Baseline Patient-reported Outcomes Research Articles

Patient-reported symptom interference with activity- and mood-related functioning prior to start of an early-phase oncology combination trial including immune checkpoint blockade.

12084 Background: We examined symptom interference with activity- and mood-related functioning at baseline in early-stage trials of combination treatments that included at least one immune checkpoint inhibitor, and its association with quality of life (QOL)-, clinical-, and trial-related factors. Methods: Patients scheduled to begin an early-phase trial of a combination treatment with immune checkpoint blockade, and who had not received trial-related treatment were recruited into a prospective longitudinal study design (NCI R01CA242565), and completed the following validated patient-reported outcome (PRO) measures prior to trial start: MD Anderson Symptom Inventory- Immunotherapy (score range: 0-10, higher scores = worse symptom interference); NCI’s PRO Common Terminology Criteria for Adverse Events (0-4, higher = worse severity); EuroQoL-5 dimensions assessing health status (0-100, higher = better health) and problems with self-care, and the Sloan Global QOL scale (0-10, higher = better QOL). Statistical tests included Spearman’s correlation rho (r) and multivariable linear regression. Results: 977 baseline PRO measures were completed by 247 patients (median age = 59 y; 46% female). Worst symptom-related interference was with activity (3.0 on a 0-10 scale), work (2.9), and enjoyment of life (2.4). Composite score means were 2.8 for symptom interference with walking, activity, and work (WAW; activity-related functioning), and 2.1 for interference with relationships, enjoyment of life, and mood (REM; mood-related functioning). Symptoms most associated with worse WAW were fatigue (P<0.001) and appetite loss (P=0.001). Worse WAW was linked to worse REM (r=0.78, P<0.001). Diminished sexual interest/mood (DSI) was associated with worse WAW (r=0.35, P<0.001) and REM (r=0.33, P<0.001). Worse WAW was linked to shorter trial duration (P=0.003) and worse response (progression of disease/immune-related progression) on the clinical trial (P=0.05). Conclusions: This first, comprehensive and prospective examination of symptom interference with functioning at trial baseline found that worse symptom interference was linked to worse QOL, poorer clinical outcomes, and shorter trial duration. These findings suggest that baseline patient-reported symptom interference with functioning can serve as a potential biomarker of poor prognosis in investigational trials, and that trial patients may benefit from initiation of supportive care prior to trial start. [Table: see text]

Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701).

577 Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxane-containing chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p<0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p<0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981 .

Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).

4502 Background: EV+P nearly doubled median progression-free survival and overall survival vs PBC in patients (pts) with previously untreated la/mUC in the phase 3 EV-302 trial. PROs are reported here. Methods: In EV-302 (NCT04223856) pts were randomized 1:1 to EV+P or PBC (gemcitabine with cisplatin or carboplatin). PRO assessments included the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), and the Brief Pain Inventory Short Form (BPI-SF) completed at baseline, weekly for 12 weeks (wks), then every 3 wks through survival follow-up, inclusive of the time post-progression. Time to pain progression (TTPP) and mean change from baseline in worst pain at wk 26 using the BPI-SF were prespecified analyses statistically tested using a gatekeeping strategy. Mean change from baseline through wk 26 and time to confirmed deterioration (TTCD) of EORTC-QLQ-C30 and BPI-SF domains were prespecified descriptive analyses. TTPP and TTCD were assessed using Kaplan-Meier methods. Results: Of 886 pts randomized, 731 (376 received EV+P; 355 PBC) completed baseline PRO questionnaires. Compliance rates differed between arms and remained >70% through wk 29 for EV+P and through only wk 17 for PBC. Median TTPP was 14.2 months (mos) with EV+P and 10.0 mos with PBC (hazard ratio [HR]=0.92; 95% CI=0.72, 1.17; 2-sided p-value=0.48). The least squares (LS) mean reduction in worst pain at wk 26 was numerically greater with EV+P vs PBC (-0.61 vs -0.03, LS mean difference [95% CI]: -0.58 [-1.05, -0.11] [nominal 2-sided p-value=0.015]). Pts with moderate to severe pain at baseline who were treated with EV+P (n=128, 34%) had a meaningful (>2 pt) improvement from baseline in BPI worst pain from wk 3 through 26. In EORTC QLQ-C30 Global Health Status/Quality of Life [GHS/QoL], EV+P demonstrated a transient worsening at wk 3 (-6.3) that returned to baseline from wks 4 through 26, while patients treated with PBC demonstrated deterioration from wk 1 through wk 17 (range -1.2 to -7.1) when scores returned to baseline. TTCD for EORTC QLQ-C30 GHS/QoL was 5.9 mos with EV+P vs 3.2 mos with PBC (HR = 0.98 [95% CI]: 0.79 – 1.2). Conclusions: Pts treated with EV+P have improved survival compared with PBC without detriment to quality of life and functioning, further supporting the value of EV+P for pts with la/mUC. Compliance, especially after progression, was lower than expected (particularly in the PBC arm) and may have impacted the results. Clinical trial information: NCT04223856 .

