Changes In Patient-reported Outcomes Research Articles

Evaluation of Osseous Incorporation After Osteochondral Allograft Transplantation: Correlation of Computed Tomography Parameters With Patient-Reported Outcomes.

Background:Studies have reported favorable clinical outcomes after osteochondral allograft (OCA) transplantation to treat osteochondral defects and have demonstrated that healing of the osseous component may be critical to outcomes. However, there is currently no consensus on the optimal modality to evaluate osseous healing.Purpose:To define parameters for OCA healing using computed tomography (CT) and to investigate whether osseous healing identified using CT is correlated with improved pain and function on patient-reported outcomes (PROs) collected closest in time to the postoperative CT scan and at final follow-up.Study Design:Case series; Level of evidence, 4.Methods:Of 118 patients who underwent OCA transplantation for articular cartilage defects of the knee over the 10-year study period, 60 were included in final analysis based on completion of CT scans at 5.8 ± 1.9 months postoperatively and PROs collected preoperatively and postoperatively. CT parameters, including osseous incorporation, bone density, subchondral bone congruency, and cystic changes, were summarized for each patient relative to the cohort. Parameters were assessed for inter- and intrarater reliability as well as for covariation with patient characteristics and surgical variables. Structural equation modeling was used to assess correlation of CT parameters with change in PROs from preoperatively to those collected closest in time to CT acquisition and at the final follow-up.Results:Bone incorporation was the most reliable CT parameter. The summarized scores for CT scans were normally distributed across the study population. Variance in CT parameters was independent of age, sex, body mass index, prior surgery, number of grafts, lesion size, and location. No significant correlation (P > .12 across all comparisons) was identified for any combination of CT parameter and change in PROs from baseline for outcomes collected either closest to CT acquisition or at the final follow-up (mean, 38.2 ± 19.9 months; range, 11.6-84.9 months). There was a uniformly positive association between change in PROs and host bone density but not graft bone density, independent of patient characteristics and surgical factors.Conclusion:CT parameters were independent of clinical or patient variables within the study population, and osseous incorporation was the most reliable CT parameter. Metrics collected from a single postoperative CT scan was not correlated with clinical outcomes at ≥6-month longitudinal follow-up.

How Do Fear-related Patient Reported Outcomes Changes Following ACL Reconstruction And Rehabilitation?

PURPOSE: The purpose was to determine whether commonly used measures of patient reported outcomes, including the Tampa scale of Kinesiophobia- 17 (TSK-17) change over time during post-operative rehabilitation following Anterior Cruciate Ligament Reconstruction (ACLR). METHODS: Data from 128 (67 females) patients with primary, unilateral, uncomplicated ACLR (21.7 ± 8.31 yr, 1.72 ± 9.4 m, 75.1 ± 18. 4 kg) were collected. Participants completed the Knee Osteoarthritis Outcome Scale (KOOS), International Knee Documentation Committee (IKDC), Tegner Physical activity level scales and the TSK-17 at 2 timepoints following ACLR; 7.6+/-8.8 months and 11.5+/-10.2 months post-surgery. Paired sample t-test were used to compare each variable between the timepoints. Effect sizes were calculated using Cohen’s D. RESULTS: Each patient reported outcome measure demonstrated a statistically significant improvement over time, with small effect sizes (Table 1). The change in TSK-17 was not statistically significant (Table 1). For TSK-17 scores, based on the frequency analysis, among 85 participants, 26 participants had lower scores on the TSK at Visit 2 compared to Visit 1, indicating experiencing less kinesiophobia, while 50 participants had higher scores over the time, 9 participants had no changes in the TSK scores. CONCLUSION: Small magnitude changes in patient reported outcomes were observed in patients recovering from ACLR. The changes in TSK-17 are varied with the majority of patients experiencing higher kinesiophobia scores. The role of changes in TSK-17 during the post-ACLR rehabilitation progression warrants further research.

Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis

ObjectiveThis study aims to increase the understanding of pain mechanisms in hand OA and explore potential risk factors for pain development or worsening in a biopsychosocial framework. Another important aim is to validate potential soluble and imaging OA biomarkers. DesignThe follow-up examination of the Nor-Hand hospital-based observational cohort study started in October 2019 and was completed in May 2021. In total, 212 of the 300 participants with hand OA who were examined at baseline attended the follow-up study. The participants underwent clinical joint examinations, medical and functional assessments, quantitative sensory testing, fluorescence optical imaging, ultrasound of the hands, acromioclavicular joints, feet, knees and hips, conventional radiographs of the hands and feet and magnetic resonance imaging of the dominant hand. Blood and urine samples were collected, and all participants answered questions about demographic factors and OA-related questionnaires. Associations between disease variables and symptoms will be examined in cross-sectional and longitudinal analyses. Longitudinal analyses will be performed to assess the predictive value of baseline variables on hand OA outcomes. ConclusionCurrent knowledge about predictors for disease progression in hand OA is limited, but with longitudinal data we will be able to explore the predictive value of baseline variables on hand OA outcomes, such as changes in patient-reported outcomes or changes in soluble and imaging biomarkers. This provides a unique opportunity to gain more knowledge about the natural disease course of hand OA.

The minimal important change for the QuickDASH in patients with thumb carpometacarpal arthritis.

Evaluating the effect of treatment through change in patient-reported outcomes requires an understanding of the minimal important change. The aim of this study was to report the minimal important change for the Quick Disability of the Arm, Shoulder and Hand questionnaire (QuickDASH) in patients receiving surgical treatment for thumb carpometacarpal joint osteoarthritis. Three hundred and fifteen patients were seen before and 6months following surgery. Two methods were used to calculate the minimal important change: a distribution-based method calculating the standard error of measurement and an anchor-based method based on the receiver operating characteristic curve. The minimal important change for QuickDASH was estimated to be 18.2 points using the anchor-based method. The area under the receiver operating curve was 0.82, indicating a satisfactory accuracy. The minimal important change was estimated to be 10.3 points using the distribution-based method. These values may be useful in future research on thumb carpometacarpal joint osteoarthritis.Level of evidence: III.

Variation in surgical treatment of degenerative spondylolisthesis in Canada: surgeon assessment of stability and impact on treatment.

Controversy exists regarding the optimal surgical treatment of degenerative lumbar spondylolisthesis (DS). Not all DS patients are the same, and the degree to which inherent stability may dictate treatment is unknown. The purpose of this study was to determine the variability in surgical approach relative to surgeon classified stability. The secondary objective was to compare patient-reported outcomes (PROs) across different surgical techniques and grades of stability. Patients prospectively enrolled from eleven tertiary care institutions and followed from 2015 to 2019. The surgical technique was at the surgeon's discretion. Surgeons were asked to grade the degree of instability based on the degenerative spondylolisthesis instability classification system (DSIC). DSIC categorizes three different types (I-stable, II-potentially unstable, and III-unstable). One-year changes in PROs were compared between each group. Multivariable regression was used to identify any characteristics that explained variability in treatment. There were 323 patients enrolled in this study. Surgeons' stability classification versus procedure [decompression alone (D)/decompression and posterolateral fusion (D-PL)/and decompression with posterior/transforaminal lumbar interbody fusion (D-PLIF/TLIF)] were as follows: type I (n = 91): D-41%/D-PL-13%/D-PLIF/TLIF-46%; type II (n = 175): D-23%/D-PL-17%/D-PLIF/TLIF-60%; and type III (n = 57):(D-0%/D-PL-14%/D-PLIF/TLIF-86%). Type I patients undergoing D-PL had some improvements in EQ-5D and NRS versus those undergoing D-PLIF/TLIF but otherwise there were no other significant differences between groups. Regression analysis demonstrated advanced age (OR = 1.06, CI 1.02-10.12) andtype I (OR = 2.61, CI 1.17-5.81) were associated with receiving decompression surgery alone. There exists considerable variation in surgical management of DS in Canada. Given similar PROs in two of the three groups, there is potential to tailor surgical intervention and improve resource utilization.

Impact of the first wave of the COVID-19 pandemic on systemic lupus erythematosus patients: Results from a multi-center prospective cohort.

