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. 2025 Jul 31;17(15):2542.
doi: 10.3390/cancers17152542.

Adverse Events After Carbon-Ion Radiotherapy (CIRT) for Hepatocellular Carcinoma and Risk Factors for Biliary Stricture After CIRT: A Retrospective Study

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Adverse Events After Carbon-Ion Radiotherapy (CIRT) for Hepatocellular Carcinoma and Risk Factors for Biliary Stricture After CIRT: A Retrospective Study

Keita Maki et al. Cancers (Basel). .

Abstract

Background/Objectives: This study investigated the timing of adverse events (AEs) after carbon-ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC) and identified the risk factors for biliary stricture post CIRT. Methods: This retrospective study included 103 patients with HCC who had undergone CIRT (60 Gy/4 fractions). The onset, frequency, and grade of AEs after CIRT were analyzed. HCC was classified into perihilar and distal types to assess the frequency of biliary stricture, and the risk factors for biliary stricture were investigated. Results: AEs after CIRT were more frequent in patients with liver dysfunction, skin redness/dermatitis, and pigmentation. Biliary stricture occurred long after CIRT (3.0-17.0 months). Most AEs were of grade 1-2. Grade ≥ 3 AEs included biliary stricture (2.9%) and radiation gastric ulcer (1.0%), whereas grade 5 AEs included biliary stricture (1.9%). Biliary stricture was exclusively observed in patients with perihilar-type HCC. Among patients with perihilar-type HCC, those having a tumor in the portal vein trunk branch area were more prone to biliary stricture than those with a tumor in the primary portal vein branch area (p = 0.0018), and all grade ≥ 3 biliary strictures (2.9%) were observed in the portal vein trunk branch area. Patients with perihilar-type HCC and biliary stricture were more likely to have macrovascular invasion (p = 0.0052) and previous local therapy targeting the perihilar region (p = 0.0371) than those without biliary stricture. Conclusions: This study reported the detailed data of AEs post CIRT for HCC and the risk factors for biliary stricture post CIRT.

Keywords: adverse events after carbon-ion radiotherapy; biliary stricture; carbon-ion radiotherapy; hepatocellular carcinoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Onset of adverse events following CIRT in patients with HCC. CIRT, carbon-ion radiotherapy; HCC, hepatocellular carcinoma.
Figure 2
Figure 2
Severity of adverse events following CIRT in patients with HCC. CIRT, carbon-ion radiotherapy; HCC, hepatocellular carcinoma.
Figure 3
Figure 3
Flowchart of selection of patients with perihilar-type HCC and biliary stricture. HCC, hepatocellular carcinoma.
Figure 4
Figure 4
Overall survival rate and local control rate of all patients after carbon-ion radiotherapy. (a) overall survival rate, (b) local control rate.

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