Quantifying Patient Expectations for Total Knee Arthroplasty: Expectations for Improvement Are Greater Than Minimal Clinically Important Difference

BackgroundAchieving a minimal clinically important difference (MCID) in patient-reported outcomes following total knee arthroplasty (TKA) is common, yet up to 20% patient dissatisfaction persists. Unmet expectations may explain post-TKA dissatisfaction. No prior studies have quantified patient expectations using the same patient-reported outcome metric as used for MCID to allow direct comparison. MethodsThis was a prospective study of patients undergoing TKA with 5 fellowship-trained arthroplasty surgeons at one academic center. Baseline Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) domains were assessed. Expected PROMIS scores were determined by asking patients to indicate the outcomes they were expecting at 12 months postoperatively. Predicted scores were generated from a predictive model validated in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) dataset. T-tests were used to compare baseline, expected, and predicted PROMIS scores. Expected scores were compared to PROMIS MCID values obtained from the literature. Regression models were used to identify patient characteristics associated with high expectations. ResultsThere were 93 patients included. Mean age was 67 years (range, 30 to 85) and 55% were women. Mean baseline PROMIS PF and PI was 34.4 ± 6.7 and 62.2 ± 6.4, respectively. Patients expected significant improvement for PF of 1.9 times the MCID (MCID = 11.3; mean expected improvement = 21.6, 95% confidence interval [CI] 19.6 to 23.5, P < .001) and for PI of 2.3 times the MCID (MCID = 8.9; mean expected improvement = 20.6, 95% CI 19.1-22.2, P < .001). Predicted scores were significantly lower than expected scores (mean difference = 9.5, 95% CI 7.7 to 11.3, P < .001). No unique patient characteristics were associated with high expectations (P > .05). ConclusionsTo our knowledge, this study is the first to quantify preoperative patient expectations using the same metric as MCID to allow for direct comparison. Patient expectations for improvement following TKA are ∼2× greater than MCID and are significantly greater than predicted outcome scores. This discrepancy challenges currently accepted standards of success after TKA and indicates a need for improved expectation setting prior to surgery.

Abstract PO1-11-10: Use of a standardized tool for the evaluation and treatment of cancer related cognitive impairment (chemo-brain) among breast cancer patients

