An In Silico Feasibility Study of Dose-Escalated Hypofractionated Proton Therapy for Rectal Cancer

<b>Background/Objectives</b>: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be possible. It is hypothesized that cCR rates will increase with increasing radiotherapy doses. By using proton therapy, doses to organs at risk (OAR) may be decreased. In preparation for a clinical trial on dose-escalated proton therapy for LARC, the purpose of this study is to establish the feasibility of proton therapy for dose-escalated hypofractionated radiotherapy of LARC. <b>Methods</b>: Ten patients, having previously received short course radiotherapy (SCRT) for LARC, were included in this planning study. Two photon plans and two proton plans were created for each patient: one with a standard 5 × 5 Gy fractionation and one dose-escalated up to 5 × 7 Gy. Proton plans were robustly optimized. For all plans the integral dose (ID) was computed, and for the proton plans relative biological effectiveness (RBE) distributions were calculated. Feasibility was assessed in terms of target coverage and OAR doses. <b>Results</b>: All treatment plans satisfied target coverage criteria. Three of the photon and two of the proton dose-escalated plans exceeded recommended OAR objectives. Proton IDs were on average lower by a factor of 1.97 compared to photon IDs. Mean doses to OAR were, in general, lower for protons. All proton RBE values in the escalated target volumes were between 1.09 and 1.16. <b>Conclusions</b>: The proposed dose escalation was found to be feasible. Protons can reduce the integral dose and mean doses to OARs compared to photons in both the dose-escalated and non-escalated cases. Differences in RBE between escalated and standard fractionation were small.