Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety

Abstract

BackgroundThe optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI.MethodsIn this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1–2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events.ResultsBetween June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3–48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99–29.14) vs. 9.27 months (95% CI 6.05–13.70), hazard ratio [HR] = 0.70 (95% CI 0.52–0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99–62.58) vs. 22.37 months (95% CI 10.84–33.91), HR = 0.68 (95% CI 0.48–0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.ConclusionHepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

Frequent fragility of randomized controlled trials for HCC treatment

“…This study identi ed 125 records through a series of PubMed searches ( Figure 2). After an initial screening of abstracts and a full-text review of the studies, 6 articles were included in the fragility analysis (Table 1, Figure 3) [6][7][8][9][10][11]. The other ve RCTs were excluded, as FI can only be calculated in RCTs that allocate 1:1 randomization (Supplementary table 1).…”

“…Five studies in the fragility analysis were for primary outcome results. Three (60%) had primary outcome trials with a FI of 0 (Fisher's exact test p > 0.05), for which a strati ed log-rank test was used to calculate the reported signi cant P value [8,9,11], and these three (60%) trials had an FQ <1% [8,9,11]. The article with the highest FI fragility index of 19 was published in the Clinical Cancer Research [10].…”

Multidisciplinary Treatment of Advanced Hepatocellular Carcinoma

“…According to a recent meta-analysis, postoperative TACE for advanced HCC was shown to increase overall survival rate [7]. Furthermore, another study found that male patients with cirrhosis, age <60 years, tumor >10 cm, and resection margin <2 cm may derive a greater survival benefit from adjuvant TACE [8].…”

The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-Stage Hepatocellular Carcinoma

“…Using a Leica inverted research microscope (Leica Microsystems, Wetzlar, Germany), the slides were examined under 100 × magni cation to identify the highest vascular density area within the tumor, and ve representative elds were observed at a higher magni cation of 200×. Microvascular invasion (MVI) was de ned as microscopic tumor invasion identi ed in the portal or hepatic vein of the surrounding liver tissue contiguous to the tumor [23]. Tumor differentiation was histologically graded according to the Edmondson system [24].…”