Abstract There is a steep linear increase in patients surviving a cancer diagnosis. Clinical solutions that address the high prevalence of cancer-related treatment effects (CRTE) are urgently needed. A stark example of this need is the dearth of screening and treatment programs for cancer related cognitive impairment (CRCI) (colloquially called “chemo-brain”). Up to 75% of cancer patients report neurocognitive changes that leave patients unable to cope with the expectations of employers, colleagues, families, and friends. The prevalence of neurological disorders is 275% higher among adult cancer patients, when compared to an adult cancer-free population. For many adolescent and young adult cancer patients, the onset of CRCI occurs during "cognitive prime time"; a time when individuals are pursuing education, careers, and raising families. To address a gap in CRTE we have implemented a virtual multi-disciplinary intervention to measure and treat CRCI. Our CRCI intervention follows National Comprehensive Cancer Network and American Society of Clinical Oncology (ASCO) guidelines for CRCI. These guidelines indicate a multi-disciplinary approach with emphasis on increasing physical activity levels, cognitive-behavioral therapy, memory adaptive training, mood management, and sleep optimization. Our approach also follows recent ASCO guidelines for nutrition counseling. Our CRCI program utilizes medical oncologists, physician assistants, mental health therapists, registered dietitians, and occupational therapists. A nationally validated patient reported outcome (PRO) measurement, analysis, and reporting platform informs clinical treatment pathways, monitors patient progress, guides clinical decision making, and improves patient/provider communication. Using health status measures for CRCI, and following American Cancer Society and ASCO guidelines, patients are risk-stratified into three personalized cancer survivor care pathways: 1) low-complexity patients; 2) medium-complexity patients; and 3) high-complexity patients. Low-complexity patients baseline PROs score in the normal range, medium-complexity patients are those who score below the norm (moderate to large effect size difference from normal), and high-complexity patients are those who score well below the norm (greater than larger effect size difference from normal). Low-complexity patients are enrolled into a self-management and continuation of care program. Medium-complexity patients are enrolled into a shared care program. High-complexity patients are enrolled into an acute care program. All three clinical pathways include continued risk-factor vital-sign surveillance. Nearly 100% (99%) of patients who enroll in our primary cancer survivor care program complete our PRO baseline (N=80). From a convenient sample of breast cancer patients (N=42), provisional results of patient-specific segmentation analyses reveal a nearly perfect bell-shaped curve, with 51% of the population classified within the definition of medium-complexity and even split of outliers (high-complexity 24% and low-complexity 24%). Additionally, of all patients in our primary cancer survivor care program who completed at least three measurement time points for health status measures of cognitive impartment (N=38), 92% had a positive experience, 71% had a clinically significant improvement in cognitive health, 21% had a no change in cognitive status, and only 8% had a decline in cognitive health. If these data, and PRO implementation approach hold true, this program could be scaled to national and international cancer survivor population suffering from CRCI. Citation Format: John Librett, Mark Kosinski, Gregory Litton. Use of a standardized tool for the evaluation and treatment of cancer related cognitive impairment (chemo-brain) among breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-10.

Abstract PO1-11-06: Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms

Abstract Background: Although treatment with an aromatase inhibitor (AI) for 5-10 years decreases 10-year breast cancer mortality by about 40%, up to 25% of patients will stop treatment early because of treatment-related, intolerable joint and muscular pain and stiffness, called aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). We previously identified that nociplastic pain, or chronic pain in the absence of tissue damage or inflammation, is associated with increased likelihood of developing AIMSS. Other studies have found that symptom clusters, such as the SPPADE symptoms (sleep disturbance, pain, physical function impairment, anxiety, depression, and low energy/fatigue) are prevalent and co-occur in patients with cancer. Here we examine the prevalence of SPPADE symptoms for patients experiencing AIMSS and willing to enroll on a clinical trial examining use of cannabidiol (CBD) to treat their symptoms. Methods: Patients with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS (defined as worst joint pain ≥4/10 during prior 7 days that developed or worsened since starting AI therapy) were eligible for enrollment in this single arm, single center phase 2 open label clinical trial (NCT04754399). Enrolled patients completed validated questionnaires at baseline and then received CBD (Epidiolex) for 15 weeks. Patient-reported outcomes (PRO) data was collected serially, including the following questionnaires which addressed SPPADE symptoms: Brief Pain Inventory (BPI) to assess pain, PROMIS Profile 29+2 v2.1 to assess multiple symptoms, and Fibromyalgia Survey (FMS) to assess nociplastic pain. Results: 39 patients enrolled on this clinical trial. The median age at enrollment was 57 (range 37-59) and 21% of patients were over age 70. The majority of patients were white (92%) and average BMI was 31 (SD 6.6). Anastrozole was the most used aromatase inhibitor (74%), followed by exemestane (18%), and letrozole (8%). 5 patients (13%) required concomitant GnRHa therapy. Baseline PRO data was obtained from 37 patients. BPI average pain score over the week prior to enrollment was 5.1 (SD 1.5) and worst pain score was 7.2 (SD 1.3). Pain interference reported on the BPI was 4.1 (SD 2.1). Compared to the general population, enrolled patients reported better physical function (T-score 60.2, SE 3.7), less depression (T-score 45.5, SE 4.7) and fatigue (T-score 46.7, SE 5.1), and similar levels of anxiety (T-score 51, SE 7.1) and sleep disturbance (T-score 49.5, SE 5.9) on the PROMIS Profile. On the FMS, 62% of patients had evidence of nociplastic pain, with average score 13.3 (SD 5.7). The median number of sites of pain in the body reported by patients was 8 (range 1-16). Conclusions: While patients enrolling on an AIMSS clinical trial reported a high degree of daily pain that regularly interferes with their activities, for most patients these symptoms did not appear to have a negative impact on mood, affect, or other symptoms that typically cluster with pain. Though it is difficult to extrapolate results from a small population, the unexpected absence of co-occurring symptoms in this population raises additional questions about the interplay of AIMSS and other symptoms commonly reported in interventional AIMSS studies. Follow-up PRO data will be obtained in this clinical trial, allowing us to examine the impact of CBD use on pain, pain interference, and other patient-reported symptoms, as well as to explore which patients are more likely to obtain benefit from CBD treatment. Funding support provided by Conquer Cancer, the ASCO Foundation and the Rising Tide Foundation for Clinical Cancer Research. Citation Format: Fleege Nicole, N. Lynn Henry. Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-06.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial

