Assessment Of Patient-reported Outcomes Research Articles

Association of genetic variants with patient reported quality of life and pain experience in patients in the UK NCRI Myeloma X Relapse [Intensive]) trial; an exploratory study

The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.

P960: HEALTH-RELATED QUALITY OF LIFE IN THE LOCOMMOTION STUDY OF REAL-LIFE CURRENT STANDARD OF CARE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Background: Assessment of patient-reported outcomes (PRO) can inform how real-life standard of care (SOC) treatments affect health-related quality of life (HRQoL) for patients with relapsed/refractory multiple myeloma (RRMM). We present measures of symptoms, functioning, and overall HRQoL from LocoMMotion (NCT04035226), the first prospective, multinational study of real-life SOC in triple-class exposed patients with RRMM. Aims: To assess HRQoL in patients with RRMM receiving real-life current SOC in the LocoMMotion study. Methods: All patients provided informed consent. LocoMMotion is a noninterventional study across 76 sites (63 Europe, 13 United States) in patients who had received ≥3 prior lines of therapy (LOT) or were refractory to proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Patients received PI, IMiD, and anti-CD38 monoclonal antibody and had disease progression during/after their last LOT. Real-life SOC treatments were defined as those used in local clinical practice. The following questionnaires were used: European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 4 single items from EORTC QLQ-myeloma-specific module (EORTC QLQ-MY20), and EuroQol 5-Dimension 5-Level (EQ 5D-5L). HRQoL data were collected at baseline (BL), day 1 of each treatment cycle, end of treatment visit, and during follow-up (every 4 weeks). Established thresholds were used to evaluate improvement compared with BL health status. Mixed models for repeated measures were used to assess within-group change. Results: The questionnaire completion rate was 75.6% during SOC treatment in the LocoMMotion study (N=248; male: 54.4%; median age: 68 years; median cycles of SOC: 4.0 [range: 1-20]). Most patients did not achieve meaningful improvement (defined by a literature-based minimally important difference of 10 points in mean score) in PRO scores. This was most pronounced in pain symptoms, with 62% of patients showing no meaningful improvement during the first 3 months of treatment and 55% showing no improvement during the full treatment duration. Least square (LS) mean changes from BL during SOC treatment and subsequent LOT for the overall population are described (Table). Patients with ≥very good partial response during SOC treatment showed greater improvement in PRO scores, including LS mean change for pain score (-14.9 [95% confidence interval: -22.9, -7.0]). Image:Summary/Conclusion: This first prospective study of real-life current SOC in triple-class exposed patients with RRMM reported limited gains in HRQoL, most notably in pain symptoms. There is an urgent and unmet need for therapies that lead to deep responses and delayed disease progression, as these are associated with improvements in HRQoL.

Implementation of patient-reported outcomes for symptom management in oncology practice through the SIMPRO research consortium: a protocol for a pragmatic type II hybrid effectiveness-implementation multi-center cluster-randomized stepped wedge trial

