Impact of a Reminder App on Physical Activity During Radiation Therapy for Lung Cancer (APPAREL)

Lung cancer belongs to the most common types of solid cancer in Europe and Northern America. A considerable number of patients with non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) receive conventionally fractionated radiation therapy with or without systemic treatment. Radiation therapy may be associated with adverse events affecting healthy tissues within the radiation field but also with fatigue and a decreased level of physical activity or function. Patients who experience significant treatment-related toxicity may not be able to receive the complete radiation therapy as planned. Maintaining or even improving the level of activity by physical exercise or walking a certain number of steps per day may be helpful in this context. A benefit of exercise has been suggested in a retrospective study of 184 cancer patients receiving neoadjuvant chemotherapy, including 31 patients with lung cancer. Adherence to an exercise program was associated with fewer dose reductions and delays of chemotherapy. Moreover, several studies performed in patients with lung cancer suggested that physical activity had a positive effect on the patient's quality of live. Furthermore, in a retrospective study of 50 patients who received chemotherapy for advanced or recurrent lung cancer, low physical activity was negatively associated with survival. Thus, physical activity prior to and during chemo- and/or immunotherapy for lung cancer appears important. This may also be true for patients with lung cancer treated with radiation therapy. However, adherence to an exercise program sometimes may be challenging for the patients, particularly if they experience treatment-related fatigue or other adverse events.

The question arose whether an app installed on the patient's smart phone reminding them several times per day to perform a certain number of steps will have a positive effect on their physical activity during a course of radiation therapy. Such an app was developed within the project Health Advancing Technologies for Elderly (HeAT). The current trial evaluates whether the use of the reminder app leads to a reduction of the intra-individual difference of the mean number of steps than without a reminder app.

The primary objective of this prospective randomized trial is to explore whether the use of a smart phone-based reminder application is associated with a change in physical activity during radiation therapy in patients with lung cancer.

The primary endpoint focuses on the within-patient change in physical activity between Week 1 and Week 5, with comparison between treatment groups to assess potential differences attributable to the intervention. Secondary objectives include the exploratory assessment of patient satisfaction with the reminder app, its impact on the use and perception of digital health technology.

This is a multicenter prospective randomized study conducted in patients undergoing radiation therapy for lung cancer. Patients will be randomized in a 1:1 ratio to receive either standard radiation therapy supported by the reminder application (Arm A) or standard radiation therapy without additional support (Arm B). In Arm A, patients are supported by a smart phone-based application that provides reminders three or four times per day (according to the patient's preference) to perform a predefined number of steps per day during the course of radiation therapy. In Arm B, patients receive standard care without the use of a reminder application. Physical activity will be assessed at predefined time point during treatment, specifically during Week 1 and Week 5 of radiation therapy, using step count data recorded by a smart phone application.

The primary analysis will be performed on the Full Analysis Set, including all randomized patients with evaluable primary endpoint data. The primary comparison between treatment groups (reminder app vs. control) will be conducted using a two-sided Wilcoxon-Mann-Whitney U test. The sample size calculation is based on the assumption of a clinically relevant difference between treatment groups corresponding to an approximate 30% relative difference in the within-patient change of steps per wear-hour. Given the non-parametric nature of the primary analysis, this assumption is interpreted as a moderate shift in the distribution of the endpoint between treatment arms, corresponding approximately to a probability of superiority of around 0.65. Assuming a two-sided significance level of α = 0.05 and a statistical power of 80%, approximately 28 evaluable patients in the Full Analysis Set , corresponding to 14 patients per treatment arm, are required to detect such an effect using the asymptotic approximation of the Wilcoxon-Mann-Whitney U test. Since the primary endpoint relies on patient-generated smart phone data, a proportion of patients may not provide evaluable data due to insufficient wear time or incomplete recording. Based on prior experience with similar datasets and practical considerations, approximately 10% of randomized patients are assumed to be non-evaluable for the primary endpoint.To ensure that at least 28 evaluable patients are included in the primary analysis population, a total of 32 patients will be randomized.

The sample size calculation is aligned with the analysis population and endpoint definition and is considered appropriate for this exploratory prospective study.

Recruitment of all patients is expected to be completed within 6 months. Each patient will participate in the study for the duration of their radiation therapy, which is scheduled to take 5 to 7 weeks. Overall, the total study duration, including recruitment and follow-up, is expected to be approximately 8 months. To account for potential differences in treatment context, randomization will be stratified by the presence or absence of concurrent systemic therapy.