This study proposed and simulated a model-based methodology to incorporate heterogeneous treatment benefit of proton therapy versus photon therapy into randomized trial designs, using radiation-induced pneumonitis (RP) as an exemple. ΔNTCP data from in silico treatment plans for photon therapy and proton therapy for patients with locally advanced lung cancer as well as randomly sampled clinical risk factors were included in simulations of trial outcomes.

By converting trial results into probability distributions, this study demonstrated large heterogeneity in predicted benefit, and provided a randomized measure of the precision of individual benefit estimates. The authors suggested quantifying the benefit of proton therapy referral, based on the combination of NTCP models, clinical risk factors, and traditional randomization.