Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
Louise Turtle, Neeraj Bhalla, Andrew Willett, Robert J. Biggar, Jonathan Leadbetter, G. Georgiou, James M. Wilson, Sindu Vivekanandan, M. Hawkins, Michael Brada, John D. Fenwick
Abstract
Abstract Background We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). Materials and methods Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MD Heart ). Reductions in MD Heart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (V Heart-50-Gy ) and left atrial wall volume receiving ≥ 63 Gy (V LAwall-63-Gy ). Results Following re-optimization, mean MD Heart , V Heart-50-Gy and V LAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MD Heart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including V Heart-50-Gy and V LAwall-63-Gy , providing some insurance against survival being more strongly related to these measures than to MD Heart . The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MD Heart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MD Heart values exceeded the median value in a published series, the average MD Heart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MD Heart values. Conclusions Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MD Heart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MD Heart levels, for whom larger reductions in heart doses can be achieved.