Changes In Patient-reported Outcomes Research Articles

Quality of Survival, Not Just Quantity of Time

Recovery of Patient-Reported Quality of Life After EsophagectomyThe Annals of Thoracic SurgeryPreviewEsophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life(QOL). Patient-reported outcomes(PRO) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PRO in the first year after esophagectomy. Full-Text PDF

The Role of Wearable Technology in Measuring and Supporting Patient Outcomes Following Total Joint Replacement: Review of the Literature

The incidence rate of total joint replacement (TJR) continues to increase due to the aging population and the surgery that is very successful in providing pain relief to and improving function among patients with advanced knee or hip arthritis. Improving patient outcomes and patient satisfaction after TJR remain important goals. Wearable technologies provide a novel way to capture patient function and activity data and supplement clinical measures and patient-reported outcome measures in order to better understand patient outcomes after TJR. We examined the current literature to evaluate the potential role of wearable devices and compare them with existing methods for monitoring and improving patient rehabilitation and outcomes following TJR. We performed a literature search by using the research databases supported by the University of Massachusetts Chan Medical School's Lamar Soutter Library, including PubMed and Scopus, supplemented with the Google Scholar search engine. A specific search strategy was used to identify articles discussing the use of wearable devices in measuring and affecting postoperative outcomes of patients who have undergone TJR. Selected papers were organized into a spreadsheet and categorized for our qualitative literature review to assess how wearable data correlated with clinical measures and patient-reported outcome measures. A total of 9 papers were selected. The literature showed the impact of wearable devices on evaluating and improving postoperative functional outcomes. Wearable-collected data could be used to predict postoperative clinical measures, such as range of motion and Timed Up and Go times. When predicting patient-reported outcomes, specifically Hip Disability and Osteoarthritis Outcome Scores/Knee Injury and Osteoarthritis Outcome Scores and Veterans RAND 12-Item Health Survey scores, strong associations were found between changes in sensor-collected data and changes in patient-reported outcomes over time. Further, the step counts of patients who received feedback from a wearable improved over time when compared to those of patients who did not receive feedback. These findings suggest that wearable technology has the potential to remotely measure and improve postoperative orthopedic patient outcomes. We anticipate that this review will facilitate further investigation into whether wearable devices are viable tools for guiding the clinical management of TJR rehabilitation.

Death Anxiety in Huntington Disease: Longitudinal Heath-Related Quality-of-Life Outcomes.

Objective: Death anxiety, represented by the HDQLIFE™ Concern with Death and Dying (CwDD) patient-reported outcome (PRO) questionnaire, captures a person's worry about the death and dying process. Previous work suggests that death anxiety remains an unremitting burden throughout all stages of Huntington disease (HD). Although palliative interventions have lessened death anxiety among people with advanced cancer, none has yet to undergo testing in the HD population. An account of how death anxiety is associated with longitudinal changes to aspects of health-related quality of life (HRQoL) would help optimize neuropalliative interventions for people with HD. Methods: HDQLIFE collected PROs concerning physical, mental, social, and cognitive HRQoL domains and clinician-rated assessments from people with HD at baseline and 12 and 24 months. Linear mixed-effects models were created to determine how baseline death anxiety was associated with follow-up changes in HRQoL PROs after controlling for baseline death anxiety and other disease and sociodemographic covariates. Results: Higher baseline HDQLIFE CwDD is associated with 12- and 24-month declines in HDQLIFE Speech Difficulties, neurology quality of life (NeuroQoL) Depression, Suicidality, HDQLIFE Meaning and Purpose, and NeuroQoL Positive Affect and Well-being. Interpretation: Death anxiety may be a risk factor for worsening mental health and speech difficulty. A further prospective study is required to evaluate whether interventions on death anxiety or mental health generally can reduce declines in HRQoL for people with HD over time.

False Atrial Fibrillation Alerts from Smartwatches are Associated with Decreased Perceived Physical Well-being and Confidence in Chronic Symptoms Management.

