Patient-reported outcomes used actively in cancer patients undergoing antineoplastic treatment: A mini-review of the Danish landscape.

Introduction: Many studies using Patient-reported outcomes (PRO) data have been conducted to monitor symptoms and health-related quality of life during follow-up after cancer treatment. However new ways of using (e)PROs have emerged. We aimed to explore the Danish landscape of the use of PRO in a research setting, where PRO is used actively in cancer patients undergoing treatment, and give an overview of how it is embraced by patients and clinicians. Methods and materials: A literature search was performed in June 2023, using the keywords Denmark, cancer, and patient-reported outcomes. An expert on literature searches identified the search terms, and double screening was performed at both abstract and screening levels and full-text stage. The software tool Covidence was used. Results: 467 articles were retrieved and 19 studies were included. They described the type of ePRO instrument used and the application of active ePRO i.e. a dialogue tool in the clinical encounter, release of alerts to clinicians, and enhancement of self-management. Finally, a development in the use of active ePROs over time is elucidated and we show how it is embraced by patients and clinicians. Conclusion: This mini-review gives an overview of how ePRO solutions are tested in oncological research in Denmark and embraced by patients and clinicians. ePRO solutions in a Danish setting seem well-suited for self-management. However, if more impact is warranted, clinicians need to engage in reviewing and using ePROs. Moreover, for successful implementation, the integration of ePROs in electronic health records must be supported by IT specialists and management.

The iBLAD study: patient-reported outcomes in bladder cancer during oncological treatment: a multicenter national randomized controlled trial.

BACKGROUND: Patient-reported outcomes (PROs) are getting widely implemented, but little is known of the impact of applying PROs in specific cancer diagnoses. We report the results of a randomized controlled trial (RCT) of the active use of PROs in patients with locally advanced or metastatic bladder cancer (BC) undergoing medical oncological treatment (MOT) with focus on determining the clinical effects of using PROs during chemo- or immunotherapy compared to standard of care. METHODS: We recruited patients from four departments of oncology from 2019 to 2021. Inclusion criteria were locally advanced or metastatic BC, initiating chemo- or immunotherapy. Patients were randomized 1:1 between answering selected PRO-CTCAE questions electronically once weekly with a built-in alert-algorithm instructing patients of how to handle reported symptoms as a supplement to standard of care for handling of side effects (intervention arm (IA)) vs standard procedure for handling of side effects (control arm (CA)). No real-time alerts were sent to the clinic when PROs exceeded threshold values. Clinicians were prompted to view the completed PROs in the IA at each clinical visit. The co-primary clinical endpoints were hospital admissions and treatment completion rate. Secondary endpoints were overall survival (OS), quality of life (EORTC's QLQ-C30 and QLQ-BLM30) and dose reductions. RESULTS: 228 patients with BC were included, 76% were male. 141 (62%) of the patients had metastatic disease. 51% of patients in the IA completed treatment vs. 56% of patients in the CA, OR 0.83 (95% CI 0.47-1.44, p = 0.51). 41% of patients in the IA experienced hospitalization vs. 32% in the CA, OR 1.48 (95% CI 0.83-2.65, p = 0.17). OS was comparable between the two arms (IA: median 22.3mo (95% CI 17.0-NR) vs. CA: median 23.1mo (95% CI 17.7-NR). Patient and clinician compliance was high throughout the study period (80% vs 94%). CONCLUSIONS: This RCT did not show an effect of PRO on completion of treatment, hospitalizations or OS for BC patients during MOT despite a high level of patient and clinician compliance. The lack of real-time response to alerts remains the greatest limitation to this study.

Patient-reported outcome (PRO) measurements in chronic and malignant diseases: ten years' experience with PRO-algorithm-based patient-clinician interaction (telePRO) in AmbuFlex.

