Structured Cardio-Oncology Rehabilitation for Cardiovascular Outcomes in Cancer Survivors (CORE-CTRCD)

With advances in anti-cancer therapies, the number of cancer survivors has increased substantially worldwide. However, cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a major long-term complication associated with increased cardiovascular morbidity, mortality, reduced quality of life, and impaired survival. Current management strategies primarily focus on pharmacologic prevention and treatment, while evidence-based non-pharmacologic interventions capable of improving hard cardiovascular outcomes remain insufficient.

Cardiac rehabilitation is a Class I recommended intervention for patients with cardiovascular diseases and has demonstrated benefits in improving cardiorespiratory fitness, reducing cardiovascular events, and enhancing quality of life. Emerging studies suggest that cardio-oncology rehabilitation may improve exercise capacity and cardiac function in cancer survivors; however, most existing studies are limited by small sample size, single-center design, and lack of hard clinical endpoints.

This study is a multicenter, prospective, parallel-group, superiority randomized controlled trial designed to evaluate the efficacy and safety of a structured cardio-oncology rehabilitation (CORE) program in patients with CTRCD or cancer survivors at high cardiovascular risk.

A total of 800 participants will be enrolled and randomized in a 1:1 ratio to either:

1. Structured cardio-oncology rehabilitation plus usual care; or
2. Usual care alone.

The intervention consists of a 12-week intensive rehabilitation phase followed by long-term maintenance guidance. Core components include:

• Individualized aerobic and resistance exercise training;
• Nutritional assessment and management;
• Psychosocial and behavioral support;
• Intensive cardiovascular risk-factor management;
• Patient education and self-management support. The primary endpoint is time to first major adverse cardiovascular event (MACE) within 12 months, including cardiovascular death, myocardial infarction, ischemic stroke, hospitalization for worsening heart failure, or urgent ICD/CRT implantation due to malignant arrhythmia or heart failure.

Secondary endpoints include:

• Changes in peak oxygen uptake (VO2peak);
• Changes in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS);
• Biomarkers including hs-cTnI and NT-proBNP;
• Quality-of-life assessments;
• Physical function measures;
• Psychological outcomes;
• Safety outcomes and health economic outcomes. Outcome assessment personnel, laboratory staff, endpoint adjudicators, and statisticians will remain blinded to treatment allocation. The study includes centralized imaging review, standardized intervention protocols, electronic data capture, and oversight by an independent Data and Safety Monitoring Board (DSMB).

The findings of this trial are expected to provide high-quality evidence supporting the implementation of standardized cardio-oncology rehabilitation strategies in cancer survivors with cardiovascular toxicity or elevated cardiovascular risk.