Cella, David

Abstract Background Electronic health record–linked portals may improve health-care quality for patients with cancer. Barriers to portal access and use undermine interventions that rely on portals to reduce cancer care disparities. This study examined portal access and persistence of portal use and associations with patient and structural factors before the implementation of 3 portal-based interventions within the Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium. Methods Portal use data were extracted from electronic health records for the 12 months preceding intervention implementation. Sociodemographic factors, mode of accessing portals (web vs mobile), and number of clinical encounters before intervention implementation were also extracted. Rurality was derived using rural-urban commuting area codes. Broadband access was estimated using the 2015-2019 American Community Survey. Multiple logistic regression models tested the associations of these factors with portal access (ever accessed or never accessed) and persistence of portal use (accessed the portal ≤20 weeks vs ≥21 weeks in the 35-week study period). Results Of 28 942 eligible patients, 10 061 (35%) never accessed the portal. Male sex, membership in a racial and ethnic minority group, rural dwelling, not working, and limited broadband access were associated with lower odds of portal access. Younger age and more clinical encounters were associated with higher odds of portal access. Of those with portal access, 25% were persistent users. Using multiple modalities for portal access, being middle-aged, and having more clinical encounters were associated with persistent portal use. Conclusion Patient and structural factors affect portal access and use and may exacerbate disparities in electronic health record–based cancer symptom surveillance and management.

PURPOSE Financial toxicity (FT) affects 20% of cancer survivors and is associated with poor clinical outcomes. No large-scale programs have been implemented to mitigate FT. We evaluated the effect of monthly FT screening as part of a larger patient-reported outcomes (PROs) digital monitoring intervention. METHODS PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomly assigned 1:1 to digital symptom monitoring (PRO practices) or usual care (control practices). Digital monitoring consisted of between-visit online or automated telephone patient surveys about symptoms, functioning, and FT (single-item screening question from Functional Assessment of Chronic Illness Therapy-COmprehensive Score for financial Toxicity) for up to 1 year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this planned secondary analysis was development or worsening of financial difficulties, assessed via the European Organisation for Research and Treatment of Cancer QLQ-C30 financial difficulties measure, at any time compared with baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. RESULTS One thousand one hundred ninety-one patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the FT screening intervention developed, or experienced worsening of, financial difficulties, compared with 39.0% treated at control practices ( P = .004). Patients and nurses interviewed stated that FT screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. CONCLUSION In this report of a secondary outcome from a randomized clinical trial, FT screening as part of routine digital patient monitoring with PROs reduced the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy.

Abstract Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the heterogeneity of these diseases has limited our understanding of these domains. The National Heart, Lung, and Blood Institute-sponsored MDS Natural History Study is a prospective cohort enrolling patients undergoing workup for suspected MDS in the setting of cytopenias. Untreated patients undergo bone marrow assessment with central histopathology review for assignment as MDS, MDS/myeloproliferative neoplasm (MPN), idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with <30% blasts, or “At-Risk.” HRQoL data are collected at enrollment, including the MDS-specific Quality of Life in Myelodysplasia Scale (QUALMS). Vulnerability is assessed with the Vulnerable Elders Survey. Baseline HRQoL scores from 449 patients with MDS, MDS/MPN, AML <30%, ICUS or At-Risk were similar among diagnoses. In MDS, HRQoL was worse for vulnerable participants (eg, mean Patent-Reported Outcomes Management Information Systems [PROMIS] Fatigue of 56.0 vs 49.5; P < .001) and those with worse prognosis (eg, mean Euroqol-5 Dimension-5 Level [EQ-5D-5L] of 73.4, 72.7, and 64.1 for low, intermediate, and high-risk disease; P = .005). Among vulnerable MDS participants, most had difficulty with prolonged physical activity (88%), such as walking a quarter mile (74%). These data suggest that cytopenias leading to MDS evaluation are associated with similar HRQoL, regardless of eventual diagnosis, but with worse HRQoL among the vulnerable. Among those with MDS, lower-risk disease was associated with better HRQoL, but the relationship was lost among the vulnerable, showing for the first time that vulnerability trumps disease risk in affecting HRQoL. This study is registered at www.clinicaltrials.gov as NCT02775383.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved ( P <0.001) on rilonacept treatment during the run‐in period. For the randomized withdrawal period, PRO scores were maintained for participants receiving rilonacept. For those receiving placebo and who experienced a recurrence, PRO scores deteriorated at the time of recurrence and then improved following rilonacept bailout. At randomized withdrawal Week 24/End of Study, scores of participants who received bailout rilonacept were similar to those of participants who had continued rilonacept. Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient‐reported health‐related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03737110.