Wrist-based wearables have been FDA approved for AF detection. However, the health behavior impact of false AF alerts from wearables on older patients at high risk for AF are not known. In this work, we analyzed data from the Pulsewatch (NCT03761394) study, which randomized patients (≥50 years) with history of stroke or transient ischemic attack to wear a patch monitor and a smartwatch linked to a smartphone running the Pulsewatch application vs to only the cardiac patch monitor over 14 days. At baseline and 14 days, participants completed validated instruments to assess for anxiety, patient activation, perceived mental and physical health, chronic symptom management self-efficacy, and medicine adherence. We employed linear regression to examine associations between false AF alerts with change in patient-reported outcomes. Receipt of false AF alerts was related to a dose-dependent decline in self-perceived physical health and levels of disease self-management. We developed a novel convolutional denoising autoencoder (CDA) to remove motion and noise artifacts in photoplethysmography (PPG) segments to optimize AF detection, which substantially reduced the number of false alerts. A promising approach to avoid negative impact of false alerts is to employ artificial intelligence driven algorithms to improve accuracy.

Patient-reported outcomes following selpercatinib treatment in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer and thyroid cancer, and RET-mutant medullary thyroid cancer in the phase II LIBRETTO-321 trial.

Patient-reported outcomes (PROs) are increasingly becoming an important part of clinical trials as they are helpful in analyzing the safety and efficacy of treatment in chronic diseases like cancer. We report PROs and health-related quality of life (HRQoL) with selpercatinib treatment among Chinese patients with rearranged in transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC), RET fusion-positive thyroid cancer (TC), and RET-mutant medullary TC (MTC) as an exploratory analysis of the LIBRETTO-321 trial. A total of 77 patients (47 RET fusion-positive NSCLC, 1 RET fusion-positive TC, and 29 RET-mutant MTC) were enrolled. Compliance for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was 100% at baseline and >90% at each time point. PROs were assessed using the EORTC QLQ-C30, and a bowel diary assessment for MTC patients with baseline diarrhea using the Systemic Therapy-Induced Diarrhea Assessment Tool. Data were collected at pre-dose; every 8 weeks from cycle 3; and every 12 weeks after cycle 13. A >10-point change from baseline was considered clinically meaningful. PRO changes were summarized through cycle 13. Most patients with NSCLC or MTC showed improvement or remained stable on the global health status and functional subscales. For global health status, 47.4% of NSCLC and MTC patients showed definite improvement with only 19.7% showing definite worsening. For functional subscales, less than 30% of the patients showed definite worsening. For symptom subscales, more than 64% of the patients either improved or remained stable for the symptoms. For MTC patients with bowel diary assessment (n = 5), there was no severity or worsening from baseline in the diarrheal episodes observed during treatment with selpercatinib. The study demonstrated favorable PROs in Chinese patients with RET fusion-positive NSCLC, TC, and RET-mutant MTC treated with selpercatinib. HRQoL was improved or stable as assessed by EORTC QLQ-30. This study was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04280081) ClinicalTrials.gov Identifier: NCT04280081.

Recovery of Patient-reported Quality of Life After Esophagectomy

BackgroundEsophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy. MethodsLongitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health–sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure. ResultsOne hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits ≤ 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P < .001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P < .001) and 17.1% (P < .001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P = .02) and 26.4% (P = .001) worse, respectively, than mean preoperative levels. ConclusionsDespite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

