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.

Quality of life and mental health in real-world patients with resected stage III/IV melanoma receiving adjuvant immunotherapy.

INTRODUCTION: Treatment with immune checkpoint inhibitors (ICI) has expanded into the adjuvant setting enhancing the importance of knowledge on the immune-related toxicities and their impact on health-related quality of life (HRQoL). Large phase 3 trials of patients with resected Stage III/IV melanoma found no effect on HRQoL during adjuvant immunotherapy. This study investigates how HRQoL was affected during and after adjuvant immunotherapy in a real-world setting. METHODS: Patients with resected melanoma treated with adjuvant nivolumab from 2018 to 2021 in Denmark were identified using the Danish Metastatic Melanoma Database (DAMMED). The study was performed as a nationwide cross-sectional analysis as a questionnaire consisting of six different validated questionnaires on HRQoL, cognitive function, fatigue, depression, fear of recurrence, and decision regret was sent to all patients in March 2021. To evaluate HRQoL during and after adjuvant treatment, patients were divided into groups depending on their treatment status when answering the questionnaire; patients in active treatment for 0-6 months, patients in active treatment for >6 months, patients who ended treatment 0-6 months ago, and patients who ended treatment >6 months ago. RESULTS: A total of 271/412 (66%) patients completed the questionnaire. Patients who ended therapy 0-6 months ago had the lowest HRQoL and had more fatigue. Patients in active treatment for >6 months had lower HRQoL and more fatigue than patients who started treatment 0-6 months ago. Patients ending therapy >6 months ago had higher HRQoL and less fatigue compared to patients who ended therapy 0-6 months ago. Multivariable analysis showed an association between HRQoL and treatment status, comorbidity, civil status, and employment status. CONCLUSIONS: Adjuvant nivolumab may affect some aspects of QoL, but the influence seems temporary. Patient characteristics, such as civil status, employment status, and comorbidity were associated with HRQoL.

Impact of patient-reported outcomes on symptom monitoring during treatment with checkpoint inhibitors: health-related quality of life among melanoma patients in a randomized controlled trial.

INTRODUCTION: In a randomized controlled trial, we previously investigated if melanoma patients receiving checkpoint inhibitors had fewer severe immune-related adverse events (irAEs) when they reported symptoms using electronic patient-reported outcomes (ePRO) with triggered alerts as an add-on to standard care, compared to standard care alone. The aim of this study is to examine between-group differences in health-related quality of life (HRQoL) and associations between irAEs severity and HRQoL. METHODS: The study population of 138 patients completed the EuroQol EQ-5D-5L Index and FACT-M questionnaires at baseline and weeks 24 and 48. We analyzed HRQoL from all patients who completed at least one questionnaire. Missing FACT-M items were imputed following existing guidelines. RESULTS: There was no difference in HRQoL at baseline as measured EQ-5D-5L between the intervention and the control group. Between baseline and 48 weeks, mean EQ-5D-5L scores were unchanged among patients in the intervention group (p = 0.81) but decreased significantly among patients in the control group (p = 0.03). Consequently, patients in the intervention group had higher mean scores than those in the control group (p = 0.05) at 48 weeks. Mean FACT-M scores did not differ significantly between the two groups at any of the time points. There were observed no between-group differences in mean EQ-5D-5 and mean FACT-M scores between patients with severe irAEs and patients who had none. CONCLUSION: Melanoma patients receiving CPIs who self-reported irAEs using ePRO with triggered alerts as a supplement to standard care maintained their HRQoL compared to patients who received standard care alone. Patients in the intervention group had a significantly better HRQoL measured by EQ-5D-5L than controls 48 weeks after baseline. The results suggest that including ePRO in standard care increases melanoma patients´ well-being. Further and larger studies are needed to confirm this finding and examine the impact of severe irAEs on cancer patients' HRQoL. TRIAL REGISTRATION: Clinicaltrials.gov NCT03073031 Registered 8 March 2017, Retrospectively registered https://clinicaltrials.gov/ .

The use of patient-reported outcomes to detect adverse events in metastatic melanoma patients receiving immunotherapy: a randomized controlled pilot trial.

