Outcome measures will be assessed at three time points, baseline, six and twelve weeks with a 6 and 12 month follow up. Table
3 outlines the study assessment schedule. Demographic, performance status (WHO) and medical data will be collected by journal review and questionnaire. Assessments will be carried out between 9:00 am and 12:00 noon by the project outcome assessors at their respective hospitals. Patients will be instructed on proper technique for the tests, and will be advised to stop if they experience pain or extreme discomfort, nausea, or dizziness. During the test sessions, the patients will be continuously monitored with a digital heart rate monitor (Polar Model) and observed for adverse reactions/events (see Monitoring Adverse Events).
Table 3
Study assessment schedule
Recruitment
| | | | | | | | |
Chart review | x | | | | | | | |
Patient approached | x | | | | | | | |
Informed consent | x | | | | | | | |
Outcome Assessments
| | | | | | | | |
6MWD | | x | | | x | x | | |
Aastrand-Rhyming test | | x | | | x | x | | |
Sit to stand test | | x | | | x | x | | |
Biceps arm curl | | x | | | x | x | | |
Patient-reported outcomes | | x | | | x | x | x | x |
Medical chart review | | x | | | | x | x | x |
Weekly assessments
| | | | | | | | |
Step counter | | x | | | x | x | | |
MDASI | | x | | | x | x | x | x |
BFI | | x | | | x | x | x | x |
PA Level | | x | | | x | x | x | x |
Randomization | | | x | | | | | |
Intervention initiation | | | | x | | | | |
Qualitative Interview | | | | | | x | | |
Secondary endpoints
Aerobic capacity. A single stage 6 min submaximal exercise test; the Aastrand-Rhyming cycle ergometer test is used to predict VO
2 max values [
48]. The test is based on the linear relationship between VO
2 and heart rate. The patients pulse will be continually monitored using a wireless heart rate transmitter. Resistance (Watt) is increased to elicit a steady-state heart rate between 125 and 170 beats/min at a speed between 60 and 65 r.p.m. If after 6 min the HR is above 125 beats/min and stable, not fluctuating more than 5 beats/min, the test is terminated. VO
2 max is determined using a nomogram with an age and body weight correction factor. VOs max is stated in ml/kg/min.
Functional performance and muscle strength comprises three endpoints:
(1) Sit to stand test will be performed as a measure of strength and performance of the lower extremity muscles. The 30 second sit to stand was developed as an assessment tool to measure lower body strength [
49]; (2) Biceps Arm Curl measures arm flexor strength, upper body strength and endurance [
50]. The aim is to perform as many arm curls as possible in 30 seconds; and (3) Measurement of weekly steps and distance with the step counter: Omron Walking Style Pro [
44].
Clinical outcomes (exploratory endpoints) will include andropometric characteristics (body mass index (wt(kg)/ht(m2)), WHO performance status, hospitalization (days), increased temperature (>38°) (days), elevated C-reactive protein (days), infections and complications (type and days), neutropenia and thrombocytopenia (days), transfusions (platelets and RBC) (number), time to relapse and survival.
Patient reported outcomes (PRO) in this study are standardized and validated questionnaires that measure physical, functional, emotional and social wellbeing, symptom prevalence, intensity including fatigue and interference in daily activities. The PRO’s will be administered and checked for completeness by the study investigator at baseline, 6 and 12 weeks, and 6 and 12 months; and coded according to the guidelines given in the questionnaires manuals: (1) The Functional Assessment of Cancer Therapy-Anemia scale (FACT-An) assesses cancer specific Health Related Quality of Life (HRQOL), the fatigue symptom subscale (An) of the FACT-An scale and the Trial Outcome Index (TOI) [
51]. (2) The 36-Item Short Form Health Survey (SF-36) assesses general wellbeing using eight scales measuring different aspects of general health with two summary scales; physical and mental component scales [
52]. (3) The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (C30 EORTC QLQ-C30) assesses Quality of Life (QOL) using a global health status scale, five functional scales (physical, role, emotional, cognitive and social functioning) and symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea) [
53,
54]. (4) The Hospital Anxiety and Depression Scale (HADS) assess psychological wellbeing and is designed to measure general anxiety and depression in patients with physical illness [
55]. (5) The M.D. Anderson Symptom Inventory (MDASI) assesses the severity of 13 symptoms and their impact as evaluated by six interference items [
56]. The MDASI will be additionally administered once a week prior to the last training session. (6) The Brief Fatigue Inventory (BFI) assesses fatigue levels and their impact as evaluated by interference items [
57]. The BFI will also be administered once a week prior to the last training session.
Physical activity, social network/relations, activation and ability, and employment (return to work) will be assessed by the (7) Leisure time physical activity [
58], (8) Physical activity level [
59], (9) Multidimensional Scale of Perceived Social Support (MSPSS) [
60], (10) Patient Activation Measure (PAM) [
61], (11) Self Efficacy Scale (GSE) [
62] and (12) Employment status and ability [
63].
A qualitative in-depth face-to-face semistructured interview (n = 25) at 12 weeks carried out by the study investigator will explore the patients’ perspectives on physical activity and health, health behavior, and the experiences and challenges (including barriers) of returning to daily life regarding issues of health (well-being, vitality/fatigue, strength, symptom control) and disease (treatment and management, symptoms, complications), social (network, family) and employment. Further, we would like to clarify whether and how the intervention has contributed to the patients’ experiences of physical, emotional and social wellbeing and adaptation. Moreover, we aim to describe the symptom experience from the patients’ perspective, as well as explore the effect of the intervention on the symptom burden and symptom interference. A topic and question guide will be used to aid the focus of the interviews.
Logbook
A 'monitoring logbook’ will be used to document screening, adherence to the intervention, unwanted symptoms, adverse events, and self-reported symptom assessment and activity levels. All components of the intervention performed will be recorded on-going including; exercise mode, frequency, intensity, duration and progression as well as subjective exercise response (BORG) and heart rate. Components performed beyond that prescribed in the intervention program, i.e. weekends or evenings, will be reported by the patient and then documented. For each individual component in the programme, adherence to the intervention will be measured by calculating the percentage of recommended exercise sessions performed by the patient (number of sessions performed /number of sessions prescribed). The
control group will receive a modified logbook and will be asked to register activity/exercise mode, frequency and duration [
59], weekly, during the study period as well as register symptom prevalence, intensity and interference (weekly) using the symptom assessment scales MDASI [
56] and BFI [
57].