Associations between cardiac irradiation and survival in patients with non-small cell lung cancer: Validation and new discoveries in an independent dataset.

Abstract

In 'IDEAL-6' patients (N = 78) treated for locally-advanced non-small-cell lung cancer using isotoxically dose-escalated radiotherapy, overall survival (OS) was associated more strongly with V_{LAwall-64-73-EQD2}, the left atrial (LA) wall volume receiving 64-73 Gy equivalent dose in 2 Gy fractions (EQD2), than with whole-heart irradiation measures. Here we test this in an independent cohort 'OX-RT' (N = 64) treated routinely. Using Cox regression analysis we assessed how strongly OS was associated with V_{LAwall-64-73-EQD2}, with whole-heart volumes receiving 64-73 Gy EQD2 or doses above 10-to-70 Gy thresholds, and with principal components of whole-heart dose-distributions. Additionally, we tested associations between OS and volumes of cardiac substructures receiving dose-ranges described by whole-heart principal components significantly associated with OS. In univariable analyses of OX-RT, OS was associated more strongly with V_{LAwall-64-73-EQD2} than with whole-heart irradiation measures, but more strongly still with V_{AortV-29-38-EQD2}, the volume of the aortic valve region receiving 29-38 Gy EQD2. The best multivariable OS model included LA wall and aortic valve region mean doses, and the aortic valve volume receiving ≥38 Gy EQD2, V_{AortV-38-EQD2}. In a subsidiary analysis of IDEAL-6, the best multivariable model included V_{LAwall-64-73-EQD2}, V_{AortV-29-38-EQD2}, V_{AortV-38-EQD2} and mean aortic valve dose. We propose reducing heart mean doses to the lowest levels possible while meeting protocol dose-limits for lung, oesophagus, proximal bronchial tree, cord and brachial plexus. This in turn achieves large reductions in V_{AortV-29-38-EQD2} and V_{LAwall-64-73-EQD2}, and we plan to closely monitor patients with values of these measures still >0% (their median value in OX-RT) following reduction.