Abstract
BACKGROUND: Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LET(d)), despite high CIRT dose. PURPOSE: This study aimed to investigate the approaches to up-modulate the CIRT LET(d) and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. METHODS: 10 LAPCs that had been irradiated by CIRT with 67.5 Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LET(d) and OER investigations. Our considerations for up-modulating LET(d) were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LET(d) could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks. The LET(d) and the corresponding OER distributions of each type of SIB plan were evaluated. RESULTS: We delivered up to 100 Gy (RBE) to GTVcore using SIB. The mean LET(d) of GTV increased significantly by 21.3% from 47.8 to 58.0 keV/μm (p < 0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p < 0.05). The GI LET(d)S in all modulated plans were not more than those in the original plans. CONCLUSIONS: SIB could effectively increase CIRT LET(d) to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.