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

Abstract

Background and Purpose To assess associations between radiation dose/volume parameters for cardiac subvolumes and different types of cardiac events in patients treated on radiation dose-escalation trials. Material and Methods Patients with Stage III non-small-cell lung cancer received dose-escalated radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective trials from 1996–2009. Volumes analyzed included whole heart, left ventricle (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into three categories: pericardial (symptomatic effusion and pericarditis), ischemia (myocardial infarction and unstable angina), and arrhythmia. Univariable competing risks analysis was used. Results 112 patients were analyzed, with median follow-up 8.8 years for surviving patients. Nine patients had pericardial, seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial events were correlated with whole heart, RA, and LA dose (eg, heart-V30 [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart-V30 [p=0.048]). Arrhythmic events showed borderline significant associations with RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30 [p=0.051]). Cardiac events were associated with decreased survival on univariable analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased survival on multivariable analysis. Conclusions Cardiac events were heterogeneous and associated with distinct heart subvolume doses. These data support the hypothesis of distinct etiologies for different types of radiation-associated cardiotoxicity.

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury

“…Wang et al assessed the types of cardiac events in patients treated on dose-escalation trials for stage III non-small-cell lung cancer. Pericardial (pericardial effusions or pericarditis), ischemic (myocardial infarction or unstable angina), and arrhythmic (significant arrhythmia) events were correlated with whole-heart doses and other parameters [57]. Ventricular dysfunction from cardiac RT can also lead to systolic or diastolic function.…”

Positive association between heart dosimetry parameters and a novel cardiac biomarker, solubleST‐2, in thoracic cancer chest radiation

“…30 In stage III non-small-cell lung cancer, different cardiac events were associated with distinct heart volume doses; for example, ischemic events were correlated with left ventricle and whole heart dose. 27 The mean V 5 , V 10 , V 20 , V 30 We recognize that the study presents several limitations. First, this is a longitudinal study with a small sample size.…”

“…Accumulated results from clinical studies have shown that high cardiac radiation dose is directly associated with RIHDs. 24,[27][28][29] Oncologists must also consider the rate of cancer control and the dose of cardiac radiation when formulating a RT regimen. In childhood cancer survivors, a large sample case control study revealed that heart failure often occurred in patients that received ≥30 Gy to the median volume of the heart.…”

The Role of Mitochondrial Dysfunction in Radiation-Induced Heart Disease: From Bench to Bedside

“…Cardiac events occurred within the first 5 years and continued several decades post-radiotherapy (7). Other studies have also examined the association between mean heart dose and cardiac events/disease, finding an ∼4-16% increased risk per Gy of mean heart dose (7)(8)(9). Studies have also suggested RIHD can occur in non-small cell lung cancer patients within 2 years post-radiation exposure (8)(9)(10)(11).…”

“…Other studies have also examined the association between mean heart dose and cardiac events/disease, finding an ∼4-16% increased risk per Gy of mean heart dose (7)(8)(9). Studies have also suggested RIHD can occur in non-small cell lung cancer patients within 2 years post-radiation exposure (8)(9)(10)(11). In a number of lung cancer studies, mortality rates were cardiac dose-dependent, either based on mean heart dose (12) or with the percent of heart receiving 5 Gy (13), 30 Gy (13), or 50 Gy (10).…”