ASCENT1: A Phase 2 Trial to Evaluate the Efficacy and Safety of Oral Decitabine-Tetrahydrouridine (NDec) in Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is driven by the polymerization of mutated hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) mitigates the effects of HbS polymerization, but the HbF gene expression is silenced in infancy by DNA methyltransferase 1 (DNMT1). Decitabine induces HbF expression by direct inhibition of DNMT1. NDec is an innovative combination treatment with decitabine, the active component, and the pharmacokinetic enhancer tetrahydrouridine (THU). Hydroxyurea (HU), the current standard of SCD care, indirectly induces HbF by inducing bone marrow stress. As the indirect effect of HU on HbF is clinically variable, the direct HbF induction of NDec is hypothesized to provide a sustainable treatment option for patients with SCD. In a previous trial in high-risk patients with SCD by Molokie R et al. (2017), oral decitabine (0.16 mg/kg) and THU vs placebo significantly increased total Hb, HbF, proportion of HbF-enriched RBCs (%F-cells) and improved RBC health markers, without triggering grade ≥3 non-hematologic toxicity. NDec formulations were further investigated in 2 phase 1 trials in healthy people. The ASCENT1 trial (NCT05405114) aims to study the efficacy and safety of once- or twice-weekly NDec vs placebo in patients with SCD. This study will provide proof of concept and determine the optimal dose for future trials. Study design: ASCENT1 is a randomized, placebo-controlled phase 2 trial with an additional exploratory open-label HU block (Figure). To ease the operational aspects for patients and sites, trial design, visit schedule and trial materials were developed together with patient groups, study nurses and coordinators. The HU non-eligible block will include those who are HU-naïve or who cannot be treated with HU for any reason. Participants randomized to NDec in the HU active block will discontinue HU during a 4-week washout period. Study population: All SCD genotypes are eligible for inclusion; other criteria are ≥18 years of age, 2-10 documented vaso-occlusive crises (VOCs) ≤12 months before screening, Hb ≥5.0-≤10.5 g/dL and reticulocyte count >1.5x upper limit of normal at screening. HU active participants are eligible only if deemed inadequately controlled by investigators despite being prescribed HU in the preceding 6 months and being on a stable dose >3 months. Exclusion criteria include chronic transfusion therapy or treatment 28 days before screening/during trial with hematopoietic growth factors and treatment with voxelotor, crizanlizumab or L-glutamine 12 weeks before signing informed consent. Study treatment and endpoints: HU non-eligible (n=60) and HU active (n=24) participants will be randomized 1:1:1 to NDec once weekly, NDec twice weekly (2 consecutive days) or placebo/open-label HU. The trial consists of a main and extension phase (24 weeks each). NDec will be administered orally, with a meal, according to body weight intervals to attain a decitabine dose level of 0.16−0.25 mg/kg and THU dose level of 8−12.5 mg/kg. The primary endpoint is change in total Hb (g/dL) from baseline (BL) to Week 24. Secondary efficacy endpoints include change in HbF (g/dL and %HbF of total Hb), change in %F-cells of total RBCs, and change in hemolysis markers from BL to Week 24. Secondary efficacy endpoints also include numbers of VOCs, acute chest syndrome and transfused RBC units from BL to Week 48. The secondary safety endpoint is the number of adverse events (grade ≥3) from BL to Week 52. Changes in patient-reported outcomes from BL to Week 48 will be assessed using 5 validated questionnaires for SCD. Statistical analysis: The primary endpoint will be analyzed using an ANCOVA model with treatment, historical VOC rate and sex as fixed factors, and BL Hb as covariate. Treatment policy estimand will be used to handle intercurrent events. Considerations: In this trial, VOCs are defined as ≥1 predefined clinical events requiring a medical visit, including home and telemedicine visits, for those with limited regular access to medical management at a clinic/hospital. NDec and HU both induce HbF and will not be given together due to a theoretical potentiation of hematologic toxicity. The exploratory HU active block enables preliminary comparisons of the efficacy and safety between NDec and HU. The extension phase allows for analyses that may require longer follow-up to show clinical benefits and sustainability of NDec in SCD. The recruitment to ASCENT1 started in summer 2022. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody: Patient-Reported Outcomes from MonumenTAL-1