BACKGROUND: A randomized controlled pilot trial was conducted to assess if melanoma patients treated with immunotherapy had the number of grade 3 or 4 adverse events during treatment reduced by 50% using a tailored electronic patient-reported outcomes tool in addition to standard toxicity monitoring compared to standard monitoring alone. Secondary endpoints were: if more AEs were reported in the intervention group, if there was a difference between the two groups in the number of telephone consultations, extra out-patient visits, number of days in the hospital, days in steroid treatment and the time patients experienced grade 2 or higher toxicity. PATIENTS AND METHODS: Melanoma patients receiving immunotherapy at the Department of Oncology, Odense University Hospital, Denmark participated. Standard care included assessment of AEs by a clinician before each treatment cycle using the Common Terminology Criteria for Adverse Events. In addition, patients randomized to the intervention reported their AEs weekly by an electronic PRO-tool based on the PRO-CTCAE platform. RESULTS: One hundred forty-six melanoma patients were randomized. In this study, we did not detect a difference between the two groups in the number of grade 3 or 4 AEs (P = 0.983), in the overall number of AEs (P = 0.560) or in the time the patients in the two groups experienced grade 2 or higher toxicity (0.516). The number of phone contacts was significantly higher in the intervention group (P = 0.009) and there was a tendency towards patients in the intervention group having more extra visits (P = 0.156). CONCLUSION: It has been examined if the number of severe AEs for melanoma patients receiving immunotherapy could be reduced by involving the patients in the reporting of symptoms. The results do not justify the expansion of the pilot study into a regular phase III study with this particular set-up. However, a significant difference in the number of phone contacts was found as patients in the intervention group called more frequently, indicating that their attention to AEs was increased. Even though the use of an electronic PRO tool could not reduce the number of severe AEs in this melanoma population, a positive impact on other endpoints such as QoL, communication, or treatment-planning, cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT03073031 Registered 8 March 2017, Retrospectively registered.

Patient-Reported Outcomes During Immunotherapy for Metastatic Melanoma: Mixed Methods Study of Patients' and Clinicians' Experiences.

BACKGROUND: The benefits of electronic patient reported outcomes (PRO) questionnaires have been demonstrated in many settings, including in hospitals and patient homes. However, it remains to be investigated how melanoma patients and their treating clinicians experience the electronic self-reporting of side effects and the derived communication. OBJECTIVE: The primary objective of this study was to examine patients' and clinicians' experiences with an eHealth intervention for weekly monitoring of side effects during treatment with immunotherapy. METHODS: An eHealth intervention based on questions from the PRO-Common Terminology Criteria for Adverse Events (CTCAE) library was used and tested in a randomized clinical trial with patients receiving immunotherapy for malignant melanoma and clinicians at a university hospital in Denmark. On a weekly basis, patients reported their symptoms from home during the treatment via a provided tablet. The electronic patient reports were available to clinicians in the outpatient clinic. A mixed methods approach was applied to investigate the patients' and clinicians' experiences with the intervention. Data from patient experiences were collected in a short survey, the Patient Feedback Form. Moreover, a subset of the patients participating in the survey was interviewed about their experience. Furthermore, one focus group interview with clinicians was carried out to elucidate their views. RESULTS: A total of 57 patients completed the Patient Feedback Form, and 14 patients were interviewed. The focus group interview included 5 clinicians. Overall, patients and clinicians were satisfied with the tool. They believed it enhanced patients' awareness of side effects and increased their feeling of involvement. The patients reported that it was easy to fill out the questionnaire and that it made sense to do so. However, a minority of the patients expressed in the interviews that they did not believe that the health care professionals had seen their reports when they came to the clinic, and that the reporting did not lead to increased contact with the department. CONCLUSIONS: Overall, satisfaction with the eHealth intervention was high among patients and their treating clinicians. The tool was easy to use and contributed to greater symptom awareness and patient involvement. Thus, in terms of patient and clinician satisfaction with the tool, it makes sense to continue using the tool beyond the project period. TRIAL REGISTRATION: ClinicalTrials.gov NCT03073031; https://tinyurl.com/tjx3gtu.

Selection of patient reported outcomes questions reflecting symptoms for patients with metastatic melanoma receiving immunotherapy.