BACKGROUND: Patient-reported Outcome (PRO) measures may be used as the basis for out-patient follow-up instead of fixed appointments. The patients attend follow-up from home by filling in questionnaires developed for that specific aim and patient group (telePRO). The questionnaires are handled in real time by a specific algorithm, which assigns an outcome color reflecting clinical need. The specific questionnaires and algorithms (named solutions) are constructed in a consensus process with clinicians. We aimed to describe AmbuFlex' telePRO solutions and the algorithm outcomes and variation between patient groups, and to discuss possible applications and challenges. METHODS: TelePRO solutions with more than 100 processed questionnaires were included in the analysis. Data were retrieved together with data from national registers. Characteristics of patients, questionnaires and outcomes were tabulated for each solution. Graphs were constructed depicting the overall and within-patient distribution of algorithm outcomes for each solution. RESULTS: From 2011 to 2021, 29 specific telePRO solutions were implemented within 24 different ICD-10 groups. A total of 42,015 patients were referred and answered 171,268 questionnaires. An existing applicable instrument with cut-off values was available for four solutions, whereas items were selected or developed ad hoc for the other solutions. Mean age ranged from 10.7 (Pain in children) to 73.3 years (chronic kidney disease). Mortality among referred patients varied between 0 (obesity, asthma, endometriosis and pain in children) and 528 per 1000 patient years (Lung cancer). There was substantial variation in algorithm outcome across patient groups while different solutions within the same patient group varied little. DISCUSSION: TelePRO can be applied in diseases where PRO can reflect clinical status and needs. Questionnaires and algorithms should be adapted for the specific patient groups and clinical aims. When PRO is used as replacement for clinical contact, special carefulness should be observed with respect to patient safety.

Individualizing the Oncological Treatment of Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma by Using Gene Sequencing and Patient-Reported Outcomes: Protocol for the INDIGO Study.

BACKGROUND: No phase 3 studies have yet been conducted for patients with non-clear cell (CC) renal cell carcinoma (RCC) exclusively due to the rare occurrence of the disease and the heterogenicity in tumor morphology. Consequently, there is no evidence of the optimal treatment, and new approaches are needed. One approach is individualizing treatment based on the gene sequencing of tumor tissue. Additionally, recent studies involving the patient-reported outcomes (PROs) of patients treated for metastatic cancer have shown significant benefits for quality of life, median overall survival, and overall survival. The use of gene sequencing and PROs can be of great importance to patients with rare cancer types, including patients with non-CC RCC, and should be investigated in clinical trials, especially for cases where evidence based on phase 3 studies is difficult to obtain. OBJECTIVE: We describe the INDIGO study, in which patients, based on gene analyses, will be allocated into 4 treatment arms containing 14 treatments and use electronic PROs. We aim to improve the treatment of patients with non-CC RCC. The end points in the study will be the overall response rate (complete and partial) in the total patient population, which will be based on the RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, and the time to treatment failure. METHODS: INDIGO is a prospective phase 2 trial, and 30 patients will be enrolled. The patients will receive systemic treatment based on genetic analyses of their tumor tissue. All patients will receive electronic questionnaires in a dedicated app-a questionnaire regarding symptoms and side effects and another regarding health-related quality of life. Depending on the treatment regimen, the patients will be seen by a medical doctor every third, fourth, or sixth week, and the effect of the systemic treatment will be evaluated every 6 weeks via a computed tomography scan. The study has been approved by the Danish Medicines Agency and the National Committee on Health Research Ethics (approval number: H-19041833), complies with good clinical practice guidelines, follows the General Data Protection Regulation, and is registered at the Capital Region of Denmark. RESULTS: Recruitment started in March 2020, and at the time of submitting this paper (June 2022), a total of 9 patients have been enrolled. CONCLUSIONS: We aim to explore methods for improving the treatment outcomes of patients with non-CC RCC, and the INDIGO study will contribute further data on personalized medicine for rare types of RCC and provide new knowledge on the active use of electronic PROs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04644432, https://clinicaltrials.gov/ct2/show/NCT04644432 ; European Union Drug Regulating Authorities Clinical Trials Database 2019-001316-38, https://tinyurl.com/2p8mb4aw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36632.

Patient-Reported Outcomes, Health-Related Quality of Life, and Clinical Outcomes for Urothelial Cancer Patients Receiving Chemo- or Immunotherapy: A Real-Life Experience.

Patients with urothelial cell carcinoma (UCC) often have comorbidities, which cause trouble for the completion of oncological treatment, and little is known about their quality of life (QoL). The aim of the present study was to obtain and describe patient-reported outcomes (PRO) and QoL data from UCC patients in the treatment for locally advanced muscle-invasive or metastatic UCC. A total of 79 patients with UCC completed four questionnaires (EORTC QLQ-C30, QLQ-BLM30, HADS, and select PRO-CTCAE™ questions) once weekly during their treatment. From those, 26 patients (33%) underwent neoadjuvant treatment for local disease while 53 patients (67%) were treated for metastatic disease. Of all patients, 54% did not complete the planned treatment due to progression, nephrotoxicity, death, or intolerable symptoms during treatment. The five most prevalent PRO-CTCAE grade ≥ 2 symptoms were frequent urination (37%), fatigue (35%), pain (31%), dry mouth (23%), and swelling of the arms or legs (23%). The baseline mean overall QoL was 61 (±SD 24) for all patients (neoadjuvant (73, ±SD 19) and metastatic (54, ±SD 24)) and remained stable over the course of treatment for both groups. A stable overall QoL was observed for the patients in this study. More than half of the patients did not, however, complete the planned treatment. Further supportive care is warranted for bladder cancer patients.

