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

Abstract

Background/Aim: Determination of failure of transarterial chemoembolization (TACE) for treatment of Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) has become important because of the development of tyrosine kinase inhibitor (TKI) treatment. We evaluated the usefulness and efficacy of the newly proposed time to TACE progression (TTTP). Patients and Methods: From 2006 to 2016, 192 BCLC-B HCC patients [median age 72 years, male/female ratio = 149/43, Child-Pugh score 5/6/7 = 106/56/30, albumin-bilirubin (ALBI) grade 1/2 = 64/128, Kinki criteria B1/B2 = 64/128] were enrolled. TTTP was defined based on a previous report and first imaging performed 3 months after initial TACE had been used to obtain baseline images. The patients were divided into three groups according to TTTP (<5, 5-10, and ≥10 months; group I, II, and III, respectively). We evaluated the relationship between TTTP and overall survival (OS) as well as the prognostic factors for death. Results: The median number of TACE procedures was 4 (interquartile range 3-7). There was a moderate correlation between TTTP and OS (r = 0.527, 95% CI 0.416-0.622, p < 0.001). The median survival for group I (n = 78), II (n = 49), and III (n = 65) was 24.6, 34.7, and 49.5 months, respectively (group I vs. group II, p = 0.023; group I vs. group III, p < 0.001; group II vs. group III, p = 0.037; Holm's method). ALBI grade 2 (HR 1.548, 95% CI 1.004-2.388, p = 0.048), alpha-fetoprotein (>100 ng/mL) (HR 1.540, 95% CI 1.035-2.291, p = 0.033), and TTTP (<5 months) (HR 2.157, 95% CI 1.447-3.215, p < 0.001) were significant prognostic factors for death in multivariate Cox hazard analysis. Conclusion: In patients with reduced TTTP, especially <5 months, it might be difficult to improve prognosis with a repeated TACE procedures. In such cases, reconsideration of the therapeutic strategy might be needed when possible.

Skeletal muscle volume loss during transarterial chemoembolization predicts poor prognosis in patients with hepatocellular carcinoma

“…Evaluation of TACE refractory status is important to select other therapeutic options such as a tyrosine kinase inhibitor . Moreover, TTTP is proposed as a prognostic predictor in patients undergoing repeated TACE . In the present study, CPMI was also associated with the TACE period as well as OS.…”

“…Transcatheter arterial chemoembolization (TACE) is standard therapy for patients with intermediate‐stage HCC . Transcatheter arterial chemoembolization is generally repeated until an insufficient response occurs during relatively long‐term treatment, and time to TACE progression (TTTP) is a prognostic predictor of patients treated with TACE . However, the effect of skeletal muscle mass on mortality or TTTP is poorly understood.…”

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

“…As such, we believe that TTTP could be a good surrogate for OS as a primary endpoint in clinical trials of TACE. Izumoto et al [20] confirmed that TTTP is indeed a good surrogate for OS in trials of TACE.…”

A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements

“…A number of reports, such as the global observational study OPTIMIS and 2 other studies, indicate that repeated TACE procedures lead to a deterioration of liver function in up-to 7 criteria out patients [56,57,[73][74][75]. In terms of liver function, ALBI grade 2 especially mALBI grade 2b is a poor prognostic factor for OS after TACE [73,75].…”