Estimating Potential Benefits of Online Adaptive Proton Therapy for Head-and-Neck Cancer: A Retrospective Study

Abstract

Proton therapy is highly sensitive to anatomical changes and setup variations in head-and-neck (HN) treatments. To address this issue, proton centers often acquire patient CT images weekly to monitor patient anatomical changes during the treatment course and perform offline plan adaptation when needed. However, offline adaptation cannot fully account for daily setup variations or the anatomical changes occurring with high frequency. There are a few groups endeavoring to develop advanced technologies to enable online adaptive proton therapy (APT). However, the necessity of online APT remains controversial, as it is unknown that whether online APT will significantly improve treatment quality and outcomes compared to offline APT. The purpose of this study is to estimate the clinical potential of online APT in the management of HN cancers in relation to the current offline APT. Our retrospective study was conducted with four HN patients (35 fractions per patient), who had been treated with intensity modulated proton therapy and had offline adaptation once or twice during their treatment courses. Synthetic CT (sCT) images were generated from 140 daily CBCT images for us to recalculate the dose of the treatment plan in patient's actual treatment anatomy for each treatment fraction and adapt the plan when warranted. These adaptations were assumed to be performed online before treatment delivery to mimic an online APT course. Accumulative doses were calculated for both courses using the CBCT-based sCT images of every fraction for us to compare the target coverage, organ at risk (OAR) sparing, tumor control probability (TCP) and normal tissue complication probability (NTCP). An in-house script was developed to semi-automate this process in a commercial treatment planning system to facilitate our study. All patients would benefit from online APT to different extents. For the first patient, with OAR doses comparable to the actual offline course, the retrospective online APT course improved dose coverages of the three CTVs from 95.2%, 98.64% and 89.53% to 98.88%, 99.81%, 98.97%, which would lead to a 4.52% improvement in TCP. Similarly, online APT would yield a 2.66% improvement in TCP for the second patient. For the third patient, with comparable CTV dose coverages, the mean doses of right parotid and oral cavity were decreased from 29.52 Gy relative biological effectiveness (RBE) and 41.89 Gy RBE to 22.16 Gy RBE and 34.61 Gy RBE, leading to a reduce of 1.67% and 3.40% in NTCP. The mean dose of right parotid was decreased from 21.71 Gy RBE to 19.37 Gy RBE for the last patient, leading to a reduce of 0.73% in NTCP. Our results showed that online APT could better maintain the treatment plan quality than offline APT for all the four patients, despite their significant anatomical changes. Future investigation will focus on collecting more patient data to obtain statistically significant results and help identify the patients to whom the online APT will be of most benefit.