The NIH announced 2 grants last November to address the problem. One is an R21 exploratory grant and the other is an R01 grant. Both require collaboration between oncologists and cardiologists, and aim to identify and characterize which patients are at risk for developing cancer treatment-related cardiotoxicity.
“We’re interested in clinical applications. We really want to focus on the translation,” said Ms. Shelburne. “There are clinics out there treating these patients and we need to figure out how to best manage them.”
The EORTC has called for predictive markers that are universally applicable and capable of detecting early myocardial loss.10 The organization stated that decrease in left ventricular ejection fraction measured either by echocardiography or nuclear scans lacks the sensitivity necessary to serve as an effective predictive marker.10
Some evidence exists to support alternative biomarkers. For example, in 2015, Armstrong et al published findings that suggested abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D left ventricular ejection fraction, and may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who might benefit from early medical intervention.13
In addition, researchers at the University of Pennsylvania believe they may have discovered other biomarkers. In results published online by JACC: Cardiovascular Imaging in April, Narayan et al found that ventricular-arterial coupling and circumferential strain were strongly predictive of cancer therapeutics-related cardiac dysfunction (CTRCD) in patients assigned to doxorubicin and trastuzumab.14
Researchers analyzed 517 echocardiograms collected from 135 adult women enrolled in the Cardiotoxicity of Cancer Therapy study—an ongoing, prospective longitudinal cohort study of women with breast cancer.14
They found that a 0.1 unit difference in Ea/Eessb, a 1% difference in circumferential strain, and a 0.1 s-1 difference in circumferential strain rate were all individually associated with a 21% to 38% increased odds of CTRCD.14
When researchers evaluated the relationships between changes in measures from baseline and CTRCD, they again found that changes in Ea/Eessb, circumferential strain, and circumferential strain rate were each individually associated with a 17% to 23% increased odds of CTRCD. They also determined that a 1% change in longitudinal strain, a 1% change in radial strain, and a 0.1 s-1 change in radial strain rate was associated with a 3% to 25% increased odds of CTRCD.14
“Overall, our data provide several new insights into echocardiography-derived measures of myocardial mechanics and CTRCD,” the researchers wrote. “First, these measures can be used to predict CTRCD across a broad range of time and treatment regimens. Second, ventricular-arterial coupling is a promising new measure to predict CTRCD. Third, circumferential strain may have more relevance to the cardio-oncology population than previously reported. Finally, noninvasive measures of myocardial mechanics may help to identify high-risk patients both before and during therapy.”14
However, Narayan et al acknowledged that it is difficult to extrapolate from a relatively small sample size.14 Likewise, Dr Hamad said the results are promising, but they are just a start.
“There are many small studies evaluating strain imaging,” she said. “The problem is that the numbers are small. Once we prove in a large, multicenter, randomized study that these evaluation processes do work, detect cancer, do save lives, and do detect cancer effects sooner, then we will be able to use them.”
- Chen MH, Colan SD, Diller L. Cardiovascular disease: cause of morbidity and mortality in adult survivors of childhood Cancers. Circ Res. 2011;108:619-628. doi: 10.1161/CIRCRESAHA.110.224519.
- Armstrong GT, Liu Q, Yasui Y, Neglia JP, et al. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27:2328-2338. doi: 10.1200/JCO.2008.21.1425.
- Meinardi MT, Gietema JA, van der Graaf WTA, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18,1725-1732.
- Armstrong GT, Pan Z, Ness KK, Srivastava D, Robison LL. Temporal trends in cause-specific late mortality among 5-year survivors of childhood cancer. J Clin Oncol. 2010;28:1224-1231. doi: 10.1200/JCO.2009.24.4608.
- Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015. doi: 10.1161/CIRCULATIONAHA.114.013777.
- Nakamura S, Narimatsu H, Sasahara Y, et al. Health management in cancer survivors: Findings from a population-based prospective cohort study—the Yamagata Study (Takahata). Cancer Sci. 2015. doi: 10.1111/cas.12811.
- van Nimwegen FA, Schaapveld M, Janus CPM, et al. JAMA Intern Med. Cardiovascular disease after Hodgkin Lymphoma treatment: 40-Year disease risk. 2015. doi: 10.1001/jamainternmed.2015.1180.
- Kahkoo AY, Yeh ETH. Therapy insight: management of cardiovascular disease in patients with cancer and cardiac complications of cancer therapy. Nat Clin Pract Oncol. 2008. doi:10.1038/ncponc1225.
- Steinherz LJ, Steinherz PG, Tan CTC, et al. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991. doi: 10.1001/jama.1991.03470120074036.
- Aleman BMP, Moser EC, Nuver J, et al. Cardiovascular disease after cancer therapy. EJC Suppl. 2014. doi: 10.1016/j.ejcsup.2014.03.002.
- Saigal CS, Gore JL, Krupski TL, et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007. doi: 10.1002/cncr.22933.
- Shelburne N, Adhikari B, Brell J, et al. Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. J Natl Cancer Inst. 2014. 106(9). doi: 10.1093/jnci/dju232.
- Armstrong GT, Joshi VM, Ness KK, et al. Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer. Results from the St. Jude Lifetime Cohort Study. J Am Coll Cardiol. 2015;65(23):2511-2522. doi: 10.1016/j.jacc.2015.04.013.
- Narayan HK, French B, Khan AM, et al. Noninvasive measures of ventricular-arterial coupling and circumferential strain predict cancer therapeutics-related cardiac dysfunction. JACC Cardiovasc Imaging. 2016. doi: 10.1016/j.jcmg.2015.11.024.