Cardiac radiation exposure a modifiable CV risk factor in NSCLC patients
Patients with non–small-cell lung cancer (NSCLC) who underwent radiotherapy had a high risk for major adverse cardiac events (MACE) within 2 years post-therapy, with the cardiac radiation dose exposure being an independent predictor of MACE and all-cause mortality, a large retrospective study shows.
“Despite the competing risks of cancer-related death, patients with locally advanced NSCLC may benefit from reduction of cardiac radiation dose, preventive post-radiotherapy cardiac care, and earlier recognition and treatment of cardiovascular [CV] events,” the researchers noted.
In the retrospective study, the researchers analysed 748 consecutive patients (median age 65 years, 49.2 percent women) with locally advanced NSCLC who received thoracic radiotherapy. Among these patients, 35.8 percent had pre-existing coronary heart disease (CHD), indicating the high coexistence of both diseases. [J Am Coll Cardiol 2019;73:2976-2987]
After a median 20.4 months follow-up, 77 patients (10.3 percent) developed ≥1 MACE (2-year cumulative incidence, 5.8 percent). The 77 patients comprised 5.6 percent of CHD-negative patients compared with 18.7 percent of CHD-positive patients (p<0.0001), showing that patients with pre-existing CHD were at a greater risk of developing MACE than those without (unadjusted hazard ratio [HR], 3.58; p<0.001).
The researchers further found that the greater the exposure to cardiac radiation, the higher the risk of MACE — with every 1 Gy increase in mean heart dose (MHD), there was a 5 percent greater risk of MACE, after adjusting for age, radiotherapy technique, and baseline CHD or arrhythmia (adjusted HR [AHR], 1.05/Gy; p<0.001).
Similar association was also observed between increasing MHD and the risk of all-cause mortality (AHR, 1.02/Gy; p=0.003).
In particular, MHD of ≥10 Gy was associated with a significant increase in both the risk of MACE (HR, 3.01; p=0.025) and the risk of all-cause mortality (HR, 1.34; p=0.014) compared with MHD <10 Gy in patients without pre-existing CHD, but not among those with prior CHD.
“As cardiac radiation dose is modifiable during the radiotherapy planning process, these results underscore the importance of more stringent avoidance of high cardiac radiotherapy dose … and reconsideration of stricter cardiac radiation dose constraints than those recently published (MHD<20),” the researchers stressed. “Specifically, we recommend MHD <10 Gy.”
“If recommended doses must be exceeded due to tumour location and/or lung dose safety, we advocate for early, frequent cardiology follow-up for primary or secondary prevention with aggressive risk factor management,” they added.
Among CHD-positive patients, the lack of a significant association between MHD ≥10 Gy vs <10 Gy and the risk of MACE/all-cause mortality does not mean that cardiac dose is not important in these patients, the researchers pointed out. They believe that in the setting of pre-existing CHD, any radiation dose can heighten the risk disproportionately, saying “there may not be a ‘safe’ cardiac dose threshold in this setting, and these patients may warrant dose limits that are significantly lower.”
“Most importantly, the authors teach us that adverse events occur very early — within 1 and 2 years of exposure — definitively laying to rest the notion that radiation to the heart has predominantly delayed effects,” wrote Dr Guilehermore Oliviera of Case Western Reserve University School of Medicine in Cleveland, Ohio, US in an editorial. [J Am Coll Cardiol 2019;73:2988-2989]
“The message is clear: in this day and age, no cancer patient undergoing chest radiation should fail to see a cardio-oncologist,” he stated.
“Accordingly, we recommend that all NSCLC patients undergo age appropriate screening for cardiac risk factors with estimation of 10-year CV risk using either Framingham or AHA*/ACC** risk scores,” urged the researchers.