The aim of this study was to evaluate the initial impact of the COVID-19 pandemic on individuals with systemic lupus erythematosus (SLE). Patients with SLE participating in a multi-center longitudinal cohort study in New York and Boston were invited to complete a supplemental web-based questionnaire in the summer of 2020. Participants completed standardized patient-reported outcome (PRO) measures and a combination of Likert scale and open-ended questions exploring the impact of the COVID-19 pandemic on their health and access to health care. Changes in PROs were evaluated with paired t-tests and frequencies of worsened symptoms were calculated. A thematic qualitative analysis was conducted on free text responses. Of 97 patients invited, 63 (65%) completed a supplemental questionnaire. Nearly 50% of respondents exhibited increases in anxiety (47.5%) and depression (48.3%) and over 40% scored worse in measures of pain interference, fatigue, and cognitive abilities. Respondents with pre-existing diagnoses of anxiety did not differ from other participants in PRO scores, but were more than three times as likely to report worsened health status. Patients denied difficulties accessing medications (85%) or medical care (84%) and over 50% participated in telehealth visits. Anxiety and increased health risks due to immunosuppression were recurring themes in free text responses. SLE patients experienced a significant physical and emotional toll in the initial months of the COVID-19 pandemic. Comprehensive patient-centered care, including monitoring and addressing anxiety and health-related quality of life, is critical to improving health outcomes in this population during the ongoing health crisis.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention

BackgroundErenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results.MethodsPatients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response.ResultsWe included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A—BoNT/A—had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%).ConclusionsIn real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Neither Residual Anterior Knee Laxity Up to 6 mm nor a Pivot Glide Predict Patient-Reported Outcome Scores or Subsequent Knee Surgery Between 2 and 6 Years After ACL Reconstruction

Background: A primary goal of anterior cruciate ligament reconstruction (ACLR) is to reduce pathologically increased anterior and rotational laxity of the knee, but the effects of residual laxity on patient-reported outcomes (PROs) after ACLR remain unclear. Hypothesis: Increased residual laxity at 2 years postoperatively is predictive of a higher risk of subsequent ipsilateral knee surgery and decreases in PRO scores from 2 to 6 years after surgery. Study Design: Cohort study; Level of evidence, 2. Methods: From a prospective multicenter cohort, 433 patients aged <36 years were identified at a minimum 2 years after primary ACLR. These patients underwent a KT-1000 arthrometer assessment and pivot-shift test and completed PRO assessments with the Knee injury and Osteoarthritis Outcome Score and International Knee Documentation Committee (IKDC) scores. Patients completed the same PROs at 6 years postoperatively, and any subsequent ipsilateral knee procedures during this period were recorded. Subsequent surgery risk and change in PROs from 2 to 6 years postoperatively were compared based on residual side-to-side KT-1000 arthrometer differences (<−1 mm, −1 to 2 mm, 2 to 6 mm, and >6 mm) in laxity at 2 years postoperatively. Multiple linear regression models were built to determine the relationship between 2-year postoperative knee laxity and 2- to 6-year change in PROs while controlling for age, sex, body mass index, smoking status, meniscal and cartilage status, and graft type. Results: A total of 381 patients (87.9%) were available for follow-up 6 years postoperatively. There were no significant differences in risk of subsequent knee surgery based on residual knee laxity. Patients with a difference >6 mm in side-to-side anterior laxity at 2 years postoperatively were noted to have a larger decrease in PROs from 2 to 6 years postoperatively (P < .05). No significant differences in any PROs were noted among patients with a difference <6 mm in side-to-side anterior laxity or those with pivot glide (IKDC B) versus no pivot shift (IKDC A). Conclusion: The presence of a residual side-to-side KT-1000 arthrometer difference <6 mm or pivot glide at 2 years after ACLR is not associated with an increased risk of subsequent ipsilateral knee surgery or decreased PROs up to 6 years after ACLR. Conversely, patients exhibiting a difference >6 mm in side-to-side anterior laxity were noted to have significantly decreased PROs at 6 years after ACLR.

Patient-reported outcomes following autologous stem cell transplant for patients with multiple myeloma.

We evaluated changes in patient‐reported outcomes and cognitive function from pre‐ to 3–6 months post‐treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS‐29. There were statistically significant improvements in physical (p < .001) and mental health (p < .001) but not cognition from pre‐treatment to 3–6 month follow‐up. Similar results were seen within age or comorbidity strata. Patients with myeloma undergoing transplant experienced generally improved short‐term health outcomes with no significant declines in cognition.

