Comparison between 4D robust optimization methods for carbon-ion treatment planning

Intensity-modulated particle therapy (IMPT) with carbon ions is comparatively susceptible to various uncertainties caused by breathing motion, including range, setup, and target positioning uncertainties. To determine relative biological effectiveness-weighted dose (RWD) distributions that are resilient to these uncertainties, the reference phase-based four-dimensional (4D) robust optimization (RP-4DRO) and each phase-based 4D robust optimization (EP-4DRO) method in carbon-ion IMPT treatment planning were evaluated and compared. Based on RWD distributions, 4DRO methods were compared with 4D conventional optimization using planning target volume (PTV) margins (PTV-based optimization) to assess the effectiveness of the robust optimization methods. Carbon-ion IMPT treatment planning was conducted in a cohort of five lung cancer patients. The results indicated that the EP-4DRO method provided better robustness ( P = 0.080 ) and improved plan quality ( P = 0.225 ) for the clinical target volume (CTV) in the individual respiratory phase when compared with the PTV-based optimization. Compared with the PTV-based optimization, the RP-4DRO method ensured the robustness ( P = 0.022) of the dose distributions in the reference breathing phase, albeit with a slight sacrifice of the target coverage ( P = 0.450). Both 4DRO methods successfully maintained the doses delivered to the organs at risk (OARs) below tolerable levels, which were lower than the doses in the PTV-based optimization ( P < 0.05 ). Furthermore, the RP-4DRO method exhibited significantly superior performance when compared with the EP-4DRO method in enhancing overall OAR sparing in either the individual respiratory phase or reference respiratory phase ( P < 0.05 ). In general, both 4DRO methods outperformed the PTV-based optimization in terms of OAR sparing and robustness.