In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. AstraZeneca.

Hip Osteoarthritis in Patients Undergoing Surgery for Severe Adult Spinal Deformity: Prevalence and Impact on Spine Surgery Outcomes.

Hip osteoarthritis (OA) is common in patients with adult spinal deformity (ASD). Limited data exist on the prevalence of hip OA in patients with ASD, or on its impact on baseline and postoperative alignment and patient-reported outcome measures (PROMs). Therefore, this paper will assess the prevalence and impact of hip OA on alignment and PROMs. Patients with ASD who underwent L1-pelvis or longer fusions were included. Two independent reviewers graded hip OA with the Kellgren-Lawrence (KL) classification and stratified it by severity into non-severe (KL grade 1 or 2) and severe (KL grade 3 or 4). Radiographic parameters and PROMs were compared among 3 patient groups: Hip-Spine (hip KL grade 3 or 4 bilaterally), Unilateral (UL)-Hip (hip KL grade 3 or 4 unilaterally), or Spine (hip KL grade 1 or 2 bilaterally). Of 520 patients with ASD who met inclusion criteria for an OA prevalence analysis, 34% (177 of 520) had severe bilateral hip OA and unilateral or bilateral hip arthroplasty had been performed in 8.7% (45 of 520). A subset of 165 patients had all data components and were examined: 68 Hip-Spine, 32 UL-Hip, and 65 Spine. Hip-Spine patients were older (67.9 ± 9.5 years, versus 59.6 ± 10.1 years for Spine and 65.8 ± 7.5 years for UL-Hip; p < 0.001) and had a higher frailty index (4.3 ± 2.6, versus 2.7 ± 2.0 for UL-Hip and 2.9 ± 2.0 for Spine; p < 0.001). At 1 year, the groups had similar lumbar lordosis, yet the Hip-Spine patients had a worse sagittal vertebral axis (SVA) measurement (45.9 ± 45.5 mm, versus 25.1 ± 37.1 mm for UL-Hip and 19.0 ± 39.3 mm for Spine; p = 0.001). Hip-Spine patients also had worse Veterans RAND-12 Physical Component Summary scores at baseline (25.7 ± 9.3, versus 28.7 ± 9.8 for UL-Hip and 31.3 ± 10.5 for Spine; p = 0.005) and 1 year postoperatively (34.5 ± 11.4, versus 40.3 ± 10.4 for UL-Hip and 40.1 ± 10.9 for Spine; p = 0.006). This study of operatively treated ASD revealed that 1 in 3 patients had severe hip OA bilaterally. Such patients with severe bilateral hip OA had worse baseline SVA and PROMs that persisted 1 year following ASD surgery, despite correction of lordosis. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.MethodsCross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.ResultsOf 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.ConclusionsPatient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

Relating preoperative MCS-12 to microdiscectomy outcomes

PurposeTo determine the impact of poor mental health on patient-reported and surgical outcomes after microdiscectomy.MethodsPatients ≥ 18 years who underwent a single-level lumbar microdiscectomy from 2014 to 2021 at a single academic institution were retrospectively identified. Patient-reported outcomes (PROMs) were collected at preoperative, three-month, and one-year postoperative time points. PROMs included the Oswestry Disability Index (ODI), Visual Analog Scale Back and Leg (VAS Back and VAS Leg, respectively), and the mental and physical component of the short form-12 survey (MCS and PCS). The minimum clinically important differences (MCID) were employed to compare scores for each PROM. Patients were categorized as having worse mental health or better mental health based on a MCS threshold of 50.ResultsOf 210 patients identified, 128 (61%) patients had a preoperative MCS score ≤ 50. There was no difference in 90-day surgical readmissions or spine reoperations within one year. At 3- and 12-month time points, both groups demonstrated improvements in all PROMs (p < 0.05). At three months postoperatively, patients with worse mental health had significantly lower PCS (42.1 vs. 46.4, p = 0.004) and higher ODI (20.5 vs. 13.3, p = 0.006) scores. Lower mental health scores were associated with lower 12-month PCS scores (43.3 vs. 48.8, p < 0.001), but greater improvements in 12-month ODI (− 28.36 vs. − 18.55, p = 0.040).ConclusionWhile worse preoperative mental health was associated with lower baseline and postoperative PROMs, patients in both groups experienced similar improvements in PROMs. Rates of surgical readmissions and reoperations were similar among patients with varying preoperative mental health status.

Preoperative Function Affects Ability to Achieve One-Year Minimum Clinically Important Difference for Patients Undergoing Total Knee Arthroplasty

BackgroundMinimum clinically important difference (MCID) values are commonly used to measure treatment success for total knee arthroplasty (TKA). MCID values vary according to calculation methodology, and prior studies have shown that patient factors are associated with failure to achieve MCID thresholds. The purpose of this study was to determine if anchor-based 1-year Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS-JR) MCID values varied among patients undergoing TKA based on patient-specific factors. MethodsThis was a retrospective review of patients undergoing TKA from 2017-2018. Patients without baseline or 1-year KOOS-JR or Patient-Reported Outcome Measurement Information System Global Health data or that underwent procedures other than primary TKA were excluded. MCIDs were calculated and compared between patient groups according to preoperative characteristics. ResultsAmong the included 976 patients, 1-year KOOS-JR MCIDs were 26.6 for men, 28.2 for women, 30.7 for patients with a diagnosis of anxiety and/or depression, and 26.7 for patients without a diagnosis. One-year MCID values did not differ significantly according to gender (P = .379) or mental health diagnosis (P = .066), nor did they correlate with body mass index (β = −0.034, P = .822). Preoperative KOOS-JR decile demonstrated an inverse relationship with 1-year MCID values and attainment of MCID. ConclusionsThe proportion of patients attaining KOOS-JR MCID values demonstrated an inverse relationship with preoperative baseline function. Future investigation may identify patient factors that allow surgeons to better capture patient satisfaction with their procedure despite failure to attain a 1-year MCID.

Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report

PurposeA novel form of lung function imaging has been developed that uses 4DCT data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side-effects. A 4DCT-ventilation functional avoidance, phase II, multi-center clinical trial was completed. The purpose of this work is to quantify patient reported outcomes (PRO) changes for patients treated with functional avoidance and to determine which metrics are predictive of PRO changes. Materials and MethodsPatients with locally advanced lung cancer receiving curative intent radiotherapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, administered pre-treatment, 3, 6, and 12 months post-treatment. FACT-TOI (Trial Outcome Index) and the FACT-LCS (Lung Cancer Subscale) percentage of clinically meaningful declines (CMD) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. Results59 patients completed baseline PRO surveys. 83% of patients had non-small-cell lung cancer, with 75% having stage III disease. The median dose was 60 Gy in 30 fractions. CMD FACT-TOI decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-LCS decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. While an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all p>0.053). ConclusionThe current work provides an innovative combination of functional avoidance and PROs and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

Impact of Self-Reported Loss of Balance and Gait Disturbance on Outcomes following Adult Spinal Deformity Surgery.

