CTC landscape during HCC immunotherapy.

Abstract

4112 Background: The treatment of hepatocellular carcinoma (HCC), the third leading cause of global cancer death, has significantly improved with the advent of immune checkpoint inhibitor regimens. Circulating tumor cells (CTCs) contain the precursors of metastasis and can be serially sampled while patients receive therapy. Quantification of CTC dynamics during HCC treatment with immune checkpoint inhibitor therapy may yield early insight into the systemic anticancer response profile. Methods: We used a commercially available microfluidic CTC purification methodology followed by quantification of CTCs expressing HCC cell surface markers (EPCAM, ASGR1, GPC3) and PD-L1 from patients receiving immune therapies, prior to cycle 1 and cycle 3 of therapy. We also captured and correlated clinical data, including conventional markers of liver function (Child-Pugh score) and radiographic tumor response for correlation with early changes in CTC number. Results: In this pilot study,we collected a total of 29 specimens from 14 participants, 10 of whom provided serial samples. The quantities of CTCs detected was (median:10, range: 1-516); (median:1, range: 0-139) were PD-L1 high,(median: 8, range: 1-312) were PD-L1 medium, and (median: 3, range: 0-190) were PD-L1 low. There was no clear statistical difference in serial CTC enumeration data while on treatment, although the numbers of CTCs and CTC subsets numerically declined in many participants. Conclusions: There was no statistically significant relationship between CTC quantity and subsequent radiographic response. Future studies will involve enrollment of expanded numbers of participants, comparisons with circulating tumor DNA dynamics, and transcriptional profiling of CTCs to further explore these phenomena.