendering Reproductive Health Within Oncologic Survivorship)—ECOG-ACRIN E1Q11 in recruitment of minority patients.

11124 Background: The average recruitment of minority subjects in oncology trials is 4%. The ECOG-ACRIN EROS trial was designed to be inclusive of minority subjects by inviting Minority/Underserved NCI Community Oncology Research Program (MU-NCORP) sites first, with remaining sites fulfilled by inviting NCORP sites. Our objective is to examine if the EROS study recruited more than 4% minority patients, and if MU-NCORP sites provided higher rates of minority recruitment than NCORP sites. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. Intervention included RH didactics and decision aids. With respect to self-reported minority status, patients were classified into one of two categories, White and non-Hispanic/Latino or minority (non-White or Hispanic/Latino). Chi-square tests were used to evaluate distribution difference between groups and binomial tests were used for testing proportions against reference points. Results: Of the 434 patients enrolled to the trial, MU-NCORP sites recruited 266/434 (61.3%) and NCORP sites 168/434 (38.7%) patients. Among all enrolled patients, 422 patients’ race/ethnicity status could be classified. 202/422 (47.9%) self-reported as Hispanic/Latino or non-White (p&lt;.0001 0.48 against 0.04). In MU-NCORP (174/258) 67.4% and NCORP sites (28/164) 17.1% were of minority status. (p &lt; .0001). Conclusions: The EROS trial was designed with minority inclusion for generalizability of results. Prioritization to include MU-NCORP sites in the EROS trial did result in substantially increased minority recruitment, with the overall minority recruitment rate above usual cancer trials. Such strategy may be followed to increase minority recruitment to oncology trials.

EROS: Engendering reproductive health within oncologic survivorship—ECOG-ACRIN E1Q11 paradoxical provision of reproductive health.

11123 Background: For the 10% of women diagnosed with cancer in the reproductive age, reproductive health (RH) is a critical component of oncologic survivorship. RH includes oncocontraception (OC), oncofertility (OF) and sexuality. Guidelines segregate these components resulting in fragmented reproductive health care management. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. Intervention included RH didactics and decision aids. Childbearing interest was dichotomous, not completed childbearing (including either pregnant or future childbearing interest) or completed childbearing. The objective of this study is to determine provision of OC and OF referral by providers at the baseline visit based on patient’s self-reported childbearing interest at study entry. Chi-square tests were used to compare distribution differences in the referral status (receipt: yes vs. no) between treatment arms. Results: The EROS study enrolled 420 subjects. Of the 63.6% (267/420) completed childbearing, 62.4% (58/93) in the intervention arm and 40.2% (70/174) in the non-intervention arm received an OC referral (p=0.0006), whereas 98.9% (92/93) in the intervention arm and 93.7% (163/174) in the non-intervention arm received an OF referral (p=0.0487). Of the 36.4% (153/420) not completed childbearing, 48.3% (28/58) in the intervention arm and 33.72% (32/95) in the non-intervention arm received an OC referral (p=0.0729), while 77.6% (45/58) in the intervention arm and 70.5% (67/95) in the non-intervention arm received an OF referral (p=0.3388). Conclusions: While the intervention increased the rates of provision of oncocontraception and oncofertility for patients with completed childbearing, our study shows provision of oncofertility referrals at a markedly higher rate than oncontraception. Referral patterns were inconsistent with patient need particularly in completed (receiving OF referral) or delayed childbearing (not receiving OC referral) interest of the patient. The bias favoring oncofertility referral may reflect oncology guidelines emphasizing this aspect of reproductive health despite comprehensive needs of patient.

Beyond the “teachable moment”: Smoking cessation during cancer treatment remains challenging despite high motivation to quit.

e24141 Background: Continued smoking throughout cancer treatment, including surgery, is associated with treatment-related complications and a higher total symptom burden during treatment. This can lead to interruptions and delays in therapy that can compromise treatment efficacy and survival. Approximately 1 in 3 patients smoke at or around time of cancer diagnosis. Despite this “teachable moment” for smoking cessation, at least half of patients with cancer are unsuccessful in their attempts, and relapse rates for post-surgical cancer patients are high. Better understanding of quit motivation among these patients can help guide tobacco treatment interventions in the post-operative and adjuvant treatment time periods. Methods: This is an analysis of a longitudinal nationwide multicenter study of 1003 patients through the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) that assessed treatment type, treatment-related symptoms, smoking status, and motivation to quit smoking for patients with a new diagnosis of cancer. Patients supplied demographic and clinical information at enrollment with assessments at two weeks pre- adjuvant treatment, post adjuvant treatment, and 6 months. Chi-square, multinomial logistic regression, and ANOVA were used to analyze the difference between smokers and nonsmokers, and those with previous surgical treatment. Results: The majority of patients had surgery as part of their cancer treatment (n = 718, 71.6%). Of these (n = 222, 30.9%) had a diagnosis of a tobacco-associated cancer, which was associated with smoking status at pre-treatment (p &lt; 0.05). For those with previous surgery, n = 90 (68.7%, p &lt; 0.001) were current smokers before starting adjuvant treatment. Post-surgical patients who smoke had both higher total symptom burden ( M= 23.7 vs M= 17.0; p &lt; 0.05) and higher symptom severity ( M =1.97 vs M= 1.42; p &lt; 0.001) pre-adjuvant treatment and at 6 month follow up [( M =31.3 vs M= 22.2; p &lt; 0.05);( M= 2.6 vs M= 1.8; p &lt; 0.05)] compared to post-surgical patients who were not smokers. Motivation to quit was sustained among current smokers between the pre- and post- adjuvant treatment periods (p &lt; 0.001), as well as for those that had previous surgery (p &lt; 0.05). Despite motivation to quit among 64.4% of current smokers with previous surgery, 15.4% reported being able to quit by post-adjuvant treatment with 50% relapsing to smoking at 6-month follow up. Conclusions: For patients that continue to smoke after surgical treatment, cessation rates are much lower than motivation to quit with high rates of relapse. Early intervention around the time of surgery presents an ideal opportunity to optimize the “teachable moment” by providing longitudinal tobacco treatment as part of cancer care to improve treatment-related symptoms, as well as overall survival.