Patient reported outcomes interfering with daily activities in prostate cancer patients receiving antineoplastic treatment.

BACKGROUND: Patient-reported outcome (PRO) can give information to caregivers and doctors about adverse effects and give real-world data on symptom burden for patients during treatment. We here report PROs from patients with metastatic castration resistant prostate cancer (mCRPC) receiving oncological treatment. Our findings are compared with adverse events from published findings in relevant registration studies and we discuss possible applications by looking at the level of interference with usual or daily activities. MATERIAL AND METHODS: An electronic PRO-Common Terminology Criteria for Adverse Events (ePRO-CTCAE) questionnaire, with 41 items corresponding to 22 symptoms/adverse events associated with the treatment regimens commonly used for mCRPC, were collected from 54 patients with mCRPC receiving medical oncological treatment. Eleven symptoms attributing interference with usual or daily living were selected and stratified by antineoplastic treatment administered. The responses were pooled and compared with data from relevant registration studies for docetaxel, cabazitaxel, radium-223 and abiraterone. RESULTS: 168 questionnaires were completed, and among responses from patients receiving docetaxel, 89% of responses shows that fatigue interfered with their usual or daily activities to some degree and 22% to a high or very high degree. In the registration study for docetaxel fatigue is reported with 53% for all grades and 5% for grade 3 or above. For cabazitaxel, radium-223 and abiraterone the percentage of responses with interference of daily activities from fatigue range from 58% to 82%. Between four and six of the eleven chosen PRO-CTCAE symptoms are not reported in the registration studies as common side effects. CONCLUSION: PRO may help inform caregivers about symptoms not previously reported, interfering with usual or daily activities but also point to the use of this information to inform new patients. This may help clinicians and patients decide a treatment plan with an acceptable benefit-to-harm ratio.

Experiences of Social Isolation During the COVID-19 Lockdown Among Adolescents and Young Adult Cancer Patients and Survivors.

Purpose: COVID-19 is a worldwide pandemic affecting populations by massive lockdowns, including strict precautions and quarantines. Research on the lives of adolescents and young adults (AYAs) with cancer during the COVID-19 pandemic is highly relevant to meet potential challenges regarding their physical and mental well-being. Therefore, the purpose of this study was to investigate how AYA cancer patients and survivors experience social isolation during the COVID-19 lockdown. Methods: Individual semistructured telephone interviews were performed with 13 AYA cancer patients and survivors aged 18-29 years. All participants were users of Kræftværket, a youth support center and social organization for AYAs with cancer at The University Hospital Rigshospitalet, Denmark. Data were analyzed by using thematic analysis. Results: The following themes were found. The need for giving and receiving support, Difficulty of the community spirit, The lockdown's effect on recovery, Disrupted youth, and Being alone. Conclusion: The participants in this study experienced loneliness, anxiety, lack of psychosocial support, and lack of physical contact. In addition, lack of rehabilitation and lack of support during hospital visits, which may specifically influence the disease trajectory, were reported. Thus, health care professionals have an important task to follow up on the AYA's well-being during and after the COVID-19 lockdown. A positive side effect of the lockdown period was the experience of getting a respite to recover physically and mentally after cancer.

Patient-Reported Outcome Measures Used in Routine Care Predict for Survival at Disease Progression in Patients With Advanced Lung Cancer.

BACKGROUND: Patient-reported outcome (PRO) measures have been increasingly implemented in routine care to aid in clinical decision-making. However, the prognostic value of PRO measures as a tool for decision making is not easily interpreted by clinicians. Our aims were to explore the prognostic value of PRO measures at disease progression and the changes in PRO measures between treatment start (baseline) and disease progression. PATIENTS AND METHODS: Since 2014, patients with lung cancer have completed an electronic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and LC-13 before every outpatient visit at the Department of Oncology, Hospital Unit West, Jutland, Denmark. The patients' responses were used in routine care. Patients receiving palliative antineoplastic treatment were eligible for analysis if the questionnaire had been completed at the initiation of first-line treatment and at disease progression. The prognostic value of the scores was evaluated using a Cox proportional hazard model. A P value < .01 was considered statistically significant. RESULTS: A total of 94 screened patients were included. At disease progression, survival could be predicted from the absolute score of the global health scale, 3 functional scales (physical, role, emotional), and 7 symptom scales (fatigue, pain, dyspnea, hemoptysis, lung cancer dyspnea, chest pain). In addition, changes in hemoptysis, dysphagia, dyspnea, and chest pain predicted for survival at progression. CONCLUSION: PRO measures used in routine care can provide clinicians with relevant prognostic information about patients with lung cancer at disease progression. These results show the potential value of PRO measures when used in clinical decision-making.

