Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward?

OBJECTIVES: Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. METHODS: The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. RESULTS: The response criteria and volume measurements were reproducible (k > 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios >1.1 (p = 0.04). CONCLUSIONS: Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO.

Curative therapies for hepatocellular carcinoma: an update and perspectives.

Curative treatments, including liver transplantation, surgical resection and percutaneous treatments, are the recommended therapies in BCLC-0 (Barcelona Clinic of Liver Cancer) or BCLC-A hepatocellular carcinoma (HCC). This review provides an overview of some issues of clinical importance concerning curative treatments in HCC.

Correlation between LDH levels and response to sorafenib in HCC patients: an analysis of the ITA.LI.CA database.

BACKGROUND: Lactate dehydrogenase (LDH) is a predictor of clinical outcome in hepatocellular carcinoma (HCC) patients. However, its predictive role in the clinical outcomes of sorafenib treatment has been poorly documented. The correlation between LDH levels and clinical outcomes in HCC patients treated with sorafenib and included in the nationwide Italian database ITA.LI.CA was investigated here. PATIENTS AND METHODS: The ITA.LI.CA database contains data for 5,136 HCC patients. All patients treated with sorafenib treatment and with available LDH values were considered. Overall survival (OS) and time to progression (TTP) were compared in patients with LDH levels above and below a defined threshold, determined through an ROC analysis. An explorative analysis investigated the relationship between the variation of LDH levels during treatment and response to sorafenib. RESULTS: Baseline LDH levels were available for 97 patients. The most accurate cutoff value for LDH concentration was 297 U/L. Patients with LDH values above (n=45) and below (n=52) this threshold showed equal OS (12.0 months) and TTP (4.0 months) values. Data on LDH levels during sorafenib treatment were reported for 10 patients. LDH values decreased in 3 patients (mean difference = -219 U/L) who also reported a prolonged OS and TTP versus those with unmodified/increased LDH (OS: NE (not evaluated) vs. 8.0 months, p=0.0083; TTP: 19.0 vs. 3.0 months, p=0.008). CONCLUSIONS: The clinical benefits of sorafenib do not seem to be influenced by baseline LDH. According to the results of an explorative analysis, however, a decreased LDH concentration during sorafenib might be associated with improved clinical outcomes.

Assessment of clinical and radiological response to sorafenib in hepatocellular carcinoma patients.

Sorafenib is an effective anti-angiogenic treatment for hepatocellular carcinoma (HCC). The assessment of tumor progression in patients treated with sorafenib is crucial to help identify potentially-resistant patients, avoiding unnecessary toxicities. Traditional methods to assess tumor progression are based on variations in tumor size and provide unreliable results in patients treated with sorafenib. New methods to assess tumor progression such as the modified Response Evaluation Criteria in Solid Tumors or European Association for the Study of Liver criteria are based on imaging to measure the vascularization and tumor volume (viable or necrotic). These however fail especially when the tumor response results in irregular development of necrotic tissue. Newer assessment techniques focus on the evaluation of tumor volume, density or perfusion. Perfusion computed tomography and Dynamic Contrast-Enhanced-UltraSound can measure the vascularization of HCC lesions and help predict tumor response to anti-angiogenic therapies. Mean Transit Time is a possible predictive biomarker to measure tumor response. Volumetric techniques are reliable, reproducible and time-efficient and can help measure minimal changes in viable tumor or necrotic tissue, allowing the prompt identification of non-responders. Volume ratio may be a reproducible biomarker for tumor response. Larger trials are needed to confirm the use of these techniques in the prediction of response to sorafenib.

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives.

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium(90)), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.