Use of single-energy proton pencil beam scanning Bragg peak for intensity-modulated proton therapy FLASH treatment planning in liver-hypofractionated radiation therapy.

Abstract

The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single-energy Bragg peak beams with a similar beam arrangement as clinical intensity-modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs-at-risk (OARs), and FLASH dose rate percentage. An in-house platform was developed to enable inverse IMPT-FLASH planning using single-energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg-400 MU and Bragg-800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT-SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT-FLASH using single-energy Bragg peaks delivered 50Gy in five fractions with similar or identical beam arrangement to the clinical IMPT-SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose-ADR (DADR), were all studied. The novel spot map optimization can fulfill the inverse planning using single-energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver-gross tumor volume (GTV) Dmean and heart , compared to SBRT-IMPT. The Bragg-800 MU plans resulted in 18.3% higher clinical target volume (CTV) compared with SBRT (p<0.05), and no significant difference was found between Bragg-400 MU and SBRT plans. For the CTV Dmax , SBRT plans resulted in 10.3% (p<0.01) less than Bragg-400 MU plans and 16.6% (p<0.01) less than Bragg-800 MU plans. The Bragg-800 MU plans generally achieved higher ADR, DADR, and DTDR dose rates than Bragg-400 MU plans, and DADR mostly led to the highest V40Gy/s compared to other dose rate calculation methods, whereas ADR led to the lowest. The lower dose rate portions in certain OARs are related to the lower dose deposited due to the farther distances from targets, especially in the penumbra of the beams. Single-energy Bragg peak IMPT-FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT-SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.