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.

RTOG 0617, a randomized phase III cooperative group trial using 2 x 2 factorial design, with radiation dose as one factor and cetuximab as the other factor. Materials/Methods: Patients enrolled in RTOG 0617 with retrievable RT dosimetry were eligible for this study. Circulating immune cells, including rapidly circulating ones in the heart, lung and blood vessels, and slowly circulating ones in the lymphatic system and blood reservoirs (a portion of veins/capillaries), were considered as a surrogate for OARIS. The effective dose to the immune cells (EDIC) was modeled with assumptions that in each fraction, radiation dose was uniformly delivered to all cells for rapidly circulating ones, and only to those in the irradiated volume for slowly circulating ones. EDIC was thus calculated as a function of the number of RT fractions and doses to the lung, heart, and the whole body (integral dose). Associations between EDIC and local tumor control, denoted as local progression-free survival (LPFS), and OS were assessed using Cox regression model. Results: The analysis included 464 patients (261 from 60-Gy arm and 203 patients from 74-Gy arm). EDIC was significantly higher in the 74-Gy group (6.9 AE 2.1 Gy) than in the 60-Gy group (5.7 AE 1.7 Gy) (P < 0.0001). EDIC was associated with LPFS (P < 0.0001) and OS (P < 0.0001) in the whole group of all 464 patients, and within the 60-Gy (P Z 0.007 for LPFS and P < 0.0001 for OS) and 74-Gy groups (P Z 0.04 for LPSF and P Z 0.003 for OS). The 2-year OS rates were 72, 52, 49, and 15% for EDIC in the range of <4.0, 4.0-6.5, 6.5-9.5, and >9.5 Gy, respectively (P < 0.0001). Conclusion: Radiation dose to OARIS was significantly associated with local tumor control and overall survival for patients with stage-III NSCLC, suggesting that radiation-induced immune toxicity could be an important contributing factor to tumor progression and death. In-depth study of OARIS is warranted and will be reported at the meeting.Purpose/Objective(s): Recent data demonstrate an association between radiation (RT) dose to the heart and Grade 3+ cardiac events (CEs) in patients with locally advanced non-small cell lung cancer. Those with baseline coronary artery disease (CAD) were at particularly increased risk. A majority of patients, however, do not have overt pretreatment CAD and we sought to determine which combinations of pretreatment cardiac risk and RT dose are associated with an elevated CE rate.

Visual assessment of CAC on CTAC should be performed during SPECT/CT MPI because it affects diagnostic certainty and may improve risk stratification.