Electronic reporting of patient-reported outcomes in a fragile and comorbid population during cancer therapy - a feasibility study.

BACKGROUND: Electronic collection of patient-reported outcomes (ePROs) is becoming widespread in health care, but the implementation into routine cancer care during therapy remains to be seen. Especially, little is known of the use and success of electronic reporting during active cancer treatment in fragile and comorbid patients. The aim of this study was to test the feasibility of ePRO and its incorporation into routine cancer care, measured by physician compliance, for a fragile and comorbid bladder cancer (BC) population receiving chemo- or immunotherapy. METHODS: All BC patients initiating treatment for locally advanced or metastatic bladder cancer at Rigshospitalet or Herlev Hospital, Denmark, were approached during an 8 month period. Exclusion criteria were patients not speaking Danish or not being signed up for electronic communication with health authorities. Enrolled patients were prompted to complete weekly ePROs from home. Patients completed the European Organisation for Research and Treatment of Cancer's general quality of life questionnaire, QLQ-C30, and the module for muscle-invasive bladder cancer QLQ-BLM30, the Hospital Anxiety and Depression Scale, HADS, and selected items from the Patient Reported-Outcomes version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE), in total 158 questions weekly. If failing to report when prompted, patients were sent two e-mail reminders. Patients were informed that the physician would have an overview of the reported ePROs at their following clinical visits. Physicians were at all clinical visits informed to look at the ePROs in a software solution separate from the medical records. Physicians were logged to check their compliance to the task. No continuous surveillance of ePROs was established. RESULTS: Of 91 patients screened for enrolment, 19 patients (21%) were not found eligible for standard treatment, eight patients (9%) were not signed up for electronic communication with the health authorities and nine patients (10%) declined participation. Another six patients did not meet other inclusion criteria. In total 49 BC patients were enrolled, 29 initiating chemotherapy and 20 initiating immunotherapy. A total of 466 electronic questionnaires were completed. The overall adherence of the patients to complete ePROs was at an expected level for an elderly cancer population (75%) and remained above 70% until the 6th cycle of treatment. The physician' compliance was in contrast low (0-52%) throughout the course of treatment. CONCLUSIONS: Electronic reporting of PROs is feasible in a fragile and comorbid population of patients during routine active cancer treatment. Despite clear implementation strategies the physician compliance remained low throughout the study proving the need for further implementation strategies.

Patient-reported outcomes item selection for bladder cancer patients in chemo- or immunotherapy.

BACKGROUND: Selection of specific patient-reported outcomes (PROs) for cancer patients requires careful consideration to the purpose and population at aim. Here we report the process of choosing which items to include in a bladder cancer population in chemo- or immunotherapy based on the Patient-Reported Outcomes Version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE). METHODS: Initial PRO-CTCAE symptoms were chosen through 1) medical record audit 2) patient interviews 3) summary of product characteristics from European Medicines Agency and Food and Drug Administration for the applied chemotherapies, and 4) toxicity reporting from Phase 2 and 3 trials for immunotherapies applied in patients with urothelial cancer. The selected questions were applied in a prospective cohort of 78 bladder cancer patients receiving chemo- or immunotherapy at Rigshospitalet and Herlev Hospital, Denmark. Symptoms tested in this population were selected for the final module if they appeared in ≥3 of the following groupings a) the most prevalent PRO-CTCAE symptoms grade ≥ 2 overall during treatment b) the PRO-CTCAE symptoms reported in conjunction with hospital admissions or mentioned in focus group interviews discussing which symptoms were prevalent in this patient group with specialized c) nurses or d) physicians. The authors also included symptoms in the final module if they were present in two of the above groups and defined as actionable by clinicians. RESULTS: From the initial selection of PRO-CTCAE symptoms, a total of 45 PRO-CTCAE symptoms explored by 84 PRO-CTCAE questions were retrieved. Through the second selection process based on the described criteria, the study group agreed on 15 PRO-CTCAE symptoms explored by 30 PRO-CTCAE items to be appropriate and relevant for the bladder population during medical oncological treatment. CONCLUSIONS: The selection of disease specific PROs in a bladder cancer population was feasible. The process revealed several steps of selection needed in order to reach a final module for clinical application.

Comparison of EORTC QLQ-C30 and PRO-CTCAE™ Questionnaires on Six Symptom Items.

CONTEXT: Clinical studies have over the past decade paid increasing attention to health-related quality of life data. Multiple questionnaires are often administered resulting in overlapping questions increasing patient burden. OBJECTIVES: To examine the correlations between the commonly used European Organization for Research and Treatment of Cancer Quality of Life Questionnnaire-C30 (QLQ-C30) and the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) on six coinciding items to determine consistency between overlapping items. METHODS: Data were prospectively collected from patients attending two cancer centers in the U.K. Participants completed the QLQ-C30 version 3.0 every four weeks and the PRO-CTCAE at least once a week for 12 weeks. Data were collected via the Internet or an interactive voice response. For the six coinciding items in QLQ-C30 and PRO-CTCAE: pain, nausea, vomiting, constipation, diarrhea, and fatigue, comparisons were made between all possible related responses by aligning the four responses in the QLQ-C30 with two condensed versions of the five responses in the PRO-CTCAE. Consistency and reliability was determined with the intraclass correlation coefficient (ICC) and Cronbach's α. RESULTS: About 247 patients completed 785 QLQ-C30 and 2501 PRO-CTCAE questionnaires. Moderate (ICC >0.5) to good (ICC >0.75) reliability and Cronbach's α >0.7 were found on all coinciding questions except for questions concerning the severity of nausea and vomiting as a result of relatively few patients responding to these questions. Items on frequency showed better correlations than the severity and interference items. CONCLUSION: The good reliability and consistency between the QLQ-C30 and PRO-CTCAE support future attempts to minimize patient burden by shortening health-related quality of life questionnaires.

Risk of recurrence, prognosis, and follow-up for Danish women with cervical cancer in 2005-2013: A national cohort study.

BACKGROUND: In developed countries, women attend follow-up after treatment for cervical cancer to detect recurrence. The aim of this study was to describe the Danish population of women with early-stage cervical cancer at risk for recurrence and death due to recurrence. METHODS: Data were extracted from 3 nationwide databases to find women diagnosed with stage 1A1 to 1B1 cervical cancer in 2005-2013. Recurrences were determined from data on oncological or surgical treatment more than 3 months after the initial diagnosis and were cross-checked with patient journals. RESULTS: In all, 1523 patients were diagnosed with stage 1A1 to 1B1 cervical cancer. Eighty women experienced recurrences: 8 at International Federation of Gynecology and Obstetrics (FIGO) stage 1A1, 0 at FIGO stage 1A2, and 72 at FIGO stage 1B1. The 5-year recurrence rate was 6.4%; 67.5% of the women had symptomatic recurrences, and 28.8% had asymptomatic recurrences. At significantly greater risk for recurrence were women at stage 1B1, regardless of their lymph node (LN) status at diagnosis (hazard ratio with a positive LN, 5.10; 95% confidence interval [CI], 1.65-15.76; P = .0047; hazard ratio with a negative LN, 3.14; 95% CI, 1.25-7.93; P = .0153; hazard ratio with LN data missing, 6.33; 95% CI, 1.80-22.26; P = .004), women older than 50 years (hazard ratio, 1.81; 95% CI, 1.12-2.94; P = .0158), and women with lymphatic and lymphovascular space invasion (LVSI; hazard ratio, 1.92; 95% CI, 1.11-3.30; P = .0188). In a multivariate analysis, significantly inferior survival was found after recurrence for patients with lymphatic LVSI (hazard ratio, 2.23; 95% CI, 1.04-4.80; P = .0401), a symptomatic diagnosis of recurrence (hazard ratio, 2.52; 95% CI, 1.08-5.90; P = .0332), and multiple sites of recurrence (hazard ratio, 2.72; 95% CI, 1.32-5.61; P = .0066). CONCLUSIONS: This study has identified a group of women at FIGO stage 1A1 in no need of specialized, hospital-based follow-up. Many of the recurrences at FIGO stage 1B1 are asymptomatic, and this may show a need for follow-up in this group. Further prospective investigation is needed. Cancer 2018;124:943-51. © 2017 American Cancer Society.