BackgroundMany cancer patients experience high symptom burden. Healthcare in the USA is reactive, not proactive, and doctor-patient communication is often suboptimal. As a result, symptomatic patients may suffer between clinic visits. In research settings, systematic assessment of electronic patient-reported outcomes (ePROs), coupled with clinical responses to severe symptoms, has eased this symptom burden, improved health-related quality of life, reduced acute care needs, and extended survival. Implementing ePRO-based symptom management programs in routine care is challenging. To study methods to overcome the implementation gap and improve symptom control for cancer patients, the National Cancer Institute created the Cancer-Moonshot funded Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium.MethodsSymptom Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) is one of three research centers that make up the IMPACT Consortium. SIMPRO, a multi-disciplinary team of investigators from six US health systems, seeks to develop, test, and integrate an electronic symptom management program (eSyM) for medical oncology and surgery patients into the Epic electronic health record (EHR) system and associated patient portal. eSyM supports real-time symptom tracking for patients, automated clinician alerts for severe symptoms, and specialized reports to facilitate population management. To rigorously evaluate its impact, eSyM is deployed through a pragmatic stepped wedge cluster-randomized trial. The primary study outcome is the occurrence of an emergency department treat-and-release event within 30 days of starting chemotherapy or being discharged following surgery. Secondary outcomes include hospitalization rates, chemotherapy use (time to initiation and duration of therapy), and patient quality of life and satisfaction. As a type II hybrid effectiveness-implementation study, facilitators and barriers to implementation are assessed throughout the project.DiscussionCreating and deploying eSyM requires collaboration between dozens of staff across diverse health systems, dedicated engagement of patient advocates, and robust support from Epic. This trial will evaluate eSyM in routine care settings across academic and community-based healthcare systems serving patients in rural and metropolitan locations. This trial’s pragmatic design will promote generalizable results about the uptake, acceptability, and impact of an EHR-integrated, ePRO-based symptom management program.Trial registrationClinicalTrials.gov NCT03850912. Registered on February 22, 2019. Last updated on November 9, 2021.

The symptom experience of hereditary angioedema (HAE) patients beyond HAE attacks: literature review and clinician interviews

BackgroundHereditary angioedema (HAE) is a genetic disorder characterized by re-occurring swelling episodes called “attacks,” usually in the limbs, face, airways, and intestinal tract. New prophylactic therapies have reduced the frequency of these attacks. This study describes results from a literature review and clinician interviews assessing patient HAE symptom experiences and timing, and then evaluates whether existing patient-reported outcome (PRO) tools adequately reflect this experience.MethodsA targeted literature review as well as interviews with key opinion leaders (KOLs), were conducted to capture information about the patient experience and their symptoms. An assessment of various PROs was then conducted to determine how well they each covered HAE symptoms and impacts.ResultsNineteen HAE symptoms were identified. KOLs reported that patients on prophylactic therapy experienced some symptoms indicating an attack was imminent, but then never experienced an attack. The comparison of the different PROs found that the Hereditary Angioedema Patient-Reported Outcome was the instrument that most thoroughly examined the symptoms of patients with HAE.ConclusionsGiven the introduction of new prophylactic therapies, further research is needed to determine the effect of being attack-free for longer periods of time on health-related quality of life.

Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): A randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing

BackgroundGermline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing. MethodsThis is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing. ResultsParticipants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results. ConclusionOur hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling.ClinicalTrials.gov Identifier: NCT04447703

Patient reported outcomes in adult patients with neuroendocrine neoplasms.

