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.

Routine surveillance for symptomatic toxicities with real-time clinician reporting in Danish breast cancer patients-Organization and design of the first national, cluster randomized trial using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE).

The Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed by the National Cancer Institute to capture patient self-reports of symptomatic toxicities during cancer treatment. The aim of this short communication is to describe the design of a national study, which examine the effect of using patients' electronic PRO-CTCAE reporting with real-time feedback to clinicians on treatment events for breast cancer patients receiving adjuvant chemotherapy. The study's end-points are defined as dose reduction, hospitalization, and febrile neutropenia. This is the first report on the impact of PRO-CTCAE in a national breast cancer population during chemotherapy treatment.

Consequences of a false-positive mammography result: drug consumption before and after screening.

Background Previous research showed women experiencing false-positive mammograms to have greater anxiety about breast cancer than women with normal mammograms. To elucidate psychological effects of false-positive mammograms, we studied impact on drug intake. Methods We calculated the ratio of drug use for women with false-positive versus women with normal mammograms, before and after the event, using population-based registers, 1997-2006. The ratio of the ratios (RRR) assessed the impact. Results Before the test, 40.3% of women from the false-positive group versus 36.2% from the normal group used anxiolytic and antidepressant drugs. There was no difference in use of beta blockers. Hormone therapy was used more frequently by the false-positive, 36.6% versus 28.7%. The proportion of women using anxiolytic and antidepressant drugs increased with 19% from the before to the after period in the false-positive group, and with 16% in the normal group, resulting in an RRR of 1.02 (95% CI 0.92-1.14). RRR was 1.03 for beta blockers, 0.97 for hormone therapy. Conclusion(s) Drugs used to mitigate mood disorders were used more frequently by women with false-positive than by women with normal mammograms already before the screening event, while the changes from before to after screening were similar for both groups. The results point to the importance of control for potential selection in studies of screening effects.

Machine learning applied in patient-reported outcome research-exploring symptoms in adjuvant treatment of breast cancer.

BACKGROUND: Patient-reported outcome (PRO) data may help us better understand the life of breast cancer patients. We have previously collected PRO data in a national Danish breast cancer study in patients undergoing adjuvant chemotherapy. The aim of the present post-hoc explorative study is to apply Machine Learning (ML) algorithms using permutation importance to explore how specific PRO symptoms influence nonadherence to six cycles of planned adjuvant chemotherapy in breast cancer patients. METHODS: We here investigate ePRO-data from the 347 patients. The ePRO presented 42 PROCTCAE questions on 25 symptoms. Patients completed the ePRO before each cycle of chemotherapy. Number of patients with completion of the scheduled six cycles of chemotherapy were registered. Two ML models were applied. One aimed at discovering the individual relative importance of the different questions in the dataset while the second aimed at discovering the relationships between the questions. Permutation importance was used. RESULTS: Out of 347 patients 238 patients remained in the final dataset, 15 patients dropped out. Two symptoms: aching joints and numbness/tingling, were the most important for dropout in the final dataset, each with an importance value of about 0.04. Model's average ROC-AUC-score being 0.706. In the second model a low performance score made the results very unreliable. CONCLUSION: In conclusion, this explorative data analysis using ML methodologies in an ePRO dataset from a population of women with breast cancer treated with adjuvant chemotherapy unravels that the symptoms aching joints and numbness/tingling could be important for drop out of planned adjuvant chemotherapy.

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.

Clinical effects of assessing electronic patient-reported outcomes monitoring symptomatic toxicities during breast cancer therapy: a nationwide and population-based study.

The involvement of cancer patients in symptom reporting talks into our cultural narrative of empowerment and participation in decisions in health of both patients and professionals. Electronic patient-reported outcome (ePRO) is a tool applied for use in such interaction. Based on limited evidence and few empirical studies, health systems are rapidly implementing this instrument in managing patients in active treatment and in follow-up. In a cluster randomized trial of all Danish oncology departments treating breast cancer with adjuvant chemotherapy, we applied ePRO in 347 patients consecutively recruited. Our primary outcome, which was at least one treatment adjustment, was not significantly influenced using ePRO, 34% in the ePRO arm and 41% in the usual care arm received at least one treatment adjustment, p = 0.095. Number of hospitalizations and events of febrile neutropenia were not influenced by the intervention. We believe that one of the main reasons for this finding could be the application of PRO in a well-regulated treatment setting within a public health care system where the most impacting symptomatic toxicities are already taken care off.Trial registration: Clinicaltrials.gov identifier: NCT02996201, registered 19 Dec 2016, retrospectively registered.

