Secondary cancer risk in six anatomical sites when using PAT, IMPT, and VMAT/IMRT radiotherapy

Compared to intensity modulated proton therapy (IMPT), proton arc therapy (PAT) is expected to improve dose conformality, delivery efficiency, and provide a more favorable LET distribution. Alternatively, the low-dose bath is potentially spread over larger volumes, which could impact the likelihood of developing a radiation-induced, secondary cancer (SC). The goal of this study was to evaluate this risk in several anatomical sites using newly developed commercial tools.

Treatment plans encompassing six anatomical sites, five patients per site, and three techniques per patient were created using RayStation. Techniques included PAT and IMPT for protons, and either volumetrically modulated radiotherapy (VMAT) or intensity modulated radiotherapy (IMRT) for photons. Risk estimates were based on the organ-equivalent dose (OED) concept using both Schneider's mechanistic dose-response model for carcinoma induction and a linear dose-response model.

With few exceptions, mean and integral dose were lowest with PAT. For protons, the factor OED_IMPT/OED_PAT ranged from 0.7 to 1.8 with both the mechanistic and linear model, while for photons OED_photon/OED_PAT ranged from 1.5 to 10 using the mechanistic model and 1.3 to using the linear model. A strong correlation was found between mean dose and OED for organs with significant repopulation/repair (high R value) and less cell death from single hit interactions (low α value).

Based on results from both mechanistic and linear risk models, the transition from IMPT to PAT should not substantially affect SC risk in patients treated with proton therapy. Additionally, when using Schneider's model, the shapes of the dose-response curves can be used as a good predictor of how SC risk will respond to shifts from intermediate dose to low dose as anticipated when moving from IMPT to PAT.