Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

Abstract

PurposeA relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD.Patients and MethodsThe cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data.ResultsThe median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91).ConclusionA significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer

“…Another question is whether some cardiac subvolumes should take priority over others during the treatment planning process. 8–10 Our data provide preliminary information linking cardiac subvolume dose to subsequent toxicity. Given that the three event types showed different patterns of associations with heart subvolumes, it seems advisable to minimize dose to the entirety of the heart if possible.…”

“…38,39 In a recent analysis of over 900 patients with breast cancer treated with radiation, van den Bogaard et al reported that LV dose had the greatest association with ischemic events. 10 Thus, the common perception that acute coronary syndrome is related to LV dose may also apply to patients with lung cancer.…”

“…There are only limited data addressing cardiac subvolume dosimetry. 8–10 We herein assess associations between RT dose to different cardiac subvolumes and different cardiac toxicity endpoints in our previously-studied cohort. We grouped events into three categories: pericardial, ischemic, and arrhythmic.…”

Early detection of cardiovascular changes after radiotherapy for breast cancer: Protocol for a European multicenter prospective cohort (MEDIRAD EARLY HEART Study) (Preprint)

“…However, cardiac damage was shown to be correlated with the mean heart dose, with 7.4% rate increase of acute coronary events per one Gray (95% confidence interval, 2.9-14.5; P<0.001), with no minimum threshold for risk [8]. The risk of acute coronary events within the first 9 years after RT was recently confirmed by an additional publication [12], showing significant relationships between cardiac radiation dose and the incidence of acute coronary events. Therefore, as there appears to be no threshold dose below which cardiac complications do not appear, radiation-induced cardiac diseases remain potential severe late complications of BC RT.…”

Radiotherapy After Organ-Sparing Surgery for I-Iia Stages of Left-Sided Breast Cancer

“…[3]. На основании резуль-татов исследования авторы сделали вывод о том, что доза 5 Гр, подведенная к левому желудочку сердца, является важным прогностическим фактором параметра доза-объем [4].…”