Intrahepatic Biliary Stricture Following Carbon-Ion Radiotherapy: A Narrative Review

We conducted a narrative review to synthesize the limited and fragmented evidence on intrahepatic biliary strictures following carbon-ion radiotherapy (CIRT) for liver tumors, with a focus on biliary-specific risks amid CIRT's advantages in dose conformity, particularly given the current scarcity of direct clinical data. A focused narrative literature search was performed across academic databases to evaluate study designs, patient populations, and biliary complications. Due to the high clinical heterogeneity and limited sample sizes, we conducted a conceptual qualitative synthesis utilizing a stratified synthesis approach rather than a quantitative meta-analysis. Proxy populations such as those with pancreatic cancer and conventional photon therapy data were referenced selectively to contextualize radiation-related biliary injury, while strictly not considering them as direct evidence. Intrahepatic biliary stricture was observed as a late-onset complication. Notably, one cohort reported an incidence of 11% (five out of 47 patients) in a specific subgroup with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B cirrhosis, although this finding has not been consistently reproduced across broader populations. Key risk factors identified included perihilar-type tumors, macrovascular invasion, and prior perihilar treatments. Additionally, susceptibility appeared to be elevated by high radiation doses such as biliary V10% ≥ 40 Gy (RBE) and tumor proximity to major biliary structures. For mild cases, conservative care was typically utilized, whereas percutaneous drainage or stenting was required for severe instances. Biliary stricture contributed to liver function deterioration in 23% (one of five) of affected patients in the aforementioned cohort. While many cohorts report manageable toxicities, rare but fatal outcomes such as a 1-2% incidence of grade 5 toxicities, including uncontrollable cholangitis and liver failure, have been documented across broader studies. Overall, while CIRT demonstrates a generally acceptable safety profile, it is imperative to acknowledge that rare, severe ischemic strictures can precipitate fatal infectious cascades or liver failure. Careful monitoring and adherence to dosimetric constraints are warranted in high-risk patients.