Introduction: Studies of multiple myeloma (MM) populations indicate that patients with more advanced and heavily pretreated disease have worse health-related quality of life (HRQoL) than those at earlier stages. In addition, treatment options are limited for triple-class exposed relapsed/refractory MM (RRMM), with little hope of improving HRQoL. Talquetamab is a first-in-class, off-the-shelf, T-cell redirecting bispecific antibody targeting both GPRC5D and CD3 receptors. MonumenTAL-1 is a phase 1/2 trial (NCT03399799/NCT04634552) of talquetamab in patients with RRMM. Patient-reported outcomes (PROs) data on HRQoL, symptoms, and functioning were collected in the phase 2 cohorts of MonumenTAL-1. Here, we report PROs, focusing on global health status (GHS), physical functioning, pain, and fatigue, for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort. Data for the 0.8 mg/kg SC every 2 weeks (Q2W) cohort are immature currently. Methods. Patients enrolled in phase 2 must have previously received ≥3 prior lines of therapy, including ≥1 proteosome inhibitor, ≥1 immunomodulatory drug, and ≥1 anti-CD38 monoclonal antibody (ie, triple-class exposed). After screening, patients received talquetamab step-up doses, requiring hospitalization, before cycle 1. The European Organization for Research and Treatment of Cancer Quality of Life Core 30-item (EORTC QLQ-C30) questionnaire is a cancer-specific PRO instrument administered at screening, cycle 1, and then every other cycle. It includes a subscale to measure HRQoL, 5 functional scales, 3 symptom subscales, and 6 additional single items. Scores range from 0 to 100; higher scores indicate better GHS and functioning, whereas a higher score represents more symptom severity. Compliance with PROs was calculated as the number of completed assessments divided by the number of patients on study treatment at each assessment time point. Treatment effect was assessed with a mixed-effects model with repeated measures. For the analysis of the proportion of patients with meaningful improvement, the threshold for meaningful improvement from baseline was defined as a change of ≥10 points. Time to worsening was determined using the Kaplan-Meier estimate. Results: For patients treated with 0.4 mg/kg SC QW (n=122), compliance with completing the EORTC QLQ-C30 was 96% at screening and over 80% at most post-treatment visits. After an immediate decline in overall HRQoL between screening and cycle 1, patients reported meaningful improvements in EORTC QLQ-C30 GHS and a meaningful reduction in pain symptoms compared with baseline (Figure). Least squares [LS] mean change for fatigue symptoms was -8 (95% CI, -13.83, -2.26) at cycle 9 and reached a mean decrease (ie, improvement) of 11.2 points (95% CI, -18.9, -3.53) at cycle 13. Similar results were observed in the physical (LS mean change at cycle 9: 6.5 [95% CI, 2.05, 10.93]) and role (LS mean change at cycle 9: 11.4 [95% CI, 4.55, 18.25]) functioning subscales. With treatment, the proportion of patients with meaningful improvement was high; for example, at cycle 9 for the 0.4 mg/kg cohort, 42% improved in GHS, 34% in physical functioning, 40% in role functioning, 86% in pain symptoms, and 78% in fatigue symptoms. Median time to worsening ranged from 2 (role and social functioning) to 9 months (nausea/vomiting). Overall, changes in PROs were similar in the 0.8 mg/kg SC Q2W cohort in early cycles, but conclusions are limited due to short follow-up and small sample size. The 0.8 mg/kg SC Q2W cohort will be updated with additional follow-up. Conclusions: With talquetamab treatment, patients in the 0.4 mg/kg SC QW cohort reported improvement in overall HRQoL and physical and role functioning and a decrease in pain and fatigue. These findings are consistent with the clinical benefits of talquetamab as demonstrated by the efficacy results from the MonumenTAL-1 study. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Patient-Reported Outcomes Among Recipients of Axicabtagene Ciloleucel for Relapsed/Refractory Large B Cell Lymphoma

Introduction: Limited data exist regarding patient-reported outcomes (PROs) of chimeric antigen receptor (CAR) T-cell therapy, with no published longitudinal studies to our knowledge reporting on patients treated as standard of care. The goal of the current study was to report on real-world changes in PROs (i.e., patient-reported symptoms and quality of life) in the first year after treatment with axicabtagene ciloleucel (axi-cel). Methods: Patients scheduled to receive axi-cel outside the context of a clinical trial were recruited between March 2020 and June 2022. They completed a baseline questionnaire at recruitment prior to conditioning chemotherapy before axi-cel. Patients completed subsequent questionnaires at 14, 30, 60, 90, 180 and 360 days post-infusion of axi-cel. PROs were assessed using the EORTC QLQ-C30. Mixed models evaluated change in EORTC global quality of life and subscales using all available data. Meaningful change was defined as a difference of 10 points, consistent with previous studies.1 Results: A total of 50 patients participated [mean age 62 (SD=13); 64% male; 72% diffuse large B cell lymphoma; 14% transformed follicular lymphoma, 14% follicular lymphoma]. The majority of patients (64%) would have been eligible at apheresis for the ZUMA-1 pivotal axi-cel trial; those who were ineligible typically had follicular lymphoma, poor performance status, and/or comorbidity. Regarding PROs, despite transient worsening at day 14, statistically-significant improvements in global quality of life (Panel 1), physical functioning, role functioning, social functioning, fatigue, insomnia, appetite loss, and constipation were observed over the course of the year (p values <0.05). Of these, clinically-significant improvements were observed at day 360 relative to baseline in global quality of life, role functioning, fatigue, insomnia, appetite loss, and constipation. Pain and financial concerns demonstrated statistically and clinically meaningful improvements to day 180, then worsened to baseline (i.e., pre-conditioning) levels or slightly below at day 360 (p values <0.05). Conclusions: Real-world data suggest that axi-cel is associated with transient worsening of quality of life and symptoms at day 14, with statistically and clinically significant improvements thereafter in overall quality of life and several functional and symptom domains. These data are generally consistent with PROs reported from clinical trials of CAR T-cell therapy. However, these findings extend previous research by reporting on patients' perspectives on CAR T-cell therapy received as standard of care in the real-world setting. 1Osoba, D., Rodrigues, G., Myles, J., Zee, B., & Pater, J. (1998). Interpreting the significance of changes in health-related quality-of-life scores. Journal of Clinical Oncology, 16(1), 139-144. Panel 1. Change in overall quality of life in the year following receipt of axicabtagene ciloleucel as part of standard of care. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial

BackgroundSelective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength...

Magnetic Resonance Imaging-Guided vs. Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer (MIRAGE): Primary Endpoint Analysis of a Phase III Randomized Trial

<h3>Purpose/Objective(s)</h3> Magnetic resonance imaging (MRI) guidance offers multiple potential advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Herein we report the outcomes of a phase III randomized trial comparing acute grade ≥2 genitourinary (GU) toxicity after MRI- vs. CT-guided prostate SBRT. <h3>Materials/Methods</h3> Following stratification based on IPSS (≤15 or >15) and prostate volume (≤50 or >50 mL), patients were randomized to receive SBRT with CT- vs. MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary endpoint was the incidence of acute (i.e., within 90 days of SBRT completion) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). The trial had a superiority design, hypothesizing that 154 patients would provide 89% power to detect a 14% reduction in acute grade ≥2 GU toxicity with MRI-guidance with a one-sided significance level of 0.025. Changes in patient-reported outcomes were compared using a chi-square test with the same significance level. <h3>Results</h3> Between May 2020 and October 2021, 156 patients (n=77 CT and n=79 MRI) were randomized. 81% of patients had NCCN unfavorable intermediate-, high, or very high-risk disease, 44% had placement of a spacer and 27% had nodal radiation. Rates of acute grade ≥2 GU toxicity were significantly lower with MRI- vs. CT-guidance (24.4% [95%CI 15.4-35.4%] vs. 43.4% [95%CI 32.1-55.3%], p=0.01). Rates of acute grade ≥2 GI toxicity were also significantly lower with MRI-guidance (0.0% [95% CI 0-4.6%] vs. 10.5% [4.7-19.7%], p=0.003). On multivariable analysis adjusting for trial arm, age, IPSS, gland volume, spacer use, lymph node radiation, and use of a simultaneous integrated boost dose to gross disease, trial arm remained associated with a 60% reduction in odds of grade ≥2 GU toxicity (odds ratio 0.40 [95%CI 0.19-0.84], p=0.02). MRI-guidance was associated with a significantly smaller proportion of patients with a ≥15-point increase in IPSS approached (6.8% vs. 19.4%, p=0.011). MRI-guidance was associated with a significantly reduced proportion of patients with a clinically significant (>12 point) significant decrease in EPIC-26 bowel scores (25.0% vs. 50.0%, p=0.0013). <h3>Conclusion</h3> MRI-guidance significantly reduced acute grade ≥2 GU and GI toxicity. Patient-reported outcomes were also improved at 1 month with MRI-guidance, and trial arm was a significant predictor of lower odds of moderate GU toxicity after adjusting for other important covariates. Differences in late toxicity will take years to manifest, but in the interim, these data strongly suggest that MRI-guided prostate SBRT affords significantly reduced toxicity compared with CT-guided SBRT.

Evaluating the Feasibility of a Digital Therapeutic Program for Patients With Cancer During Active Treatment: Pre-Post Interventional Study.

BackgroundIncreasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring.ObjectiveWe aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability. In addition, we explored the effects of the program on cancer-related QoL.MethodsWe conducted a 4-week single-arm trial in Iceland, where DTx was delivered through a smartphone app. The intervention consisted of patient education about mindfulness, sleep, stress, and nutrition; lifestyle coaching; and the completion of daily missions for tracking physical activity and exercise, reporting patient-reported outcomes (PROs), practicing mindfulness, and logging healthy food intake. Information on program engagement and retention, step goal attainment, as well as PROs were collected throughout the study. QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and follow-up.ResultsIn total, 30 patients with cancer undergoing active therapy were enrolled, and 29 registered in the app (23 female, 18 with breast cancer; mean age 52.6, SD 11.5 years). Overall, 97% (28/29) of participants were active in 3 of the 4 weeks and completed the pre- and postprogram questionnaires. The weekly active days (median) were 6.8 (IQR 5.8-6.8), and 72% (21/29) of participants were active at least 5 days a week. Users interacted with the app on average 7.7 (SD 1.9) times per day. On week 1, all 29 participants used the step counter and logged an average of 20,306 steps; 21 (72%) participants reached their step goals of at least 3000 steps per day. On week 4, of the 28 active users, 27 (96%) were still logging their steps, with 19 (68%) reaching their step goals. Of the 28 participants who completed the satisfaction questionnaire, 25 (89%) were likely to recommend the program, 23 (82%) said the program helped them deal with the disease, and 24 (86%) said it helped them remember their medication. QoL assessment showed that the average global health status, functioning, and symptom burden remained stable from baseline to follow-up. In all, 50% (14/28) of participants reported less pain, and the average pain score decreased from 31 (SD 20.1) to 22.6 (SD 23.2; P=.16). There was no significant change in PROs on the quality of sleep, energy, and stress levels from the first to the last week.ConclusionsThe high retention, engagement, and acceptability found in this study demonstrate that multidisciplinary DTx is feasible for patients with cancer. A longer, full-scale randomized controlled trial is currently being planned to evaluate the efficacy of the intervention.

Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b–2, open-label study

CARTITUDE-1 is a phase 1b-2 study evaluating ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma. Primary efficacy outcomes have previously been reported. Here, we report health-related quality of life (HRQOL) secondary outcomes evaluated using patient-reported outcomes. This single-arm, open-label, phwase 1b-2 study was done at 16 centres in the USA. Patients were aged 18 years or older with diagnosis of multiple myeloma and Eastern Cooperative Oncology Group performance status of 1 or less with three or more previous lines of therapy, or were double refractory to a proteasome inhibitor and immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR+ T cells per kg) was administered 5-7 days after lymphodepletion. Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30-item, pre-specified items from the EORTC myeloma module, and EuroQol five-dimensional descriptive system questionnaire. Clinically meaningful changes in patient-reported outcomes were defined by anchor-based minimally important differences. This trial is registered with ClinicalTrials.gov, NCT03548207. This trial is completed but feeding into a long-term follow-up study. Between July 16, 2018, and Oct 7, 2019, 78 patients were enrolled and underwent apheresis in phase 2 of the study. 68 patients were treated (43 [63%] male, 49 [72%] White), and their patient-reported outcomes assessed (median follow-up 16·9 months, IQR 15·7-17·5). After infusion, a transient decline was observed, followed by improvements in global health status (mean change from baseline to day 464 +8·0 points, SD 20·9), physical (+4·6 points, 21·1), and emotional functional scales (+1·9 points, 23·7) over time, and declines for symptom-based scores (-14·1 pain, SD 31·5 and -15·4 fatigue; SD 29·5), indicating improved patient HRQOL following treatment with cilta-cel. These durable HRQOL improvements are consistent with clinical findings, in which a single cilta-cel infusion led to substantial and durable responses in heavily pre-treated patients with relapsed or refractory multiple myeloma. These results support the use of cilta-cel in patients with relapsed or refractory multiple myeloma. Janssen Research & Development and Legend Biotech USA.

Comparison of raw and regression approaches to capturing change on patient-reported outcome measures.

Patient-reported outcome (PRO) analyses often involve calculating raw change scores, but limitations of this approach are well documented. Regression estimators can incorporate information about measurement error and potential covariates, potentially improving change estimates. Yet, adoption of these regression-based change estimators is rare in clinical PRO research. Both simulated and PROMIS® pain interference items were used to calculate change employing three methods: raw change scores and regression estimators proposed by Lord and Novick (LN) and Cronbach and Furby (CF). In the simulated data, estimators' ability to recover true change was compared. Standard errors of measurement (SEM) and estimation (SEE) with associated 95% confidence limits were also used to identify criteria for significant improvement. These methods were then applied to real-world data from the PROMIS® study. In the simulation, both regression estimators reduced variability compared to raw change scores by almost half. Compared to CF, the LN regression better recovered true simulated differences. Analysis of the PROMIS® data showed similar themes, and change score distributions from the regression estimators showed less dispersion. Using distribution-based approaches to calculate thresholds for significant within-patient change, smaller changes could be detected using both regression estimators. These results suggest that calculating change using regression estimates may result in more increased measurement sensitivity. Using these scores in lieu of raw differences can help better identify individuals who experience real underlying change in PROs in the course of a trial, and enhance the established methods for identifying thresholds for meaningful within-patient change in PROs.

