Comparison of in-field secondary cancer risk based on therapeutic proton dose between proton arc therapy and intensity-modulated proton therapy in lung cancer patients.
Xu Yuankang Y, Chen Wenguang W, Wu Junxiang J, Guo Hao H et al.
Proton arc therapy (PAT) is an emerging delivery modality that delivers proton beams through continuous gantry rotation combined with spot scanning. Compared with intensity-modulated proton therapy (IMPT), PAT improves target conformity and spares organs at risk. However, the dynamic multi-angle irradiation pattern may alter the low-dose region distribution: the low-dose bath expands while the integral dose decreases. The net effect on secondary cancer risk, especially in radiosensitive lungs, remains unclear. Quantitative risk assessment is essential for clinical translation of PAT. To quantitatively compare secondary lung cancer risk between PAT and IMPT using organ equivalent dose (OED) and lifetime attributable risk (LAR) models, and to assess cross-population robustness across China, France, Sweden, and Germany. Data from 25 lung cancer patients (60 Gy/30 fractions) were retrospectively included. For each patient, robustly optimized IMPT and PAT plans were generated with a 3 mm setup and 3% range uncertainties across 21 error scenarios. Dosimetric parameters-ipsilateral lung V 5 , V 20 , and mean dose; whole lungs V 5 , V 20 , and mean dose; and esophageal mean dose-were compared between the two techniques. The mechanistic OED model (with repopulation factor R) and its simplified linear model were used to calculate OED for the ipsilateral lung, both lungs, and the esophagus. LAR was computed by integrating excess absolute risk over the remaining lifetime using patient age, sex, and population-specific parameters (China, France, Sweden, Germany). Relative risk was assessed via the LAR ratio (IMPT/PAT). Paired t-tests or Wilcoxon tests were used with p < 0.05. Under the linear model, PAT produced statistically markedly but modest reductions in absolute LAR for lungs (p < 0.001). Under the mechanistic model, reductions were markedly only in certain populations: ipsilateral lung in France (p = 0.001), Sweden (p < 0.001), Germany (p = 0.003); whole lungs in France (p = 0.046) and Sweden (p = 0.014); but not in China (p = 0.083; p = 1.000) or Germany for whole lungs (p = 0.317). No marked esophageal differences (p > 0.05). LAR ratios were consistent across countries (ipsilateral lung: 1.07-1.09; esophagus: 1.04-1.13), demonstrating robustness. PAT does not increase the modeled in-field secondary cancer risk in the lungs compared with IMPT and shows comparable risk for the esophagus. The risk reduction trend is robust across Chinese and European populations. These findings suggest that PAT does not increase modeled secondary lung cancer risk compared with IMPT and may even provide a modest risk reduction, providing quantitative evidence for clinical application.