Analyses of intermediate stage hepatocellular carcinoma patients from the point of view of designing clinical trials comparing transarterial chemoembolization and systemic therapies

2018 ◽  
Vol 68 ◽  
pp. S208
Author(s):  
K. Koroki ◽  
S. Ogasawara ◽  
Y. Ooka ◽  
M. Inoue ◽  
T. Chiba ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Transarterial Chemoembolization ◽  
Intermediate Stage ◽  
Point Of View ◽  
Systemic Therapies

scholarly journals Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 596-612
Author(s):  
Keisuke Koroki ◽  
Sadahisa Ogasawara ◽  
Yoshihiko Ooka ◽  
Hiroaki Kanzaki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Transarterial Chemoembolization ◽  
Checkpoint Inhibitors ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Durable Response ◽  
High Burden ◽  
High Tumor Burden ◽  
Stage Disease

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.

Lack of Response to Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: Abandon or Repeat?

Radiology ◽  
2021 ◽  
Vol 298 (3) ◽  
pp. 680-692
Author(s):  
Shuling Chen ◽  
Zhenwei Peng ◽  
Yaojun Zhang ◽  
Minshan Chen ◽  
Jiaping Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Intermediate Stage

scholarly journals Management of patients with intermediate stage hepatocellular carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097084
Author(s):  
David Prince ◽  
Ken Liu ◽  
Weiqi Xu ◽  
Minjiang Chen ◽  
Jin-Yu Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Current Standard ◽  
Current Management ◽  
Heterogenous Group ◽  
Patient Subgroups ◽  
Significant Health ◽  
Systemic Therapies

Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.

scholarly journals Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1721 ◽  
Author(s):  
Jun Sik Yoon ◽  
Dong Hyun Sinn ◽  
Jeong-Hoon Lee ◽  
Hwi Young Kim ◽  
Cheol-Hyung Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cohort Study ◽  
Tumor Marker ◽  
Systemic Therapy ◽  
Transarterial Chemoembolization ◽  
External Validation ◽  
Intermediate Stage ◽  
Prognostic Impact ◽  
High Baseline ◽  
Definition Of

Background: For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC. Methods: This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149). Results: The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37–3.46, p = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54–8.76, p < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts. Conclusion: The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.

scholarly journals The Combination Strategy of Transarterial Chemoembolization and Radiofrequency Ablation or Microwave Ablation against Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhentian Xu ◽  
Haiyang Xie ◽  
Lin Zhou ◽  
Xinhua Chen ◽  
Shusen Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Clinical Data ◽  
Transarterial Chemoembolization ◽  
Microwave Ablation ◽  
Great Majority ◽  
Intermediate Stage ◽  
Combination Strategy ◽  
Term Outcome ◽  
Long Term Outcome

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but great majority of patients are already in advanced stage on the first diagnosis and lose the surgery opportunity. Multifarious image-guided interventional therapies, termed as locoregional ablations, are recommended by various HCC guidelines for the clinical practice. Transarterial chemoembolization (TACE) is firstly recommended for intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) B class) HCC but has lower necrosis rates. Radiofrequency ablation (RFA) is effective in treating HCCs smaller than 3 cm in size. Microwave ablation (MWA) can ablate larger tumor within a shorter time. Combination of TACE with RFA or MWA is effective and promising in treating larger HCC lesions but needs more clinical data to confirm its long-term outcome. The combination of TACE and RFA or MWA against hepatocellular carcinoma needs more clinical data for a better strategy. The characters and advantages of TACE, RFA, MWA, and TACE combined with RFA or MWA are reviewed to provide physician a better background on decision.

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