Discussion
toxicity, cancer, anxiety, breast cancer
CANCER, METASTATIC MELANOMA, SIDE EFFECT, BREAST CANCER
In this multicenter randomized trial testing the active use of PROs during systemic oncological treatment for BC patients, we found a high rate of completed questionnaires and a high rate of clinician viewing of the patient-reported symptoms. For the primary endpoints, no statistically significant differences were found, although a higher rate of hospital admissions and lower rate of treatment completion was found in the IA. During the study period, global QoL increased for the IA and decreased for the CA, however these finding were not statistically significant. Emotional functioning was significantly higher for the IA. No differences were found in OS between the two study arms.Unlike previously reported PRO trials testing the impact of systematic symptom reporting and enhanced handling of side effects, our study was unable to demonstrate differences in the chosen endpoints. Many explanations for this may exist. A major difference between ours and previous studies testing the use of PRO for cancer patients in treatment is that previously reported studies have implemented study staff to, on a daily basis, react upon alarming symptoms reported from home and then contacting the patient to initiate the appropriate supported care [In this study we found a mean questionnaire completion rate of 80% through the study period which is at level with previously conducted PRO studies [Clinician reluctance to the use of PROs and the importance of clinician endorsement to achieve effects of PRO have been described in several previous publications [Although not statistically significant, we found a higher rate of hospitalizations and lower rate of treatment completion in the intervention group when compared with the control group. Though unintentional to the initial hypothesis and aim of the study, the enhanced focus on symptom handling and toxicity may have led to an increase in hospitalizations and earlier treatment cessations. In a previous study in the breast cancer population increased awareness to toxicity was previously described to lead to early treatment cessation [Despite a small increase in global quality of life was observed for the intervention group compared to the control group we did not find a statistically significant difference between the two groups. However, a randomized study with an ePRO intervention in a population of metastatic melanoma patients showed that quality of life between the two arms did not separate until months after the applied ePRO intervention [Strengths of the study include the randomized trial design conducted at four university hospitals across Denmark. Also, the extensive pilot studies leading to this design, in terms of choice of endpoints and item selection process involving patients, nurses, physicians and review of literature is a major strength of this study. The conduction of the pilot studies spread over 1½ year allowing for familiarity with PROs as a part of daily clinic was in this study reflected in the high level of clinician compliance.The lack of multicomponent handling of PROs exceeding threshold values to clinicians to allow for real-time handling of symptoms remains the greatest limitation in terms of not reaching the specified endpoints. Also, a limitation of the study may have been that no standard procedures were given to clinicians of how to handle a given side effect as reported by the patient in the ePROs. The study was planned as such to allow for individual physician-led treatment of a given side effect. However, there may at one or more sites have been a high clinical standard of handling of side effects before study initiation, thereby diminishing the impact of the intervention. The lack of this guidance specific to this study may across four study sites have led to vast differences in the handling of side effects for both arms in the study. In a study by Maguire et al. from 2021 they achieved improvements in anxiety, health related quality of life, self-efficacy and supportive care needs in the intervention group despite the multinational setup and may be explained by their extensive symptom management flow charts [