Abstract Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute’s Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer.

Abstract Aims Heart failure (HF) is a common and morbid condition impacting multiple health domains. We previously reported the development of the PROMIS®-Plus-HF (PROMIS+HF) profile measure, including universal and HF-specific items. To facilitate use, we developed shorter, PROMIS+HF profiles intended for research and clinical use. Methods and results Candidate items were selected based on psychometric properties and symptom range coverage. HF clinicians (n = 43) rated item importance and clinical actionability. Based on these results, we developed the PROMIS+HF-27 and PROMIS+HF-10 profiles with summary scores (0–100) for overall, physical, mental, and social health. In a cross-sectional sample (n = 600), we measured internal consistency reliability (Cronbach's alpha and Spearman–Brown), test–retest reliability (intraclass coefficient; n = 100), known-groups validity via New York Heart Association (NYHA) class, and convergent validity with Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. In a longitudinal sample (n = 75), we evaluated responsiveness of baseline/follow-up scores by calculating mean differences and Cohen's d and comparing with paired t-tests. Internal consistency was good to excellent (α 0.82–0.94) for all PROMIS+HF-27 scores and acceptable to good (α/Spearman–Brown 0.60–0.85) for PROMIS+HF-10 scores. Test–retest intraclass coefficients were acceptable to excellent (0.75–0.97). Both profiles demonstrated known-groups validity for the overall and physical health summary scores based on NYHA class, and convergent validity for nearly all scores compared with KCCQ scores. In the longitudinal sample, we demonstrated responsiveness for PROMIS+HF-27 and PROMIS+HF-10 overall and physical summary scores. For the PROMIS+HF overall summary scores, a group-based increase of 7.6–8.3 points represented a small to medium change (Cohen's d = 0.40–0.42). For the PROMIS+HF physical summary scores, a group-based increase of 5.0–5.9 points represented a small to medium change (Cohen's d = 0.29–0.35). Conclusions The PROMIS+HF-27 and PROMIS+HF-10 profiles demonstrated good psychometric characteristics with evidence of responsiveness for overall and physical health. These new measures can facilitate patient-centred research and clinical care, such as improving care quality through symptom monitoring, facilitating shared decision-making, evaluating quality of care, assessing new interventions, and monitoring during the initiation and titration of guideline-directed medical therapy.

12094 Background: The Functional Assessment of Cancer Therapy patient-reported outcomes (PRO) item GP5 (“I am bothered by side effects of treatment”) estimates treatment tolerability. We aimed to extend our previous finding that GP5 predicts early aromatase inhibitor (AI) discontinuation (E1Z03, 96% White) in the racially diverse E1Z11 trial cohort. Methods: E1Z11 was coordinated by the ECOG-ACRIN NCI Community Oncology Research Program (NCORP) Research Base. Postmenopausal women initiating anastrozole per clinical care for ER+ stage I-III breast cancer with a pain score 0-3/10 and no rheumatologic comorbidities were eligible. Accrual of a racially diverse cohort of 1,000 women, including Black and Asian women, was planned. GP5 was administered prior to initiating anastrozole (trial baseline) and at 3, 6, 9 and 12 months. GP5 was scored on a 5-point Likert scale from 0 (not at all) to 4 (very much) and dichotomized as no/little treatment bother (0/1) or moderate/high treatment bother (2-4), consistent with previous analyses. A univariate Cox proportional hazards model estimated baseline GP5’s association with treatment duration via hazard ratio (HR). Early treatment discontinuation status was defined as treatment duration < 12 months with discontinuation not attributed to disease progression or death (n = 4), consistent with previous analyses. Results: 1,046 women enrolled from 6/2013-10/2018 (640 White, 201 Black, 205 Asian), including 590 (56%) from NCORP Community or Minority/Underserved Sites. Approximately 10% (100/987 with GP5 data) reported moderate/high treatment bother prior to initiating anastrozole. Anastrozole discontinuation rate at 1-year was 26.2% overall; it was lower among women with no/little treatment bother (25.7%, GP5 = 0-1) compared to moderate/high treatment bother prior to initiating anastrozole (34.7%, GP5 = 2-4; HR = 1.50, 95% confidence interval [CI]:1.04-2.15, p = 0.027). Subgroup analyses by racial cohort showed a similar predictive effect of GP5 in the White (n = 606, HR = 1.76, 95% CI: 1.12-2.77, p = 0.014) and Black (n = 184, HR = 1.85, 95% CI: 0.92-3.71, p = 0.079) cohorts, but not in the Asian cohort (n = 197, HR = 0.40, 95% CI: 0.10-1.62, p = 0.20). Conclusions: Moderate/high treatment bother prior to starting anastrozole was observed in 10% of patients and associated with a higher risk of early discontinuation, except in Asian patients. Our findings support the presence of a treatment tolerability threshold which can be compromised by pre-treatment burden. Treatment tolerability may also be influenced by cultural and genetic factors, which will be explored in further analysis of genetic and PRO data. Clinical trial information: NCT01824836.

