Exploring the Relationship Among Financial Hardship, Anxiety, and Depression in Patients With Cancer: A Longitudinal Study.

PURPOSE: Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer. METHODS: This prospective, longitudinal cohort study analyzed data from 2,305 participants from the Northwestern University Improving the Management of Symptoms during and following Cancer Treatment trial. Outcomes assessed at baseline and at 3, 6, 9, and 12 months postbaseline included depressive symptoms, anxiety, and FH. Analysis involved random intercept cross-lagged panel models to explore between- and within-person effects, incorporating factors such as age, sex, insurance status, neighborhood area deprivation, health care charges, out-of-pocket costs, and health literacy. RESULTS: The cohort had a mean age of 60.7 (standard deviation [SD] = 12.7) years and was mostly female (64.9%) and White (86.2%). Correlations were found between FH and depressive symptoms (r = 0.310) and anxiety (r = 0.289). A predictive relationship was observed between FH and depressive symptoms, with baseline and 6-month depressive symptom levels predicting later FH (baseline ß = .079, P = .070; 6-month ß = .072, P = .081) and 9-month FH significantly predicting 12-month depressive symptoms (ß = .083, P = .025), even after accounting for health care charges and out-of-pocket costs. Baseline and 9-month anxiety showed a predictive relationship with subsequent FH (baseline ß = .097, P = .023; 9-month ß = .071, P = .068). CONCLUSION: FH emerged as a prominent issue, with nearly half of participants experiencing some level of FH. Depressive symptoms and anxiety were related to FH. These findings underscore the need for a comprehensive approach in cancer care that concurrently addresses anxiety, depressive symptoms, and FH, recognizing their interconnected impact.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

PURPOSE: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC. METHODS: We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. RESULTS: Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3 months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3 months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3 months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001). CONCLUSION: GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Shared decision-making and disease management in advanced cancer and chronic kidney disease using patient-reported outcome dashboards.

OBJECTIVES: To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD). MATERIALS AND METHODS: We developed a clinical PRO dashboard within the Northwestern Medicine Patient-Reported Outcomes system, enhanced through co-design involving 20 diverse constituents. Using a single-group, pretest-posttest design, we evaluated the dashboard's use among patients with advanced cancer or CKD between June 2020 and January 2022. Eligible patients had a visit with a participating clinician, completed at least two dashboard-eligible visits, and consented to follow-up surveys. PROs were collected 72 h prior to visits, including measures for chronic condition management self-efficacy, health-related quality of life (PROMIS measures), and SDM (collaboRATE). Responses were integrated into the EHR dashboard and accessible to clinicians and patients. RESULTS: We recruited 157 participants: 66 with advanced cancer and 91 with CKD. There were significant improvements in SDM from baseline, as assessed by collaboRATE scores. The proportion of participants reporting the highest level of SDM on every collaboRATE item increased by 15 percentage points from baseline to 3 months, and 17 points between baseline and 6-month follow-up. Additionally, there was a clinically meaningful decrease in anxiety levels over study period (T-score baseline: 53; 3-month: 52; 6-month: 50; P < .001), with a standardized response mean (SRM) of -0.38 at 6 months. DISCUSSION: PRO clinical dashboards, developed and shared with patients, may enhance SDM and reduce anxiety among patients with advanced cancer and CKD.

Overall side effect assessment of oxaliplatin toxicity in rectal cancer patients in NRG oncology/NSABP R04.

PURPOSE: Regulatory guidance suggests capturing patient-reported overall side effect impact in cancer trials. We examined whether the Functional Assessment of Cancer Therapy (FACT) GP5 item ("I am bothered by side effects of treatment") post-neoadjuvant chemotherapy/radiotherapy differed between oxaliplatin vs. non- oxaliplatin arms in the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial of stage II-III rectal cancer patients. METHODS: The R-04 neoadjuvant trial compared local-regional tumor control between patients randomized to receive 5-fluorouracil or capecitabine with radiation, with or without oxaliplatin (4 treatment arms). Participants completed surveys at baseline and immediately after chemoradiotherapy. GP5 has a 5-point response scale: "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). Logistic regression compared the odds of reporting moderate-high side effect impact (GP5 2-4) between patients receiving oxaliplatin or not after chemoradiotherapy, controlling for relevant patient characteristics. We examined associations between GP5 and other patient-reported outcomes reflecting side effects. RESULTS: Analyses were performed among 1132 study participants. Participants receiving oxaliplatin were 1.58 times (95% CI: 1.22-2.05) more likely to report moderate-high side effect bother at post-chemotherapy/radiation. In both arms, worse overall side effect impact was associated with patient-reported diarrhea, nausea, vomiting, and peripheral sensory neuropathy (p < 0.01 for all). CONCLUSION: This secondary analysis of R-04 found that GP5 distinguished between patients receiving oxaliplatin or not as part of their post-neoadjuvant chemoradiotherapy, adding patient-centric evidence on the reduced tolerability of oxaliplatin and demonstrating that GP5 is sensitive to known toxicity differences between treatments. CLINICALTRIALS: GOV: NCT00058474.