CONTEXT: Toxicity-monitoring plays an important role in all cancer treatment, however, early recognition is vital for detecting and treating immune-related symptoms. Preparing a Patient Reported Outcomes tool and including melanoma patients receiving immunotherapy in the reporting of symptoms, may optimize toxicity-monitoring. OBJECTIVES: The objective of this study was to identify the symptoms and their equivalent questions to include from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) library for melanoma patients, receiving immunotherapy and, further, to evaluate if all relevant symptoms are covered by this tool. METHODS: To establish the relevant symptoms, three measures were taken. First, a literature search was carried out in three databases. Second, a chart audit was performed including medical records from melanoma patients receiving immunotherapy. Finally, the product information for the relevant immunotherapies was studied. RESULTS: Ten articles were included as a result of the literature search. As for the chart audit, a total of 37 patients (48 treatments with immunotherapy) were included. Overall, the reported symptoms from the literature review aligned with those identified in the chart audit. The examination of the product information supported the findings from review and chart audit, revealing only one additional symptom. In total, 28 PRO-CTCAE symptoms were selected comprising of 56 PRO-questions plus an additional question on blood in stool. CONCLUSION: When preparing a Patient Reported Outcomes tool it is important that the preparatory work of selecting questions is done properly. By going through the literature, performing a chart audit, and examining the product information, the most important and relevant symptoms have been uncovered, facilitating the design of a PROquestionnaire, based on PRO-CTCAE, that fits the patient population under investigation.

Danish translation, cultural adaption and initial psychometric evaluation of the patient feedback form.

AIM: No suitable Danish questionnaire exists to evaluate patient satisfaction with various patient reported outcome measures. Thus, the aim of this research project was to conduct a study on the translation and cultural adaption of an American patient reported experience measures questionnaire, "Patient Feedback Form", among Danish patients, and to examine selected psychometric properties within reliability. MATERIAL AND METHODS: In the first phase of the study, the Patient Feedback Form was forward and backward translated following the methodology of existing guidelines. Subsequently, cognitive interviewing was performed with seven cancer patients and seven healthy persons (19-86 years old/6 men and 8 women) to ensure that questions were easy to understand and made sense to Danish interviewees. In the second phase, phone interviews were carried out with 95 prostate cancer patients after they had responded to the same Patient Feedback Form. Missing data was imputed using the Expectation-Maximization technique. To examine the structure of the questionnaire, an exploratory factor analysis was conducted. Cronbach's alpha was calculated to investigate internal consistency. RESULTS: There were only minor disagreements in the translation process, and the reconciliation went smoothly (phase 1). With regard to one item, however, it was difficult to reach a consensus. Through the qualitative validation process, the right solution was found. The results from the psychometric testing (phase 2) showed that four factors had an Eigen value > 1, but only one factor was extracted as the Scree plot had a clear "elbow", showing a one factor structure that explained 46.1% of the variance. The internal consistency was high as Cronbach's alpha was 0.89. CONCLUSION: The translated, culturally adapted, and validated version of the Patient Feedback Form seems to be suitable for measuring satisfaction with patient reported outcome measures in a Danish setting. While the results should be treated with caution due to the small sample size, psychometric testing indicates that the questionnaire is a valid instrument. However, additional psychometric testing such as hypotheses testing, responsiveness, and test-retest on a larger and more diverse sample size is required to further verify the validity of the instrument.

Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies.

INTRODUCTION: Vandetanib has recently demonstrated clinically meaningful benefits in patients with unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). Given the potential for long-term vandetanib therapy in this setting, in addition to treatment for disease-related symptoms, effective management of related adverse events (AEs) is vital to ensure patient compliance and maximize clinical benefit with vandetanib therapy. METHODS: This expert meeting-based review aims to summarize published data on AEs associated with vandetanib therapy and to provide clinicians with specific practical guidance on education, monitoring, and management of toxicities induced in patients treated with vandetanib in advanced and metastatic MTC. The content of this review is based on the expert discussions from a multidisciplinary meeting held in October 2012. RESULTS: Characteristics, frequency, and risk data are outlined for a number of dermatological, cardiovascular, gastrointestinal, and general AEs related to vandetanib treatment. Preventive strategies, practical treatment suggestions, and points for clinical consideration are provided. CONCLUSIONS: Good patient and team communication is necessary for the prevention, early detection, and management of AEs of vandetanib. Physicians, nurses, and other healthcare providers play a critical role in providing AE management and patient support to optimize outcomes with vandetanib in MTC.