The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.

The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825 ).

The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.

For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480 ).

“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.

The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.

Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.

The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.

ACE incidence was not significantly associated with the maximum dose of radiation to the heart.

LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.

There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.


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