Abstract
PurposeThe heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy.Methods and MaterialsDosimetric and survival data were analyzed for 78 patients. The whole heart, pericardium, AV node, and walls of left and right atria (LA/RA-Wall) and ventricles (LV/RV-Wall) were outlined on radiation therapy planning scans, and differential dose-volume histograms (dDVHs) were calculated. For each structure, dDVHs were approximated using the average dDVH and the 10 highest-ranked structure-specific principal components (PCs). ECGs at baseline and 6 months after radiation therapy were analyzed for 53 patients, dichotomizing patients according to presence or absence of “any ECG change” (conduction or ischemic/pericarditis-like change). All-cause death rate (DR) was analyzed from the start of treatment using Cox regression.Results38% of patients had ECG changes at 6 months. On univariable analysis, higher scores for LA-Wall-PC6, Heart-PC6, “any ECG change,” and larger planning target volume (PTV) were significantly associated with higher DR (P=.003, .009, .029, and .037, respectively). Heart-PC6 and LA-Wall-PC6 represent larger volumes of whole heart and left atrial wall receiving 63 to 69 Gy. Cardiac doses ≥63 Gy were concentrated in the LA-Wall, and consequently Heart-PC6 was highly correlated with LA-Wall-PC6. “Any ECG change,” LA-Wall-PC6 scores, and PTV size were retained in the multivariable model.ConclusionsWe found associations between higher DR and conduction or ischemic/pericarditis-like changes on ECG at 6 months, and between higher DR and higher Heart-PC6 or LA-Wall-PC6 scores, which are closely related to heart or left atrial wall volumes receiving 63 to 69 Gy in this small cohort of patients.
Highlights
Definitive chemoradiation (CRT) is the standard of care for locally advanced non-small cell lung cancer (NSCLC) [1]
Interest in Radiation-induced heart disease (RIHD) after NSCLC radiation therapy has increased with the emergence of evidence suggesting that RIHD affects Overall survival (OS) earlier than was previously thought [18, 19]. In this post-hoc analysis of the prospective data from IDEAL-CRT [20], we aimed to identify the impact of cardiac irradiation on the all-cause death rate (DR) using a dose-volume histogram-wide analysis approach based on principal components analysis (PCA)
The mean whole-heart differential dose-volume histograms (dDVHs) is plotted in Figure 1, alongside the 10 varimax-rotated wholeheart PCs that described more than 95% of total variance
Summary
Definitive chemoradiation (CRT) is the standard of care for locally advanced non-small cell lung cancer (NSCLC) [1]. Overall survival (OS) is poor at these dose levels, with high local failure rates stimulating interest in dose escalation. Outcomes modeling suggests a tumor dose response [4], and results from early-phase studies indicated that concurrent CRT might be safe up to 74 Gy [5,6,7,8,9,10,11,12]. The RTOG0617 phase 3 trial of dose escalation has reported a significantly lower OS for 74 Gy than for 60 Gy in daily 2-Gy fractions, triggering efforts to identify reasons for the reduced survival [13]. A recent metaanalysis of randomized trials in NSCLC found that for concurrent CRT treatments, higher radiation doses result in poorer OS, possibly partly because of higher levels of toxicity in the presence of concurrent chemotherapy [15]
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