Impact of and interplay between proton arc therapy and range uncertainties in proton therapy for head-and-neck cancer

Objective. Proton therapy reduces the integral dose to the patient compared to conventional photon treatments. However, in vivo proton range uncertainties remain a considerable hurdle. Range uncertainty reduction benefits depend on clinical practices. During intensity-modulated proton therapy (IMPT), the target is irradiated from only a few directions, but proton arc therapy (PAT), for which the target is irradiated from dozens of angles, may see clinical implementation by the time considerable range uncertainty reductions are achieved. It is therefore crucial to determine the impact of PAT on range uncertainty reduction benefits. Approach. For twenty head-and-neck cancer patients, four different treatment plans were created: an IMPT and a PAT treatment plan assuming current clinical range uncertainties of 3.5% (IMPT3.5% and PAT(3.5%)), and an IMPT and a PAT treatment plan assuming that range uncertainties can be reduced to 1% (IMPT1% and PAT(1%)). Plans were evaluated with respect to target coverage and organ-at-risk doses as well as normal tissue complication probabilities (NTCPs) for parotid glands (endpoint: parotid gland flow <25%) and larynx (endpoint: larynx edema). Main results. Implementation of PAT (IMPT3.5%-PAT(3.5%)) reduced mean NTCPs in the nominal and worst-case scenario by 3.2 percentage points (pp) and 4.2 pp, respectively. Reducing range uncertainties from 3.5% to 1% during use of IMPT (IMPT3.5%-IMPT1%) reduced evaluated NTCPs by 0.9 pp and 2.0 pp. Benefits of range uncertainty reductions subsequently to PAT implementation (PAT(3.5%)-PAT(1%)) were 0.2 pp and 1.0 pp, with considerably higher benefits in bilateral compared to unilateral cases. Significance. The mean clinical benefit of implementing PAT was more than twice as high as the benefit of a 3.5%-1% range uncertainty reduction. Range uncertainty reductions are expected to remain beneficial even after PAT implementation, especially in cases with target positions allowing for full leveraging of the higher number of gantry angles during PAT.