Subclassification of BCLC B Stage Hepatocellular Carcinoma and Treatment Strategies: Proposal of Modified Bolondi's Subclassification (Kinki Criteria)

2015 ◽  
Vol 33 (6) ◽  
pp. 751-758 ◽  
Author(s):  
Masatoshi Kudo ◽  
Tadaaki Arizumi ◽  
Kazuomi Ueshima ◽  
Toshiharu Sakurai ◽  
Masayuki Kitano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Treatment Strategies ◽  
Intermediate Stage ◽  
Heterogeneous Population ◽  
Recommended Treatment ◽  
Tumor Number ◽  
Weak Points ◽  
Bclc Staging ◽  
Heterogeneous Tumor

Intermediate stage hepatocellular carcinoma (HCC) is a very heterogeneous tumor in terms of tumor size (>3 cm ∼ over 10 cm), tumor number (4 ∼ over 20) and liver function (Child-Pugh score 5-9). However, transarterial chemoembolization is the only recommended treatment option according to the Barcelona Clinic Liver Cancer (BCLC) staging. Bolondi's subclassification of BCLC B stage is feasible; however, there are several weak points. Therefore, by modifying Bolondi's subclassification, we have proposed a more simplified subclassification, Kinki criteria. The Kinki criteria consist of 2 factors: liver function (Child-Pugh score 5-7 or 8, 9) and tumor status (Beyond Milan and within up-to-7 criteria; IN and OUT). The Kinki criteria classifies BCLC B stage from B1 (Child-Pugh score 5-7 and within up-to-7), B2 (Child-Pugh score 5-7 and beyond up-to-7) and B3 (Child-Pugh score 8, 9 and any tumor status). These criteria are simple and easy to apply to clinical practice. Therefore, these criteria will stratify the heterogeneous population of BCLC B group patient well and give the treatment indication according to each substage. These criteria should be further validated both retrospectively and prospectively.

scholarly journals Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Manabu Morimoto ◽  
Kun-Ming Rau ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Intermediate Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Locoregional Therapy ◽  
Hazards Model ◽  
Bclc Staging

<b><i>Background:</i></b> Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. <b><i>Methods:</i></b> A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. <b><i>Results:</i></b> Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. <b><i>Conclusions:</i></b> Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

scholarly journals An Evidence-Based Multidisciplinary Approach to the Management of Hepatocellular Carcinoma (HCC): The Alberta HCC Algorithm

2010 ◽  
Vol 24 (11) ◽  
pp. 643-650 ◽  
Author(s):  
Kelly W Burak ◽  
Norman M Kneteman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Function ◽  
Potential Role ◽  
Staging System ◽  
Evidence Based ◽  
Transarterial Radioembolization ◽  
Bclc Staging ◽  
Tumour Characteristics

Hepatocellular carcinoma (HCC) is one of only a few malignancies with an increasing incidence in North America. Because the vast majority of HCCs occur in the setting of a cirrhotic liver, management of this malignancy is best performed in a multidisciplinary group that recognizes the importance of liver function, as well as patient and tumour characteristics. The Barcelona Clinic Liver Cancer (BCLC) staging system is preferred for HCC because it incorporates the tumour characteristics (ie, tumour-node-metastasis stage), the patient’s performance status and liver function according to the Child-Turcotte-Pugh classification, and then links the BCLC stage to recommended therapeutic interventions. However, the BCLC algorithm does not recognize the potential role of radiofrequency ablation for very early stage HCC, the expanding role of liver transplantation in the management of HCC, the role of transarterial chemoembolization in single large tumours, the potential role of transarterial radioembolization with90Yttrium and the limited evidence for using sorafenib in Child-Turcotte-Pugh class B cirrhotic patients. The current review article presents an evidence-based approach to the multidisciplinary management of HCC along with a new algorithm for the management of HCC that incorporates the BCLC staging system and the authors’ local selection criteria for resection, ablative techniques, liver transplantation, transarterial chemoembolization, transarterial radioembolization and sorafenib in Alberta.

scholarly journals The Effect of Transarterial Chemoembolization in Combination With Kang’ai Injection on Patients With Intermediate Stage Hepatocellular Carcinoma: A Prospective Study

2017 ◽  
Vol 17 (2) ◽  
pp. 477-485 ◽  
Author(s):  
Yue-Meng Wan ◽  
Yu-Hua Li ◽  
Zhi-Yuan Xu ◽  
Hua-Mei Wu ◽  
Ying Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Transarterial Chemoembolization ◽  
Intermediate Stage ◽  
Primary Endpoints ◽  
Tumor Number ◽  
Tace Group ◽  
Extrahepatic Metastases ◽  
A Prospective Study ◽  
Postembolization Syndrome

Background: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. Objective: This study aimed to investigate the effect of combining TACE with Kang’ai (KA) injection for treating patients with intermediate stage HCC. Methods: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). Results: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. Conclusion: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

scholarly journals Multidisciplinary Management of Hepatocellular Carcinoma in Clinical Practice

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Gemma Bruera ◽  
Katia Cannita ◽  
Aldo Victor Giordano ◽  
Rosa Manetta ◽  
Roberto Vicentini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Practice ◽  
Liver Function ◽  
Rating Scale ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Multidisciplinary Management ◽  
Disease Extension ◽  
Surgical Treatments

