Purpose: Whereas malignancies including HCC and colorectal cancer metastatic to the liver have evidence guiding optimal dose-response thresholds for Y90 radioembolization, 90Y in the treatment of intrahepatic cholangiocarcinoma (ICC) lacks clear guidelines regarding personalized dosimetry. This retrospective study aims to establish a preliminary dose-response threshold for optimizing tumor control post-90Y radioembolization with resin microspheres.
Materials and Methods: A total of 33 patients were reviewed for this study, of which 25 patients met inclusion criteria (diagnosis of ICC, availability of planning SPECT/CT, availability of follow-up imaging at 1 month, 90Y-radioembolic treatment with resin microbeads, and no concurrent systemic therapy). Of these, 17 patients - representing 28 treated hepatic lobes - were not censored due to exclusion criteria (prior intra-arterial therapy, additional intra-arterial therapy before follow-up imaging, and/or tumor not differentiable from background liver). At the 1-month time point when evaluated by RECIST criteria there were 25 responders (SD, PR, or CR) and 3 non-responders (PD). 90Y resin microsphere dose-response relationship was explored by via 3 analyses: identifying the threshold at which AUC was maximized using logistic regression, identifying the minimal dose above which we saw no non-responders, and exploring a potential upper-limit for safe dosing. Dose-response analyses performed in Python.
Results: The responder group received significantly (p < 0.001) higher doses (mean = 111.6 Gy, 25% = 60.6, 75% = 142.8), than the non-responders (mean = 62.5, 25%=42.9, 75%=72.6). Our analysis revealed that all patients responded at doses >110 Gy and the dose at which AUC was maximized was 97 Gy. No significant Spearman’s correlation was seen between radioembolic dose delivered to normal liver and lab-based hepatotoxicity CTCAE measures at follow-up in either the complete cohort (p >0.6), nor in the subcohort of patients undergoing first-time unilateral treatment (p >0.7), though we did not a trend towards significant (p < 0.09) increases in bilirubin with higher radioembolic doses.
Conclusion: Our study suggests that a dose of no less than 110 Gy should be delivered for radioembolic treatment of ICC with Y90 resin micropheres. Further research is warranted to validate these findings in a larger cohort, investigate whether this relationship holds over longer follow-up periods, and ascertain the upper limit of the maximum safe dose.