BED-optimized multi-IMPT: a biologically comparable alternative to proton ARC therapy

Proton spot-scanning arc therapy (ARC) is an emerging technique that can enhance high-dose conformity to targets compared with standard intensity-modulated proton therapy (IMPT). Although proton ARC is highly desirable, it is not yet clinically available. Multiple IMPT plans delivered over different fractions and optimized simultaneously provide a practical means to approximate ARC plan quality. However, existing multiple IMPT approaches are not optimized to be biologically comparable to proton ARC because they neglect the fractionation effect during treatment planning. This work proposes a biologically optimized multiple IMPT (multi-IMPT) framework that achieves comparable performance to proton ARC in terms of the biologically effective dose (BED). This is achieved through direct optimization of BED by explicitly incorporating the fractionation effect during planning, thereby ensuring biological comparability between multi-IMPT and proton ARC treatments. The proposed multi-IMPT method utilizes a different subset of limited number of beam angles in each fraction for dose delivery. Due to the different dose delivered to organs at risk (OAR) in each fraction, biologically effective dose (BED) delivered to OAR and the physical dose delivered to target is optimized in each fraction. The BED-based multi-IMPT inverse optimization problem is solved via iterative convex relaxation method and the alternating direction method of multipliers. The effectiveness of the proposed multi-IMPT method is evaluated in terms of BED objectives in comparison with ARC and IMPT. Multi-IMPT provided similar plan quality with ARC. For example, multi-IMPT provided better OAR sparing and slightly better target dose coverage for the prostate case; similar dose distribution for the lung case; slightly worse dose coverage for the brain case; better dose coverage but slightly higher BED in OAR for the head-and-neck case. A multi-IMPT approach is proposed that delivers ARC-comparable plan quality under the evaluated conditions in terms of biologically effective dose.