Patients' experience of communication and handling of symptomatic adverse events in breast cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The study is based on a national cluster randomized trial investigating the effect of electronic patient-reported outcomes (ePRO) on treatment outcomes in breast cancer patients receiving adjuvant chemotherapy. All 13 oncology departments (11 clusters) treating breast cancer patients in Denmark were randomized to use electronic patient-reported outcomes with real-time clinician feedback (ePRO arm) to track symptoms or usual care for eliciting symptoms using a short paper tracking list (usual care arm). The impact of ePRO on clinical outcomes were examined, which is reported elsewhere. The purpose of the present study was to examine patient-reported experience measure (PREM) regarding communication and handling of side effects/symptoms. METHODS: For this sub-study, patient representatives were involved in the development of a PREM questionnaire. Patients enrolled in the cluster randomized trial completed the PREM questionnaire at their last treatment visit. Semi-structured telephone-interviews were performed with a subgroup of patients. The interviews were based on an interview guide comprised of the questions from the PREM questionnaire and aimed to elaborate on the PREM questionnaire data. RESULTS: A 12 item PREM questionnaire was developed in partnership with patient representatives. In total, 439 out of 682 patients (64.4%) included patients completed the PREM questionnaire. Telephone semi-structured interviews were performed with 22 patients. In total, 52% (ePRO arm) and 65% (usual care arm) reported having talked with the oncologist/nurse about their responses in the tracking systems before each chemotherapy cycle. Fewer patients in the ePRO arm compared to the usual care arm experienced side effects/symptoms not included in the side effect questionnaire. Patients experienced high satisfaction with oncologists' and nurses' handling of side effects/symptoms. CONCLUSIONS: Patients experienced high satisfaction with oncologists' and nurses' handling of chemotherapy adverse events. The study indicates a need for a more comprehensive side effect questionnaire as tracking system covering more symptoms than the one used in usual care today. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02996201. Registered 19 December 2016, retrospectively registered.

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.

Feasibility and acceptability of electronic symptom surveillance with clinician feedback using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Danish prostate cancer patients.

BACKGROUND: The aim was to examine the feasibility, acceptability and clinical utility of electronic symptom surveillance with clinician feedback using a subset of items drawn from the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a cancer treatment setting. METHODS: Danish-speaking men with castration-resistant metastatic prostate cancer receiving treatment at the Department of Oncology, Rigshospitalet, Copenhagen between March 9, 2015 and June 8, 2015 were invited to participate (n = 63 eligible). Participants completed the PRO-CTCAE questionnaire on tablet computers using AmbuFlex software at each treatment visit in the outpatient clinic. In total, 22 symptomatic toxicities (41 PRO-CTCAE items), corresponding to the symptomatic adverse-events profile associated with the regimens commonly used for prostate cancer treatment (Docetaxel, Cabazitaxel, Abiraterone, Alpharadin), were selected. Participants' PRO-CTCAE responses were presented graphically to their treating oncologists via an AmbuFlex dashboard, for real-time use to enhance the patient-clinician dialogue that occurs during the consultation prior to each treatment cycle. Technical and clinical barriers and acceptability were evaluated through semi-structured interviews with both patients and oncologists. Patients receiving active treatment at the end of the study period completed an evaluation questionnaire. RESULTS: Fifty-four out of sixty-three (86%) eligible patients were enrolled. The PRO-CTCAE questionnaire was completed a total of 168 times by 54 participants (median number per patient was 3, range 1-5). Eight surveys were missed, resulting in a compliance rate of 97%. At the end of the study period, 35 patients (65%) were still receiving active treatment and completed the evaluation questionnaire. Patients reported that their PRO-CTCAE responses served as a communication tool. Oncologists stated that the availability of the PRO-CTCAE self-reports during the consultation improved patient-clinician communication about side effects. CONCLUSION: Electronic capture of symptomatic toxicities using PRO-CTCAE and the submission of self-reports to clinicians prior to consultation were feasible among metastatic prostate cancer patients receiving chemotherapy in an outpatient setting, and this procedure was acceptable to both patients and clinicians. Continued research, including a cluster-randomized trial, will evaluate the effects of submitting patients' PRO-CTCAE results to clinicians prior to consultation on the quality of side-effects management and resultant clinical outcomes.

Danish Translation and Linguistic Validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

CONTEXT: The Common Terminology Criteria for Adverse Events (CTCAE) is the basis for standardized clinician-based grading and reporting of adverse events in cancer clinical trials. The U.S. National Cancer Institute has developed the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) to incorporate patient self-reporting of symptomatic adverse events. OBJECTIVES: The aim of the study was to translate and linguistically validate a Danish language version of PRO-CTCAE. METHODS: The U.S. English language PRO-CTCAE was translated into Danish using forward and backward procedures with reconciliation. The linguistic validity of the PRO-CTCAE Danish was examined in two successive rounds of semistructured cognitive interviews in a sample of 56 patients equally distributed by gender and cancer type (prostate, head and neck, lung, breast, gynecological, gastrointestinal, and hematological cancer), and who were currently undergoing cancer treatment. RESULTS: In the first round of linguistic validation (n = 42), the phrasing of five symptomatic toxicities was adjusted, and the refined phrasing was retested in a second round of interviews (n = 14). Agreement about phrasing that was both culturally acceptable and semantically comprehensible was achieved in the second round. Statements from participants describing the meaning of the PRO-CTCAE symptomatic toxicities support conceptual equivalence to the U.S. English language version. CONCLUSION: Availability of the NCI PRO-CTCAE in languages beyond English will support international congruence in self-reporting of side effects of cancer treatment. A rigorous methodology was used to develop the Danish language version of PRO-CTCAE. Results provide preliminary support for the use of PRO-CTCAE in cancer clinical trials that include Danish speakers.