e24122 Background: Neuroendocrine neoplasm (NEN) is a broad term that includes both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). These rare malignancies most often occur in the gastrointestinal tract, pancreas, lung, adrenal medulla, and thyroid. Clinical symptoms depend upon several factors including tumor location, length of time since diagnosis, secretion of hormones, and tumor growth. Physical symptoms may include fatigue, gastrointestinal complaints, shortness of breath, and fluctuations in blood pressure, weight, and appetite. Patient reported outcomes (PROs) are critical in understanding the clinical spectrum of patients with NENs including their physical and social-emotional response to disease course and treatments. The aim of the current study was to assess physical, social, and emotional domains of PROs amongst a cohort of adult participants with NENs over time. Methods: Patients were enrolled on an ongoing NIH natural history study (NCT03739827). Annual PROs were electronically administered to adult participants (≥18 years) using the PRO Measurement Information System (PROMIS) forms for Anxiety, Depression, Fatigue, Mobility, Upper Extremity, Pain Interference, Cognitive Function, and Emotional Support ( www.nihpromis.org ). PROMIS forms are standardized on a T-Scale with a mean of 50 and a standard deviation of 10. Pain intensity was assessed from 0 (no pain) to 10 (worst pain imaginable) using the Numeric Rating Scale for Pain (NRS) (Wolters, 2013). The Pain Interference Index (PII) was used to assess the impact of pain on daily functioning on a 7-point Likert scale (Martin et al., 2015). Results: A total of 49 out of 85 patients provided completed PROs: 47 NET and 2 NEC. Mean (M) age was 58.8 years and 61.2% of the sample was female. Amongst NET patients (n = 47), primary tumor locations were the small bowel (45.7%), pancreas (21.7%), and lungs (13.0%). Other primary sites (19.6%) included the appendix, rectum, thyroid, kidney, and prostate. 46.8% had metastatic disease. Fatigue was the primary symptom complaint; 34% of NET patients reported fatigue in the moderate to severe range (Mean: 54.1; Standard Deviation: 11.2). Self-perceived mobility (M:47.4; SD: 9.1) and pain interference (M: 51.8; SD: 9.0) were a moderate concern for 19.1% and 17.0% of patients, respectively. At follow-up, 24 patients have returned PROs to date. Fatigue and mobility remained prevalent concerns; 29.1% of patients reported moderate to severe fatigue and 25% reported moderate concerns with mobility. Challenges with upper extremity mobility were endorsed by 20.8% of the sample. Conclusions: Our prospective and comprehensive PRO assessment confirms previously reported fatigue as the most prevalent symptom in patients with NET. Assessment of PROs over time will inform the development of clinical interventions and assessment of their impact on patient quality of life and functioning.

Health-related quality of life in patients with relapsed/refractory multiple myeloma (RRMM) treated with teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody: Patient-reported outcomes in MajesTEC-1.

8033 Background: As multiple myeloma (MM) negatively affects patients’ (pts) health-related quality of life (HRQoL), assessment of patient-reported outcomes (PROs) in addition to clinical outcomes is important. Teclistamab (tec; JNJ-64007957) is an off-the-shelf bispecific antibody that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing MM cells. Initial results from the pivotal cohort of the phase 1/2 MajesTEC-1 study demonstrated that tec was well tolerated with encouraging efficacy in pts who received ≥3 prior lines of treatment (LOT; including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody). Here we report PROs from this cohort. Methods: Pts (aged ≥18 years) had documented RRMM (International Myeloma Working Group criteria), progressive/measurable disease, and had previously received ≥3 prior LOT; prior anti-BCMA treatment (tx) was not allowed. Pts received weekly subcutaneous tec at the recommended phase 2 dose (1.5 mg/kg with step-up doses of 0.06 and 0.3 mg/kg). PROs were assessed at screening and every even cycle (cycles 2–8 reported here) using the EORTC QLQ-C30 (range: 0–100; higher scores indicate better global health status [GHS] but greater symptom severity [symptom scales]) and the EuroQol 5-dimensional descriptive system (visual analog scale [VAS] range: 0 [worst imaginable health state] to 100 [best imaginable]). Tx effect was assessed by a mixed-effects model with repeated measures; the proportion of pts with meaningful improvement was defined as a change ≥10 points. Time to worsening was determined using the Kaplan-Meier estimate. Results: A total of 110 pts were included (median follow-up: 7.8 mos). Overall PRO compliance rates were high (baseline [BL]: 85–90%; cycles 2–8: 80–94%). Tec improved overall HRQoL as evidenced by improvements in GHS scores (cycles 2–8) and reduction in pain (-4.2 [cycle 2] to -15.1 [cycle 8]; Table), with no overall change in physical functioning and fatigue. The proportions of pts with meaningful improvements from BL at cycle 8 were GHS: 50%; physical functioning: 35%; pain: 65%; fatigue: 73%; 50% of pts reported meaningful improvement in their overall health (VAS). Median time to improvement from baseline was ̃1.5 months (with nausea/vomiting and fatigue taking longer to improve), while median time to worsening (all symptoms) ranged from 2 months to not estimable. Conclusions: Consistent with clinical outcomes, pts treated with tec reported rapid, clinically meaningful improvements in HRQoL. Clinical trial information: NCT04557098. [Table: see text]

Patient-reported outcomes from the GARNET trial in patients with advanced or recurrent mismatch repair deficient (dMMR) colorectal cancer (CRC): A post hoc subgroup analysis.