Background. Hepatocellular carcinoma (HCC) patients require different treatment strategies according to disease extension, liver function, and patient’s fitness. We evaluated HCC multidisciplinary management in clinical practice.Methods. Consecutive patients were followed and treated with tailored medical, locoregional, and surgical treatments, according to disease stage and patient’s fitness (age, Cumulative Illness Rating Scale (CIRS)). Activity, efficacy, and safety were evaluated.Results. Thirty-eight patients were evaluated: median age, 74; elderly 92%; CIRS secondary 28 (74%); Child-Pugh A 20 (53%), B 11 (29%); and Barcelona Clinic Liver Cancer (BCLC) 0 2 (5%), A 9 (24%), B 10 (26%), C 13 (34%), and D 4 (11%). Overall survival (OS) was 30 months. At 9 months median follow-up, among 25 unresectable HCC, OS was 10 months; BCLC B–D unfit for sorafenib showed OS 3 months. Ten patients (40%) received sorafenib: Child-Pugh A 5 (50%) and B 5 (50%) and disease control rate 89%, progression-free survival 7 months, and OS 9 months. G3-4 toxicities: anorexia, hypertransaminaemia, hyperbilirubinemia, and hypercreatininemia. Limiting toxicity syndromes were 40%, all multiple sites.Conclusion. HCC patients require multidisciplinary clinical management to properly select tailored treatments according to disease stage, fitness, and liver function. Patients suitable for sorafenib should be carefully selected, monitored for individual safety, and prevalently characterized by limiting toxicity syndromes multiple sites.

Treatment of Hepatocellular Carcinoma

2016 ◽  
Vol 34 (5) ◽  
pp. 597-602 ◽  
Author(s):  
Álvaro Díaz-González ◽  
María Reig ◽  
Jordi Bruix
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Liver Function ◽  
Primary Liver Cancer ◽  
Performance Status ◽  
Intermediate Stage ◽  
Extrahepatic Disease ◽  
Stage Migration ◽  
Advanced Stage ◽  
Tumour Burden

Hepatocellular carcinoma (HCC) represents the most frequent primary liver cancer. This disease usually arises as a result of a chronic liver disease, but may appear without any underlying disease. In most units, the staging and treatment decision in patients with HCC follows the Barcelona Clínic Liver Cancer (BCLC) strategy. Following this approach, patients diagnosed with HCC are classified according to tumour burden, liver function and ECOG-Performance Status (PS). This stratifies patients according to prognosis and links each stage with the evidence-based treatment approach to be first considered. Patients correspond to BCLC stage 0 (very early) when the tumour burden accounts for just one nodule and it measures 2 cm or less. BCLC stage A includes patients with just one nodule or 3 nodules under 3 cm. Both stages 0 and A gather patients with preserved liver function according to Child-Pugh score, being Child-Pugh A. Patients in BCLC B stage (intermediate stage) are patients with multinodular liver cancer confined to the liver, without extrahepatic disease, ECOG-PS 0 and preserved liver function (Child-Pugh A or B). Patients with portal venous invasion, extrahepatic disease or cancer-related symptoms measured by PS (1-2) and still with preserved liver function correspond to BCLC C (advanced) stage. Finally, patients classified in BCLC stage D are those with a severe alteration of liver function (Child-Pugh C) or severe cancer-related symptoms with PS above 2. In very early and early stages (BCLC 0 and A), treatment options include surgical treatment, ablation and liver transplantation. Intermediate stage (BCLC B) patients should be considered for transarterial chemoembolization. At advanced stage (BCLC C), the recommended treatment is sorafenib. Finally, at the end stage (BCLC D), symptomatic treatment is the suggested option. The treatment stage migration concept refers to patients who at first glance would be treated with the option that corresponds to their BCLC stage but, because of any coexisting comorbidity, technical issue or even treatment failure/progression but still within the original stage cannot be treated by the initial suggested treatment. These patients then move to the treatment that would correspond to the next stage/s.

scholarly journals Novel Therapies for Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3049
Author(s):  
Lorenza Rimassa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Novel Therapies ◽  
Multikinase Inhibitor

Since 2007, for patients with advanced- or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for locoregional treatments and with preserved liver function, the multikinase inhibitor (MKI) sorafenib has been the worldwide standard of care [...]

scholarly journals Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2906
Author(s):  
Takeshi Hatanaka ◽  
Satoru Kakizaki ◽  
Tamon Nagashima ◽  
Masashi Namikawa ◽  
Takashi Ueno ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Platelet Count ◽  
Liver Function ◽  
Predictive Factors ◽  
Intermediate Stage ◽  
Class B ◽  
Low Platelet Count ◽  
Pugh Class ◽  
Careful Screening

The aim of this multicenter retrospective study was to assess the change in liver function in patients with hepatocellular carcinoma treated with lenvatinib. Among 139 consecutive patients receiving lenvatinib treatment between March 2018 and July 2019, 28 patients with Child-Pugh class B and one patient with inadequate patient information were excluded. Remaining 110 patients with Child-Pugh class A were analyzed. The median age of 110 patients was 73 years (IQR 66.7–80) and 88 patients (80.0%) were men. Child-Pugh score was 5 (CP5A) and 6 (CP6A) in 58 (52.7%) and 52 patients (47.3%), and ALBI grade was 1 and 2 in 38 (34.5%) and 72 patients (65.5%), respectively. The deterioration to Child-Pugh class B was found in 43 patients (39.1%) during the lenvatinib treatment. The favorable factors related to preserving liver function were significantly shown to be male, ALBI grade 1, CP5A and BCLC early or intermediate stage in the multivariate analysis. The formation of ascites was found in 32 patients (28.6%). The significant unfavorable factors associated with the formation of ascites were found to be low platelet count and CP6A. Among the 79 patients, there were 36 (45.6%) and 11 patients (13.9%) who fulfilled the criteria for candidate for the post-progression treatment and ramucirumab treatment, respectively. The predictive factors of the post-progression treatment were shown to be ALBI grade 1 and CP5A in multivariate analysis. In conclusion, male, ALBI grade 1, CP5A and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and CP6A.

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