Intermediate hepatocellular carcinoma: current treatments and future perspectives

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.

Section: Resultsmentioning

confidence: 99%

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

Izumoto¹,

Hiraoka²,

Ishimaru

et al. 2017

“…TACE is recommended for the majority of intermediate-stage HCC patients. When tumors are shown to be refractory to TACE, switching to sorafenib should be considered for improving prognosis [31,32,33,34,35]. Among intermediate-stage HCC patients treated with TACE, Takayasu et al [12] noted that the overall median period of survival was 3.3 years and that the 5-year survival rate was 34%.…”

Section: Discussionmentioning

confidence: 99%

Proposed New Sub-Grouping for Intermediate-Stage Hepatocellular Carcinoma Using Albumin-Bilirubin Grade

Hiraoka

Kumada²,

Nouso³

et al. 2016

Aim: We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for evaluation of the prognosis of intermediate-stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer criteria stage B, BCLC-B). Patients and Methods: We enrolled 754 naïve BCLC-B patients (multiple tumors) and retrospectively analyzed their clinical features [surgical resection (hepatectomy), n = 170; radiofrequency ablation (RFA), n = 110; percutaneous ethanol injection, n = 7; transcatheter arterial chemoembolization, n = 396; others, n = 25; best supportive care, n = 46]. Four sub-groups were defined for the Modified Intermediate Stage of Liver Cancer (MICAN) criteria as follows: B1 (ALBI-1/within up-to-7 criteria), B2 (ALBI-2/within up-to-7 criteria), B3 (ALBI-1 and ALBI-2/multiple and beyond up-to-7 criteria), and B4 (ALBI-3/any). Results: The median survival time of patients classified as B1 (n = 94), B2 (n = 175), B3 (n = 452), and B4 (n = 33) was 65.1, 48.1, 29.6, and 14.6 months, respectively (p < 0.01 for each). Those in B1 treated with hepatectomy and RFA comprised 67.0%, while that ratio was 51.4% in B2, 28.3% in B3, and 12.1% in B4. Conclusion: The MICAN criteria based on ALBI grade are simple and useful for prediction of prognosis and therapy decision-making in the heterogeneous population of BCLC-B patients.

“…To improve the prognosis of HCC patients after becoming intermediate stage, we consider it important to predict those who are refractory to TACE in order to promptly switch the therapeutic modality. Criteria and scoring for establishing the TACE-refractory status [5,6] as well as an algorithm for switching to sorafenib in cases of TACE against intermediate-stage HCC [14] have been proposed. Those studies recommended that the TACE-refractory status should be determined after no more than 2 sessions or serial TACE sessions.…”

Section: Discussionmentioning

confidence: 99%

Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization

Hiraoka¹,

Ishimaru²,

Kawasaki

et al. 2015

Background/Aim: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). Materials and Methods: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. α-Fetoprotein ≥100 ng/ml, fucosylated α-fetoprotein ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC. Results: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (<2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014). Conclusion: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (≥2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC.