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Background: QOL can be affected by disease burden, side effects of treatment, and psychosocial effects of living with cancer. Although MZL is considered incurable, we previously found that patients diagnosed from 2002-2015 had a good QOL both at baseline (BL) and the first decade after diagnosis, regardless of treatment choice (Bommier et al., submitted). Here, we evaluate whether these findings can be extended to the 2015-2020 treatment era and a more diverse US cohort. Methods: Adults with newly diagnosed MZL from 8 academic centers were prospectively enrolled within 6 months of diagnosis from 2015-2020 in the LEO cohort (NCT02736357). Participants were actively followed for disease progression/relapse, retreatment and death. QOL was measured at BL, and at 1, 2, 3 and 5 years after diagnosis using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale (range 0-164), which consists of the FACT-General (FACT-G, range 0-104) plus a lymphoma-specific scale (range 0-60). Total FACT-G measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). We also used the Trial Outcome Index (TOI; range 0-112), which consists of FACT-G physical and functional WB plus the lymphoma-specific scale and is commonly used as an endpoint in treatment trials. All MZL patients with both BL and at least one follow-up QOL questionnaire were eligible for analysis. Patients were grouped by initial management: active surveillance (observation), local/antibiotic therapy (radiation, surgery, or anti- H. pylori therapy), or systemic therapy (chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and initial treatment groups were compared. Results: Of 384 patients, 60% were female, 91% were White, 6.6% were Black/African American, and 13% were Hispanic (all races). The median age was 64 years (range 19-94). For initial management, 28% (N=106) were observed, 31% (N=118) received local/antibiotic therapy, and 42% (N=160) received systemic therapy. Across treatment groups, there were no significant differences by age, gender, race, or performance status, while there were differences by Hispanic ethnicity (p=0.006), Ann Arbor stage (p<0.001) and MALT-IPI score (p<0.001) (Table). At BL, patients receiving systemic therapy had lower physical WB (p=0.008), emotional WB (p=0.04), functional WB (p=0.03), FACT-G total score (p=0.008), lymphoma subscale (p<0.001), FACT-Lym (p=0.001) and TOI (p<0.001) compared to observation and local/antibiotic therapy (Table). While FACT-G total scores were largely stable through 5 years after diagnosis, social/family WB declined from BL for patients initially receiving either local/antibiotic therapy (mean at 1-year -1.4, p<0.05; 2-year -2.1, p<0.05; 3-year -1.6, p<0.05; 5-year-2.9, p<0.05) or systemic therapy (mean at 2-year -1.2 , p<0.05; 3-year -1.4, p<0.05; and 5-year -1.2, p<0.05), while this was stable for observed patients. In patients receiving initial systemic therapy, there was a transient improvement in the lymphoma-specific scale (mean +1.7, p<0.05) and TOI (mean +3.7, p<0.05). Otherwise, QOL remained stable over time and global QoL (FACT-G, FACT-Lym), TOI, Lymphoma-specific scale (Figure), and the other FACT-G subscales (physical, emotional, or functional WB) did not differ by initial treatment strategy. Conclusions: In the diverse LEO cohort from the recent treatment era, we confirm our prior findings for newly diagnosed MZL patients that QOL is globally stable over the first 5 years after diagnosis; emotional WB is not associated with initial treatment type, providing evidence that being initially observed does not negatively impact emotional health; and there is a decline in social/family WB (support from friends and family, family acceptance of illness, family communication, close to partner), which supports the need to consider interventions for patients to address these unmet needs. In addition, this study extends these findings to the lymphoma-specific scale, FACT-Lym, and TOI, which all showing largely stable trends in the 5 years after diagnosis and suggest that recent MZL treatment strategies, including systemic therapies, neither impair nor improve QOL.

Background: Marginal Zone Lymphoma (MZL) is considered indolent but incurable, with a variety of initial treatment strategies including observation. Quality of life (QOL) can be affected by disease burden, side effects of treatment, and psychosocial effects of living with an incurable cancer. However, little is known about long-term QOL in patients with MZL. We investigated QOL at baseline (BL), and up to nine years after a diagnosis of MZL. Methods: Newly diagnosed MZL patients aged 18 years and older were prospectively enrolled within 9 months of diagnosis in the Iowa/Mayo Clinic Molecular Epidemiology Resource from 9/2002 - 6/2015. Pathology was reviewed by a hematopathologist. All MZL participants with both BL and at least one follow-up (FU) QOL questionnaire were eligible for this analysis. QOL was measured at BL and years 1-, 2-, 3-, 6- and 9-year FU with the Functional Assessment of Cancer Therapy-General (FACT-G) scale (range 0-108), which measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). Clinical data were abstracted according to a standard protocol and patients were systematically followed for events (progression, re-treatment, and death). Patients were grouped into initial management with active surveillance (observation), local/antibiotic therapy (including radiation, surgery, and anti- H. pylori therapy), or systemic therapy (including chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and comparisons were made according to initial treatment group. Results: Of 324 participants in the analysis, 59% were female, 98% were White and the median age was 63 years. For initial management, 36% (N=118) were observed, 30% (N=96) received local/antibiotic therapy and 34% (N=110) received systemic therapy. Across the initial treatment groups, there were no statistically significant differences by age, gender, or performance status, while there were differences for Ann Arbor Stage IV (observation 50%, local/antibiotic 27%, systemic 67%, p<0.001) and MALT-IPI score 2+ (observation 23%, local/antibiotic 18%, systemic 28%, p<0.001). At BL, mean FACT-G total score was 85.7 (SD 13.1), and physical, social/family, emotional, and functional WB scores were 20.3 (SD 4.2), 24.4 (SD 3.9), 18.9 (SD 3.5), 22.1 (SD 5.3); these scores were similar across initial treatment groups (all p>0.05). FACT-G total score was largely stable over time by treatment group (Panel 1). However, it declined at years 6 (mean -4.0, p<0.05) and 9 (mean -3.7, p<0.05) in the observation group (Panel 2), driven by a decline in functional WB, although this change was not significantly different from the other treatment groups. Further, in comparison with other treatment groups, local therapy was associated with a short-term 1-year improvement of FACT-G total score (mean +2.8, p=0.04), driven by improvements in both functional and emotional WB. For the subscales, we identified two major trends irrespective of treatment group: an overall improvement from BL of emotional WB at years 1 (mean +0.6, p<0.05), 2 (mean +0.7, p<0.05), 3 (+1.3, p<0.05), 6 (+1, p<0.05), and 9 (+1.3, p<0.05) and an overall decline of social/family WB at years 1 (mean -1.1, p<0.05), 2 (mean -1.7, p<0.05), 3 (-2.1, p<0.05), 6 (-2.7, p<0.05), and 9 (-2.2, p<0.05). There was no notable change from BL for physical or functional WB. Conclusions: This analysis is the first to provide prospective real-world QOL data on a longitudinal cohort of MZL patients with long follow-up. At BL, initial treatment was associated with stage and MALT-IPI score, but not QOL. Except for the transient 1-year QOL improvement in patients under local/antibiotic therapy, initial treatment groups had no impact on QOL over time. Irrespective of treatment group, emotional WB showed improvement over time, suggesting psychosocial adaptation by the patient, as it was found in aggressive lymphomas (Thompson et al., 2018). Further, emotional WB over time did not vary across treatment groups, suggesting that being initially observed did not lead to more emotional stress than being actively treated. Finally, decline in social/family WB (support from friends, family, family acceptance of illness, family communication, close to partner) suggests a need to consider interventions to patients and families to address these needs.

Introduction: The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past two decades, from finite duration chemoimmunotherapy (CIT) to an era of targeted agents such as Bruton Tyrosine Kinase (BTK) inhibitors, BCL2 inhibitors, and anti-CD20 monoclonal antibodies. Little is known about how initial management strategy (watch and wait [W&W] vs. treatment) at diagnosis impacts patient reported outcomes (PROs) in CLL survivors over time, particularly in light of therapeutic advances over the last decade. Methods: Newly diagnosed CLL patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER1) study between 9/1/02 and 6/30/15, and within 6 months of diagnosis in the MER Phase 2 (MER2) study between 7/1/15 and 5/1/20. PROs were measured using the Functional Assessment of Cancer Therapy-General scale (FACT-G), which generates Physical (PWB, range 0-28), Social/Family (SFWB, 0-28), Emotional (EWB, 0-24), and Functional Well-Being (FWB, 0-28) scores and a Total Score (0-108), with higher scores indicating better WB. In both cohorts, FACT-G was measured at enrollment and at years 1, 2, and 3 after diagnosis, while the timing of later assessments varied slightly by study (MER1: 6 yrs and 9 yrs; MER2: 5 years). We employed a generalized linear mixed model to evaluate change from baseline between groups with groups defined by each participant's initial management strategy (W&W vs. upfront systemic treatment). Initial management strategy was determined by the treating physician. The study was approved by the Mayo Clinic IRB. Results: A total of 722 patients were identified in MER1 and 256 patients in MER2. The median age at diagnosis was 63 years in MER1 and 66 years in MER2 (P<0.05); 66% were male in MER1 and 68% were male in MER2 (P>0.05). More patients initiated upfront systemic therapy in MER1 (n=380, 53%) than in MER2 (n=110, 43%). Other baseline clinical characteristics were similar between the cohorts ( Table 1). There was no statistical difference in the mean FACT-G total score at baseline between MER1 (85.0, SD 12.5) and MER2 (85.2, SD 12.7). In the MER1 cohort, statistically significant lower baseline QOL scores were observed in patients initiating upfront treatment compared to W&W on the FACT-G total score (P=0.002) as well as the PWB (P=0.01), EWB (P=0.03), and FWB (P=0.006) subscales. We also observed that over time, EWB and FWB scores were consistently lower amongst those treated upfront compared to W&W. Further, EWB scores steadily improved over time regardless of initial management ( Figure 1), whereas the FWB and PWB subscales were largely stable over time. Mean SFWB scores dropped amongst patients who received upfront therapy at 3 years, which then steadily improved through year 9 but did not recover back to baseline. SFWB scores were stable among W&W patients. In the MER2 cohort, no statistically significant differences in any of the baseline QOL scores were noted between the W&W vs. initial treatment groups. Despite this, we observed consistently lower mean EWB scores among patients who initiated upfront treatment compared to W&W pts over time. No other statistically significant differences in mean QOL scores over time were observed between groups. Similar to MER1, we did observe a drop in mean SFWB scores amongst patients initiating upfront therapy at 3 years of follow-up that remained decreased at year 5. Conclusion: This is the largest longitudinal study of CLL survivors that spanned over 18 years and two treatment eras. We demonstrated that in the novel treatment era, QOL metrics were similar between initial management strategies (W&W vs. treatment), suggesting that initial management had little to no impact on QOL at baseline or over time. In contrast, in the CIT era, we observed differences in QOL metrics at baseline between groups. In both treatment eras, patients with CLL who required upfront therapy demonstrated a decrease in SFWB from baseline at year 3 of follow-up, and the mean EWB scores were lowest at baseline regardless of initial management strategy (W&W vs. upfront treatment) or treatment era (CIT vs. novel agents), but steadily improved over time. These findings suggest opportunities for interventions to improve QOL in patients with CLL, and additional analyses are ongoing. Further follow-up in the era of novel agents is needed.

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.