Background: The objective of this study was to evaluate if imbalance influences complication rates, radiological outcomes, and patient-reported outcomes (PROMs) following adult spinal deformity (ASD) surgery. Methods: ASD patients with baseline and 2-year radiographic and PROMs were included. Patients were grouped according to whether they answered yes or no to a recent history of pre-operative loss of balance. The groups were propensity-matched by age, pelvic incidence-lumbar lordosis (PI-LL), and surgical invasiveness score. Results: In total, 212 patients were examined (106 in each group). Patients with gait imbalance had worse baseline PROM measures, including Oswestry disability index (45.2 vs. 36.6), SF-36 mental component score (44 vs. 51.8), and SF-36 physical component score (p < 0.001 for all). After 2 years, patients with gait imbalance had less pelvic tilt correction (-1.2 vs. -3.6°, p = 0.039) for a comparable PI-LL correction (-11.9 vs. -15.1°, p = 0.144). Gait imbalance patients had higher rates of radiographic proximal junctional kyphosis (PJK) (26.4% vs. 14.2%) and implant-related complications (47.2% vs. 34.0%). After controlling for age, baseline sagittal parameters, PI-LL correction, and comorbidities, patients with imbalance had 2.2-times-increased odds of PJK after 2 years. Conclusions: Patients with a self-reported loss of balance/unsteady gait have significantly worse PROMs and higher risk of PJK.

Automating Patient-reported Data Collection: Does it Work?

There are several electronic patient-reported outcomes (ePROs) vendors that are being used at institutions to automate data collection. However, there is little known about their success in collecting patient-reported outcomes (PROs) and it is unknown which patients are more likely to complete these surveys. In this study, we assessed rates of PRO completion, as well as determined factors that contributed to the completion of baseline and follow-up surveys. We queried our ePRO platform to assess rates of completion for baseline and follow-up surveys for patients from October 2019 to June 2022. All baseline surveys were administered before pediatric orthopaedic procedures, and follow-up surveys were sent at 3 months, 6 months, 1 year, and 2 years after surgery to patients with baseline data. Descriptive statistics were used to summarize the data. Univariate and multivariate analyses were performed to assess differences in patients who did and did not complete surveys. This study included 1313 patients during the study period. Baseline surveys were completed by 66% of the cohort (n = 873 patients). There was a significant difference in race/ethnicity and language spoken in the patients who did and did not complete baseline surveys ( P < 0.01) with lower rates of completion in African American, Hispanic, and Spanish-speaking patients. At least one follow-up was obtained for 68% of patients with baseline surveys (n = 597 patients). There were significant differences in completion rates based on race/ethnicity ( P = 0.03) and language spoken ( P = 0.01). There were lower rates of baseline completion for patients with government insurance in our multivariate analysis (odds ratio: 0.6, P < 0.01). Baseline and follow-up PRO data can be obtained from the majority of patients using automated ePRO platforms. However, additional focus is needed on collecting data from traditionally underrepresented patient groups to better understand outcomes in these patient populations. Level III-retrospective cohort study.

Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult and adolescent patients with atopic dermatitis in France treated with dupilumab: Real-world insights 1 year into the GLOBOSTAD multinational prospective observational study

Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult and adolescent patients with atopic dermatitis in France treated with dupilumab: Real-world insights 1 year into the GLOBOSTAD multinational prospective observational study

Safety of Same-Day Discharge Following Total Ankle Arthroplasty: A Retrospective Cohort Analysis.

Joint replacement procedures have traditionally been performed in an inpatient setting to minimize complication rates. There is growing evidence that total ankle arthroplasty (TAA) can safely be performed as an outpatient procedure, with the potential benefits of decreased health care expenses and improved patient satisfaction. Prior studies have not reliably made a distinction between outpatient TAA defined as length of stay <1 day and same-day discharge. The purpose of our study was to compare a large volume of same-day discharge and inpatient TAA for safety and efficacy. Patients undergoing TAA at our US-based institution are part of an institutional review board-approved registry. We queried the registry for TAA performed by the single highest-volume surgeon at our institution between May 2020 and March 2022. Same-day discharge TAA was defined as discharge on the day of the procedure. Patient demographics, baseline clinical variables, concomitant procedures, postoperative complications, and patient-reported outcomes were collected. Postoperative outcomes were compared after 1:1 nearest-neighbor matching by age, sex, Charlson Comorbidity Index (CCI), and American Society of Anesthesiologists (ASA) score. Multivariable models were created for comparison with the matched cohort outcome comparison analysis. Our same-day discharge group was younger (median 58 vs 67 years; P < .001), with proportionally fewer females (36.4% vs 51.4%; P = .044) and lower Charlson Comorbidity Indices (median 1 vs 3; P < .001) than the inpatient group. At a median follow-up of 1 year, after matching by age, sex, CCI, and ASA score, there was no difference in complications (P = .788), reoperations (P = .999), revisions (P = .118), or Patient-Reported Outcomes Measurement Information System (PROMIS) scores between the 2 groups. Multivariable analyses performed demonstrated no evidence of association between undergoing same-day discharge TAA vs inpatient TAA and reoperation, revision, complication, or 1-year PROMIS scores (P > .05). In our system of health care, with appropriate patient selection, same-day discharge following TAA can be a safe alternative to inpatient TAA. Level III, retrospective cohort study.

