Early prediction of response of sorafenib on hepatocellular carcinoma by CT perfusion imaging: an animal study

Objective:

This study evaluated the feasibility of CT perfusion parameters for the early efficacy prediction of sorafenib in the treatment of hepatocellular carcinoma (HCC) in rats.

Methods:

CT hepatic perfusion measurements were performed in the livers of 40 rats implanted with rat HCC. The rats in the experimental group (n = 28) were treated by oral gavage with sorafenib (20 mg per day), whereas the rats in the control group (n = 12) were treated by normal saline. Rats were classified into the responder group if the maximum diameter of their tumour had decreased 21 days after treatment, whereas the other rats were classified into the non-responder group. Data were analysed using the Pearson correlation analysis or analysis of variance.

Results:

CT perfusion was used to depict haemodynamic changes before and after treatment. The arterial liver perfusion was significantly decreased in the responder group on Day 11 after treatment with sorafenib (from 71.5 to 53.4 ml min⁻¹ 100 ml⁻¹), whereas no significant changes were observed in the non-responder group (p = 0.87). The maximum diameter of the tumour was also significantly decreased in the responder group on Day 21 after treatment (p = 0.042), whereas the maximum tumour diameter was significantly increased in the control group (p = 0.001).

Conclusion and advances in knowledge:

CT perfusion could be used to quantitatively analyse the haemodynamic changes in the treatment of HCC with sorafenib, which indicates that this approach may be developed for the early prediction of treatment efficacy for sorafenib.Hepatocellular carcinoma (HCC) is ranked as the fifth most common cancer worldwide and the third most common cause of cancer-related deaths.¹ In the past few years, with increasing knowledge of molecular regulatory mechanisms of cancer progression, targeted antineoplastic drugs have been rapidly developed. Sorafenib, a molecular inhibitor of multiple protein kinases,² is the first approved molecular targeted drug for the treatment of HCC. It has been demonstrated that sorafenib can prolong the survival of patients with advanced HCC.³ Although sorafenib has been proven effective in the treatment of HCC, some patients develop adverse reactions or show no treatment effects, and, in some extreme cases, sorafenib has been shown to shorten survival in patients.⁴ If imaging techniques could be used to predict the therapeutic efficacy of sorafenib during the early stage of treatment, unnecessary treatment could be avoided, which would undoubtedly have a significant effect on reducing the physiological distress and financial burden of patients.The New Response Evaluation Criteria in Solid Tumors⁵ are currently the primary criteria for evaluating therapeutic efficacy in solid tumours. The evaluation criteria for tumour progression or remission measure the changes in the maximum diameter of a tumour, although this measure is not reliable in clinical practice. For example, tumour necrosis occurs within the mass after treatment, but tumour size is not simultaneously reduced. Under these circumstances, false-positive results may occur in the imaging evaluation, which would hide the true therapeutic efficacy. Perfusion imaging techniques are based on dynamic contrast-enhanced CT scans that can detect the haemodynamic status and functional changes in organs and tissues earlier than the morphological changes; as a result, these techniques can be used for the early detection and diagnosis of tumours.^6–8 This study sought to investigate whether CT perfusion imaging could be used to depict the effects of sorafenib on the inhibition of tumour angiogenesis in the treatment of HCC using a rat model.