Overall Disability Response Score: An integrated endpoint to assess disability improvement and worsening over time in patients with multiple sclerosis

Background: Overall Disability Response Score (ODRS) is a composite endpoint including Expanded Disability Status Scale, Timed 25-foot Walk, and 9-Hole Peg Test, designed to quantify both disability improvement and worsening in multiple sclerosis (MS). Objective: To assess the sensitivity and clinical meaningfulness of ODRS using natalizumab Phase 3 data sets (AFFIRM in relapsing-remitting MS and ASCEND in secondary progressive MS). Methods: Differences in ODRS over 96 weeks, ODRS at Week 96, and slope of ODRS change per year between natalizumab and placebo groups were analyzed. Correlation between ODRS and changes in patient-reported outcomes was also analyzed. Results: The difference (95% confidence interval (CI)) in the ODRS over 96 weeks between natalizumab and placebo groups was 0.34 (0.21–0.46) in AFFIRM (p < 0.001), and 0.18 (0.03–0.34) in ASCEND (p = 0.021). Significant differences between treatment arms were also observed in ODRS at Week 96 and in the slope of change per year in both studies. There was a significant linear correlation between ODRS at Week 96 and the change from baseline in both the physical and mental components of the 36-item Short Form Survey (SF-36) in both studies. Conclusion: This analysis supports ODRS as a sensitive and potentially clinically meaningful disability outcome measure in MS.

Correlating Biomechanical Gait Analysis With Patient-Reported Outcomes After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Background:Postoperative biomechanics after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) are an outcome of interest, but correlation with patient-reported outcomes (PROs) remains unclear.Purpose/Hypothesis:The purpose of this study was to assess the correlation between changes in hip biomechanics in FAIS patients after hip arthroscopy and changes in PRO scores. We hypothesized that gait analysis would demonstrate significant correlations between pre- and postoperative changes in biomechanics and changes in PRO scores.Study Design:Descriptive laboratory study.Methods:FAIS patients without dysplasia or arthritis who underwent primary hip arthroscopy for labral repair and femoroplasty underwent preoperative and 1-year postoperative 3-dimensional motion tracking and biomechanical testing during normal gait. Joint kinematics calculated included flexion/extension (sagittal plane), abduction/adduction (frontal plane), and internal/external rotation (transverse plane). Peak hip angles and moments were compared between baseline and 1-year postoperative measures. At baseline, 1-year, and 2-year postoperatively, patients completed the following PRO surveys: 12-Item Short Form Health Survey (SF-12), modified Harris Hip Score (mHHS), and Hip disability and Osteoarthritis Outcome Score (HOOS). Joint kinematics that significantly improved 1 year after surgery were assessed for correlations with PRO scores.Results:A total of 10 patients (12 hips) were enrolled prospectively. PROs significantly improved at 1 and 2 years postoperatively compared with baseline values for HOOS, mHHS, and SF-12 Physical Component Score, with all patients achieving the minimal clinically important difference (MCID) on the HOOS Sport/Recreation and Quality of Life subscales. From preoperatively to 1-year postoperatively, significant improvements were seen in peak hip abduction angle (from −2.3° ± 1.8° to −4.6° ± 1.8°; P = .0058) and peak hip extension moment (from −1.03 ± 0.19 to −0.85 ± 0.20 N·m/kg; P = .014); however, there were no significant correlations between these changes and the pre- to postoperative changes on any PRO scores.Conclusion:Gait analysis of FAIS patients after hip arthroscopy demonstrated small, albeit significant, changes in postoperative hip kinetics and kinematics; however, these changes did not correlate with the large, clinically significant improvements in PROs at 1 year after surgery.Clinical Relevance:The results of this study suggest that the degree of improvement in short-term PROs after hip arthroscopy for FAIS may not be related to small changes in biomechanics postoperatively.

