The Japanese Nationwide Cohort Data of Proton Beam Therapy for Liver Oligometastasis in Breast Cancer Patients.

PURPOSE/OBJECTIVE(S): A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology (JASTRO) in Japan. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers.

MATERIALS/METHODS: Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors, and no more than three liver lesions. The treatment indication and strategy were discussed at cancer boards in each institution. The dose and fraction of PBT were determined by referring to the unified treatment policy established by JASTRO. We used the following protocol: 64 gray (Gy) (relative biological effectiveness [RBE])/8 fraction (fr) for the hepatic periphery area away from the GI tract, and 72.6 GyE/22 fr for the adjacent hilar region type. Regarding safety, the HCC irradiation protocols of 66 GyE/10 fr, 72.6-76 GyE/20-22 fr, and 74-76 GyE/37-38 fr could be used. The local control (LC), overall survival (OS), and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Factors possibly related to OS, such as tumor size, number of liver tumors, intervention of chemotherapy, and/or hormone therapy, were investigated. The cut-off values were estimated using the receiver operating characteristic curve and area under the curve. Univariate analysis was performed using the log-rank test.

RESULTS: Fourteen females, with a median age of 57 (range, 44-73) years and twenty-two lesions were included. Nine patients had one lesion, two patients had two lesions, and three patients had three lesions. PBT was selected because nine patients had underlying disease and five patients had general conditions (age, etc.). The median lesion size, fraction size, and biological effective dose using the linear-quadratic model with α/β = 10 Gy ((BED)10 ) were 44 (20-130) mm, 6.6 (2-8) (relative biological effectiveness [RBE])/fraction (fr), and 109.6 (52.7-115.2) Gy, respectively. The median follow-up period of breast cancers was 22.8 (4-54) months. The 1-, 2-, and 3-year LC rates of liver metastasis from breast cancers were 100% for all. The 1-, 2-, and 3-year OS rates were 85.7%, 62.5%, and 62.5%, respectively. The 1-, 2-, and 3-year PFS rates were 50.0%, 33.3%, and 16.7%, respectively, and median PFS time was 16 months. Tumor size, the number of liver tumors, and the intervention of chemotherapy and/or hormone therapy at any time were not significantly related to the OS. Only one patient did not complete PBT due to current disease progression. The other patients completed PBT without interruption. One patient had grade 3 radiation-induced dermatitis.

CONCLUSION: Based on the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancer patients.