The OnkoFit trials are two independent, single-center, randomized prospective phase III trials that have been certified by the working group radiological oncology of the German Cancer Society. After providing informed consent, patients will be randomized to a standard arm (arm A) or 1 of 2 interventional arms (arm B and C) in a 1:1:1 ratio (Figure 1). All patients will be recruited by the Department of Radiation Oncology at the University Hospital Tuebingen.

The OnkoFit I trial is exclusively designed for patients with breast cancer, while the OnkoFit II trial is open to patients undergoing preoperative, definitive, or postoperative radiotherapy for various tumor sites. The separation of the tumor entities in two different trials allows for two different end points. Although the end point of the OnkoFit I trial—fatigue at 3 months after radiotherapy—has been evaluated in a pilot trial that was conducted in our department [2], it was determined that for patients undergoing neoadjuvant radiochemotherapy, this end point might be too early, especially for patients who undergo surgery after neoadjuvant radiochemotherapy.

A summary of key inclusion and exclusion criteria is provided in Textbox 1. We anticipate the recruitment of 50 patients per year in each trial. The course of the study is displayed in Figure 2.

After providing informed consent, patients will be included into either the OnkoFit I trial or OnkoFit II trial and randomized into 1 of the 3 arms of the studies (Figure 1). Both studies aim to include 201 subjects each.

To further expand our knowledge on the possible pathomechanisms behind CRF and the potential effects that exercise has on the course and severity of CRF, blood samples will be taken from patients before radiotherapy, at the end of radiotherapy, and at 6 months after radiotherapy for the evaluation of inflammatory markers, such as neutrophil counts and interleukin-6 and C-reactive protein levels.

Based on patients’ preferences, patients can keep the activity tracker after the completion of treatment. Independent of this decision, patients will be seen for follow-up at 3, 6, and 12 months after the completion of radiotherapy. Thereafter, follow-ups will take place yearly for up to 5 years.

Previous studies were able to demonstrate a medium to high effect size with regard to the influence that physical activity has on the fatigue and HRQoL of patients with cancer. Based on a medium effect size (Cohen f=0.25) with an α error of 5% and a power of 80%, a one-way independent sample analysis of variance was conducted. Per the results of this analysis, 201 patients (67 patients per arm) will be recruited for each trial [27]. A dropout rate of 20% was assumed for the calculation of the number of patients. Randomization will be carried out via block randomization with variable block lengths.

It will not be possible to record the position of patients in terms of their geographical location via the activity tracker. The clinical and personal data of patients will not be stored on the device. The assignment of the fitness trackers to the patients will be pseudonymized. The storage of fitness data and the linking of patient-related data will only be carried out within the hospital's information technology system. Therefore, these data will be subject to the hospital's data protection and data security regulations. For the purpose of publication, all data will be presented anonymously.

The benefit of physical activity both during and after various kinds of cancer treatments has been shown in several randomized trials. Physical activity not only improves HRQoL but also has the capability to reduce the severity of negative treatment effects. With regard to patients undergoing radiotherapy, the feasibility and positive impact of combining radiotherapy with physical activity has been observed, and further clinical studies are currently being conducted (Exercise Therapy in Radiation Therapy [EXERT] trial; NCT03905356) [28]. However, measured variables as well as definitions of end points greatly vary between different studies on using activity trackers in cancer care, and there is a great need for randomized trials that clarify optimal time points as well as strategies [24]. The rationale behind the OnkoFit trials is to test a physical activity program that requires only few resources and is easy to implement even in the workflow of departments that treat a very large numbers of patients (≥1000 patients per year). Even though there is no doubt that a one-to-one supervised physical activity program that is conducted over several weeks would be desirable, this is often not feasible due to costs, limitations in geographical reach, and a lack of qualified personal [29]. Moreover, in a qualitative interview study conducted by Hardcastle et al [30], survivors of breast cancer expressed that they would favor home-based programs for exercise. The high acceptance of activity trackers among patients with cancer has been reported previously [31-33]. In our pilot study, which investigated the feasibility of continuous activity monitoring, 19 of 23 patients regularly used a commercially available activity tracker during radiotherapy. In the same study, we observed very plausible results regarding changes in physical activity during the course of treatment [33]. These results are also supported by a study conducted by Ohri et al [34], who showed a correlation between decreasing step counts and a forthcoming need for the inpatient treatment of patients with lung cancer during radiotherapy.

We see several advantages in an activity tracker–based training program. First, most activity tracker devices are easy to use and can be intuitively used by most older patients without any previous experience with such devices. Second, these devices provide real-time feedback to patients, which results in self-awareness and motivation. Third, the quantitative measures of physical activity levels can be remotely shared with caregivers, thereby providing an objective view on a patient’s constitution and whether activity goals have been met [17]. The OnkoFit I and II trials have been designed as 3-arm trials. By introducing an arm in which patients receive an activity tracker but no predefined goals, we hope to study whether patients in the interventional arm, which provides weekly targets, actually have a higher level of physical activity and whether any potential effects that are observed at the end of the study are associated with the intervention.

Since acute and long-term side effects vary widely between patients with breast cancer undergoing radiotherapy and patients receiving preoperative or definitive radiotherapy, different end points were defined for the OnkoFit I and OnkoFit II trials. Additionally, the time points for assessment vary. In the OnkoFit II trial, the end point will be assessed 6 months after the end of radiotherapy and therefore later than in the OnkoFit I trial (the assessment will be conducted at 3 months), since patients receiving preoperative radiotherapy may still be in reconvalescence from surgery 3 months after the end of radiotherapy.

Patients undergoing radiochemotherapy in a neoadjuvant setting are at risk of increased side effects during and after concomitant surgery if they experience (severe) toxicity after the completion of radiation treatment. The concept of prehabilitation, which is defined as a rehabilitation program that is initiated before treatment, has gained more and more recognition in the field of oncology in recent years [35]. In two studies on colorectal patients, a prehabilitation program markedly improved functional recovery after resection, thereby underscoring the program’s potentially large benefit for patients [36,37]. In the context of neoadjuvant treatment, a study is currently underway for evaluating the effect that a concomitant prehabilitation program (conducted during chemotherapy) has on treatment outcomes and morbidity in patients with ovary cancer [38]. Similarly, another group has evaluated the effect that a prehabilitation program has on functional outcomes, particularly swallowing and the quality of life among patients undergoing radiochemotherapy for head and neck cancer [39]. Available data have been recently summarized by Squires and colleagues [40], with an emphasis on cardiovascular health after cancer therapy. In the context of the OnkoFit II trial, we aim to investigate whether the proposed fitness tracker–based exercise program can function as a prehabilitation program for patients undergoing neoadjuvant radiotherapy and thus decrease the number of postoperative complications.

One of the limitations of the proposed study is the lack of a supervised preintervention and postintervention fitness test (eg, ergometry), which would provide a more objective perspective on the fitness levels of patients than the fitness questionnaire—the one that will be used in our trials—alone. Furthermore, the trials were designed as monocenter trials that will be conducted at a single institution, which might limit the generalizability of the data.

The randomized OnkoFit I and II trials will investigate a unique approach to conducting a patient-executed fitness program during and after radiation therapy. In these trials, activity trackers will be used to improve HRQoL; reduce the severity of treatment side effects, including CRF; and improve the preoperative health status of patients. The findings of these trials will help to further our knowledge on combining exercise therapy with radiation treatment that focuses on the patient point of view.