Yost, Kathleen J.

Background: Understanding the symptoms and quality of life (QOL) over time of adults with follicular lymphoma (FL) is important for treatment decision-making and clinical management. However, there are limited population-level data on the long-term QOL of adults with FL. We aim to describe the real-world, long-term QOL of adults with newly diagnosed FL up to 5/6 years after diagnosis. Methods: We used the Mayo Clinic/Iowa Molecular Epidemiology Resource (MER) and the multi-institutional Lymphoma Epidemiology of Outcomes (LEO) to identify adults with grade 1-3A FL who completed QOL surveys at baseline and follow-up. Participants with lymphoma were prospectively enrolled within 9 months of diagnosis in the MER cohort from 2002-2015 and within 6 months of diagnosis in the multi-institutional LEO cohort study across 8 cancer centers from 2015-2020. The LEO/MER cohort studies systematically collected information on disease status, QOL, health behaviors, and functional assessment. Treatments, disease relapses, and deaths were verified by medical record review. Treating physicians determined clinical management. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G) at years 1, 2, 3, and 5/6 post-diagnosis. A higher FACT-G total score (range 0-108) indicated better QOL across 4 subscales (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being. We categorized participants based on their frontline management at time of diagnosis: “observation” (surveillance), “treatment” (systemic treatment with immunotherapy +/- chemotherapy), and “local” (radiation) groups. We employed a generalized linear mixed model to evaluate and compare the changes in QOL scores (as a continuous variable) from baseline for the observation, treatment, and local groups, adjusting for sex, race/ethnicity, age, FLIPI risk, and cohort (i.e., LEO or MER). We also evaluated QOL changes by FLIPI risk. Results: Our study included 1,544 participants with FL and QOL data. At the time of enrollment, median age was 61 years (range 19-91), 88% were non-Hispanic White, and 49% were female. Based on initial management, 529 (34%) were in the observation group, 880 (57%) were in the treatment group, and 135 (9%) were in the local group. FLIPI risk was high for 17% in the observation group, 29.3% in the treatment group, and 3% in the local group. The mean (standard deviation) baseline FACT-G total score was lowest in the treatment group with the following baseline scores: 86 (13) for the observation group, 83 (14) for the treatment group, and 88 (12) for the local group (Table 1). The observation and local groups reported a greater worsening of their baseline FACT-G total score vs the treatment group at both the 2-year (-1.2, -0.8 vs +1.8, respectively) and 5/6 year (-5.4, -6 vs. -1.6, respectively) timepoints (Figure 1). This appeared to be driven by worsened physical and functional well-being in the observation (-1.3, -2.2, respectively) and local (-0.9, -2.4, respectively) groups vs the treatment group (0, -0.3, respectively). These differences were statistically significant between the observation vs treatment groups. There were no statistically significant differences in the other subscales, i.e., social/family and emotional well-being, by frontline management. Social/family well-being decreased across all groups by 5/6 years (-2.3 in observation, -2.2 in treatment, and -3 in local, p<0.05). Regardless of FLIPI risk, the total FACT-G scores decreased within each FLIPI risk group at 5/6 years (-4.4 for low, -3.8 for intermediate, and -4.9 for high, p<0.05). This was primarily due to worsened social/family well-being (-2.4 for low, -2.2 for intermediate, and -3 for high, p<0.05) at 5/6 years. There was no statistically significant difference in QOL between FLIPI risk groups. Conclusion: This is one of the first and largest studies with real-world longitudinal QOL data for FL. Our study suggests that frontline systemic treatment initially improved QOL and resulted in a lower degree of QOL decline over time. Social/family well-being decreased over time regardless of frontline management or FLIPI risk. Further research is warranted to explore the impact of timing and specific systemic treatments on QOL, incorporate the patient/caregiver experience to address social/family well-being, and identify the clinical significance of our findings.

Abstract Background Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored. Objective Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease. Animals Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey. Methods Retrospective case-control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models. Results Five thousand forty-seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4-4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6-13.9; P < .001) for neutered males. Conclusions and Clinical Importance The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.

AbstractBackgroundSomali immigrants and refugees constitute one of the largest African ethnic groups immigrating to the United States over the past three decades with the majority resettling in the state of Minnesota. Previous studies have documented significant cancer screening disparities between the Somali population and the general population. However, little is known about cancer incidence among Somali groups living in the United States.MethodsWe determined the incidence of 18 types or sites of malignancy using ICD‐9 and ICD‐10 codes and compared them between Somali and non‐Somali populations in Olmsted County, Minnesota utilizing the Rochester Epidemiology Project medical records‐linkage infrastructure for the years 2000–2020. Poisson regression models were used to model the rates for each malignancy.ResultsThere was a higher incidence and relative risk of liver malignancies among the Somali population versus non‐Somali population, but lower relative risk and incidence of the following malignancies: breast, cervical, and melanoma. After direct age‐sex adjustment to the United States 2000 Census population, liver was the most common cancer in Somali men, while breast cancer was the most common malignancy in women.ConclusionMalignancies related to infectious agents such as viral hepatitis have a higher incidence in the Somali immigrant population of Olmsted County. There is a lower incidence of malignancies related to lifestyle factors in this Somali population. Findings of this study may help inform cancer prevention and screening strategies among Somali communities in the United States.