Abstract 134: Blood Pressure Control And Hypertension Diagnosis Six Months After Completing Ambulatory Blood Pressure Diagnostic Testing

Importance: Undiagnosed hypertension contributes to excess morbidity and mortality. Objective: To examine the effect of hypertension diagnostic testing on hypertension diagnoses and blood pressure (BP) control months at 6 months. Design, Setting, and Participants: BP CHECK was a randomized diagnostic study of 510 adults aged 18-85 without diagnosed hypertension with elevated BP in clinic and at baseline, conducted from 2017 to 2019 in primary care centers of an integrated healthcare system. Participants were randomization to one of three diagnostic regimens: (1) Clinic BP, (2) Home BP, or (3) Kiosk BP. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM) at 3 weeks. ABPM results were sent to participants and their primary care providers and uploaded into the electronic health records (EHR). Main Outcomes and Measures: The primary outcomes were BP control and receipt of a new hypertension diagnosis at 6 months. We further examined whether changes in patient-reported outcomes relating to health behaviors or 6-month health attitudes were associated with BP control or a new hypertension diagnosis. Results: Mean baseline BP was 150/88 mmHg. Among 467 study participants completing ABPM, 335 (72%) were confirmed to have hypertension. At 6 months, 47% (156/335) of participants with hypertension achieved BP &lt;140/90 mmHg and 41% (137/335) had a new hypertension diagnosis recorded in the EHR with no differences by randomized group. Participants with a new hypertension diagnosis (n=137) experienced significantly greater reductions from baseline in systolic and diastolic BP (mean difference, -4.9 mmHg [95% CI: -7.8,-2.1]) and diastolic BP (-2.3 mmHg [-4.3, -0.4]) compared to individuals with undiagnosed hypertension (n=198). Significantly higher proportions of participants with adequate BP control and diagnosed hypertension felt sharing home BP readings with their provider was helpful or very helpful in managing their BP. Conclusion and Relevance: Most participants with high BP on screening and ABPM diagnostic testing did not achieve adequate BP control or receive a hypertension diagnosis within 6 months. New strategies are needed to increase diagnosis of hypertension in clinical practice

Increased Rate Of Force Development Is Correlated To Symptom Improvement In Patients With Rotator Cuff Tendinopathy

Rotator cuff (RC) tendinopathy is the most common cause of shoulder pain. Exercise is a beneficial treatment, but many patients have recurrence of pain within one year. Disability is associated with RC muscle performance deficits. However, there is poor understanding of the neuromuscular mechanisms associated with these deficits. Exercise-based clinical trials have shown limited effects on isometric strength as the metric of muscle performance. Exploring neuromuscular mechanisms that account for both neural and muscular components of muscle performance, such as rate of force development (RFD) are warranted. PURPOSE: Determine the effects of an exercise intervention on strength and RFD, and the relationship to changes in patient-reported outcomes. METHODS: Participants (n = 7; age = 26.8 ± 5) diagnosed with RC tendinopathy underwent an exercise protocol for 2 weeks, progressing from exercise with the arm below 90°, to exercise above 90° and increased resistance. Measures were taken at baseline and post-intervention. Pain and function outcomes were measured with the Penn Shoulder Score. Maximum isometric strength via peak force, and RFD for scaption and external rotation (ER) were measured using a fixed hand-held dynamometer. RFD was defined as the area under the force-time curve from 0 to 50, 100 and 200 ms. Paired t-tests compared pre to post-intervention measures. Pearson’s correlation defined the relationship between changes in strength and RFD with outcomes. RESULTS: There were significant changes in pain [mean difference (MD) = -3.3; (95%CI: -0.32, -6.24); p = 0.03], and function [MD = 3.3 (95%CI: 0.05, 6.5); p = 0.04] pre- to post-intervention. There was a significant high correlation between the change in pain and ER RFD at 50 ms (r = 0.81; p = 0.02) and 100 ms (r = 0.74; p = 0.05), but not with maximum isometric strength. CONCLUSIONS: The change in pain can be explained by RFD at 50 ms, and to a lesser extent at 100 ms. RFD at 75 ms or above is associated with muscle contractile properties, while below is associated with neural changes. Our results suggest that neural changes in force production may be more relevant to decreased pain with exercise. Selecting exercises that target an increase in RFD may be beneficial, but more research is needed to explore if this potential mechanism also plays a role in long-term improvements.

How Do Fear-related Patient Reported Outcomes Changes Following Acl Reconstruction Among Competitive And Recreational Athletes?

How Do Fear-related Patient Reported Outcomes Changes Following Acl Reconstruction Among Competitive And Recreational Athletes?