Session Item

For small-sized primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed for the use of PBT or XRT in these cases. The aim of this study is to investigate factors predicting benefits in PBT based on the estimated incidence of hepatic toxicity.

Eligible patients were those who underwent PBT for single or multiple primary liver tumors with maximum diameters of ≤5 cm between March 2015 and April 2021. The dose prescriptions were as follows: 66 GyE in 10 fractions, 72.6 GyE in 22 frations, or 76 GyE in 20 fractions. To compare the PBT plan (PBT-plan), the treatment plan using volumetric modulated arc therapy was generated as the XRT plan (XRT-plan). In target contouring, the CTV was defined as the GTV with a 0-5 mm margin depending on the case. The PTV was defined as the CTV with a 5 mm margin around the entire circumference. Generally, the dose was prescribed for 99% of the volume of the CTV (CTV D99) in the PBT-plan. In these cases, the dose prescription for the XRT-plan was set at PTV D95. The methods of adding margin and dose prescriptions in the XRT-plan were the same as in our routine clinical practice. As for tumor location, the hilar region of the liver was defined as within 20 mm of main stem or first branch of the portal vein. The predicted rate of hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with different endpoints. In setting appropriate thresholds of the difference in NTCP values (ΔNTCP), a threshold of 5% was applied. Factors predicting the PBT to provide superior benefits were analyzed by logistic regression analysis.

A total of 45 patients were analyzed: Forty-one patients with hepatocellular carcinomas (91.1%) and four (8.9%) with intrahepatic cholangiocarcinoma. The median of maximum tumor diameter was 29 mm (range: 6-50 mm) and of total tumor diameter (the sum of the diameters of each tumor) was 30 mm (6-72 mm). Two lesions were treated simultaneously in 11 cases (24.6%). The identified factors predicting benefits in PBT differed depending on the selected NTCP model. In the analysis of Child-Pugh grade A cases, the total tumor diameter was a significant factor (p<0.01) in three NTCP models predicting ≥grade 3 radiation-induced liver disease (RILD). Tumor location (hilum vs others) and number of tumors (1 vs 2) were also significant factors (p<0.01) in the other two models predicting changes in the Child-Pugh score or albumin-bilirubin (ALBI) grade. Around two-thirds of patients with ≥2 factors may benefit from PBT in Child-Pugh grade A (Figure)

From radiation-related hepatic toxicity considerations, the total tumor diameter, location, and number of tumors were suggested to be important factors to predict benefits of PBT in Child-Pugh grade A cases, with the maximum diameter of ≤5 cm. These factors may allow us to predict the benefits of PBT in advance.