Abstract Background: Adherence to recommended colorectal cancer (CRC) screening among US adults is below the public health target of 80%. The multi-target stool DNA assay (mt-sDNA) is a self-administered CRC screening test that may remove barriers to adherence. To improve understanding of long-term outcomes and the real-world impact of mt-sDNA screening, Mayo Clinic and Exact Sciences Laboratories are collaborating on a prospective cohort study of CRC incidence and mortality outcomes in individuals screened with mt-sDNA. We conducted an embedded experiment to identify the optimal incentive protocol for maximizing participation while managing study costs. Methods: A subset of the opt-in cohort was randomized to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year one of recruitment, as well as the incentive experiment, are reported. Results: During year 1 of the Voyage trial, a total of 600,258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26,429 (4.4%) opted in, 14,365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2,333 were randomized to the pre-incentive arm while 2,342 were randomized to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs. 52.0% for the post-consent incentive arm (1217/2432), p<0.001). A cost reduction was observed for the pre-consent incentive group. Higher response rates were seen among older vs. younger individuals, reflecting a common pattern in healthcare-related survey research participation. Age adjusted incidence rates for CRC have been shown to vary regionally; thus, adjustment for differential response by region will be important to ensure representativeness. Conclusions: CRC incidence and mortality vary with age; thus, adjusting for differential participation by age will be important in analyses of Voyage data. Pre-consent incentive option was associated with a higher participation rate and lower costs, and will be used for the remainder of the study recruitment. Trial Registration: NCT04124406; October 11th, 2019

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-15-01.

Background. Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death. Methods. We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy. Results. Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL. Conclusions. Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.

OBJECTIVE Facial nerve function, hearing preservation, and tumor control have been the primary benchmarks used to assess vestibular schwannoma (VS) outcomes. Acknowledging the frequent discrepancy between what physicians prioritize and what patients value, there has been increasing prioritization of patient-reported outcome measures when evaluating the impact of VS diagnosis and its treatment. Motivated by reported limitations of prior instruments used to assess quality of life (QOL) in patients with VS, the authors describe the development and validation of a new disease-specific QOL measure: the Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS The content development phase comprised identification of clinically important domains and prioritization of feelings or concerns individuals with VS may have. The validation phase encompassed determining how items were grouped into domains and eliminating redundant items. Both phases leveraged data from cross-sectional and longitudinal surveys, expertise from a multidisciplinary working group, and patients with a broad range of experiences with VS (n = 42 during content development and n = 263 during validation). Domain scores from the new instrument were assessed for reliability and correlation with other measures of similar constructs. RESULTS The VSQOL Index consists of 40 items that evaluate the impact of VS diagnosis and its management on QOL, treatment satisfaction, and employment and is estimated to take 8–10 minutes to complete. Domain scores range from 0 (worst) to 100 (best) and demonstrate excellent psychometric properties, including content, construct, and convergent validity and both internal consistency (Cronbach’s alphas 0.83 to 0.91) and test-retest reliability (reliability coefficients 0.86 to 0.96). CONCLUSIONS The VSQOL Index is a valid and reliable measure that overcomes several limitations of prior instruments, including omission or underrepresentation of domains that frequently impact well-being, such as pain, cognition, satisfaction or regret surrounding treatment decisions, and occupational limitations, to comprehensively evaluate the impact of VS diagnosis or its treatment on QOL.

Objective: To compare patient-reported outcomes before and after implementation of evidence-based, procedure-specific opioid prescribing guidelines. Background: The opioid epidemic remains a significant public health issue. Many institutions have responded by reducing opioid prescribing after surgery. However, the impact of this on patient-reported outcomes remains poorly understood. Methods: Opioid-naïve adults undergoing 12 elective general surgery procedures at a single institution prospectively completed telephone surveys at median 26 days from discharge. Patients were compared before (March 2017–January 2018) and after (May 2019–November 2019) implementation of evidence-based, procedure-specific opioid prescribing guidelines. Results: A total of 603 preguideline and 138 postguideline patients met inclusion criteria and completed surveys. Overall, 60.5% of preguideline and 92.5% of postguideline prescriptions fell within recommendations (P<0.001), while refill rates were similar (4.5% vs 5.8%, P=0.50). A statistically significant drop in median morphine milligram equivalent prescribed was observed for 9 of 12 procedures (75%). No opioids were prescribed for 16.7% of patients in both cohorts (P=0.98). While 93.3% of preguideline and 87.7% of postguideline patients were very/somewhat satisfied with their pain control, the proportion of patients who were very/somewhat dissatisfied increased from 4.2% to 9.4% (P=0.039). Conclusions: Prescribing guidelines successfully reduced opioid prescribing without increased refill rates. Despite decreased prescribing overall, there was a continued reluctance to prescribe no opioids after surgery. Although most patients experienced good pain control, there remains a subset of patients whose pain is not optimally managed in the era of reduced opioid prescribing.