3558 Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the US as a monotherapy in patients (pts) with dMMR advanced/recurrent endometrial cancer that has progressed on or after prior treatment with a platinum-containing regimen or in pts with dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. Here we report on patient-reported outcomes (PROs) in pts with dMMR CRC, a post hoc subgroup analysis. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Cohort F enrolled pts with dMMR/microsatellite instability–high or POLε-mutated non-endometrial solid tumors. Pts with CRC must have received prior fluoropyrimidine, oxaliplatin, and irinotecan. Pts received 500 mg of IV dostarlimab Q3W for 4 cycles, then 1000 mg Q6W until discontinuation. PRO assessment, an exploratory endpoint, was measured using the EORTC-QLQ-C30. PROs were collected at baseline, at each dose cycle, and after discontinuation. Multi-item and item-level analyses were collected and scored; improvement was defined as mean change from baseline (directional change dependent on item). A 10-pt change in mean from baseline was considered clinically significant for the analysis. Results: PRO data at baseline were available for 96 pts with CRC who received ≥1 dose of dostarlimab. Improvements from baseline for quality of life (QOL) and most gastrointestinal symptom scales were observed and maintained from cycle 2 through 7 (Table). Stability in diarrhea was seen from cycles 2 through 7. Conclusions: PROs from the GARNET trial in pts with dMMR CRC show that QOL and disease-related gastrointestinal symptoms were improved or maintained while on dostarlimab treatment. These data, with the previously reported efficacy and safety profile, support the use of dostarlimab in pts with dMMR CRC. Clinical trial information: NCT02715284. [Table: see text]

Predictive value of baseline patient-rated treatment bother for early anastrozole discontinuation in a racially diverse cohort: Results from ECOG-ACRIN E1Z11.

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

Remote symptom monitoring after hospital discharge.

1517 Background: Strategies to improve transitions from the hospital to home for patients with cancer are considered an important component of quality, patient-centered care in oncology. CMS evaluates cancer hospital performance based on the 30-day unplanned hospital readmission rate, and this measure has been endorsed by the National Quality Forum. Nationally, the 30-day readmission rate for oncology patients ranges from 19%-27%. These readmissions come at high psychosocial, physical, and financial costs for patients and caregivers. A remote monitoring intervention that includes frequent contacts with the patient is likely to be effective in improving this transition. Methods: We evaluated the feasibility, acceptability, and perceived value of a mobile health intervention to monitor and manage symptoms of adult medical and surgical oncology patients discharged from an NCI-designated cancer center to home. Patients were monitored for 10 days, which is the median time to readmission for an oncology patient. The technology supporting the program included: 1) a patient portal enabling daily electronic patient-reported outcomes assessments; 2) a pulse oximeter to provide data on blood oxygen level and heart rate; 3) alerts for concerning symptoms; 4) an application to allow staff to review and trend symptom data; 5) a secure platform to support communications and televisits between staff and patients; 6) an advanced feedback report to provide just-in-time patient symptom education. Feasibility and acceptability were evaluated through engagement (goal: > 50% response rate) and symptom alerts and perceived value was measured through a patient engagement survey that included a net promoter score (how likely the patient is to recommend the program to similar patients; goal > 0.7). Results: Between September 27, 2020 to December 31, 2021, the program enrolled 1,091 medical oncology (median age: 63 years, 55% female) and 4,222 surgical oncology patients (median age: 63 years,55% female). Of those enrolled, 65% of medical and 74% of surgical oncology patients participated in home remote monitoring by self-reporting symptom data. This resulted in 2,869 completed symptom assessment from medical and 16,009 completed assessments from surgical patients. Sixty-three percent of medical oncology assessments resulted in a yellow (moderate) or red (severe) symptom alert compared with 26% for surgical oncology patients. Pain was the predominant symptom generating red alerts for medical oncology patients (17%). Fifty-two percent of patients completed the engagement survey, and the net promoter score was 0.82. Conclusions: A remote monitoring program after discharge was feasible, acceptable, and perceived to be of value by oncology patients discharged from a cancer center. Surgical and medical patients have similar response rates but differ in symptom burden. Future work will evaluate the value of a remote symptom monitoring platform in decreasing readmissions.

