Postoperative circulating tumor cells predict the benefits of tyrosine kinase inhibitor for hepatocellular carcinoma after transplantation

Abstract

Aim

Circulating tumor cells (CTC) have shown promise in predicting the outcomes of adjuvant treatments for several malignancies. The clinical significance of CTC in predicting the efficacy of tyrosine kinase inhibitor (TKI) administration in patients with hepatocellular carcinoma (HCC) was unclear.

Methods

A total of 429 patients who underwent liver transplantation for HCC had provided 335 preoperative and 373 postoperative blood samples that could be used for CTC detection (pre-CTC and post-CTC). The association of the pre-CTC and post-CTC findings with the efficacy of TKI administration was assessed. Additionally, CTC surveillance was performed in 27 patients during TKI administration.

Results

Patients with detectable post-CTC, instead of pre-CTC, showed a significantly longer time to recurrence when receiving a TKI after liver transplantation for HCC (hazard ratio 0.57; P = 0.042). Whereas patients without detectable post-CTC did not benefit from the TKI administration (P = 0.270). Furthermore, we also found that patients who persistently harbored CTC during TKI administration showed significantly higher early recurrence rates (≤1 year; 40% vs. 5.9%, P < 0.001) and a shorter time to recurrence (HR 7.03; P < 0.001) than those whose CTC status switched from positive to negative. In addition, longitudinal CTC monitoring demonstrated that CTC tended to reflect drug resistance during TKI administration.

Conclusions

The postoperative CTC level could predict the efficacy of TKI treatment for HCC patients after liver transplantation. Dynamic monitoring for CTC during treatment could sensitively reflect the response to the TKI, the development of drug resistance, and foresee tumor recurrence.