AbstractBackgroundE3805 (CHAARTED) is a phase 3 trial demonstrating improved survival for men with metastatic hormone‐sensitive prostate cancer (mHSPC) randomized to treatment with docetaxel (D) and androgen‐deprivation therapy (ADT) versus ADT alone. We assessed the association of baseline body mass index (BMI) and metformin exposure with quality of life (QOL) and prostate cancer outcomes including survival in patients enrolled in the CHAARTED study.MethodsWe performed a posthoc exploratory analysis of the CHAARTED trial of men with mHSPC randomized to treatment with ADT with or without D between 2006 and 2012. Cox proportional hazards models and Kruskal–Wallis test were used to evaluate the association between BMI with QOL and prostate cancer outcomes and between metformin exposure and survival.ResultsIn 788 of 790 enrolled patients with prospectively recorded baseline BMI and metformin exposure status, lower BMI was not associated with survival, but was associated with high volume disease (p < 0.0001) and poorer baseline QOL on functional assessment of cancer therapy–prostate (p = 0.008). Only 68 patients had prevalent metformin exposure at baseline in the CHAARTED trial. Four groups were identified: ADT + D + metformin (n = 39); ADT + D (n = 357); ADT + metformin (n = 29); and ADT alone (n = 363). Baseline clinicopathologic characteristics were similar between groups. In this small exploratory multivariable analysis, metformin exposure was not associated with survival (hazard ratio: 1.15; 95% confidence interval: 0.81–1.63, p = 0.44).ConclusionsThere was no link between baseline BMI and survival, but lower baseline BMI was associated with features of greater cancer burden and poorer QOL.

Background In clinical trials and clinical practice, patient-reported outcomes are almost always assessed using multiple patient-reported outcome measures at the same time. This raises concerns about whether patient responses are affected by the order in which the patient-reported outcome measures are administered. Methods This questionnaire-based study of order effects included adult cancer patients from five cancer centers. Patients were randomly assigned to complete questionnaires via paper booklets, interactive voice response system, or tablet web survey. Linear Analogue Self-Assessment, Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, and Patient-Reported Outcomes Measurement Information System assessment tools were each used to measure general health, physical function, social function, emotional distress/anxiety, emotional distress/depression, fatigue, sleep, and pain. The order in which the three tools, and domains within tools, were presented to patients was randomized. Rates of missing data, scale scores, and Cronbach’s alpha coefficients were compared by the order in which they were assessed. Analyses included Cochran–Armitage trend tests and mixed models adjusted for performance score, age, sex, cancer type, and curative intent. Results A total of 1830 patients provided baseline patient-reported outcome assessments. There were no significant trends in rates of missing values by whether a scale was assessed earlier or later. The largest order effect for scale scores was due to a large mean score at one assessment time point. The largest difference in Cronbach’s alpha between the versions for the Patient-Reported Outcomes Measurement Information System scales was 0.106. Conclusion The well-being of a cancer patient has many different aspects such as pain, fatigue, depression, and anxiety. These are assessed using a variety of surveys often collected at the same time. This study shows that the order in which the different aspects are collected from the patient is not important.