Implementation of a Co-Design Strategy to Develop a Dashboard to Support Shared Decision Making in Advanced Cancer and Chronic Kidney Disease.

Background: Shared decision making (SDM) is the process by which patients and clinicians exchange information and preferences to come to joint healthcare decisions. Clinical dashboards can support SDM by collecting, distilling, and presenting critical information, such as patient-reported outcomes (PROs), to be shared at points of care and in between appointments. We describe the implementation strategies and outcomes of a multistakeholder collaborative process known as "co-design" to develop a PRO-informed clinical dashboard to support SDM for patients with advanced cancer or chronic kidney disease (CKD). Methods: Across 14 sessions, two multidisciplinary teams comprising patients, care partners, clinicians, and other stakeholders iteratively co-designed an SDM dashboard for either advanced cancer (N = 25) or CKD (N = 24). Eligible patients, care partners, and frontline clinicians were identified by six physician champions. The co-design process included four key steps: (1) define "the problem", (2) establish context of use, (3) build a consensus on design, and (4) define and test specifications. We also evaluated our success in implementing the co-design strategy using measures of fidelity, acceptability, adoption, feasibility, and effectiveness which were collected throughout the process. Results: Mean (M) scores across implementation measures of the co-design process were high, including observer-rated fidelity and adoption of co-design practices (M = 19.1 on a 7-21 scale, N = 36 ratings across 9 sessions), as well as acceptability based on the perceived degree of SDM that occurred during the co-design process (M = 10.4 on a 0 to 12 adapted collaboRATE scale). Capturing the feasibility and adoption of convening multistakeholder co-design teams, min-max normalized scores (ranging from 0 to 1) of stakeholder representation demonstrated that, on average, 95% of stakeholder types were represented for cancer sessions (M = 0.95) and 85% for CKD sessions (M = 0.85). The co-design process was rated as either "fully" or "partially" effective by 100% of respondents, in creating a dashboard that met its intended objective. Conclusions: A co-design process was successfully implemented to develop SDM clinical dashboards for advanced cancer and CKD care. We discuss key strategies and learnings from this process that may aid others in the development and uptake of patient-centered healthcare innovations.

Obstacles to Biosimilar Acceptance and Uptake in Oncology: A Review.

Importance: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars. Observations: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems. Conclusions and Relevance: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.

The challenge of using patient reported outcome measures in clinical practice: how do we get there?

BACKGROUND: As patient-reported outcome measures (PROMs) become available to clinicians for routine clinical decision-making, many wonder how to define a meaningful change in a patient's PROM score. Some PROMs have a specific threshold that indicates meaningful change, but since those numbers are based on population averages, they do not necessarily apply to the varying experiences of each individual patient. Rather than viewing this as a weakness of PROMs, it is worth considering how clinicians use other existing measures in clinical decision-making-and whether PROMs can be used similarly. BODY: An informal survey of 43 clinicians reported using measures such as weight, blood pressure, and blood chemistry to inform clinical decision-making. Although clinicians were very consistent with what constituted a meaningful change for some measures (e.g., ECOG performance status), other measures had considerable variability (e.g., weight), often informed by their specialization (for example, differing thresholds for meaningful weight change for adult primary care, pediatrics, and oncology). For interpreting change in measures, they relied on clinical experience (44%), published literature (38%), and established guidelines (35%). In open-response comments, many clarified that the results of any measure had to be taken in the context of each individual patient before making treatment decisions. In short, clinicians already apply individualized clinical judgment when interpreting score changes in existing clinical measures. As clinicians gain familiarity with PROMs, PROMs will likely be utilized in the same way. CONCLUSION: Like other clinical measures from weight to blood chemistry, change in a PROM score is but one piece of a patient's clinical story. Rather than relying on a hard-and-fast number for defining clinically meaningful change in a PROM score, providers should-and many already do-consider the full scope of a patient's experience as they make treatment decisions.

Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma.

Importance: There is substantial interest in capturing cancer treatment tolerability from the patient's perspective using patient-reported outcomes (PROs). Objective: To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. Design, Setting, and Participants: This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. Exposures: GP5 response options were "very much," "quite a bit," "somewhat," "a little bit," and "not at all." Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, "very much," and "quite a bit") and low adverse event bother (ie, "somewhat," "a little bit," or "not at all"). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. Main Outcome and Measure: ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Results: Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). Conclusions and Relevance: In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.

[Special issue PRO] Considering endpoints for comparative tolerability of cancer treatments using patient report given the estimand framework.

Regulatory agencies are advancing the use of systematic approaches to collect patient experience data, including patient-reported outcomes (PROs), in cancer clinical trials to inform regulatory decision-making. Due in part to clinician under-reporting of symptomatic adverse events, there is a growing recognition that evaluation of cancer treatment tolerability should include the patient experience, both in terms of the overall side effect impact and symptomatic adverse events. Methodologies around implementation, analysis, and interpretation of "patient" reported tolerability are under development, and current approaches are largely descriptive. There is robust guidance for use of PROs as efficacy endpoints to compare cancer treatments, but it is unclear to what extent this can be relied-upon to develop tolerability endpoints. An important consideration when developing endpoints to compare tolerability between treatments is the linkage of trial design, objectives, and statistical analysis. Despite interest in and frequent collection of PRO data in oncology trials, heterogeneity in analyses and unclear PRO objectives mean that design, objectives, and analysis may not be aligned, posing substantial challenges for the interpretation of results. The recent ICH E9 (R1) estimand framework represents an opportunity to help address these challenges. Efforts to apply the estimand framework in the context of PROs have primarily focused on efficacy outcomes. In this paper, we discuss considerations for comparing the patient-reported tolerability of different treatments in an oncology trial context.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.

PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.

Using IT to Improve Outcomes for Children Living With Cancer (SyMon-SAYS): Protocol for a Single-Institution Waitlist Randomized Controlled Trial.

BACKGROUND: Children and adolescents with cancer may experience multiple disease- and treatment-related symptoms that negatively affect health-related quality of life. Routine symptom surveillance thus constitutes an important component of supportive care in pediatric oncology. The Symptom Monitoring and Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) system will administer, score, interpret, and display the results of symptom assessments captured weekly using patient-reported outcomes presented via the electronic health record (EHR) portal between clinic visits in oncology ambulatory settings, when patients are likely to be more symptomatic. This study is testing a digital system for routine symptom surveillance that includes EHR-based reports to clinicians and alerts for severe symptoms. OBJECTIVE: In this randomized trial, we are examining the effects of the SyMon-SAYS system on perceived barriers to symptom management, self-efficacy, and symptom severity. Better self-management and timely clinical intervention to address symptoms promote adherence to treatment plans, strengthen child and parent self-efficacy, improve interactions between children, parents, and their clinical providers, and optimize clinical outcomes. METHODS: The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptoms to clinicians using EHR (Epic) messaging functionalities. Children (aged 8 to 17 years) complete the weekly symptom assessment and review the symptom report by logging into the patient portal (Epic MyChart). This single-institution waitlist randomized controlled trial is recruiting 200 children (aged 8-17 years) with cancer and their parents, guardians, or caregivers. Participating dyads are randomly assigned to receive the intervention over 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then an 8-week SyMon-SAYS intervention). Analyses will (1) evaluate the efficacy of SyMon-SAYS at week 8 and the maintenance of those effects at week 16; (2) evaluate factors associated with those efficacy outcomes, including contextual factors, adherence to the SyMon-SAYS intervention, demographic characteristics, and clinical factors; and (3) evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care. RESULTS: Data collection is currently in progress. We hypothesize that at 8 weeks, those receiving the SyMon-SAYS intervention will report decreased parent-perceived barriers to managing their children's symptoms, increased parent and child self-efficacy, decreased child symptom burden, and ultimately better child health-related quality of life, compared to waitlist controls. Feasibility, acceptability, and engagement from the perspectives of the children with cancer, their parents, and their clinicians will be examined using mixed methods. CONCLUSIONS: We anticipate that this system will facilitate prompt identification of problematic symptoms. Additionally, we hypothesize that with the availability of graphical symptom reports over time, and timely provider responses, children or parents will become better informed and take an active role in managing their symptoms, which will further improve clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04789720; https://clinicaltrials.gov/study/NCT04789720. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50993.

