Radiological appearance of hepatocellular carcinoma predicts the response to trans-arterial chemoembolization in patients undergoing liver transplantation

Abstract

BackgroundThe ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE.MethodsFrom January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT.ResultsEighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis.ConclusionsThe well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Quantitative assessment of HCC wash-out on CT is a predictor of early complete response to TACE

“…Several studies aimed to find predictive preoperative imaging biomarkers for early CR of HCC after chemoembolization. Our results confirmed the findings by Zhang et al [11] and Vesselle et al [10], about smooth margins and smaller size of the lesions being good predictors of higher susceptibility to TACE. In a previously published surgical series [28], HCC nodules without smooth margins showed a higher rate of histopathologic proven microvascular invasion which can explain, at least in part, their lower CR rate.…”

“…Our data showed an overall CR rate of 49.6%, in line with those reported in other per-lesion analyses [11,13,27]. Vesselle et al reported an overall CR rate of 26% [10]; it is to note, however, that their CR rate increased to 39% for lesions ≤ 5 cm.…”

“…3), which could also explain the null predictive value of the quantitative estimates for wash-in CER and LLC, despite some authors reporting a favorable predictive value of clear tumor wash-in when subjectively assessed during CECT [11] or preprocedural DSA [12,29]. It is worth to note the fact that Zhang et al [11] evaluated the wash-in rate only in a qualitative way.…”

“…The qualitative evaluation of tumor margins was performed in a blinded manner on the delayed phase, according to a previous study [11], by the same two radiologists, and then dichotomized as smooth vs others (lobular or irregular).…”

“…In view of an optimal treatment allocation, several studies tried to identify preoperative imaging-based predictive factors for good response to chemoembolization, mainly based on tumor size, growth rate, margins, location, and, especially, grade of hypervascularization in the arterial phase [10][11][12][13][14]. Up to approximately 30% of HCCs, however, lack a clear arterial phase hyper-enhancement [15,16], including very early HCCs, poorly differentiated HCCs, and HCC nodules with small hypervascular foci [17,18].…”