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Focus on modifiable risk factors paramount for CVD prevention in childhood cancer survivors
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In a new study, 5-year survivors of childhood cancer have a two to 10 times higher risk for developing CVD compared with cancer-free individuals of similar age.
According to data published in Circulation, in a cohort of 5-year childhood cancer survivors (n = 7,289; median age at diagnosis, 7 years; median age at end of follow-up, 24 years), 2.8% of survivors experienced one or more CV events during the median 10-year follow-up, compared with a rate of 0.9% in the general population (n = 36,205). These findings represented 3.2 cardiac events per 1,000 person-years (95% CI, 2.8–3.6) in the cancer survivor group and 0.9 cardiac events per 1,000 person-years in the general population (95% CI, 0.9–1.9).
“Much of the focus in the past has been on two specific kinds of heart problems: heart failure and coronary artery disease, but there has been a lot less work looking at other structures in the heart,” Paul Nathan, MD, MSc, FRCP(C), oncologist in the division of hematology/oncology and senior associate scientist in the Child Health Evaluative Sciences program at The Hospital for Sick Children in Toronto, told Cardiology Today. “What this study shows is that survivors are at risk for the whole range of cardiac complications over time. Physicians need to be aware of more than just looking for heart failure in childhood cancer survivors. They really need to think of all of the heart structures and be more aware that these patients, many of whom are quite young, can develop problems in those areas.”
According to the results, cause-specific HRs were significantly higher for all CVD subtypes among cancer survivors compared with the general population:
- any cardiac event (cause-specific HR = 3.2; 95% CI, 2.7-3.8);
- HF (cause-specific HR = 9.7; 95% CI, 6.8-14);
- arrhythmia (cause-specific HR = 1.9; 95% CI, 1.5-2.6);
- pericardial disease (cause-specific HR = 1.8; 95% CI, 1.1-3);
- ·valvular disease (cause-specific HR = 4.7; 95% CI, 2.4-9); and
- CAD (cause-specific HR = 3.4; 95% CI, 1.5-7.7).
In other findings, childhood relapse and subsequent cancer (HR = 1.7; 95% CI, 1.1- 2.7), exposure to at least 250 mg/m2 doxorubicin-equivalent anthracycline chemotherapy compared with a lower dose or no anthracycline therapy (HR = 2; 95% CI, 1.4-2.9) and type 2 diabetes diagnosis (HR = 3; 95% CI, 1.6-5.8) were associated with higher risk for CVD in cancer survivors. The aforementioned risk factors, in addition to hypertension, were identified as significant predictors of HF in this population.
Survivors with type 2 diabetes had a three-times greater risk for CVD and four-times greater risk for HF compared with the general population, according to the study. Survivors diagnosed with hypertension were also three times more likely to develop HF.
“We often treat these kids when they’re really young, sometimes toddlers, and it sometimes takes decades for us to start to see the impact of our therapies,” Nathan said. “We need to be thinking of not only how we cure the cancer, but also about the long-term implications of the treatments we use. If we can make modifications to our treatments at the time we treat these kids, we can potentially save them from developing some of these late complications, heart diseases being a major one.”
Researchers used the Pediatric Oncology Group of Ontario Networked Information System to identify 5-year survivors of childhood cancer who received treatment from 1987 to 2010 in Ontario, Canada. Each patient was matched with five cancer-free individuals from the general population group, based on age, sex and postal code.
While researchers are aware that cardiotoxic exposures to cancer treatments are a concern, they recognize that these treatments are required for these patients to live, and thus stress the importance of identifying modifiable risk factors that may reduce incidence of CVD in the cancer survivor population.
“Having the ability to link these patients to the province's health care administrative data makes it easy to follow them over time,” Nathan said. “We plan to revisit this cohort in 5 to 10 years to see if, with further follow-up, these risks have changed or progressed. There are many other groups doing work in the cancer survivor realm that have looked, in detail, at the impacts of radiation. Radiation is a risk factor for every single kind of heart disease. I suspect that as our cohort ages, we're going to see some of the same patterns here as well. It just may be too early to see the full impact right now, as our median length of follow-up was approximately 10 years.” – by Scott Buzby
For more information:
Paul Nathan, MD, MSc, FRCP(C), can be reached at paul.nathan@sickkids.ca.
Disclosures: Nathan reports no relevant financial disclosures. The other authors report no relevant financial disclosures.
Perspective
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Anita Szady, MD
Patients are living longer due to advances in cancer therapy, and we are now seeing the long-term effects of cancer treatment on the body. The association between anthracycline therapy and HF is well documented in the literature. Data on other CV complications in pediatric cancer survivors are not as robust. The findings from this study bring to light the importance of continued surveillance of pediatric cancer survivors, not only for cancer recurrence, but the development of CV complications associated with their cancer therapy. This study identifies diabetes and hypertension as important risk factors for the development of CV complications after childhood cancer treatment. It is unknown whether or not the development of hypertension or diabetes in these survivors was a result of their treatment, but these risk factors are potentially modifiable and at the very least can serve as a marker for increased CV surveillance.
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