Comment on “combination treatment including targeted therapy for advanced hepatocellular carcinoma”

454 Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p < 0.001) and the corresponding R2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.

Download Full-text

Myeloid-deprived suppressor cell mediated the prognostic value of platelet-to-lymphocyte ratio for advanced hepatocellular carcinoma patients.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.331 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 331-331

Author(s):

Xing Li ◽

Xiang-yuan Wu ◽

Nan Jiang ◽

Yan-Fang Xing ◽

Dong-hao Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Therapy ◽

Prognostic Value ◽

Mononuclear Cells ◽

Suppressor Cell ◽

Advanced Hepatocellular Carcinoma ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Platelet Counts ◽

Healthy Donors

331 Background: Myeloid Deprived Suppressor Cell (MDSC) has been recoganized as a promising target for hepatocellular carcinoma (HCC). However, targeted therapy on MDSC failed to display convincing efficacy. Optimization of patient selection to find the most potential beneficiaries might be a solution to this issue. In the present study, we aimed to identify clinical parameters relevant to MDSC level in HCC patients for future MDSC targeted therapy. Methods: In the present study, a series of 55 HCC patients (prospective group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). Results: As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p< 0.0001). The monocytes (r2= 0.2875, p< 0.0001), neutrophils (r2= 0.3630, p< 0.0001) and platelet counts (r2= 0.0828, p= 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 243 HCC patients (retrospective group). The baseline characteristics of prospective and retrospective group were similar. Platelet-to-lymphocyte ratio (PLR) were confirmed to be an independent predictor for OS ( p= 0.003) with the rest parameters presented negative results. Then, advanced HCC patients were divided into two groups based on PLR value ≤111.23 or > 111.23 according to ROC analysis. Patients with low PLR presented higher 3-month survival rate (57.6% vs 37.6%) compared with patients with high PLR. PLR was associated with aggressive behavior of malignancies, such as distant metastasis and portal vein thrombosis. Conclusions: In summary, the present study firstly indentified blood platelet counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher PLR might be the optimal patient subgroup for MDSC targeted therapy.

Download Full-text

Molecular targeted therapy for advanced hepatocellular carcinoma

Targeted Oncology ◽

10.1007/s11523-007-0058-1 ◽

2007 ◽

Vol 2 (4) ◽

pp. 199-210 ◽

Cited By ~ 5

Author(s):

Ying Chun Shen ◽

Chiun Hsu ◽

Ann Lii Cheng

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Therapy ◽

Molecular Targeted Therapy ◽

Advanced Hepatocellular Carcinoma

Download Full-text

TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials

British Journal of Cancer ◽

10.1038/bjc.2016.322 ◽

2016 ◽

Vol 115 (10) ◽

pp. 1201-1205 ◽

Cited By ~ 8

Author(s):

Dae-Won Lee ◽

Myoung-Jin Jang ◽

Kyung-Hun Lee ◽

Eun Ju Cho ◽

Jeong-Hoon Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Therapy ◽

Randomised Controlled Trials ◽

Molecular Targeted Therapy ◽

Meta Analysis ◽

Surrogate Endpoint ◽

Controlled Trials ◽

Advanced Hepatocellular Carcinoma ◽

Randomised Controlled

Download Full-text

Early Changes in DCE-MRI Biomarkers May Predict Survival Outcomes in Patients with Advanced Hepatocellular Carcinoma after Sorafenib Failure: Two Prospective Phase II Trials

Cancers ◽

10.3390/cancers13194962 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4962

Author(s):

Bang-Bin Chen ◽

Zhong-Zhe Lin ◽

Yu-Yun Shao ◽

Chiun Hsu ◽

Chih-Hung Hsu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Targeted Therapy ◽

Phase Ii ◽

Survival Outcomes ◽

Advanced Hepatocellular Carcinoma ◽

Phase Ii Trials ◽

Dce Mri ◽

Clinical Variables ◽

Prospective Phase

In this paper, our main objective was to predict survival outcomes using DCE-MRI biomarkers in patients with advanced hepatocellular carcinoma (HCC) after progression from 1st-line sorafenib treatment in two prospective phase II trials. This study included 74 participants (men/women = 64/10, mean age 60 ± 11.8 years) with advanced HCC who received 2nd-line targeted therapy (n = 41 with lenalidomide in one clinical trial; n = 33 with axitinib in another clinical trial) after sorafenib failure from two prospective phase II studies. Among them, all patients underwent DCE-MRI at baseline, and on days 3 and 14 of treatment. The relative changes (Δ) in the DCE-MRI parameters, including ΔPeak, ΔAUC, and ΔKtrans, were derived from the largest hepatic tumor. The treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The Cox model was used to investigate the associations of the clinical variables and DCE-MRI biomarkers with progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was 10.8% (8/74) and the disease control rate (DCR) was 58.1% (43/74). The median PFS and OS values were 1.9 and 7.8 months, respectively. On day 3 (D3), participants with high reductions in ΔPeak_D3 (hazard ratio (HR) 0.4, 95% confidence interval (CI) 0.17–0.93, p = 0.017) or ΔAUC_D3 (HR 0.51, 95% CI 0.25–1.04, p = 0.043) were associated with better PFS. On day 14, participants with high reductions in ΔPeak_D14 (HR 0.51, 95% CI 0.26–1.01, p = 0.032), ΔAUC_D14 (HR 0.54, 95% CI 0.33–0.9, p = 0.009), or ΔKtrans_D14 (HR 0.26, 95% CI 0.12–0.56, p < 0.001) had a higher PFS than those with lower reduction values. In addition, high reductions in ΔAUC_D14 (HR 0.53, 95% CI 0.32–0.9, p = 0.016) or ΔKtrans_D14 (HR 0.47, 95% CI 0.23–0.98, p = 0.038) were associated with a better OS. Among the clinical variables, ORR was associated with both PFS (p = 0.001) and OS (p = 0.005). DCR was associated with PFS (p = 0.002), but not OS (p = 0.089). Cox multivariable analysis revealed that ΔKtrans_D14 (p = 0.002) remained an independent predictor of PFS after controlling for ORR and DCR. An early reduction in tumor perfusion detected by DCE-MRI biomarkers, especially on day 14, may predict favorable survival outcomes in participants with HCC receiving 2nd-line targeted therapy after sorafenib failure.

Download Full-text