Impact of the COVID-19 pandemic on treat-to-target strategies and physical consultations in >7000 patients with inflammatory arthritis.

ObjectivesTo explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease.MethodsPatients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment).ResultsWe included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21–72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%).ConclusionIn this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

Patient-reported Outcomes After Metabolic Surgery Versus Medical Therapy for Diabetes: Insights From the STAMPEDE Randomized Trial.

The aim of this study was to investigate the long-term effects of medical and surgical treatments of type 2 diabetes mellitus (T2DM) on patient-reported outcomes (PROs). Robust data on PROs from randomized trials comparing medical and surgical treatments for T2DM are lacking. The Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial showed that 5 years after randomization, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were superior to intensive medical therapy (IMT) alone in achieving glycemic control in patients with T2DM and obesity. A subset of 104 patients participating in the STAMPEDE trial were administered two generic health-related quality of life (QoL) questionnaires (RAND-36 and EQ-5D-3L) and a diabetes-specific instrument at baseline, and then on an annual basis up to 5 years after randomization. On longitudinal analysis, RYGB and SG significantly improved the domains of physical functioning, general health perception, energy/fatigue, and diabetes-related QoL compared with IMT group. In the IMT group, none of the QoL components in the generic questionnaires improved significantly from baseline. No significant long-term differences were observed among the study groups in measures of psychological and social aspects of QoL. On multivariable analysis, independent factors associated with improved general health perception at long-term included baseline general health (P < 0.001), insulin independence at 5 years (P = 0.005), RYGB versus IMT (P = 0.005), and SG versus IMT (P = 0.034). Favorable changes following RYGB and SG were comparable. In patients with T2DM, metabolic surgery is associated with long-term favorable changes in certain PROs compared with IMT, mainly on physical health and diabetes-related domains. Psychosocial well-being warrants greater attention after metabolic surgery.

Disease Behaviour During the Peri-Diagnostic Period in Patients with Suspected Interstitial Lung Disease: The STARLINER Study.

IntroductionDisease behaviour may guide diagnosis and treatment decisions in patients with interstitial lung disease (ILD). STARLINER aimed to characterise disease behaviour in patients with suspected ILD during the peri-diagnostic period using real-time home-based assessments.MethodsSTARLINER (NCT03261037) was an international, multicentre study. Patients ≥ 50 years old with suspected ILD were followed throughout the peri-diagnostic period, consisting of a pre-diagnostic period (from enrolment to diagnosis) and a post-diagnostic period (from diagnosis to treatment initiation). Study length was variable (≤ 18 months). The primary endpoint was time-adjusted semi-annual forced vital capacity (FVC) change measured during the peri-diagnostic period using daily home spirometry in patients with idiopathic pulmonary fibrosis (IPF). Secondary outcomes included changes in FVC (home spirometry) in patients with non-IPF ILD, changes in FVC (site spirometry), changes in physical functional capacity measured by daily home accelerometry and site 6-min walk distance (6MWD), and changes in patient-reported outcomes (PROs) in IPF or non-IPF ILD.ResultsOf the 178 patients enrolled in the study, 68 patients were diagnosed with IPF, 62 patients were diagnosed with non-IPF ILD, 9 patients received a non-ILD diagnosis and 39 patients did not receive a diagnosis. Technical and analytical issues led to problems in applying the prespecified linear regression model to analyse the home FVC data. Time-adjusted median (quartile [Q]1, Q3) semi-annual FVC change during the peri-diagnostic period measured using home and site spirometry, respectively, was – 147.7 (– 723.8, 376.2) ml and – 149.0 (– 314.6, 163.9) ml for IPF and 19.1 (– 194.9, 519.0) ml and – 23.4 (– 117.9, 133.5) ml in non-IPF ILD. A greater decline in steps per day was observed for IPF versus non-IPF ILD, whereas an increase in 6MWD was observed for patients with IPF versus a decline in 6MWD for patients with non-IPF ILD. No clear patterns of disease behaviour were observed for IPF versus non-IPF ILD for PROs.ConclusionsDespite home spirometry being feasible for most patients and centres, technical and analytical challenges in the home-based assessments prevented firm conclusions regarding disease behaviour. This highlights that further optimisation of the technology and analysis methods is required before widespread implementation.Trial RegistrationNCT03261037.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01790-y.

