Exercise Stress Test Emerges as Gold Standard for Childhood Cancer Survivors’ Heart and Lung Fitness

Every year, hundreds of thousands of children around the world are diagnosed with cancer, and thanks to decades of progress in oncology, the overwhelming majority of them now survive. But survival has a price. Long after the last chemotherapy session ends and the final scan comes back clear, many childhood cancer survivors carry invisible damage to their hearts, lungs, muscles, and metabolism. One of the most consistent and consequential findings in survivorship research is that these patients have markedly reduced cardiorespiratory fitness, the capacity of the cardiovascular and respiratory systems to supply oxygen to working muscles during sustained physical activity. A new review published in Supportive Care in Cancer by Maxime Caru of Penn State Health Children’s Hospital and colleagues at Dana-Farber Cancer Institute and Harvard Medical School argues that the single most powerful tool for measuring that deficit, cardiopulmonary exercise testing, deserves a far more central role in the clinical care of survivors.

Cardiorespiratory fitness is usually expressed as peak oxygen uptake, or VO2peak, the maximum rate at which the body can consume oxygen during incremental exercise. It is not merely a number for athletes. Across pediatric and adult populations, VO2peak is one of the strongest predictors of long-term cardiovascular health and all-cause mortality, and low fitness in adulthood tracks back to low fitness in childhood. For childhood cancer survivors, the stakes are even higher. Treatments that save lives, including anthracycline chemotherapy agents such as doxorubicin, chest-directed radiation, and certain targeted therapies, can impair cardiac contractility, reduce lung capacity, blunt the autonomic regulation of heart rate, and accelerate vascular aging. A landmark study by Lipshultz and colleagues in the New England Journal of Medicine as far back as 1991 documented late cardiac effects of doxorubicin in children treated for acute lymphoblastic leukemia, and subsequent work has repeatedly linked treatment exposure to measurable declines in exercise capacity.

The scale of the problem was quantified in a 2026 systematic review and meta-analysis by Weinkauf and colleagues in the European Journal of Preventive Cardiology, which pooled fitness data from childhood cancer survivors across multiple studies and found substantially reduced cardiorespiratory fitness compared with healthy peers. Earlier work by Caru and colleagues reached a similar and striking conclusion: survivors of childhood acute lymphoblastic leukemia had significantly lower fitness levels than healthy Canadians even when their self-reported physical activity levels were clinically equivalent. That dissociation is critical. It suggests that the fitness deficit is not simply a matter of survivors exercising less, but reflects underlying physiological impairment, whether cardiac, pulmonary, skeletal muscle mitochondrial, or autonomic, that only objective testing can reveal.

This is where cardiopulmonary exercise testing, commonly abbreviated as CPET, enters the picture. Unlike a simple treadmill time or a six-minute walk distance, CPET directly measures the exchange of oxygen and carbon dioxide at the mouth while the patient exercises on a cycle ergometer or treadmill with progressively increasing intensity. Breath-by-breath gas analysis, combined with continuous electrocardiography, blood pressure monitoring, and often pulse oximetry, allows clinicians to distinguish among the multiple organ systems that can limit exercise performance. A cardiac limitation, a ventilatory limitation, a peripheral muscular limitation, or simply poor effort each leaves a characteristic fingerprint in the CPET data. In a population where multiple organ systems may be quietly compromised by treatment, that diagnostic specificity is invaluable.

The technical foundations of modern CPET were established decades ago. The 1983 study by Buchfuhrer and colleagues in the Journal of Applied Physiology demonstrated how to optimize incremental exercise protocols so that the test lasts long enough to capture true maximal oxygen uptake but short enough to avoid fatigue-driven underestimation. Consensus statements from the American Thoracic Society and the American College of Chest Physicians in 2003, and from the European Association for Cardiovascular Prevention and Rehabilitation and the American Heart Association in 2012, codified how CPET data should be collected and interpreted in specific patient populations. Applied to children, the test is safe, well tolerated, and feasible even in patients treated for leukemia, as demonstrated in feasibility studies of post-chemotherapy leukemia patients published in Annals of Rehabilitation Medicine.

The evidence that CPET detects real, subclinical dysfunction in survivors is compelling. A 2020 study by Long and colleagues in Medicine and Science in Sports and Exercise showed that cardiovascular exercise testing uncovered underlying dysfunction in childhood leukemia survivors that standard resting assessments missed. Caru’s own work has shown that doxorubicin exposure induces significant changes in the cardiac autonomic nervous system of long-term survivors, alterations that manifest during the dynamic stress of exercise long before they would appear at rest. Because exercise places simultaneous demand on the heart, lungs, blood vessels, and muscles, it functions as a physiological stress test for the entire integrated system, exposing vulnerabilities that a resting echocardiogram or a routine checkup would never reveal.

The clinical significance of these measurements extends beyond diagnosis. Exercise intolerance in adult survivors of childhood cancer has been linked to mortality and organ system impairment in a major study by Ness and colleagues published in the Journal of Clinical Oncology, making fitness a genuine prognostic marker rather than a soft measure of wellbeing. If low VO2peak identifies survivors at elevated risk, it also creates a target for intervention. A 2026 meta-analysis by Van Ermengem and colleagues in the same journal, Supportive Care in Cancer, examined the impact of exercise interventions on cardiorespiratory fitness in childhood cancer survivors and found that structured training programs can improve fitness, echoing earlier meta-analyses of exercise interventions and cardiovascular health in childhood cancer. Randomized trials, including a dose-graded aerobic exercise regimen studied by Elnaggar and colleagues and a home-based program tested by Manchola-González and colleagues, have shown that carefully prescribed aerobic training improves cardiopulmonary fitness and physical functioning in pediatric survivors of acute lymphoblastic leukemia.

Translating those findings into practice requires qualified professionals. The authors emphasize the role of the exercise physiologist, a health professional with formal training in exercise science, exercise physiology, or kinesiology, often certified by recognized bodies such as the American College of Sports Medicine, who is qualified to conduct exercise testing, assess cardiovascular and metabolic responses, and prescribe individualized, evidence-based exercise programs. In a survivorship clinic, such a specialist can administer a CPET safely, interpret the ventilation and gas-exchange curves in the context of the patient’s specific treatment exposures, and convert the results into a training prescription with appropriate intensity, progression, and safety margins. Fitness gains in this population also ripple outward: research by Dubnov-Raz and colleagues has linked improvements in fitness to improvements in body composition and bone health in children after cancer, both of which are common sites of treatment-related harm.

Despite this accumulating evidence, CPET remains underused in routine pediatric oncology follow-up, where surveillance typically focuses on imaging, blood counts, and endocrine function. The authors’ argument is essentially a call to close the gap between what the literature shows and what clinics do. Objective measurement of cardiorespiratory fitness would allow clinicians to identify the most impaired survivors early, track their response to rehabilitation, and intervene before deficits compound into adult cardiovascular disease. It would also standardize outcome measures across trials of exercise interventions, making it easier to compare programs and establish dose-response relationships between training and health outcomes.

For a generation of survivors who will live decades beyond their diagnosis, the message is clear: the heart, lungs, and muscles that carried them through treatment need to be measured, monitored, and trained, not assumed healthy. Cardiopulmonary exercise testing offers a precise, safe, and scientifically validated window into the long-term physiological cost of curing childhood cancer, and, paired with structured exercise prescription, a practical pathway to repairing it. As the survivor population continues to grow, integrating this technology into standard survivorship care may prove to be one of the most consequential steps yet in ensuring that children who beat cancer do not simply survive, but thrive.

Subject of Research: Cardiopulmonary exercise testing to assess cardiorespiratory fitness in childhood cancer survivors

Article Title: Cardiopulmonary exercise testing to measure cardiorespiratory fitness in childhood cancer survivors

Article References: Caru, M., Wilson, R. L., Sholler, C., & Dieli-Conwright, C. M. (2026). Cardiopulmonary exercise testing to measure cardiorespiratory fitness in childhood cancer survivors. Supportive Care in Cancer, 34(10), Article 1068. https://doi.org/10.1007/s00520-026-11285-7

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11285-7

Keywords: cardiopulmonary exercise testing, cardiorespiratory fitness, childhood cancer survivors, VO2peak, pediatric oncology, anthracycline cardiotoxicity, exercise physiology, survivorship care, acute lymphoblastic leukemia, exercise interventions, cardiovascular health, Supportive Care in Cancer