Identification of Responders to Sorafenib in Hepatocellular Carcinoma: Is Tumor Volume Measurement the Way Forward?

Abstract

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.

Assessment of tumor volume and density as a measure of the response of advanced hepatocellular carcinoma to sorafenib: Application of automated measurements on computed tomography scans

“…RECIST 1.1‐based radiological assessment is used widely for treatment response classification and as a surrogate end‐point both in clinical trials and in routine practice. However, the development of molecular targeted therapies to lessen tumor vascularity has shown that the RECIST 1.1 assessment has limitations . Some modifications to RECIST 1.1 for HCC treatment have been proposed, including mRECIST, EASL, and the Choi criteria, which are considered to better reflect treatment effects .…”

“…However, the development of molecular targeted therapies to lessen tumor vascularity has shown that the RECIST 1.1 assessment has limitations. 7,9,17,21 Some modifications to RECIST 1.1 for HCC treatment have been proposed, including mRECIST, EASL, and the Choi criteria, which are considered to better reflect treatment effects. 9 However, these modifications are still based on a unidimensional manual assessment and are strongly affected by heterogeneities in tumor appearance, that is, CT enhancement pattern, induced by sorafenib and other locoregional therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE).…”

“…9,12 Consequently, three-dimensional volumetry of tumor masses is proposed as a more reproducible and sensitive method. [13][14][15][16][17] Indeed, several computer software packages have been developed to assist the taking of objective measurements from CT scans. Previously, we used such software for patients with lung cancer or multiple myeloma 18,19 ; these studies demonstrated the efficacy and utility of this software for evaluating responses to cancer treatment in a standardized way.…”

Challenges of advanced hepatocellular carcinoma

“…According to recently published studies focused on HCC patients, a 10% increase in volume rate after two months of therapy correlates with a poor prognosis[80,81]. The role of MR diffusion weighted imaging has also been investigated in response assessment.…”

Radiology in Transplant

“…There are several standard oncological methods for assessing tumor treatment response such as monitoring for decreases in alpha fetoprotein (AFP) [12], and different criteria have been put forth by liver societies: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and Choi's criteria, which monitors change in tumor density and arterial-enhancing tumor volume variations. These methods for assessing tumor response were compared in sorafenib-treated patients (n=22), showing that response criteria and volume measurements were reproducible (k> 0.80).…”