Dose–Response and survival analysis after transarterial radioembolization for intrahepatic cholangiocarcinoma: A multicenter multicompartment dosimetry study

Aim: We aimed to report real-world outcomes of transarterial radioembolization (TARE) in patients with intrahepatic cholangiocarcinoma (ICC), focusing on different microsphere types and posttreatment dosimetric approaches in relation to dose–response and survival analyses. Materials and methods: This multicenter retrospective single-arm cohort study included adult patients with intrahepatic cholangiocarcinoma treated with Y-90 glass or resin microspheres using lobar or segmental approaches between January 2014 and December 2024 across 13 centers. All posttreatment Y-90 Bremsstrahlung single photon emission tomography (SPECT)/ computed tomography (CT) or Y-90 positron emission tomography (PET) images were reviewed. Post-treatment dose estimations were performed centrally by a nuclear medicine physician with 10 years of experience in dosimetric calculations using the VoxelDosimetry tool of Hermia software (Hermes Medical Solutions, Sweden). Mean perfused liver absorbed dose (PLAD), mean tumor absorbed dose (TAD), and mean whole-liver absorbed dose (WLAD) were calculated. Dosimetric analysis for Y-90 SPECT/CT and PET/CT were performed separately. Tumor response was assessed by comparing imaging obtained within 6 weeks before treatment and 2–4 months after treatment. Response categories were grouped as objective response (complete response + partial response) and nonresponse (stable disease + progressive disease) for treated lesions. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) using serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and bilirubin levels within 3 months after TARE. Additionally, albumin–bilirubin (ALBI) scores were calculated before and after treatment, and changes in ALBI grade were analyzed. Results: Initially, data from 194 (110 female, 84 male; mean age 53.8 ± 16.6 years) patients were included. After excluding patients without survival status data, 180 patients were included in the overall survival (OS) analysis. Seventeen patients were excluded from dose–response evaluation due to suboptimal posttreatment Y-90 imaging for dosimetric calculations. Survival analyses were performed on a per-patient basis, whereas dosimetric and response analyses were performed on a per-treatment-session basis. For dose response analysis, a total of 194 TARE sessions in 163 (101 female, 62 male; mean age 51.4 ± 12.6 years) patients were analyzed. Median (min–max) of administered activities were 2.7 (1.4–6.1) GBq for glass microspheres and 1.4 (0.6–1.8) GBq for resin microspheres (p = 0.004). In separate analyses of SPECT and PET studies, higher TAD and PLAD values were observed in sessions analyzed with PET-based dosimetry (for mean TAD; 249.2 ± 26.6 Gy vs 114.8 ± 15.7 Gy, p < 0.001, for mean PLAD; 102.1 ± 10.4 Gy vs 59.4 ± 11.3 Gy, p = 0.031). A significant positive trend between TAD and response category was observed in the resin microsphere sessions using Y-90 PET–based dosimetry (Area Under Curve 0.693, p = 0.028). In the OS analysis of 180 patients (median follow-up 13.3 months, range 7–81), 128 deaths occurred. Medians of OS did not differ between patients treated with glass versus resin microspheres [17.4 (13.2–21.5, 95%CI) vs 16.6 (7.7–25.5, 95%CI) months, p = 0.80]. Among 107 patients included in time to progression (TTP) analysis, no significant difference in medians of TTP was observed between patients treated with glass and resin microspheres [12.1 (7.8–12.4, 95%CI) vs 14.5 (5.6- 14.4, 95%CI) months, p = 0.11]. One patient developed grade 2 hepatotoxicity and irreversible hepatic failure 10 months after a second TARE session due to tumor progression. In addition, cholangitis occurred in 1 patient and gastritis in 3 patients following TARE. Conclusion: This multicenter analysis suggests that TARE may provide encouraging survival outcomes with acceptable toxicity in patients with ICC, including salvage settings. A potential dose–response association was identified in the resin microsphere subgroup evaluated with Y-90 PET-based dosimetry. Given the retrospective multicenter design and heterogeneity of imaging modalities, these findings should be considered hypothesis-generating and require confirmation in prospective studies using standardized posttreatment dosimetry.