A Phase II Trial of Hypofractionated High-Dose Proton Beam Therapy for Unresectable Liver Metastases

Background and purpose: Proton beam therapy (PBT) is an effective treatment option for primary malig-nant liver disease. However, evidence regarding liver metastasis is insufficient. We aimed to investigate the efficacy and safety of hypofractionated high-dose PBT in the treatment of metastatic liver disease.Materials and methods: From January 2019 to January 2021, patients with unresectable liver metastases were enrolled. For PBT, the dose schemes of 60 Gy relative biological effectiveness (GyRBE) in 5 fractions (fx) (biologically effective dose [BED] 132 GyE) or 70 GyRBE in 10 fx (BED 119 GyE) were used. Either a passive scattered beam or pencil beam scanning (PBS)-based intensity-modulated proton therapy (IMPT) was performed with proper respiratory management. The primary endpoint of the study was 6-month freedom from local progression (FFLP) rate; and the Kaplan-Meier method was used to calculate the FFLP and survival rates.Results: Of the 49 liver metastases in 46 patients, the colorectum accounted for 60% of the primary cancer sites, followed by the gastrointestinal organs and pancreas/biliary tract. Forty patients presented only 1 liver metastasis, while the other 6 patients had 2 to 4 metastases. The Six-month FFLP rate was 95.2%. The 1-year FFLP rate in patients with <3 cm liver metastasis was 87.4%, while that was 74.1% in patients with > 3 cm group (p = 0.087). With regard to systemic treatment, the 1-year FFLP rate after PBT was bet-ter (94.1%) than that without systemic treatment (75.8%; p = 0.051). Regarding PBT-related toxicity, one patient developed a grade 2 gastric ulcer, while none of the patients developed grade >= 3 toxicities.Conclusions: Hypofractionated PBT with a BED > 100 GyRBE for liver metastasis is safe and effective, given the high rate of 6-month FFLP without grade >= 3 treatment-related toxicities. However, further improvements are required for larger tumors and/or those without prior systemic therapy.(c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 176 (2022) 9-16