Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer

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).

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).

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.

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.