Mortality is twice as high for cancer survivors undergoing cardiac surgery to correct damage done by thoracic radiation therapy as it is among matched patients who are undergoing the same procedures but who haven’t been exposed to radiotherapy, according to a report published online April 8 in Circulation.
In what they described as "the largest study to assess long-term survival in this population undergoing complex cardiac surgery and compare them to a well-matched comparison population," investigators found that mortality was 55% in the patients who had received radiation therapy, compared with 28% in the nonexposed controls. At least half of the deaths among the cancer survivors were attributed to cardiopulmonary disease, while only 5% were due to recurrent malignancy.
"Surgical intervention should be applied cautiously to patients who have had significant thoracic radiation previously," including survivors of breast, lung, hematologic, thyroid, and other cancers.
Trying to gauge mortality risk in such patients solely by using their preoperative scores on standard risk-prediction measures is inaccurate at best. In this study population, the survivors of breast, lung, hematologic, thyroid, and other cancers would have been deemed at intermediate risk for undergoing cardiac surgery, with an expected mortality of only 3%-5% based on their preoperative assessments – 10 times lower than their actual postoperative mortality, said Dr. Willis Wu and his associates at the Heart and Vascular Institute at the Cleveland Clinic.
"Our findings suggest that surgical intervention should be applied cautiously to patients who have had significant thoracic radiation previously," they wrote. Cardiac surgery that is considered conventional or even routine in most patients – including coronary artery bypass graft, valve repair, valve replacement, vascular surgery, pericardiectomy, left ventricular assist device implantation, and myectomy – may actually worsen the condition of radiation-exposed patients.
"It seems appropriate to examine other types of treatment options in patients with radiation heart disease who have significant valvular, coronary, or myocardial disease," the researchers noted.
Dr. Wu and his associates performed their retrospective observational study because of the dearth of information regarding long-term outcomes in cancer survivors who were exposed to chest irradiation. This knowledge gap makes treatment decisions "especially difficult" once radiation-related heart disease is discovered.
Such patients are known to have high rates of coronary artery, valvular, pericardial, myocardial, and conduction disease that progresses over time and may not become evident until decades after cancer treatment was completed.
Surgery is often thought necessary to effectively address these cardiac complications of prior radiation therapy. "These patients have multiple cardiac lesions and [often] have comorbidities such as pulmonary or vascular disease related to radiation," the investigators said.
They analyzed the medical records of 478 patients undergoing cardiac surgery at their tertiary care center in 2000-2003. A total of 173 had a prior history of malignancy treated with chest irradiation; the remaining 305 patients had no such history and were matched to the radiation group for age, sex, type of surgery, and date of surgery.
The patients exposed to radiation were relatively young but had advanced symptoms. Forty-five percent had obstructive proximal coronary artery disease; one-fourth had already undergone open heart surgery, including 16% who had prior coronary artery bypass graft surgery. There also was a high prevalence of valvular disease, with 51% of patients showing at least moderate mitral regurgitation, 6% showing severe mitral stenosis, 29% showing at least moderate aortic regurgitation, 23% showing severe aortic stenosis, and 34% showing at least moderate tricuspid regurgitation.
The mean interval between the current cardiac surgery and the last thoracic radiation treatment was 18 years. Approximately 53% of the study patients had survived breast cancer, 27% had survived Hodgkin’s lymphoma, 7% had survived lung cancer, 6% had survived non-Hodgkin’s lymphoma, and 8% had survived other malignancies including thyroid and testicular cancers.
Approximately 75% of both study groups were women.
During a mean follow-up of 7.6 years, overall mortality was 37%. Despite the success of the cardiac procedures, a significantly higher proportion of radiation-exposed patients died (55%), compared with the unexposed patients (28%), for a hazard ratio of 2.54, Dr. Wu and his colleagues said (Circulation 2013 April 8; doi:10.1161/CIRCULATIONAHA.13.001435).
Mortality was significantly higher across all subgroups of patients exposed to radiation. In particular, it was high among patients expected to have low mortality: 43% in patients aged younger than 65 years and 45% in those with lower preoperative risk scores. In fact, the youngest patients in the radiation group fared worse than the oldest patients in the comparison group.
Mortality also was significantly higher for the radiation-exposed patients than for controls across all types of cardiac surgery.