Radiology Reports Do Not Accurately Portray the Severity of Cervical Neural Foraminal Stenosis.

Retrospective study. (1) To compare cervical magnetic resonance imaging (MRI) radiology reports to a validated grading system for cervical foraminal stenosis (FS) and (2) to evaluate whether the severity of cervical neural FS on MRI correlates to motor weakness or patient-reported outcomes. Radiology reports of cervical spine MRI are often reviewed to assess the degree of neural FS. However, research looking at the association between these reports and objective MRI findings, as well as clinical symptoms, is lacking. We retrospectively identified all adult patients undergoing primary 1 or 2-level anterior cervical discectomy and fusion at a single academic center for an indication of cervical radiculopathy. Preoperative MRI was assessed for neural FS severity using the grading system described by Kim and colleagues for each level of fusion, as well as adjacent levels. Neural FS severity was recorded from diagnostic radiologist MRI reports. Motor weakness was defined as an examination grade <4/5 on the final preoperative encounter. Regression analysis was conducted to evaluate whether the degree of FS by either classification was related to patient-reported outcome measure severity. A total of 283 patients were included in the study, and 998 total levels were assessed. There were significant differences between the MRI grading system and the assessment by radio-logists ( P < 0.001). In levels with moderate stenosis, 28.9% were classified as having no stenosis by radiology. In levels with severe stenosis, 29.7% were classified as having mild-moderate stenosis or less. Motor weakness was found similarly often in levels of moderate or severe stenosis (6.9% and 9.2%, respectively). On regression analysis, no associations were found between baseline patient-reported outcome measures and stenosis severity assessed by radiologists or MRI grading systems. Radiology reports on the severity of cervical neural FS are not consistent with a validated MRI grading system. These radiology reports underestimated the severity of neural foraminal compression and may be inappropriate when used for clinical decision-making. Level III.

Preoperative diagnosis of mental health disorder and dysphagia following anterior cervical spine surgery.

Mental health disorders (MHDs) have been linked to worse postoperative outcomes after various surgical procedures. Past studies have also demonstrated a higher prevalence of dysphagia in both acute and community mental health settings. Dysphagia is among the most common complications following anterior cervical spine surgery (ACSS); however, current literature describing the association between an established diagnosis of an MHD and the rate of dysphagia after ACSS is sparse. All patients who underwent ACSS between 2014 and 2020 with a minimum of 6 months of follow-up were retrospectively evaluated at a single institution. Patients were divided into cohorts depending on an established diagnosis of an MHD: the first had no established MHD (non-MHD); the second included patients with a diagnosed MHD. Outcomes were measured using pre- and postoperative patient-reported outcome scores, which included the Swallowing Quality of Life survey for dysphagia, as well as physical and mental health questionnaires. Postoperative dysphagia surveys were obtained at final follow-up for both patient cohorts. A total of 68 and 124 patients with and without a diagnosis of a MHD were assessed. The MHD group reported significantly worse baseline Patient-Reported Outcomes Measurement Information System depression scale scores (p < 0.001), 12-Item Short-Form Health Survey (p < 0.001), and Veterans RAND 12-Item Health Survey (p = 0.001) mental health components compared to non-MHD group. This group continued to have worse mental health status in the postoperative period, as reported by Patient-Reported Outcomes Measurement Information System depression scale scores (p = 0.024), 12-Item Short-Form Health Survey (p = 0.019), and Veterans RAND 12-Item Health Survey (p = 0.027). Postoperative assessment of Swallowing Quality of Life scores (expressed as the mean ± SD) also showed worse dysphagia outcomes in the MHD cohort (80.1 ± 12.2) than in the non-MHD cohort (86.0 ± 12.1, p = 0.001). ACSS is associated with significantly higher postoperative dysphagia in patients diagnosed with an MHD when compared to patients without an established mental health diagnosis. Given the high prevalence of MHDs in patients with spinal pathology, it is important for spine surgeons to take note of the increased incidence of dysphagia faced by this patient population.