Automated assessment of illness and treatment understanding (ITU) via the Memorial Sloan Kettering Patient Portal.

e24146 Background: Patient-reported outcome (PRO) technology offers opportunities to address research questions and unmet clinical needs of cancer patients’ ITU. We tested the feasibility of PRO assessment of ITU. Methods: With the same 5-item questionnaire (2 open- [about expectations of cancer outcome and treatment intent] and 3 validated [Weeks JC NEJM 2012] closed-ended items) administered by medical oncology nurses in clinic in a previous pilot (Shin P ASCO 2020), we used the electronic patient portal in our cancer center to elicit responses from all gastrointestinal medical oncology patients scheduled for clinic follow-up. Patients registered on the portal received this questionnaire automatically the day before the second follow-up visit and then quarterly, with a brief explanation that it applied to all patients for quality improvement. Responses were available for review in the electronic health record by all oncology team members, who were offered a 20-minute Zoom introduction to this initiative. Workflow and content of communications about prognosis, treatment intent, and goals of care stayed within clinicians’ discretion. Results: From 5/2021 through 12/2021, 5000 questionnaires were sent to 3852 patients (1-3 times per patient, quarterly), of which all but one was returned, including 3863 with open- and closed-ended responses and 1135 with closed answers only. Patients: 55% male, 83% white, median age 64 (range, 15-96). Most common cancers: colorectal (54%) and pancreatic (21%). In patients with stage data (78%), 35% had stage IV disease. In closed-ended responses, patients receiving treatment (n = 2637 questionnaires) reported that based on the most recent discussions with the oncology team, they thought the treatment was at least a little likely to cure the cancer (66%), prolong life (98%), and/or help with cancer-related problems (92%). Open-ended answers ranged in length from 0-1013 words (median, 6; IQR, 10). Conclusions: Almost all patients in this large, heterogeneous cancer center cohort participated in an automatic assessment system via electronic patient portal addressing questions about their understanding of prognosis and treatment goals. PROs, traditionally focused on symptoms, represent a promising mechanism for scaling structured assessment of patients’ understanding of the prognosis and intent of their treatment. Our future research will address: effects in other cancer types/care settings; temporal changes in sequential responses: associations with clinical factors (e.g., stage, symptoms, treatment, oncologist documentation of prognosis/treatment intent, healthcare delivery and outcomes including patient reports of the quality of clinician communication); open vs. closed-ended questions for assessing ITU; administration in-person vs. via portal; and perspectives of patients and clinicians on our assessment process.

Efficacy of a nurse monitoring service at preventing disease- or therapy-related symptoms in patients receiving targeted therapy or immunotherapy.

