A team of almost 30 experts has compiled the first-ever guidelines on monitoring children for heart damage during cancer treatment.
Heart complications are the second leading cause of death among childhood cancer survivors, right after cancer recurrence. Survivors are 15 times more likely to have heart failure and eight times more likely to have heart disease than the general population.
The guidelines were the work of 29 specialists in pediatric cardiology, oncology, and radiology from Australia and New Zealand. The team was led by researchers from the Murdoch Children's Research Institute, Melbourne.
The guidelines were published recently by the American College of Cardiology in JACC: Advances.
The advice goes beyond two well-known causes of cardiac problems ― inadvertent radiation to the heart and treatment with doxorubicin and other anthracyclines ― to include immunotherapies and targeted biologics that carry their own unique cardiovascular risks.
The goal of the guidelines is to mitigate the problems. Although much of the advice is in line with cardiac monitoring for adults, pulling it all together into one document is "incredibly important for pediatric cancer patients" and the people who treat them, including oncologists, pediatricians, and, increasingly, specialists in the new but burgeoning field of cardio-oncology, commented Michael Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia. He was not involved in compiling the new guidelines and was approached by Medscape Medical News for comment.
"There was no defined approach for surveillance or follow up of pediatric patients during treatment despite new therapeutics having early heart complications such as high blood pressure, abnormal heart beats, and heart failure," senior author and pediatric oncologist Rachel Conyers, PhD, a researcher at the Murdoch Institute, said in a press release.
The new guidelines are "an indispensable tool for clinicians to significantly reduce the harmful impact of cancer drugs on children's hearts," she said.
Fradley noted that although cardiac damage can emerge years after anthracycline treatment and chest radiation, problems with targeted therapies and immunotherapies seem to be limited to the acute treatment phase.
Scores of Recommendations
Drugs acting as inhibitors of VEGF, mTOR, proteasomal, kinases, and immune checkpoints all put children at risk for cardiovascular complications, the authors point out. Then, when these patients are adults, developing metabolic syndrome or kidney disease, and even pregnancy, increase the risk of cardiovascular complications still further.
Children should be assessed at least once by a cardio-oncologist during treatment, and testing should ideally include a 3-dimensional transthoracic echocardiogram, the authors advise.
Among scores of specific recommendations, the team made a unanimous recommendation for dexrazoxane, "the sole cardio-protective agent used in pediatric oncology," for children receiving 250 mg/m2 or more of doxorubicin or its equivalent. Fradley said the "very clear" guidance on when to use dexrazoxane should help in light of the wide variations in current practice.
They also recommend electrocardiograms and troponin I levels within 48 hours of each immune checkpoint inhibitor dose to check for myocarditis. If myocarditis is suspected, the immunotherapy should be withheld.
In addition, children should be checked for hypertension within a month of starting a VEGF inhibitor, and for those who receive treatment with an mTOR inhibitor, blood pressure, glucose levels, lipid profiles, and renal function should be checked every 6 months.
For patients receiving BCR-Abl tyrosine kinase inhibitors, the authors emphasize that the initial cardio-oncology assessment should include an electrocardiogram, owing to the risk of QT prolongation.
Similarly, they call for a review of toxicities at least every 3 months for children who are treated with the Bruton tyrosine kinase inhibitor ibrutinib, with a quick referral to cardiology for any signs of arrhythmia, including palpitations, dizziness, and loss of consciousness.
The work was funded by the Heart Foundation. One co-author has received funding from Novo Nordisk. The other authors and Fradley have disclosed no relevant financial relationships.
JACC Adv. 2022 Dec 1;100155. Full text
M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: firstname.lastname@example.org
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Cite this: First Guideline for Cardioprotection in Children With Cancer - Medscape - Feb 14, 2023.