Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis

Abstract

Background/Aim: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. Methods: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143). Changes in hepatic function along with CP and albumin-bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after introducing sorafenib in Study 2 were evaluated. Results: Hepatic function worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of classification from ALBI-1 to ALBI-2. When the prognosis of patients with the best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI-1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4 months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4 vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. Conclusion: The rate of patients with downgraded hepatic function during r-TACE, especially with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better hepatic function assessment tool than CP in patients receiving sorafenib treatment. Strict judgment of TACE-refractory status in patients with unresectable HCC is needed to improve prognosis before downgrading the hepatic function.

Validation of Newly Proposed Time to Transarterial Chemoembolization Progression in Intermediate-Stage Hepatocellular Carcinoma Cases

“…In our previous study, hepatic function worsened with repeated TACE procedures [43] , as determined with the use of the newly proposed ALBI score [44][45][46] . Some reports have noted the usefulness of ALBI grade for patients undergoing sorafenib treatment and for subclassification of BCLC-B HCC [47][48][49] .…”

Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

“…The first-line treatment for patients with intermediate-stage HCC is transcatheter arterial chemoembolization (TACE); however, the release of large concentrations of angiogenic factors, such as vascular endothelial growth factor (VEGF), triggered by hypoxia induced by TACE results in tumor progression and recurrence [3-5]. Another disadvantage of TACE is that repeated procedures reduce liver function [6]; therefore, minimizing the number of TACE sessions is a critical challenge in the treatment of intermediate-stage HCC patients. Several clinical trials have attempted to address this problem by combining TACE with molecular targeted agents; however, to date, all have ended in failure [7-11], and the combination of TACE and molecular targeted agents is therefore not recommended in routine practice.…”

Combination of Resection and Ablative Treatment for Hepatocellular Carcinoma: Usefulness of Complementary Radiofrequency Ablation

“…Recently, ALBI grade has been reported to have a better assessment ability for obtaining good hepatic reserve function in treated patients [10, 14, 27, 28]. Among the present 115 naïve HCC patients who had multiple countable tumors (≤5) and unmet needs, hepatic function in the Comb group was worse as compared to that in the SR group when assessed by ALBI grade (ALBI grade 1: 42.4 vs. 64.6%, p = 0.034) as well as Fib-4 index (6.30 ± 5.34 vs. 3.75 ± 2.10, p = 0.019), whereas OS and DFS rates were not significantly different between the groups.…”

“…Among the present 115 naïve HCC patients who had multiple countable tumors (≤5) and unmet needs, hepatic function in the Comb group was worse as compared to that in the SR group when assessed by ALBI grade (ALBI grade 1: 42.4 vs. 64.6%, p = 0.034) as well as Fib-4 index (6.30 ± 5.34 vs. 3.75 ± 2.10, p = 0.019), whereas OS and DFS rates were not significantly different between the groups. In previous studies, ALBI grade has shown better prognostic predictive value as compared to Child-Pugh class for various therapeutic modalities, including surgical resection [29, 30], RFA [31, 32], TACE [33], and sorafenib [28], as well as in ALBI-T [14] and mALBI-T [10, 11] scores as total scoring systems. Clinical unmet needs such as those seen in our patients might be resolved by complementary use of low invasive RFA in combination with resection.…”