Modifying the quality-adjusted life year calculation to account for meaningful change in health-related quality of life: insights from a pragmatic clinical trial.

We propose a modified quality-adjusted life year (QALY) calculation that aims to be consistent with guidance for interpreting change in patient-reported outcomes. This calculation incorporates the minimally important difference (MID) in generic preference-based health-related quality of life (HRQL) change scores to reflect what might be considered meaningful HRQL improvement/deterioration. In doing so, we review common issues in QALY calculations such as adjustment for baseline scores and standardizing for between-group differences. Using EQ-5D-5L outcome data from the Alberta TEAMCare-Primary Care Network trial in the management of depression for patients with type 2 diabetes (n = 98), this study compared results from different QALY calculation methods to investigate the impact of (i) adjusting for baseline HRQL score, (ii) standardizing between-group differences at baseline, and (iii) adjusting for 'meaningful' HRQL changes. The following QALY calculation methods are examined: area under curve (QALY-AUC), change from baseline (QALY-CFB), regression modelling (QALY-R), and incorporating an MID for HRQL changes from baseline (QALY-MID). The incremental QALY-AUC estimate favoured the Collaborative Care group (0.031) while the incremental QALY-CFB (-0.028) estimate favoured Enhanced Care. Adjusting for meaningful HRQL changes resulted in a crude incremental QALY-MID of -0.023; however, after adjusting for between-group differences at baseline, QALY-R and adjusted incremental QALY-MID estimates were -0.007 and -0.001, respectively. In addition, recursive regression analyses showed that very low baseline HRQL scores impact incremental QALY estimates. Uncertainty in incremental QALY estimates reflects uncertainty in the value of small within-individual change as well as the impact of small differences between groups at baseline. Applying a responder-definition approach yielded crude and adjusted QALY-MID estimates that were more in favour of Collaborative Care than QALY-CFB and QALY-R estimates, respectively, suggesting that ambiguous small changes in HRQL scores have the potential to influence QALY outcomes used in economic or non-economic applications.

Patient-Reported Outcomes after Intensity-Modulated Proton Therapy for Oropharynx Cancer.

PurposeTo report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation.Materials and MethodsPatients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis.ResultsFifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment.ConclusionsIMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.

Changes in patient-reported outcomes (PROs) and tumor markers (TMs) to predict treatment response and survival outcomes in patients with metastatic gastrointestinal (GI) cancer.

6560 Background: PROs assessing quality of life (QOL) and symptoms at a single timepoint frequently correlate with clinical outcomes in patients with cancer, yet efforts to understand how longitudinal changes in PROs can predict for treatment outcomes are lacking. In practice, oncologists often use changes in serum TMs (CEA and CA19-9) to monitor patients with GI cancer, and thus we sought to examine associations of 1-month changes in PROs and TMs with treatment response and survival outcomes among patients with advanced GI cancer. Methods: We prospectively enrolled patients with metastatic GI cancer prior to initiating chemotherapy at Massachusetts General Hospital from 5/2019-12/2020. At baseline (start of treatment) and 1-month later, we collected PROs (QOL [Functional Assessment of Cancer Therapy General {FACT-G}], physical symptoms [Edmonton Symptom Assessment System {ESAS}], and psychological symptoms [Patient Health Questionnaire-4 {PHQ-4}]) and TMs. We used regression models to examine associations of 1-month changes in PROs and TMs with treatment response (clinical benefit [defined as decreased or stable tumor burden] or progressive disease at the time of first scan) and survival outcomes (progression-free survival [PFS] and overall survival [OS]), adjusted for baseline values of each respective variable. Results: We enrolled 159 of 191 patients approached (83.2% enrollment); 134 had 1-month follow-up data (median age = 64 years [range: 28 to 84 years], 64.2% male, 46.3% pancreaticobiliary cancer). For treatment response, 63.4% had clinical benefit and 36.6% had progressive disease at the time of first scan (mean time to first scan = 2.01 months). Changes in PROs (ESAS-Total: OR = 0.97, p = 0.022; ESAS-Physical: OR = 0.96, p = 0.027; PHQ-4 depression: OR = 0.67, p = 0.014; FACT-G: OR = 1.07, p = 0.001), but not TMs (CEA: OR = 1.00, p = 0.836 and CA19-9: OR = 1.00, p = 0.796), were associated with clinical benefit at the time of first scan. Changes in ESAS-Total (HR = 1.03, p = 0.004), ESAS-Physical (HR = 1.03, p = 0.021), PHQ-4 depression (HR = 1.22, p = 0.042), FACT-G (HR = 0.97, p = 0.003), and CEA (HR = 1.00, p = 0.001) were predictors of PFS. Changes in ESAS-Total (HR = 1.03, p = 0.006) and ESAS-Physical (HR = 1.04, p = 0.015) were predictors of OS, but 1-month changes in TMs (CEA: HR = 1.00, p = 0.377 and CA19-9: HR = 1.00, p = 0.367) did not significantly predict for OS. Conclusions: We found that 1-month changes in PROs can predict for treatment response and survival outcomes in patients with advanced GI cancers. Notably, 1-month changes in CEA only correlated with PFS, while changes in CA19-9 did not significantly predict treatment response or survival outcomes. These findings highlight the potential for early changes in PROs to predict treatment outcomes while underscoring the need to monitor and address PROs in patients with advanced cancer.

Effect of high-intensity interval training on patient-reported outcomes and physical function in women with breast cancer receiving anthracycline-based chemotherapy.

The purpose of this study was to determine the effects of an 8-week HIIT intervention on patient-reported outcomes and physical function in breast cancer patients undergoing anthracycline-based chemotherapy. Thirty breast cancer patients were recruited prior to initiating treatment and randomized into the HIIT group (n = 15) or control (CON) group (n = 15). The HIIT group attended HIIT sessions three days per week for eight weeks. The CON group was asked to maintain their current level of physical activity. Patient-reported outcomes were assessed by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), Multidimensional Fatigue Inventory with 20 questions (MFI-20), and the 15-item Five-Facet Mindfulness Questionnaire (FFMQ-15). Physical function was assessed using the timed up and go (TUG), 30-s sit-to-stand (30STS), Margaria-Kalamen stair climb test, and 6-min walk test (6MWT). Repeated measures ANCOVA and paired t-tests were performed to assess group differences. All patients completed the 8-week study with 82.3% adherence to the intervention among the HIIT group. Post-intervention, significant improvements were found for the Margaria-Kalamen stair climb test (- 3.39%; P = 0.013) and 6MWT (+ 11.6%; P = 0.008) in the HIIT group compared to baseline and CON group. No changes in patient-reported outcomes, TUG, and 30STS were observed following the 8-week study period in both groups (P > 0.05). HIIT may be an effective strategy to improve physical function and possibly maintain QOL in breast cancer patients undergoing the anthracycline-based chemotherapy. ClinicalTrials.gov: NCT02454777.

HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress).

TPS1097 Background: Tucatinib (TUC) is an oral, reversible, small molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2) with minimal inhibition of human epidermal growth factor receptor (EGFR). In the pivotal, randomized HER2CLIMB trial (NCT02614794), the combination of TUC + trastuzumab (T) + capecitabine (C) demonstrated statistically significant and clinically meaningful improvements in progression free survival (PFS), overall survival (OS), and PFS in patients (pts) with brain metastases (BM), compared to T + C alone. These data supported regulatory approvals in the US and internationally for TUC in combination with T + C in pts with HER2+ metastatic breast cancer (MBC). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate of trastuzumab and a topoisomerase I inhibitor payload approved in the US for treatment of HER2+ MBC in pts who have received 2 or more prior anti-HER2 regimens in the metastatic setting. Approval was based on data from the single arm Destiny-Breast01 trial (NCT03248492) where treatment with T-DXd resulted in a confirmed objective response rate (cORR) of 61.4% (95% CI: 54.0, 68.5) in pts with HER2+ MBC who had prior ado-trastuzumab emtansine treatment. Despite these advances, HER2+ MBC remains incurable, and pts will eventually progress on currently available therapies. Combining TUC and T-DXd may result in further improvement on the efficacy seen with either agent alone. Methods: HER2CLIMB-04 (NCT04539938) is a single arm, open-label phase 2 trial evaluating safety and antitumor activity of TUC + T-DXd in pts with HER2+ unresectable locally-advanced or MBC who have received 2 or more prior HER2-based regimens in the metastatic setting. Pts with BM, including active BM, may be enrolled. Ten pts will be enrolled in the safety lead-in portion of the trial and followed for at least 1 cycle. If safety of the combination is acceptable, the trial will continue until approximately 60 response-evaluable pts have been enrolled, approximately evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are PFS, duration of response (DOR), and disease control rate (DCR) by INV per RECIST v1.1, OS, and safety. Exploratory endpoints will include cORR, PFS, DOR, DCR by independent central review per RECIST v1.1, pharmacokinetic analyses, biomarker analyses, and changes in patient-reported outcomes using the European Quality of Life 5-Dimension 5-Level instrument. Enrollment began in late 2020 in the United States. Clinical trial information: NCT04539938 .

