MDNews - Greater Boston

FOLLOWING RECURRENT PRIMARY cancer and the development of new cancers, cardiac disease is the third-leading cause of death in childhood cancer survivors, according to the American Heart Association. In fact, the rate of death related to cardiac disease can be as much as 10 times as high in childhood cancer survivors as in their counterparts with no history of cancer. MORE THAN 325,000 PEOPLE LIVING IN THE UNITED STATES HAVE SURVIVED CHILDHOOD CANCER, BUT TREATMENTS CRITICAL TO ACHIEVING REMISSION PLACE THESE PATIENTS INTO ANOTHER HIGH-RISK GROUP, WHERE LATENT EFFECTS CAN LEAD TO FATAL OUTCOMES DECADES AFTER THEIR CANCER HAS BEEN DEFEATED. At the Heart of Cancer By Michael Ferguson T HE FIRST GENERATIONS of childhood cancer patients who benefi ted from signifi cant treatment advances in recent decades are reaching their 30s, but the threat of treatment-related cardiotoxicity is only beginning to be fully realized. The American Heart Association (AHA) has taken the fi rst step to develop clinical guidelines that maintain the current curative trajectory of childhood cancers and assuage the possibility of cardiac disease later in life. Steven E. Lipshultz, MD, FAHA, George E. Batchelor Professor of Pediatrics and Director of the Batchelor Children's Research Institute at the University of Mia mi Miller School of Medicine, recognized cardiac risk in childhood cancer patients and published articles about his observations in the early 1990s. "I started pushing that this should be considered a lifelong diagnosis if a child is diagnosed with cancer," Dr. Lipshultz says. "In the early stage, you have to eliminate cancer, but then you wind up with late effects — toxicities and different effects over a lifespan. So, the defi nition I've been pushing over three decades is the successful treatment of cancer is the balance between the oncological cure and treatment success on one hand, and the toxicity and late effects — minimizing those — on the other." Four years ago, the AHA tapped Dr. Lipshultz to co-author a scientifi c statement about the risks childhood cancer survivors face. The paper aims to bring greater awareness of various cardiac problems endemic in this demographic. "We recognize there are a lot of people presenting early in adult life with heart disease that never would have had it if they hadn't been treated for childhood cancer," Dr. Lipshultz explains. "This statement helps us understand what sort of problems they have — who's at greatest risk and how they should be monitored and screened, [so this can] be potentially prevented." Threat of a Cure The National Cancer Institute cites Hodgkin's lymphoma as the malignancy most frequently associated with cardiovascu- lar disease. Treating this form of cancer with chemotherapy regimens utilizing anthracycline-class drugs and/or radiation therapy can result in increased risk of cardiac disease. Because thoracic radiation therapy often accompanies anthracycline regimens, it can be difficult to determine which treatment is to blame for cardiac damage. However, evidence points to total radiation dose, as well as the volume of the heart exposed to radiation and the radiation fraction of each dose, as potential risk-increasing factors. Although contemporar y radiation techniques enable physicians to pinpoint radiation dose and limit damage to healthy tissue, late effects — such as conduction defects, coronary artery disease, delayed pericarditis, functional valve injury, myopa- thy and pancarditis — have been linked to radiation therapy. The a nthrac ycline cla ss of chemotherapy dr ugs wa s introduced into the cytotoxic treatment repertoire for cancer in the 1960s. Within the family, drugs used in chemotherapy regimens can cause two different types of cardiotoxicity. Doxorubicin, doceta xel and cyclophosphamide can cause irreversible lef t ventricula r systolic dysf unction when cumulative doses surpass 200mg/m 2 to 300mg/m 2 , according to Mayo Clinic. Dr. Lipshultz's paper indicates the second type of anthracycline- related cardiotoxicity is not related to cumulative dose and the resulting myocardial dysfunction can often be reversed. Bevacizumab, lapatinib and trastuzumab are among the main culprits of such cardiotoxicity. This type of cardiotoxicity can be avoided if cardiac complications are identifi ed early and treatment is stopped. Call for Vigilance The overarching goal of the 70-page AHA paper is to present evidence-based research that opens the medical community's eyes to the problems resulting from highly effective cancer therapies provided to children. Dr. Lipshultz and his fellow authors cite more than 600 articles in the paper in an effort to present the state of cardio-oncology. While it's clear cancer therapy has made signifi cant strides, it's equally obvious much more progress must be made to prevent the latent onset of adverse heart issues following childhood cancer treatment. The establishment of evidence-based guidelines for cardiovascular surveillance during and after cancer treatment may be to come, but in the interim, Dr. Lipshultz calls for systematic vigilance over a subgroup of patients whose risk for cardiovascular distress is much higher than that of the general population. ■ "The thing you care about is, how is the patient's quality of life over the entire lifespan? If you get a 100 percent cure rate of cancer, but half of the people get congestive heart failure, that's not a very good quality of life. On the other hand, if you undertreat and half the people die of cancer — but nobody gets heart failure — that's also equally unacceptable." — Steven E. Lipshultz, MD, FAHA, George E. Batchelor Professor of Pediatrics and Director of the Batchelor Children's Research Institute at the University of Miami Miller School of Medicine CORE CORE M D N E W S . CO M ■ MD NEWS Greater Boston | 1 1

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