Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial morbidities (i.e., anxiety and depression). A reduction of physical activity levels can evoke functional limitations resulting in a vicious cycle of reduced exercise tolerance and physical deterioration. To date, there is limited evidence on the use of non-pharmacological strategies such as Cardio-Oncology Rehabilitation (CORE) including structured exercise, behavioural support and risk factor management to improve the outcomes of this underserved population. The HIMALAYAS study is a randomized controlled trial designed to evaluate the impact of a CORE intervention (consisting of six-months home and onsite-based structured moderate to high-intensity aerobic exercise training and CVD risk factor management) on CV and psychosocial health, and the cardiovascular disease risk in PAYA-CS with mild heart dysfunction (stage B heart failure) compared to standard of care (i.e. providing guidance on the current exercise recommendations for cancer survivors). The primary objective of the HIMALAYAS study is to determine whether a six-month supervised CORE intervention, consisting of individualized moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioral support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at six- months follow-up compared to standard of care (CON) in PAYA-CS with stage B heart failure. The secondary objective is to assess the same outcomes at 12- and 24-months follow-up. We will recruit 336 patients across 5 sites in Canada and upto 134 patients at UHN in 3 years and conclude in 6 years.
Be a PAYA-CS, defined as ≤39 years of age at the time of cancer diagnosis;
Be 18-45 years of age at the time of enrolment;
Received cancer treatment(s) with known cardiovascular risks (e.g., anthracyclines, trastuzumab, radiotherapy, platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors);
Be cancer-free at the time of enrollment;
Have an absolute or unresolved relative contraindication to exercise according to the American College of Sports Medicine guidelines;
Have an untreated physical or mental health concern that precludes safe and effective exercise participation;
Have established CVD (excluding mildly reduced LVEF as described above);
Be pregnant at time of recruitment;
Parallel
Cardio-oncology Rehabilitation (CORE)
BehavioralExercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period
Cardiorespiratory fitness
Assessed via cardiopulmonary exercise test and quantified as VO2peak
Cardiorespiratory fitness
Assessed via cardiopulmonary exercise test and quantified as VO2peak
Ventilatory threshold
Estimated using the V-slope method and according to the following criteria: i) an exaggerated response in the volume of carbon-dioxide (i.e., VCO2) relative to the volume of oxygen (i.e., VO2), and ii) the first identifiable break-point in in the minute ventilation (i.e., VE/VO2 vs work rate relationship).
Ventilatory threshold
Estimated using the V-slope method and according to the following criteria: i) an exaggerated response in the volume of carbon-dioxide (i.e., VCO2) relative to the volume of oxygen (i.e., VO2), and ii) the first identifiable break-point in in the minute ventilation (i.e., VE/VO2 vs work rate relationship).
Anaerobic threshold
Estimated according to the three-criterion discrimination technique: i) an excess VCO2 response relative to the VO2 response identified per the modified V-slope criteria; ii) the VE/VO2 to VO2 relationship having been flat or decreasing begins to increase without returning to baseline; and iii) there is no reciprocal decrease in PETCO2 at the point where PETO2 starts to rise systematically.
Therapeutic alliance
Measured using the Working Alliance Inventory Short-Revised (WAI-SR) form.
Testing Performance
Defined as the percent of tests that achieve 'peak' termination criteria relative to the total number of tests completed across all time points
Serious and non-serious adverse events
Defined as the number and frequency of testing-, intervention-, and non-intervention-related serious (i.e. Grade 3 to 5; NCI-CTCAE criteria) and non-serious (i.e. Grade 1 to 2; NCI-CTCAE criteria)
Exercise Adherence
This variable applies only to CORE participants. Exercise adherence is defined as the relative dose intensity (i.e. the percent of total dose of exercise performed, relative to the total dose prescribed) and quantified according to metabolic equivalents.
Click on the lead sponsor to view all of their trials.
University Health Network, Toronto
Lead sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborator
Queen Elizabeth II Health Sciences Centre
Collaborator
Alberta Health services
Collaborator
Vancouver General Hospital
Collaborator
Université de Montréal
Collaborator
Dalhousie University
Collaborator
University of Alberta
Collaborator
University of British Columbia
Collaborator
University of Toronto
Collaborator