EROS: Engendering reproductive health within oncologic survivorship—ECOG-ACRIN E1Q11 assessing discrepancy in clinician-patient importance of sexuality over 2 years post-cancer diagnosis.

e23197 Background: Cancer diagnosis and therapeutic interventions are associated with altered reproductive health including sexuality. Despite pertinence to quality of life, cancer management frequently precludes periodic assessments of sexual health. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. We report on an embedded observational study pertaining to oncosexuality. Perceived importance of patient’s sexuality maintenance was assessed for clinicians and patients on a 10-point Likert scale (1 = Not important; 10 = Extremely important). Mean and standard deviation were computed for value discrepancy (pairwise clinician-patient differential) by arm assignment and timepoint (baseline, 3-, 6-, 12- and 24-months). One-sample t-test was conducted with Bonferroni’s adjustment to evaluate cell mean of the value discrepancy against zero (α = 0.02). A mixed effect model analyzed intervention effect on value discrepancy over time, adjusting for baseline covariates (α = 0.05). Results: Mean patient importance rating within the intervention arm ranged from 8.39 (SD = 2.39) at baseline to 7.84 (SD = 2.86) at 24-month assessment; paired clinician value varied from 8.17 (SD = 2.57) to 7.77 (SD = 2.92), respectively. Within non-intervention arm, mean patient importance rating varied from 8.23 (SD = 1.95) at baseline to 8.68 (SD = 1.67) at 24-month assessment; paired clinician value ranged from 7.93 (SD = 1.86) to 8.15 (SD = 1.70). Mean clinician-patient value differentials with respect to arm assignment and timepoint were not significantly different from zero. A significant arm-by-timepoint interaction effect was noted (p = 0.0417). Post-hoc simple main effect analysis exhibited no intervention effect at any assessment timepoint. Conclusions: Data indicate high concordance of sexuality importance within oncologic clinicians and patients over the 2 years. Findings necessitate investigation to ensure management of sexual health matches level of importance to the cancer survivor. Clinical trial information: NCT01806129 .

Clinical Practice Guideline-Inconsistent Management of Fertility Preservation in Pediatric Cancer Patients in Community Settings: A Children's Oncology Group Study.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Sexual Orientation and Gender Identity Data Collection in Cancer Care: A Nationwide Landscape Assessment Update.

Routine collection of sexual orientation (SO) and gender identity (GI; collectively SOGI) in cancer clinics advances cancer care equity. In 2022, NCI Community Oncology Research Program (NCORP) practice groups were asked about routine collection of SOGI data in the electronic health record. The proportions of practice groups reporting collection of SO and/or GI data were calculated, and practice group characteristics were assessed for associations. Of 271 practice groups nationwide, 42% (n = 112) collect SO data, 58% (n = 157) collect GI data, and 35% (n = 96) collect both. In multivariate analyses, SO data collection was associated with practice groups having minority outreach staff (odds ratio [OR], 2.07 [95% CI, 1.12 to 3.81]; P = .02); GI data collection was associated with practice groups located in the Northeastern United States (OR, 2.08 [95% CI, 0.73 to 5.91]; P = .045), and those with a higher proportion of new patients who were White (OR, 1.02 [95% CI, 1.01 to 1.04]; P < .001). Practice groups in the South were least likely to collect SOGI data (OR, 0.49 [95% CI, 0.26 to 0.94]; P = .004). There were no statistically significant differences in SO and/or GI collection on the basis of the practice group's proportion of Medicaid/Medicare patients, number of new patients with cancer per year, or practice ownership. Slightly over one third of NCORP practice groups report routinely collecting SOGI data. There are regional differences in data collection, underscoring the need to craft targeted, region-specific interventions focused on boosting the capture and recording of SOGI data in an affirming manner.