Phase 3 randomized study of loncastuximab tesirine plus rituximab versus immunochemotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): LOTIS-5.

TPS7574 Background: Patients (pts) with DLBCL for whom frontline therapy is unsuccessful and who are ineligible for autologous stem cell transplantation have poor outcomes with salvage therapy. Single-agent loncastuximab tesirine (Lonca), an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer (PBD) toxin, showed antitumor activity and manageable toxicity in pts with R/R B-cell non-Hodgkin lymphoma in a Phase 1 trial (Hamadani et al. Blood 2020; blood.2020007512) and in pts with R/R DLBCL in a Phase 2 trial (Caimi et al. Blood 2020; 136(Suppl 1):35–37). Rituximab (R) is part of standard immunochemotherapy for DLBCL, both as frontline therapy and in subsequent treatments. LOTIS-5 aims to evaluate Lonca + R (Lonca-R) versus (vs) standard immunochemotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in pts with R/R DLBCL. Methods: This is a Phase 3 randomized, open-label, 2-part, 2-arm, multicenter study (NCT04384484). A non-randomized safety run-in (Part 1) will compare the safety of Lonca-R with previous safety data for Lonca after the first 20 pts have completed Cycle 1. Part 2 will be started if no significant increase in toxicity occurs; ̃330 pts will be randomized 1:1 to receive Lonca-R or R-GemOx. The primary objective of the study is to evaluate the efficacy of Lonca-R vs R-GemOx. The primary endpoint is progression-free survival by independent review. Secondary endpoints include overall survival; objective response rate; complete response rate; duration of response; frequency and severity of adverse events; changes from baseline in safety laboratory and clinical variables; concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody, and unconjugated warhead); immunogenicity; and changes in patient-reported outcomes. Time-to-event endpoints will be assessed for the intent-to-treat population using a stratified log-rank test. The dosing regimen of Lonca-R in both parts of the study will be 150 µg/kg Lonca + 375 mg/m2 R every 3 weeks (Q3W) for 2 cycles and then 75 µg/kg Lonca + 375 mg/m2 R for 6 cycles. The dose regimen of R-GemOx in Part 2 will be 375 mg/m2 R, 1000 mg/m2 Gem, and 100 mg/m2 Ox Q2W for 8 cycles. Key inclusion criteria include age ≥18 years; pathologic diagnosis of DLBCL (including pts with DLBCL transformed from indolent lymphoma) or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; ≥1 line of prior systemic therapy; not a candidate for stem cell transplantation; and measurable disease per 2014 Lugano Classification. The study opened in September 2020 and enrollment is ongoing. The trial design was presented at 62nd American Society of Hematology Annual Meeting and Exposition, December 5–8, 2020. Research Funding: ADC Therapeutics SA. Clinical trial information: NCT04384484.

The impact of weight loss on physical function and symptoms in overweight or obese breast cancer survivors: results from POWER-remote.