Establishing a common metric for physical function: Linking SARC-F and PROMIS® physical function.

INTRODUCTION: Aligned with the increasing need for standardized assessment of physical function in older individuals with cancer and other conditions, several patient-reported outcome measures (PROMs) have been developed and published. The aim of this study is to link the Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls questionnaire (SARC-F), and the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Physical Function Short Form 8c (PROMIS PF 8c), and make their scores convertible, in order to expand the use of both instruments in research and inform clinicians and researchers about the interchangeability of critical cut-off scores. MATERIALS AND METHODS: The sample included 300 participants recruited from an online panel. Participants were included if they had received a cancer diagnosis from a clinician and reported receiving anti-cancer treatment. We conducted five linking procedures and selected an optimal one to generate the crosswalk table between the two measures. RESULTS: The linked T scores of all five methods showed acceptably small mean differences from the observed T scores, and the standard deviation (SD), and root-mean-squared deviation (RMSD) of the differences were generally similar across all methods. After comparing across all statistics, the Stocking-Lord approach was considered as the optimal approach to compute the crosswalk table for converting SARC-F raw scores to PROMIS PF 8c scores. The crosswalk table shows that the SARC-F cut-off value of 4 between healthy versus symptomatic with a corresponding score of 37 fell in the range of moderate physical function limitation from 30 to 39 on the PROMI PF 8c T score metric. DISCUSSION: The linkage in this study has potential for improving clinical and research activities for people with cancer and perhaps others with a similar range of physical function. It facilitates the interpretability in scores of both measures on a common metric anchored on general population for further group-level analysis. Researchers can use this crosswalk to harmonize data collected from either instrument without requiring all cohorts to administer the same instrument for a prospective data collection or retrospective data analysis purpose or for a cross-study effectiveness study.

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure.

Importance: Patients undergoing radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) experience a range of debilitating adverse effects (AEs). Patient-reported outcome (PRO) measures to quantify these AEs are a necessary and important component of health care; however, currently available PRO options often measure only disease-related symptoms or AEs of non-RT treatments. Objective: To develop a brief PRO measure of the most common AEs associated with RT for HNSCC. Design, Setting, and Participants: This was a qualitative study that followed the US Food and Drug Administration guidelines to develop a brief measure of patient-reported RT-related AEs (the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy [FACT-HN-RAD] measure). The study included (1) a literature review of clinical trials; (2) secondary analysis of retrospective concept elicitation interviews (CEIs); (3) electronic surveys of practicing radiation oncologists; (4) mapping of existing items to inform the development of the draft version of the measure; and (5) validation of content and face validity via patient cognitive interviews. Analysis was performed of CEI data and interviews with practicing radiation oncologists. Data analysis was conducted from July 1, 2022, to April 21, 2023. Exposures: Surveys and qualitative interviews. Main Outcomes and Measures: The most common patient-reported RT-related AEs among patients with HNSCC. Results: Of 19 CEI participants, 14 (mean [range] age, 67 [49-86] years; 12 [86%] men and 2 [14%] women) described RT-related AEs and were included in the secondary analysis. Eleven (79%) patients reported difficulty swallowing; 8 (57%), oral pain; 7 (50%), dry mouth; 7 (50%), weight loss; 6 (43%), skin burning; 5 (36%), loss of taste; 5 (36%), voice changes (36%); and 5 (36%), fatigue. Nine radiation oncologists (mean [range] time in practice, 8 [1-42] years; 5 [56%] men and 4 [44%] women) reported the most common AEs: 9 (100%) reported dysgeusia; 7 (78%), xerostomia; 7 (78%), mucositis or oral pain; 8 (89%), dysphagia or odynophagia; 6 (67%), dermatitis; and 3 (33%), fatigue. Together these data informed the development of an 8-item AE-focused measure of pain, dysphagia, xerostomia, dysgeusia, voice changes, dermatitis, fatigue, and weight loss. Cognitive interviews with 10 patients (mean [range] age, 61 [29-84] years; 8 [80%] men and 2 [20%] women) demonstrated strong face validity; all (100%) reported that the measure reflected their experience with RT and stated that the length of the questionnaire was "just right." Conclusions and Relevance: The 8-item FACT-HN-RAD measure captures the most common patient- and physician-reported AEs related to RT for HNSCC. This measure offers a means to serially monitor patient-reported treatment-related AEs and recovery over time in both clinical and research settings. Future work will evaluate the psychometric validity of the measure.

Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial.

PURPOSE: To compare NFOSI-18 Disease Related Symptoms - Physical (DRSP), Total score, and side effect bother between maintenance rucaparib (600 mg twice daily) vs. placebo in the phase III ARIEL3 trial. METHODS: ARIEL3 (NCT01968213) included patients with ovarian carcinoma who responded to second-line or later platinum-based chemotherapy. The NFOSI-18 DRS-P and Total scales were secondary endpoints. The NFOSI-18 contains a side effect impact item (GP5): "I am bothered by side effects of treatment." We compared treatment arms on change from baseline of DRS-P and Total scores using mixed models with repeated measures (MRMM). Time to first and confirmed deterioration of NFOSI-18 DRS-P and Total scales were analyzed using Cox regression. We also calculated the proportion of patients reporting moderate to high side effect bother on GP5. RESULTS: In the intention-to-treat (ITT) cohort, mean change from baseline favored the placebo. Compared to placebo, rucaparib was associated with higher risk of deterioration [e.g., 4-point deteriorator definition hazard ratio (HR): 1.85; 95% CI: 1.46, 2.36; median time to first deterioration on DRSP: 1.9 vs. 7.0 months]. Confirmed deterioration results resembled those for first deterioration. Proportions of patients reporting moderate/high side effect bother on GP5 fluctuated around 20% across treatment cycles. Results in BRCA mutant and homologous recombination deficient cohorts were generally similar to those from the ITT cohort. CONCLUSION: This placebo-controlled study in the maintenance therapy setting provides a unique view of the impact of PARP inhibition on the patient-reported outcomes that are commonly used in ovarian cancer clinical trials. Information regarding the adverse side effect impact of PARP inhibitors should be weighed against their clinical benefit.

International Society for Quality of Life Research commentary on the US Food and Drug Administration draft guidance for industry on core patient-reported outcomes in cancer clinical trials.

In June 2021, the US Food and Drug Administration (FDA) released a draft guidance for industry on core patient-reported outcomes (PROs) and related considerations for instrument selection and trial design in registrational cancer clinical trials, building on prior communications about the use of PROs to assess efficacy and tolerability in oncology drug development. The International Society for Quality of Life Research (ISOQOL) Standards and Best Practices Committee led an initiative to draft a commentary about the guidance, focusing on its positive aspects and areas that would benefit from additional clarification and consideration. For comprehensiveness, the authors reviewed existing public comments on the draft guidance, and the commentary underwent a thorough review process through three ISOQOL Special Interest Groups (Psychometrics, Clinical Practice, and Regulatory and Health Technology Assessment Engagement) followed by the ISOQOL Board. The goal of this commentary is to situate this new and relevant guidance document within the context of recent regulatory efforts on PROs and highlight areas in which further work may ultimately benefit the field.

General population reference values for the Functional Assessment of Cancer Therapy-Lung and PROMIS-29.