Machine learning clustering of adult spinal deformity patients identifies four prognostic phenotypes: a multicenter prospective cohort analysis with single surgeon external validation

BACKGROUND CONTEXTAmong adult spinal deformity (ASD) patients, heterogeneity in patient pathology, surgical expectations, baseline impairments, and frailty complicates comparisons in clinical outcomes and research. This study aims to qualitatively segment ASD patients using machine learning-based clustering on a large, multicenter, prospectively gathered ASD cohort. PURPOSETo qualitatively segment adult spinal deformity patients using machine learning-based clustering on a large, multicenter, prospectively gathered cohort. STUDY DESIGN/SETTINGMachine learning algorithm using patients from a prospective multicenter study and a validation cohort from a retrospective single center, single surgeon cohort with complete 2-year follow up. PATIENT SAMPLEAbout 805 ASD patients; 563 patients from a prospective multicenter study and 242 from a single center to be used as a validation cohort. OUTCOME MEASURESTo validate and extend the Ames-ISSG/ESSG classification using machine learning-based clustering analysis on a large, complex, multicenter, prospectively gathered ASD cohort. METHODSWe analyzed a training cohort of 563 ASD patients from a prospective multicenter study and a validation cohort of 242 ASD patients from a retrospective single center/surgeon cohort with complete two-year patient-reported outcomes (PROs) and clinical/radiographic follow-up. Using k-means clustering, a machine learning algorithm, we clustered patients based on baseline PROs, Edmonton frailty, age, surgical history, and overall health. Baseline differences in clusters identified using the training cohort were assessed using Chi-Squared and ANOVA with pairwise comparisons. To evaluate the classification system's ability to discern postoperative trajectories, a second machine learning algorithm assigned the single-center/surgeon patients to the same 4 clusters, and we compared the clusters' two-year PROs and clinical outcomes. RESULTSK-means clustering revealed four distinct phenotypes from the multicenter training cohort based on age, frailty, and mental health: Old/Frail/Content (OFC, 27.7%), Old/Frail/Distressed (OFD, 33.2%), Old/Resilient/Content (ORC, 27.2%), and Young/Resilient/Content (YRC, 11.9%). OFC and OFD clusters had the highest frailty scores (OFC: 3.76, OFD: 4.72) and a higher proportion of patients with prior thoracolumbar fusion (OFC: 47.4%, OFD: 49.2%). ORC and YRC clusters exhibited lower frailty scores and fewest patients with prior thoracolumbar procedures (ORC: 2.10, 36.6%; YRC: 0.84, 19.4%). OFC had 69.9% of patients with global sagittal deformity and the highest T1PA (29.0), while YRC had 70.2% exhibiting coronal deformity, the highest mean coronal Cobb Angle (54.0), and the lowest T1PA (11.9). OFD and ORC had similar alignment phenotypes with intermediate values for Coronal Cobb Angle (OFD: 33.7; ORC: 40.0) and T1PA (OFD: 24.9; ORC: 24.6) between OFC (worst sagittal alignment) and YRC (worst coronal alignment). In the single surgeon validation cohort, the OFC cluster experienced the greatest increase in SRS Function scores (1.34 points, 95%CI 1.01–1.67) compared to OFD (0.5 points, 95%CI 0.245–0.755), ORC (0.7 points, 95%CI 0.415–0.985), and YRC (0.24 points, 95%CI -0.024–0.504) clusters. OFD cluster patients improved the least over 2 years. Multivariable Cox regression analysis demonstrated that the OFD cohort had significantly worse reoperation outcomes compared to other clusters (HR: 3.303, 95%CI: 1.085–8.390). CONCLUSIONMachine-learning clustering found four different ASD patient qualitative phenotypes, defined by their age, frailty, physical functioning, and mental health upon presentation, which primarily determines their ability to improve their PROs following surgery. This reaffirms that these qualitative measures must be assessed in addition to the radiographic variables when counseling ASD patients regarding their expected surgical outcomes.

539 - Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult atopic dermatitis patients in Japan treated with dupilumab: Real-world insights one year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study –demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-­inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; &amp;gt;21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab ­treatment.