scholarly journals Clusterin and Related Scoring Index as Potential Early Predictors of Response to Sorafenib in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Satoshi Narahara ◽  
Takehisa Watanabe ◽  
Katsuya Nagaoka ◽  
Nahoko Fujimoto ◽  
Yoki Furuta ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Predictors ◽  
Predictors Of Response ◽  
Scoring Index

scholarly journals Baseline and Early Predictors of Good Patient Candidates for Second-Line after Sorafenib Treatment in Unresectable Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1256 ◽  
Author(s):  
Hitomi Takada ◽  
Masayuki Kurosaki ◽  
Kaoru Tsuchiya ◽  
Yasuyuki Komiyama ◽  
Jun Itakura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Disease Progression ◽  
Kinase Inhibitors ◽  
Tumor Burden ◽  
Second Line ◽  
Inclusion Criteria ◽  
Sorafenib Treatment ◽  
Unresectable Hepatocellular Carcinoma ◽  
Early Predictors

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <−2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (<0.19) became stricter. For criterion 3, the value of baseline albumin (>3.8 g/dL) and ALBI (<−2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (<0.085). Furthermore, tumor burden (>11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

scholarly journals Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 182 ◽  
Author(s):  
Pei-Chang Lee ◽  
Yee Chao ◽  
Ming-Huang Chen ◽  
Keng-Hsin Lan ◽  
Chieh-Ju Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Factors Associated ◽  
Radiologic Evaluation ◽  
Predictors Of Response ◽  
Pugh Class

Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child–Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child–Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child–Pugh class determines survival by ICI treatment.

scholarly journals Biomarkers are associated with clinical and endoscopic outcomes with vedolizumab treatment in Crohn’s disease

2020 ◽  
Vol 13 ◽  
pp. 175628482097121
Author(s):  
Ariela K. Holmer ◽  
Robert Battat ◽  
Parambir S. Dulai ◽  
Niels Vande Casteele ◽  
Nghia Nguyen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Cell Adhesion ◽  
Crohn's Disease ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Early Predictors ◽  
Predictors Of Response ◽  
Endoscopic Remission ◽  
Intercellular Cell Adhesion Molecule

Background: Vedolizumab, an α4β7 integrin antagonist, is an effective therapy for Crohn’s disease (CD). Biomarkers are needed to guide therapy and predict outcomes. This study evaluated biomarker concentrations and outcomes in patients with CD undergoing vedolizumab treatment. Methods: Sera at weeks 0, 2, 6, 14, and ⩾26 were collected from vedolizumab-treated, refractory CD patients. Concentrations of soluble (s)-Vascular Cell Adhesion Molecule (VCAM)-1, s-Intercellular Cell Adhesion Molecule (ICAM)-1, s-Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1, and s-α4β7 integrin were evaluated for associations with achieving endoscopic remission. Results: A total of 22 patients with CD were included. In all patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased compared with baseline. s-VCAM-1 and s-ICAM-1 changed differentially in patients who achieved remission. At week 6, median s-VCAM-1 (859.6 ng/ml versus 460.3 ng/ml, p = 0.03) and s-ICAM-1 (545.7 ng/ml versus 286.2 ng/ml, p = 0.03) concentrations were higher in patients who achieved endoscopic remission compared with those who did not, and similar differences were observed for s-ICAM-1 concentrations in patients who achieved clinical remission, compared with those who did not (669.1 ng/ml versus 291.0 ng/ml, p = 0.04). Week 14 s-α4β7 concentrations were lower in patients who achieved endoscopic remission, compared with those who did not (7.5 ng/ml versus 17.6 ng/ml, p = 0.020). Conclusion: In all vedolizumab-treated CD patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased. However, higher concentrations of s-ICAM-1 and s-VCAM-1 at week 6 and lower concentrations of s-α4β7 at week 14 differentiated patients who achieved endoscopic remission. These findings may help identify early predictors of response to vedolizumab treatment in patients with CD. Further validation in less refractory CD patients is needed.

scholarly journals Early Predictors of Objective Response in Patients with Hepatocellular Carcinoma Undergoing Lenvatinib Treatment

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 779 ◽  
Author(s):  
Issei Saeki ◽  
Takahiro Yamasaki ◽  
Satoyoshi Yamashita ◽  
Tadasuke Hanazono ◽  
Yohei Urata ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Marker ◽  
Odds Ratio ◽  
Biochemical Markers ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Response Evaluation ◽  
Early Predictors ◽  
Significant Difference ◽  
Response Evaluation Criteria

There are limited reports regarding early predictors of objective response (OR) in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. This retrospective study including 70 patients aimed to investigate the efficacy of hepatic biochemical markers. Changes in tumor marker (alpha-fetoprotein (AFP)/des-gamma-carboxy prothrombin (DCP)) levels and albumin–bilirubin (ALBI) score between the baseline value and that estimated one month after treatment were evaluated. We identified several predictors of OR, including changes in tumor marker levels. The OR rate calculated using modified Response Evaluation Criteria in Solid Tumor (mRECIST) was 41.4%. Response was defined as a reduction in AFP and DCP levels of ≥40% from baseline. OR was significantly associated with AFP response, but not with DCP. Predictors of OR were evaluated in two groups (high-AFP group: baseline AFP ≥ 10 ng/mL; low-AFP group: remaining patients). A multivariate analysis identified AFP response (odds ratio, 51.389; p = 0.001) and ALBI score (odds ratio, 6.866; p = 0.039) as independent predictors of OR in the high-AFP and low-AFP groups, respectively. Changes in the ALBI score indicated deterioration in both responders and non-responders, with a significant difference in non-responders (p = 0.003). AFP response, baseline ALBI score, and change in the ALBI score were early predictors of OR in patients with HCC undergoing lenvatinib treatment.

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