Serum protein panel may predict cardiac toxicity risk among childhood cancer survivors
Key takeaways:
- A serum protein panel predicted risk for cardiac toxicity among childhood cancer survivors exposed to anthracyclines.
- Researchers plan to evaluate the panel in prospective studies with larger sample sizes.
Researchers at St. Jude Children’s Research Hospital identified a panel of 27 serum proteins that accurately predicted cardiomyopathy risk among childhood cancer survivors treated with anthracycline chemotherapy.
Investigators used what they described as an “untargeted, mass spectrometry-based approach” to profile 867 proteins and 218 metabolites in plasma samples. They evaluated the approach using samples from 75 asymptomatic cancer survivors with asymptomatic cardiomyopathy and 75 matched cancer survivors without cardiomyopathy from the St. Jude-Lifetime Cohort Study.
The researchers developed models based on the most influential differently expressed proteins and metabolites. They assessed the best-performing model in 23 independent survivors with severe or symptomatic cardiomyopathy and 23 matched survivors without cardiomyopathy.
The 27-protein model identified symptomatic or severe cardiomyopathy requiring heart failure medications among cancer survivors with 82.6% accuracy (95% CI, 71.4%-93.8%).
“We’ve gotten some robust data and results, but we need to acknowledge that this is still cross-sectional and with a small sample size,” Yadav Sapkota, PhD, assistant member at St. Jude, told Healio. “Future studies are planned to confirm these findings but, if everything works out, this could truly be clinically useful in addressing cardiomyopathy risk among asymptomatic patients, and potentially avoid or reduce the risk for a more severe outcome.”
Healio spoke with Sapkota about the prevalence of cardiomyopathy among cancer survivors, the efficacy the serum protein panel exhibited so far and the next steps in research.
Healio: Can you provide background on the link between anthracycline chemotherapy and cardiomyopathy risk among pediatric cancer survivors?
Sapkota: Anthracycline chemotherapy is used to treat more than 50% of pediatric cancers, and multiple studies have shown that it is cardiotoxic. Individuals who are exposed to anthracyclines are at risk for cardiac problems, especially those that start with the weakening of the heart muscle and lead to cardiomyopathy. If not treated or managed properly, this can lead to heart failure. Additionally, survivors have about a 15-fold greater risk for heart failure than the general population. Those who are exposed to anthracyclines will be at higher risk for cardiomyopathy and heart failure than those who are not exposed.
Healio: How did your group develop this panel?
Sapkota: We used a predictive modeling approach. Our general hypothesis was that there are some individuals, specifically those exposed to anthracyclines, who are not going to develop a very severe condition right away. It’s a slow process and the patients may be asymptomatic but, if we assess cardiac function, we might detect cardiomyopathy. Once they’ve already developed heart failure, the prognosis is poor.
We want to be able to detect them before they develop more severe outcomes, because that’s when we have an opportunity to intervene. We wanted to look into a population that was asymptomatic and identify some biomarkers from a blood or plasma sample that could help us detect the risk for severe outcomes.
We took a plasma sample from our population of asymptomatic survivors, and we profiled their proteins and metabolites. Using those biomarkers along with other clinical factors, we did risk-prediction modeling and found a model that contains a combination of 27 proteins. We determined that this model was the best for classifying individuals based on risk for cardiac problems.
Healio: What did you find?
Sapkota: Out of 23 matched pairs — each pair included one survivor with a severe cardiomyopathy and one survivor without cardiomyopathy — we were able to correctly classify 19 of the 23. This was quite promising, but it’s still a relatively small sample in both datasets. We also were only looking into these proteins at one time point.
Healio: What are the potential implications for clinical practice?
Sapkota: The way we envision this going forward would be to use this panel of proteins for survivors who have been exposed to anthracyclines and are still symptom free. We would use this like we do any lipid panel, and it could assess the risk for future severe outcomes. Based on that, we could plan some kind of intervention at that time. This could be very useful, and much easier compared with a detailed, comprehensive MRI or echocardiography, because this is a simple blood test that will be able to assess the risk.
Healio: What are the next steps in research?
Sapkota: To be able to take this a step further, we want to look at more than one time point in a prospective cohort to see whether these proteins are truly classifying risk based on what we observed in our current sample.
We are planning prospective studies. We’re looking at a larger sample size — almost 1,000 right now. We have submitted a grant to look at more than one time point so we can assess change in these biomarkers from the first visit to 4 or 5 years later. We want to be able to see whether this is robust enough to continuously provide an accurate estimate of risk.
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For more information:
Yadav Sapkota, PhD, can be reached at yadav.sapkota@stjude.org.
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