BACKGROUND: Therapeutic advances in lung cancer have turned attention toward patient-reported outcome measures (PROMs) as important clinical outcomes. The Functional Assessment of Cancer Therapy-Lung (FACT-L) is a common endpoint in lung cancer trials. This study calculated FACT-L reference values for the United States (US) general population. METHODS: Adults from the US general population (N = 2001) were surveyed between September 2020 and November 2020. Surveys contained 126 questions, including the FACT-L [36 items; FACT-G and four subscales (Physical Well-Being [PWB], Social Well-Being [SWB], Emotional Well-Being [EWB], and Functional Well-Being [FWB]) and the Lung Cancer Subscale (LCS), and a Trial Outcome Index (TOI)]. Reference values for each FACT-L scale were calculated with means for the total sample and separately for participants with: no comorbidities, COVID-19 as only comorbidity, no COVID-19. RESULTS: In the total sample, the reference scores were as follows: PWB = 23.1; SWB = 16.8; EWB = 18.5; FWB = 17.6; FACT-G = 76.0; LCS = 23.0, TOI = 63.7, and FACT-L Total = 99.0. Scores were lower for those reporting a prior diagnosis of COVID-19, especially for SWB (15.7) and FWB (15.3). SWB scores were lower than previous references values. CONCLUSIONS: These data provide US general adult population reference value set for FACT-L. While some of the subscale results were lower than those found in the reference data for other PROMs, these data were obtained in a more contemporaneous time frame juxtaposed with the COVID-19 pandemic and may represent a new peri-pandemic norm. Thus, these reference values will be useful for future clinical research.

Effectiveness and implementation of an electronic health record-integrated digital health intervention for managing depressive symptoms in ambulatory oncology: The My Well-Being Guide study rationale and protocol.

BACKGROUND: Rates of clinically elevated depressive symptoms among ambulatory oncology patients are higher than in the general population and are associated with poorer health-related quality of life. Furthermore, a reduction in depressive symptoms may be associated with improved cancer survival. Several interventions have demonstrated efficacy in reducing oncologic depressive symptoms, including cognitive-behavioral stress management (CBSM). However, more work is needed to understand how to best implement CBSM into practice, such as through stepped-care approaches and digital health interventions linked to electronic health records (EHR). This manuscript presents the protocol of the My Well-Being Guide study, a pragmatic type 1 effectiveness-implementation hybrid study. This trial will test the effectiveness of My Well-Being Guide, a seven-week structured, CBSM-based digital health intervention designed to reduce depressive symptoms. This trial will also evaluate My Well-Being Guide's implementation across two health systems. METHODS: The final sample (N = 4561) will be oncology patients at Northwestern Medicine or University of Miami Health System who are ≥18 years of age; have a cancer diagnosis; elevated depressive symptoms on the Patient-Reported Outcomes Measurement Information System Depression; and primary language is English or Spanish. Data collection will occur at baseline, and 2-, 6-, and 12-months post baseline. Outcome domains include depressive symptoms and implementation evaluation. DISCUSSION: This study may provide valuable data on the effectiveness of our depressive symptom management digital health intervention linked to the EHR and the scalability of digital health interventions in general.

Medical Oncologists' Knowledge and Perspectives on the Use of Biosimilars in the United States.

PURPOSE: Despite increasing availability of biosimilar cancer treatments, little is known about oncologists' knowledge and concerns regarding biosimilar use in the United States. We surveyed medical oncologists to examine their knowledge, attitudes, and experience with biosimilars. METHODS: Oncologists recruited via the ASCO Research Survey Pool completed a 29-question survey in 2020 designed with input from clinical and health care system experts and literature review. RESULTS: Of the 269 respondents, most treated patients with biosimilars (n = 236, 88%) and reported that biosimilars were required at their institution (n = 168, 63%). Approximately half (n = 140, 52%) of oncologists correctly responded that biosimilars were not the same as generic medicines. Commonly reported barriers to use of biosimilars included concerns regarding a perceived lack of relevant research (n = 85, 33% reporting quite a bit/very much), the potential for extrapolation (n = 83, 33%), and efficacy limitations (n = 77, 30%). More oncologists from university hospitals (n = 36, 22%) than from community/private hospitals (n = 28, 38%) or private practices (n = 13, 38%) were concerned about biosimilar efficacy. A high proportion of oncologists reported that information on safety (n = 259, 99%) and efficacy (n = 255, 99%) is important when considering whether to use biosimilars. Less than half reported that their institution provided education about biosimilars (n = 108, 40%). CONCLUSION: In this sample of medical oncologists, knowledge about basic features of biosimilars was limited and access to information about biosimilars was insufficient. The present study determined that educational programs on biosimilars for oncologists are needed and identified priorities for such efforts.