In pre-planned observational analysis of the POWER-remote trial, we examined the impact of weight loss on patient-reported outcomes (PROs). We hypothesized a priori that survivors with ≥ 5% weight loss would have improved physical function (PF) at 6months vs. those who did not. Patients with stage 0-III breast cancer who completed local therapy and chemotherapy with BMI ≥ 25kg/m2 were randomized to POWER-remote (telephone coaching; diet/activity tracking) or self-directed weight loss (booklet). Participants completed PROs at baseline, 6, and 12months: PROMIS PF, pain, fatigue, anxiety, depression, sleep; FACT-endocrine symptoms; MOS-sexual function. Changes in PROs among those with ≥ 5% weight loss vs. those with < 5% were tested with multivariable mixed effect models, across randomized groups. Of 94 women who completed PROs, 84 and 69 participants were evaluable at 6 and 12months, respectively. Regardless of intervention, PF improved in those with ≥ 5% weight loss vs. those with < 5% at 6months (4.4 vs. 0.3 points; p = 0.02) and 12months (3.6 vs. 0 points; p = 0.04). While endocrine symptoms, fatigue, and anxiety improved at 6months in those who lost ≥ 5%, differences were not significant vs. those who lost < 5%. There was no significant change within or between groups in sexual function, depression, or sleep. Findings at 12months were similar, except pain improved in those losing ≥ 5%. These results support the benefits of weight loss in overweight/obese breast cancer survivors. Weight management in breast cancer survivors may improve PF.

Evolution of post-traumatic stress disorder and patient reported-outcomes during the COVID-19 pandemic among cancer patients of the French longitudinal COVIPACT study.

12123 Background: Sudden COVID-19 pandemic has enforced social restrictions across the globe, including social distancing, curfews and total lockdowns, which persist in many parts of the world. Beyond these measures, cancer patients have faced up to the threat of the risk of severe COVID-19 infections and the adaptations of medical oncology practices, with potential impact on their psychological well-being. We aimed to follow Post-Traumatic Stress Disorder (PTSD) symptoms and other Patient-Reported Outcomes (PROs) over this period among cancer patients from the French COVIPACT study. Methods: The COVIPACT study (NCT04366154) included patients with solid/hematologic malignancy receiving medical treatment during the first lockdown in outpatient departments of two cancer centers. Patients were asked to fulfill validated questionnaires on PTSD symptoms (IES-R), insomnia (ISI), quality of life (FACT-G) and cognition (FACT-Cog) at baseline (M0, first lockdown, Apr/May 2020), 3 months (M3, post-lockdown, Jul/Aug 2020) and 6 months (M6, second lockdown, Oct/Nov 2020). PTSD was defined as an IES-R score ≥33 and moderate/severe insomnia as an ISI score ≥15. Higher values on the FACT-G (range 0-108) and FACT-Cog (PCI subscale range 0-72) indicated better quality of life and cognition, respectively. Changes in PROs over time were assessed using mixed models for repeated measures. Results: Among the 734 patients included in COVIPACT, 579, 347 and 328 completed the questionnaires at M0, M3 and M6, respectively: median age, 64 years, 72% women, 59% metastatic status. Patients were mostly treated for breast (44%), lung, head and neck (20%), digestive (16%) and gynecologic cancers (11%). We observed a J-shaped evolution of PTSD over time, affecting 21.2% of patients during the first lockdown, 13.6% the post-lockdown and 23.6% during the second lockdown (p for time &lt; 0.001). Moreover, patients reported linear deterioration of cognitive function over follow-up (p &lt; 0.001). No change was observed in any dimension of quality of life (p for time = 0.06). 24.3%, 27.1% and 28.1% of the patients reported insomnia at M0,M3 and M6 (p for time = 0.35). At each time, PTSD was associated with more insomnia, worst quality of life and cognitive complain. At all the times, ≥50% of patients with PTSD reported insomnia compared to ≤23% in non-PTSD patients (p &lt; 0.001). In addition, there was a clinically significant difference of ≥16 points on the FACT-G and ≥8 points on the FACT-Cog PCI between PTSD and non-PTSD patients (p &lt; 0.001) at the all times. Conclusions: More than 20% of patients have developed PTSD during the different periods of lockdown, with strong association with poor quality of life, cognitive complain and insomnia. Psychosocial support promoting emotional resilience should be largely offered to cancer patients to prevent and/or reduce PTSD. Clinical trial information: NCT04366154.