Respiratory-gated proton beam therapy for intrahepatic cholangiocarcinoma without fiducial markers.

Background: Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma.

Methods: Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41-88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48-83.6 (relative biological effectiveness) in 20-38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0-74.0) months. The median tumor size was 41 (range, 10-134) mm. Twenty-one patients were classified as having Child-Pugh class A, and three patients were classified as having Child-Pugh class B. Local progression was defined as any growth of the irradiated tumor.

Results: The median survival time was 28 months for all patients. The Kaplan-Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear.

Conclusions: Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects.