Chemoradiotherapy of locally-advanced non-small cell lung cancer: Analysis of radiation dose–response, chemotherapy and survival-limiting toxicity effects indicates a low α/β ratio

Abstract Purpose To analyse changes in 2-year overall survival (OS2yr) with radiotherapy (RT) dose, dose-per-fraction, treatment duration and chemotherapy use, in data compiled from prospective trials of RT and chemo-RT (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC). Material and methods OS2yr data was analysed for 6957 patients treated on 68 trial arms (21 RT-only, 27 sequential CRT, 20 concurrent CRT) delivering doses-per-fraction ≤4.0 Gy. An initial model considering dose, dose-per-fraction and RT duration was fitted using maximum-likelihood techniques. Model extensions describing chemotherapy effects and survival-limiting toxicity at high doses were assessed using likelihood-ratio testing, the Akaike Information Criterion (AIC) and cross-validation. Results A model including chemotherapy effects and survival-limiting toxicity described the data significantly better than simpler models (p  Conclusions Fitted dose–response curves indicate that gains of ~10% in OS2yr can be made by escalating RT and sequential CRT beyond 64 Gy, with smaller gains for concurrent CRT. Schedule acceleration achieved via hypofractionation potentially offers an additional 5–10% improvement in OS2yr. Further 10–20% OS2yr gains might be made, according to the model fit, if critical normal structures in which survival-limiting toxicities arise can be identified and selectively spared.