12118 Background: The safety profile of Targeted therapies (TT) and immunotherapy (IT) may be underestimated and negatively affect the clinical outcome. Methods: A nationwide, randomized, open-label trial (NCT04726020) conducted among 29 Italian centers involved two cohorts of 223 adult patients (pts) with a solid tumor, receiving TT (group B, 119 pts) or IT (group C, 104 pts). Pts were randomized to receive a weekly nurse monitoring phone call, together with an educational leaflet with some practical advice about toxicities (experimental arm), or only the educational leaflet (control arm). In the experimental arm, pts received their monitoring phone call before their treatment began, then every week for up to 16 weeks of treatment were completed. The primary objective was the evaluation of the difference in toxicities according to patient-reported outcome (PRO)-CTCAE. Results: Both arms were comparable in terms of pts’ characteristics (e.g. site of primary tumor, line of treatment). The adherence to the project (that is the completion of every expected call) was 62.1% in group B and 66.9% in group C. In group B, in the experimental arm, we found a higher number of pts without pain (53.7 vs 39.9%, p = 0.047); a trend of lower fatigue (29.2 vs 18%, p = 0.067) was also observed. In group C, a higher number of pts did not report fatigue (29.1 vs 17.5%, p = 0.043), shortness of breath (61.4 vs 38.5%, p = 0.002) or dry skin (72 vs 52.3%, p = 0.004). More pts also referred to be without pain (51.6 vs 38.8%, p = 0.065) and pruritus (75.9 vs 64.5%, p = 0.088), even if these difference were not statistically significant. Conclusions: The use of PRO assessment through active nurse monitoring might lead to a better tolerance of TT and IT with possible implications on pts’ quality of life and ultimately on treatment outcome. In particular, in the IT group, several symptoms were prevented from occurring, thus encouraging a major effort to implement such active monitoring in this population. Clinical trial information: NCT04726020.

Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma

BackgroundIn JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without disease progression with first-line platinum-containing chemotherapy. ObjectiveTo evaluate patient-reported outcomes (PROs) with avelumab plus BSC versus BSC alone. Design, setting, and participantsA randomized phase 3 trial (NCT02603432) was conducted in 700 patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line gemcitabine plus cisplatin or carboplatin. PROs were a secondary endpoint. InterventionAvelumab plus BSC (n = 350) or BSC alone (n = 350). Outcome measurements and statistical analysisNational Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol five-level EQ-5D (EQ-5D-5L) assessments were analyzed using descriptive statistics and mixed-effect models. Time to deterioration (TTD; prespecified definition: a ≥3-point decrease from baseline in the FBlSI-18 disease-related symptoms–physical subscale for two consecutive assessments) was evaluated via Kaplan-Meier analyses. Results and limitationsCompletion rates for scheduled on-treatment PRO assessments were >90% (overall and average per assessment). Results from descriptive analyses and mixed-effect or repeated-measures models of FBlSI-18 and EQ-5D-5L were similar between arms. TTD was also similar, both in the prespecified analysis (hazard ratio 1.26 [95% confidence interval: 0.90, 1.77]) and in the post hoc analyses including off-treatment assessments and different event definitions. Limitations included the open-label design and limited numbers of evaluable patients at later time points. ConclusionsAddition of avelumab first-line maintenance to BSC in patients with aUC that had not progressed with first-line platinum-containing chemotherapy prolonged OS, with a relatively minimal effect on quality of life. Patient summaryIn this trial of people with advanced urothelial carcinoma who had benefited from first-line chemotherapy (ie, had stable disease or reduced tumor size), treatment with avelumab maintenance plus best supportive care (BSC) versus BSC alone improved survival significantly, without compromising quality of life, as reported by the patients themselves.

The feasibility of patient-reported outcomes, physical function, and mobilization in the care pathway for head and neck cancer surgical patients

