Early prediction of response to sorafenib in patients with advanced hepatocellular carcinoma: the role of dynamic contrast enhanced ultrasound

J Hepatol. 2013 Nov;59(5):1014-21. doi: 10.1016/j.jhep.2013.06.011. Epub 2013 Jun 25.

Abstract

Background & aims: Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points.

Methods: Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant.

Results: The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS.

Conclusions: D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment.

Keywords: Dynamic contrast enhanced ultrasound; Hepatocellular carcinoma; Sorafenib; Tumour response.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Disease Progression
  • Disease-Free Survival
  • Endpoint Determination
  • Feasibility Studies
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Predictive Value of Tests
  • Prospective Studies
  • Retrospective Studies
  • Sorafenib
  • Survival Rate
  • Treatment Outcome
  • Ultrasonography

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib