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Hodgkin’s lymphoma survivors face high risk for cardiovascular diseases
Survivors of Hodgkin’s lymphoma who were treated during adolescence or adulthood faced a high lifetime risk for cardiovascular events, according to study results.
“Treatment for Hodgkin’s lymphoma has been associated with adverse late effects, such as increased risks of secondary malignant neoplasms and cardiovascular diseases,” study researcher Flora E. van Leeuwen, PhD, of the department of epidemiology at The Netherlands Cancer Institute, and colleagues wrote. “Late cardiovascular complications may arise as a consequence of radiotherapy and chemotherapy and cause substantial excess morbidity and mortality in long-term Hodgkin’s lymphoma survivors.”
The researchers evaluated data from 2,524 5-year survivors of Hodgkin’s lymphoma who were treated between 1965 and 1995. All patients were diagnosed when aged younger than 51 years (median, 27.3 years) and 54.3% (n = 1,370) were male.
More than 80% (n = 2,052) of patients were treated with mediastinal radiotherapy. Additionally, 30.6% (n = 773) of patients received chemotherapy that included an anthracycline.
After a median follow-up of 20.3 years, 1,713 cardiovascular diseases occurred in 797 patients. Over half (n = 410) of those patients experienced two or more events.
The most common cardiovascular diseases were coronary heart disease (n = 401), valvular heart disease (n = 374), and cardiomyopathy and congestive heart failure (n = 140). The median time from treatment to first cardiovascular event was 18 years for coronary heart disease, 24 years for valvular heart disease and 19 years for heart failure.
Compared with the general population, survivors of Hodgkin's lymphoma demonstrated a 3.2-fold (95% CI, 3-3.5) increased standardized incidence ratio (SIR) for developing coronary heart disease and a 6.8-fold (95% CI, 5.9-7.6) increased SIR for developing heart failure. These SIRs equated to 857 excess events per 10,000 person-years, according to the researchers.
Researchers noted the risk for cardiovascular events increased when treated at a younger age. Patients who were treated when aged younger than 25 years experienced a 4.6- to 7.5-fold increased SIR for coronary heart disease and a 10.9- to 40.5-fold increased SIR for heart failure (P ˂ .001 for trend). However, patients treated when aged 35 to 50 years experienced a 2- to 2.3-fold increased SIR for coronary heart disease and a 3.1- to 5.2-fold increased SIR for heart failure.
The 40-year cumulative incidence of cardiovascular disease in the entire cohort was 50% (95% CI, 47-52), and 51% of patients with cardiovascular disease developed multiple events.
Patients treated when aged younger than 25 years faced 60-year cumulative risks of 20% for coronary heart disease, 31% for valvular heart disease and 11% for heart failure as first events.
Mediastinal radiotherapy increased the risk for coronary heart disease (HR = 2.7; 95% CI, 2-3.7), valvular heart disease (HR = 6.6; 95% CI, 4-10.8) and heart failure (HR = 2.7; 95% CI, 1.6-4.8) compared with treatment without mediastinal radiotherapy. Anthracycline-based chemotherapy also increased the risk for coronary heart disease (HR = 1.5; 95% CI, 1.1-2.1) and heart failure (HR = 3; 95% CI, 1.9-4.7) as first events compared with treatment without anthracyclines. Researchers noted the risks associated with mediastinal radiotherapy, anthracyclines and smoking appeared to be additive.
The researchers acknowledged they were unable to study radiation dose–response interactions in the entire patient cohort.
“A sizeable proportions of Hodgkin’s lymphoma survivors develop multiple events over time,” van Leeuwen and colleagues concluded. “Treating physicians and patients should be aware of the persistently increased risk of cardiovascular diseases throughout life, and the results of our study may direct guidelines for follow-up of patients with Hodgkin’s lymphoma.”
These data suggest the importance of follow-up care in this setting, Emily Tonorezos, MD, MPH, of the Weill Cornell Medical School, and Linda Overholser, MD, MPH, of the University of Colorado Denver School of Medicine, wrote in an accompanying editorial.
“Previous work has suggested that primary care physicians may not be comfortable caring for adult survivors of childhood cancer and have gaps in knowledge regarding what additional screening and surveillance this population may require,” Tonorezos and Overholser wrote. “Furthermore, the oncology field has not increased to match demand, such that ongoing care in an oncologist setting will not be possible for most survivors. It is clear that, although the best models for follow-up care for cancer survivors may vary with the context of individual care settings and local resources, there is a role for specialists involved in cancer care and primary care to address the comprehensive needs of cancer survivors … In this context, it is necessary for primary care physicians to rise to the challenge of health promotion in cancer survivors.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopThe simplest way would be to ask all of our patients if they have been treated for cancer. Most patients with cancer will know if they have had chest radiotherapy or chemotherapy. If these patients respond in the affirmative, we should begin the screening process for cardiovascular disease. Most practitioners know of and understand how to work with the Framingham risk factors for cardiovascular disease. Certainly, these patients could be considered in a very similar fashion. With appropriate follow-up questioning, patients then can be selected for a variety of cardiac stress testing modalities. Echocardiography can be used quite easily to screen for cardiomyopathy and valvular heart disease. The cardiology community can and should be asked to help with this effort.
As further long-term prospective clinical trials are completed, we should be able to determine the time intervals for routine screening after completion of chest radiotherapy or chemotherapy. Importantly, now that Nimwegen and others (Hudson MM, et al. JAMA. 2013;doi:10.1001/jama.2013.6296) have confirmed the disturbingly high rate of adverse health outcomes in adult survivors, providers who care for survivors must focus their efforts on prevention. Given the known risks, redoubling our efforts to educate survivors about the critical importance of not smoking, maintaining a healthy weight, eating a plant-based diet and exercising regularly is critical. These often are the “low-hanging fruit” of survivorship care — inexpensive lifestyle changes, yet with far-reaching implications.