Short summary

Through a randomized pilot study, it will be examined if melanoma patients who report their adverse events to immunotherapy weekly by the use of the web-based tool PRO-CTCAE experience an overall reduction of grade 3 and 4 events with 50% compared to patients who receive standard AE-monitoring carried out by a clinician every three weeks.

Focus group interviews will also be conducted to explore how patients in the intervention arm experience reporting their adverse events by using PRO-CTCAE and how patients in the control arm experience standard monitoring of adverse events. Patient-reported experience measures (PREM) regarding involvement and satisfaction with the PRO-CTCAE in the intervention arm, will also be investigated using a patient feedback questionnaire.

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Rationale

Background:
In recent years, there has been an increasing awareness within the health care system that patients are not sufficiently involved when it comes to treatment and care. When it comes to cancer treatment, there has also been an increased focus on involving the patient and one of the ways in which to engage the patient more is to use patient reported outcome (PRO). `A PRO is a measurement of any aspect of a patient's health status that comes directly from the patient (i.e., without the interpretation of the patient's responses by a physician or anyone else)´. By involving the patients their level of satisfaction can be increased, quality of life improved and the risk of late effects reduced. The development of IT-solutions has eased electronic data collection and made patient reported outcome even more accessible to the majority of patients. Even though PRO has been used more extensively in the field of routine clinical cancer treatment within the last decade, standardization is still lacking. The focus of the PRO-tool used in routine cancer care or clinical trials differs, however; focus can be on health-related quality of life, physical symptoms, treatment toxicities or psychosocial problems. In this project, the focus will be on patient-reported adverse events and shared reporting supplemented by health related quality of life related to immunotherapy and on the level of patient satisfaction.

Malignant melanoma, immunotherapy and treatment-related adverse events:
The number of Danes who are diagnosed with malignant melanoma have increased significantly during the last 50 years.  Approximately 2200 new cases are reported every year in Denmark. Malignant melanoma is the most common cancer form in the 15-34 year old and app. 400 persons are diagnosed with metastatic disease each year. A large number of these patients are being treated with immunotherapy. The toxicity profile of immunotherapy differs considerably from that of chemotherapy, but as with chemotherapy it would be interesting to explore if the intensity and frequency of adverse events are underreported when doctors register/score side effects in the out-patient clinic. If patients report their adverse events electronically using the PRO-CTC-AE on a routine basis i.e.once a week, there is a presumption that side effects are discovered at an earlier time point enabling relevant treatment to be initiated earlier. When immune related adverse events are treated early there is a chance that major complications can be avoided. Also the patient-physician communication may be improved. By including the patient reports from the PRO-CTCAE in their talks with the patients, doctors may be able to focus on the toxicities which the patients find the most burdensome, thus making communication more fruitful and improving clinical decision making.

The Common Terminology Criteria for Adverse Even in a PRO format (PRO-CTCAE):
The American National Cancer Institute (NCI) has developed standardized definitions for adverse events - CTCAE (Common Criteria for adverse events) to describe the severity of organ toxicity for patients receiving cancer therapy. The system consists of 780 adverse events and was in the beginning primarily used in clinical trials to provide standardization in the definition of treatment-related toxicity. Today it is also used in routine cancer treatment. At the Department of Oncology, OUH, a systematic evaluation using the CTCAE takes place before every cancer treatment to ensure that adverse events are registered. Evidence suggests, however, that clinicians´ reporting of symptomatic AEs lacks reliability and that clinicians tend to underreport the incidence and severity of symptoms compared to patients´ direct response. Moreover, patient self-reporting is more true to the patient perspective due the report has not been interpreted by a clinician. Furthermore, studies demonstrate that the numbers of adverse events reported are greater when the report comes directly from the patient rather than form the clinician. Consequently, the NCI has developed the paper-based CTCAE scoring system for toxicity-monitoring into a tool appropriate for patient self-reporting to give a truer picture of patients´ side effects.

A research group at Rigshospitalet has translated and linguistically validated the Danish version of PRO-CTCAE as a tool for systematic patient reporting of chemotherapy related side effects and a feasibility study has been carried out. However, the tool has not yet been used by patients who receive immunotherapy and accordingly it would be interesting to explore if the use of PRO-CTCAE has an effect on this group of patients when it comes to patient-reported adverse events. 

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Description of the cohort

(1) Men and women 18 years of age or older who read and understand Danish, (2) who have been diagnosed with malignant melanoma, (3) who are about to be treated with immunotherapy for their disease (1^st and 2^nd line, mono-therapy and combination therapy). (5) Moreover, patients must have signed and dated a written informed consent form in accordance with regulatory and institutional guidelines and (6) be willing and able to comply with the completion of PRO-CTCAE and other required questionnaires.

Data and biological material

Both quantitative data and qualitative data will be collected in this project. Patients in the intervention arm will report their adverse events weekly for the first 12 weeks of treatment. The reporting will be electronic and the tool PRO-CTCAE will be used. Furthermore, the same patients (patients in the intervention arm) will be asked to fill out a paper questionnaire on how they experience using the PRO-CTCAE. Moreover, focus group interviews will be conducted (both in the intervention and in the control arm) to examine how patients experience the use of PRO-CTCAE, and how patients experience the use of the standard reporting through focus group interviews.

Collaborating researchers and departments

Department of Oncology, Odense University Hospital

• Senior Consultant Lars Bastholt, MD, DPM 

The Danish Knowledge Centre for Rehabilitation and Palliative Care,Department of Oncology R, Odense University Hospital and University of Southern Denmark

• Senior Consultant and Professor Ann-Dorthe Zwisler, MD, PhD

Department of Oncology, The Finsen Centre, Rigshospitalet, Copenhagen University Hospital

• Senior Consultant Helle Pappot, MD, DMSc

Department of Oncology, Odense University Hospital and University of Southern Denmark

• Postdoc Karin B. Dieperink, RN, MCN, PhD