Respiratory-gated Proton Beam Therapy for Intrahepatic Cholangiocarcinoma without Fiducial Markers

Abstract 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, 10–125) 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.