Study design
The current pragmatic one-arm pilot feasibility study was carried out at VieCuri Medical Center, a large teaching hospital in Venlo, the Netherlands. The study was approved by the Medical Ethics Review Committee – Zuyderland/Zuyd (Heerlen, the Netherlands) under reference number METCZ20190150. Initially, the trial started in February 2020; however, due to restrictions caused by the worldwide COVID-19 pandemic, inclusion could only start in July 2020 and ended in September 2021. Reporting was done in accordance with the CONSORT statement extension to randomized pilot and feasibility trials (Eldridge et al. 2016).
Participants
A consecutive sample of potentially high-risk patients was recruited at the moment of suspected colorectal cancer by endoscopy. A few days after the endoscopy, patients were contacted by telephone to check for potential eligibility and willingness to participate. Patients were potentially eligible when they were ≥ 18 years of age, were able to operate a mobile phone, and had a score ≤ 7 metabolic equivalents of task (METs) on the veterans-specific activity questionnaire (VSAQ). These eligibility criteria were used as a pre-screening. Final eligibility was determined after CPET and final diagnosis, which was defined as an oxygen uptake (VO2) at the ventilatory anaerobic threshold (VAT) ≤ 11 mL/kg/min or a valid VO2 at peak exercise (VO2peak) ≤ 18 mL/kg/min during CPET in combination with confirmed diagnosis of colon or rectal cancer (stage I, II, or III) requiring elective resection with or without neoadjuvant treatment.
Intervention and assessments
A multimodal tele-prehabilitation program was embedded within the existing colorectal cancer pathway of VieCuri Medical Center. Therefore, no additional hospital visits were required for study purposes. Pre-prehabilitation measurements (T0) were planned on the day of the appointment with the surgeon, approximately 2–5 days after final inclusion. In patients receiving neoadjuvant treatment, pre-prehabilitation measurements were performed concurrent with the first appointment with the surgeon after completing neoadjuvant treatment (approximately 4 weeks before surgery). Pre-prehabilitation (T0) assessments consisted of evaluating aerobic fitness by time to exhaustion on a continuous work rate test at 80% of the peak work rate achieved during CPET. Additionally, lower limb muscle power and endurance was assessed by the number of repetitions on the 30-s chair-stand test and gait speed was measured using the 4-m gait speed test. Post-prehabilitation (T1), reassessment of the continuous work rate test, 30-s chair-stand test, and the 4-m gait speed test took place 1 or 2 days prior to surgery. In addition, participants filled out a patient appreciation questionnaire, based on the questionnaire of Dronkers et al. (Dronkers et al. 2010), and the systems usability questionnaire (Myers et al. 1994) after the post-prehabilitation assessment.
The tele-prehabilitation program consisted of a tele-monitored physical exercise training module and a nutritional support module. Encouraging smoking cessation was part of usual care and was therefore not included explicitly in the tele-prehabilitation program.
Physical exercise training
The tele-monitored physical exercise training module was delivered by using the mobile phone application of HC@Home (version HC1.12a, HC@Home B.V., Zwolle, the Netherlands) on a dedicated mobile phone (delivered to the patients for the duration of the tele-prehabilitation program) to which a heart rate monitor (Polar OH1, Polar Electro Inc., Kempele Finland) was connected. Personalized training zones were set based on the heart rate at the VAT and the respiratory compensation point as determined by CPET. Ideally, training sessions took place every other day and consisted of 30 min of aerobic moderate- to high-intensity interval training by a patient’s preferred activity (i.e., walking, cycling, stair climbing, sit-to-stand exercises, push-ups, steps). Intervals consisted of 3 min of low-intensity exercise at a heart rate below the heart rate at the VAT and/or a 6–20 Borg rating of perceived exertion (RPE) score ≤ 11, interspersed by 3 min of high-intensity exercise at a heart rate just below the heart rate at the respiratory compensation point (approximately 70–85% of the heart rate at VO2peak) or a Borg RPE score of 14–16. In-between training days, patients were advised to retain relative rest but still comply with the Dutch physical activity guidelines (e.g., > 30 min of moderate-intensity physical activity). The abovementioned training protocol was used as a blueprint, which means that training frequency, intensity, time, type, volume, and progression were personalized according to CPET results (e.g., using shorter intervals in patients with a pulmonary exercise limitation), training heart rate, training Borg RPE score, recovery after training, and participant experiences and preferences. After the first face-to-face physical exercise training at home, which was supervised by a physical therapist specialized in physical exercise training in clinical populations, participants continued the home-based physical exercise training sessions independently. Involvement of a family member or (informal) caregiver during exercising was encouraged to promote motivation. The first face-to-face session was used to validate training zones and familiarize participants with the exercises and equipment. Performed training session’s frequency, intensity, and time were automatically uploaded to an online platform, at which they could be reviewed by the physical therapist. A weekly phone call took place to monitor training progression and adjust the physical exercise program accordingly.
Nutritional counseling
Participants were screened for malnutrition using the patient-generated subjective global assessment short form (PG-SGA-SF) in combination with a comprehensive nutritional screening by a registered dietician. Preoperative nutritional counseling consisted of optimization of basic nutritional needs, as well as ensuring the recommended intake of protein, defined as 1.2–2.0 g/kg body mass (Wischmeyer et al. 2018). After an initial intake assessment, follow-up counseling was provided by a weekly phone call between the dietician and the participants in order to monitor nutritional and protein intake, as well as to compare nutritional and protein intake against calculated needs. In addition, body mass was assessed based on self-report and participants were motivated to comply with the dietary advice.
Outcomes
The primary outcome of the study was feasibility as determined by (1) study participation rate combined with reasons for non-willingness or inability to participate, (2) the number and severity of adverse events related to the physical exercise training program, (3) adherence to the physical exercise training program, (4) study dropout rate and reasons for dropouts, and (5) retention rate. Secondary outcomes were (1) participant experiences as measured by the patient appreciation questionnaire, (2) user-friendliness of the mobile phone application that was used for tele-prehabilitation assessed using the systems usability questionnaire (Myers et al. 1994), and (3) changes in physical fitness during the tele-prehabilitation program.
Statistical analyses
Statistical analyses were performed using IBM SPSS Statistics version 26.0 (IBM, Chicago, IL, USA). Participation rates were reported descriptively as numbers and percentages of the potentially eligible patients that were willing to participate in the current study. Dropout rates and adverse events were reported as numbers and as a proportion of participants enrolled in the study. Retention rate was expressed as a percentage and defined as the proportion of enrolled participants that completed the program. Adherence to the physical exercise training program with regard to training frequency, training intensity, and training time was determined as follows. For training frequency, observed training frequency was divided by the prescribed frequency and expressed as a percentage. Regarding training intensity, an exercise training session was designated as performed at an adequate intensity when, based on heart rate, at least 3 of the 5 prescribed high-intensity exercise bouts complied with the prescribed intensity, or when the training session intensity reported on the Borg RPE score was equal or higher than prescribed. The number of attended sessions in which the prescribed intensity was accomplished (based on either heart rate or Borg RPE score) was divided by the total number of attended sessions and presented as a percentage. For training time, the observed duration of the sessions was divided by the prescribed duration of the sessions and presented as a percentage. Adherence was deemed adequate if ≥ 80% as assessed individually for training frequency, training intensity, and training time. Participant appreciation of the tele-prehabilitation program, as scored by the patient appreciation questionnaire, and user-friendliness of the mobile phone application of HC@Home, as scored by the systems usability questionnaire, were reported descriptively. A systems usability questionnaire score ≥ 73 was considered good, and a score of ≥ 85 excellent user-friendliness (Bangor et al. 2008). Continuous data representing changes in aerobic fitness during the tele-prehabilitation program were presented as median and interquartile range (IQR). Pre-post analysis was performed using the non-parametric Wilcoxon signed-rank test. A P-value < 0.05 was considered statistically significant.