BackgroundHead and neck cancer (HNC) patients are an understudied population whose treatment often includes surgery, causing a wide range of side effects. Exercise prehabilitation is a promising tool to optimize patient outcomes and may confer additional benefits as a prehabilitation tool. The primary objective of this study was to assess the feasibility of measuring patient-reported outcomes (PROs), physical function, and in-hospital mobilization across the HNC surgical timeline in advance of a future prehabilitation trial. The secondary objective was to examine potential changes in these outcomes across the surgical timeline.MethodsHNC patients scheduled to undergo oncologic resection with free-flap reconstruction completed assessments of PROs and physical function at three timepoints across the surgical timeline (baseline, in-hospital, and postsurgical/outpatient). Mobilization was measured during the in-hospital period. The feasibility of recruitment and measurement completion was tracked, as were changes in both PROs and physical function.ResultsOf 48 eligible patients, 16 enrolled (recruitment rate of 33%). The baseline and in-hospital PROs were completed by 88% of participants, while the outpatient assessments were completed by 81% of participants. The baseline and in-hospital assessment of physical function were completed by 56% of participants, and 38% completed the outpatient assessment. Measuring in-hospital mobilization was completed for 63% of participants.ConclusionMeasuring PROs and in-hospital mobilization is feasible across the surgical timeline in HNC; however, the in-person assessment of physical function prior to surgery was not feasible. A multidisciplinary collaboration between exercise specialists and clinicians supported the development of new clinical workflows in HNC surgical care that will aid in the implementation of a future prehabilitation trial for this patient population.

ACE-Neuro: A tailored exercise oncology program for neuro-oncology patients – Study protocol

BackgroundPatients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise – Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness. MethodsNeuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching. ConclusionWe are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.

Digital patient-reported outcomes in inflammatory bowel disease routine clinical practice: the clinician perspective

BackgroundUse of digital health services, such as digital patient-reported outcomes, depends on many different human factors as well as digital design solutions. One factor is clinicians’ attitude towards the system, their reasoning behind the using system and their perceptions of patients’ ability to engage with digital health systems. This study aimed to explore hospital clinicians’ attitudes towards digital patient-reported outcomes used in the routine care and treatment of inflammatory bowel disease, and to explore the potential role of clinicians’ attitudes in influencing patients’ use of digital patient-reported outcomes.ResultsTwelve clinicians using digital patient-reported outcome assessments in the care of inflammatory bowel disease were interviewed about their experiences of, and perspectives on, using this service. Most participants supported the use of digital patient-reported outcome assessments in the care of most patients. Participants reported that most patients found the digital solution easy to use. They perceived digital patient-reported outcomes to have three main purposes: prioritising resources; improving patients’ quality of life; and improving quality of care. The patient-clinician relationship was of great importance to participants. Participants varied in their intention to use digital PRO, as some viewed the system as a positive but optional add-on for patients, whilst others intended to use the system with all eligible patients.ConclusionClinicians’ general support of using digital patient-reported outcomes might facilitate their use among patients with inflammatory bowel disease. The participants saw benefits in doing so for patients, clinicians and the wider health service. Clinicians’ attitudes towards the use of digital PRO in the care of their patients may influence patients’ uptake of health service.

Timing is everything: The importance of patient-reported outcome assessment frequency when characterizing symptomatic adverse events.

Although patient-reported symptoms and side effects are increasingly measured in cancer clinical trials, an appropriate assessment frequency has not yet been established. To determine whether differences in assessment frequency affect the apparent incidence and severity of patient-reported symptoms using two well-established patient-reported outcome measures used within the same clinical trial. We examined patient-reported outcome results from AURA3 (NCT02151981), a randomized open-label study comparing Tagrisso (osimertinib) with platinum-based chemotherapy in patients with previously treated estimated glomerular filtration rate/T790M mutation-positive metastatic non-small cell lung cancer. The outcome of interest was the proportion of patients in each arm that reported worsening of nausea, vomiting, fatigue, diarrhea, constipation, and appetite loss from baseline measured using the patient-reported outcome-common terminology criteria for adverse event (weekly) or European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (every 6 weeks). Similar trends were observed for all six symptoms investigated. Using nausea in the chemotherapy arm as an example, 76% of patients reported any worsening from baseline based on weekly patient-reported outcome-common terminology criteria for adverse event assessments. When using an every 6-week assessment of Quality of Life Questionnaire Core 30 nausea and restricting analysis to an every 6-week assessment for patient-reported outcome-common terminology criteria for adverse event nausea, the proportion of chemotherapy arm patients reporting any worsening of nausea was 40% for both measures. Across the six patient-reported symptomatic adverse events, we observed differential proportions when comparing frequent versus sparse assessment. This analysis demonstrates that more frequent assessment of patient-reported symptomatic adverse events will lead to improved detection, and therefore a more complete understanding of the tolerability of experimental anti-cancer therapies.

