The ePRO monitoring system, developed in Japan for soft tissue sarcoma patients, especially those undergoing drug treatment, was found to be feasible with an extremely high patient response rate and a low missing rate. In previous studies, the response rate of routinely implemented ePROs was reported to be up to 94%, even when evaluations were conducted on a monthly basis [16–18, 39, 40]. The electronic method surpassed the classical paper-based method in terms of patient compliance, thus ensuring reliability in clinical settings. The required time, determined as the sum of the median time (in seconds) of each PRO measure, was approximately 3 min per week, and within 12 min every 4 weeks. Furthermore, the response times for all questionnaires decreased as patients gained experience completing them, especially during the initial 10 weeks from enrollment. From a psychological standpoint, this could be acceptable for most people.
Gwaltney et al. [41] and Muehelhausen et al. [42] reviewed the relevant literature on of electronic and paper-based PROs measures and reported observing a high level of agreement. The present study calculated the direct test-retest correlation between the electronic and paper-based PRO measures collected in parallel from the same cases during the same period, using the same questionnaires. Coefficients, including the 95% CI range, were all > 0.6, but did not reach the average of 0.88 reported in previous studies [41, 42]. Interestingly, the agreement was not perfect even when the electronic and paper-based PROs were examined on the same day. This may reflect the fluctuation of symptoms or a limitation of PRO measures as a soft endpoint.
One of the important objectives of this study was to identify candidate items for weekly monitoring. As part of our preliminary investigation, we analyzed all answers to develop an application with an alert function based on a prognostic prediction model that can be adapted to clinical use [16–18, 43]. The restrictions and symptoms that were most frequently reported (i.e., ECOG PS, pain/discomfort and usual activities in the EQ-5D-5L, and general pain and fatigue in the PRO-CTCAE) or those for which moderate or severe grade symptoms or restrictions were reported at least once in each case (i.e., general pain, fatigue, decreased appetite, and pain/discomfort) could be meaningful. Similarly, in the PRO-CTCAE, the items of nausea, anxiety, constipation, and insomnia were identified as candidates based on their frequency and severity. Although this cohort had a 1-year overall survival rate of 86.7%, the median TTF was 2.6 months and the median time to global health status deterioration was 24 weeks from enrollment. Four adjuvant setting cases with AI therapy as 1st line at the entry were included in this cohort. If the statistical analysis is done for only advanced cases, the TTF and time to global health status deterioration result in shorter. For use in a subsequent trial for advanced cases, the protocol of the monitoring period would be reasonable.
This study presents the first Japanese version of an ePRO monitoring system focused on soft tissue sarcoma patients undergoing treatment with anti-tumor agents. The accumulation of the PRO and health-related QoL data are important for improving the treatment outcomes and satisfaction of patients with sarcoma and other rare cancers with unmet medical needs [11, 44, 45]. Further Japanese PRO measure systems should be developed and utilized in Japan because lifestyle and points of view can vary among countries and communities.
The present study had some limitations. First, the patient characteristics, including tumor location (e.g., retroperitoneum, head and neck, and other sites), were heterogenous and the cohort included patients without advanced stage disease who received neoadjuvant/adjuvant chemotherapy. Second, selection bias influenced the results of the survival analyses in our cohort. Accordingly, we cannot directly compare the results of this study to past research (e.g., randomized control trials with overall survival as a primary endpoint). Third, the ePRO monitoring system reported in this study was an incomplete version. A revised version will be applied in clinical practice after further studies.