Patient reported outcome assessment must be inclusive and equitable.

Patient-reported outcomes are increasingly collected in clinical trials and in routine clinical practice, but strategies must be taken to include underserved groups to avoid increasing health disparities.

Quality of life of patients with soft tissue sarcoma treated with doxorubicin in the ANNOUNCE phase III clinical trial.

Background: Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy. Methods: ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo. Dexrazoxane was allowed at any cycle of treatment. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0–100), and Brief Pain Inventory Short Form Modified (mBPI-sf, scored from 0–10) at each treatment cycle. A descriptive analysis of the longitudinal data was conducted overall and by cumulative dose of doxorubicin received to inform the clinical care of patients with STS. Worsening on the QLQ-C30 was defined as a change of 10 points or more at any post-baseline assessment. Worsening on the mPBI-sf was defined as an increase of ≥2 points from baseline. Results: The majority of participants completed the baseline and at least one subsequent PRO assessment within the trial (n = 460, 90.4% EORTC QLQ-C30; n = 454, 89.2%, mBPI-sf). Patients with STS enrolled to the ANNOUNCE trial had clinically meaningful problems with physical function and pain before initiating doxorubicin. Overall, those with fewer symptoms or better function at baseline received higher cumulative doxorubicin dose throughout the study. At baseline, mean QLQ-C30 fatigue was 29.9 with a median time to first worsening of 0.9 months, and mean nausea/vomiting was 6.5 with 1.4 months until worsening; mean physical function was 78.3 with median time to worsening of 2.1 months and mean health status was 66.8 with median time to first worsening of 1.6 months. Median time to worsening of pain was 7.9 months. Conclusion: Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment, with patients with poorer symptoms at baseline (specifically fatigue), subsequently receiving less doxorubicin therapy. The availability of detailed summary data from the patient perspective during doxorubicin-based treatment may inform future care of these patients and can provide a resource for the development of PRO endpoints in future trials.

Perspectives and Experiences of Parents and Adolescents Who Participate in a Pediatric Precision Oncology Program: "When You Feel Helpless, This Kind of Thing Is Very Helpful".

The SickKids Cancer Sequencing (KiCS) Program, launched in 2016, evaluates the clinical utility of paired tumor/germline Next-Generation Sequencing (NGS) in pediatric oncology patients with hard-to-cure and rare cancers. In anticipation of further widespread adoption of NGS, we aimed to characterize the experiences and perspectives of adolescents and parents of patients who have already undergone NGS evaluation, focusing on the psychosocial impact and personal utility. Parents of patients with pediatric cancer and adolescent patients who have participated in KiCS were invited to participate in semistructured interviews. Transcripts were analyzed using an inductive content analytic approach. Of 45 individuals invited, 22 parents and 10 adolescents were interviewed (71% response rate). Prominent psychosocial themes were low distress, relief, and sense of control; some expressed fear of the unknown. In exploring constructs of personal utility, parents highlighted hope for treatment options despite low expectations for results with clinical impact, whereas adolescents articulated altruistic motivations and less hope for personal clinical benefit. Bringing closure and answering the question of why the cancer occurred was a salient theme among both groups. Both parents and adolescents find benefit and clear decisional satisfaction with participation. No participants expressed regret. This study suggests that parents and adolescents benefit from NGS evaluation beyond the return of clinically relevant results. Our findings lay the framework for future work evaluating the value of NGS in pediatric precision oncology care through assessment of patient-reported outcomes and experiences. These results also guide provision of pre- and post-test education and support, which will facilitate patient-centered delivery of NGS practices.