Cargando…

Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma is the most common liver malignancy. In the population with an advanced stage of the disease, outcomes could be disappointed by treating with molecular targeting agents because of low treatment response rates. It has gained improving effects of immune checkpo...

Descripción completa

Detalles Bibliográficos
Autores principales: Hung, Hao-Chien, Lee, Jin-Chiao, Wang, Yu-Chao, Cheng, Chih-Hsien, Wu, Tsung-Han, Lee, Chen-Fang, Wu, Ting-Jung, Chou, Hong-Shiue, Chan, Kun-Ming, Lee, Wei-Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036568/
https://www.ncbi.nlm.nih.gov/pubmed/33807219
http://dx.doi.org/10.3390/cancers13071607
_version_ 1783676940664700928
author Hung, Hao-Chien
Lee, Jin-Chiao
Wang, Yu-Chao
Cheng, Chih-Hsien
Wu, Tsung-Han
Lee, Chen-Fang
Wu, Ting-Jung
Chou, Hong-Shiue
Chan, Kun-Ming
Lee, Wei-Chen
author_facet Hung, Hao-Chien
Lee, Jin-Chiao
Wang, Yu-Chao
Cheng, Chih-Hsien
Wu, Tsung-Han
Lee, Chen-Fang
Wu, Ting-Jung
Chou, Hong-Shiue
Chan, Kun-Ming
Lee, Wei-Chen
author_sort Hung, Hao-Chien
collection PubMed
description SIMPLE SUMMARY: Hepatocellular carcinoma is the most common liver malignancy. In the population with an advanced stage of the disease, outcomes could be disappointed by treating with molecular targeting agents because of low treatment response rates. It has gained improving effects of immune checkpoint inhibitor as an emerging treatment for advanced HCC (Hepatocellular carcinoma). However, this novel treatment regimen is quite expensive; to select suitable patients prior to treatment is crucial in daily practice. Here, we intend to present the effect of immunotherapy in treating advanced hepatocellular carcinoma in the real world and to assess potential factors predicting treatment responses for patient selection. ABSTRACT: Immune checkpoint inhibitors (ICI) have been applied to treat advanced stage hepatocellular carcinoma (HCC) and obtain promising effects. However, tumor response to treatment was unpredictable. A predicting biomarker of objective response or disease-control is an unmet need for patient selection. In this study, 45 advanced HCC patients who failed to sorafenib treatment and received nivolumab, 3 mg/kg bi-weekly, were included. Tumor responses to nivolumab treatment were assessed by the modified response evaluation criteria in solid tumors (mRECIST) criteria. Tumor responses were correlated to clinical characteristics to find out response predictors. In this small series, the prevalence of extrahepatic nodal metastasis, distant metastasis, and portal vein thrombus among the patients were 22.2% (n = 10), 48.9% (n = 22), and 42.2% (n = 19), respectively. The pre-treatment tumor size was 7.2 ± 4.2 cm in maximal diameter, and the calculated total tumor volume was 619.0 ± 831.1 cm(3). Among 45 patients, 3 patients had partial response (PR), 11 had stable disease (SD), and the other 31 had progression of disease. By correlating clinical data to the patients with PR and SD, serum neutrophil-to-lymphocyte ratio (NLR) (hazard ratio (HR) = 2.04) and patient-generated subjective global assessment (PG-SGA) score (HR = 2.30) were the independent factors in multivariate analysis. By receiver operating characteristic curve analysis, pre-treatment NLR ≤ 2.5 and PG-SGA score < 4 were the cutoff points to predict tumor response to ICI treatment. In conclusion, biomarkers to predict tumor response for HCC are still lacking in this costly ICI therapy. In this study, NLR ≤ 2.5 and PG-SGA score < 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy.
format Online
Article
Text
id pubmed-8036568
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80365682021-04-12 Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma Hung, Hao-Chien Lee, Jin-Chiao Wang, Yu-Chao Cheng, Chih-Hsien Wu, Tsung-Han Lee, Chen-Fang Wu, Ting-Jung Chou, Hong-Shiue Chan, Kun-Ming Lee, Wei-Chen Cancers (Basel) Article SIMPLE SUMMARY: Hepatocellular carcinoma is the most common liver malignancy. In the population with an advanced stage of the disease, outcomes could be disappointed by treating with molecular targeting agents because of low treatment response rates. It has gained improving effects of immune checkpoint inhibitor as an emerging treatment for advanced HCC (Hepatocellular carcinoma). However, this novel treatment regimen is quite expensive; to select suitable patients prior to treatment is crucial in daily practice. Here, we intend to present the effect of immunotherapy in treating advanced hepatocellular carcinoma in the real world and to assess potential factors predicting treatment responses for patient selection. ABSTRACT: Immune checkpoint inhibitors (ICI) have been applied to treat advanced stage hepatocellular carcinoma (HCC) and obtain promising effects. However, tumor response to treatment was unpredictable. A predicting biomarker of objective response or disease-control is an unmet need for patient selection. In this study, 45 advanced HCC patients who failed to sorafenib treatment and received nivolumab, 3 mg/kg bi-weekly, were included. Tumor responses to nivolumab treatment were assessed by the modified response evaluation criteria in solid tumors (mRECIST) criteria. Tumor responses were correlated to clinical characteristics to find out response predictors. In this small series, the prevalence of extrahepatic nodal metastasis, distant metastasis, and portal vein thrombus among the patients were 22.2% (n = 10), 48.9% (n = 22), and 42.2% (n = 19), respectively. The pre-treatment tumor size was 7.2 ± 4.2 cm in maximal diameter, and the calculated total tumor volume was 619.0 ± 831.1 cm(3). Among 45 patients, 3 patients had partial response (PR), 11 had stable disease (SD), and the other 31 had progression of disease. By correlating clinical data to the patients with PR and SD, serum neutrophil-to-lymphocyte ratio (NLR) (hazard ratio (HR) = 2.04) and patient-generated subjective global assessment (PG-SGA) score (HR = 2.30) were the independent factors in multivariate analysis. By receiver operating characteristic curve analysis, pre-treatment NLR ≤ 2.5 and PG-SGA score < 4 were the cutoff points to predict tumor response to ICI treatment. In conclusion, biomarkers to predict tumor response for HCC are still lacking in this costly ICI therapy. In this study, NLR ≤ 2.5 and PG-SGA score < 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy. MDPI 2021-03-31 /pmc/articles/PMC8036568/ /pubmed/33807219 http://dx.doi.org/10.3390/cancers13071607 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hung, Hao-Chien
Lee, Jin-Chiao
Wang, Yu-Chao
Cheng, Chih-Hsien
Wu, Tsung-Han
Lee, Chen-Fang
Wu, Ting-Jung
Chou, Hong-Shiue
Chan, Kun-Ming
Lee, Wei-Chen
Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title_full Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title_fullStr Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title_full_unstemmed Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title_short Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
title_sort response prediction in immune checkpoint inhibitor immunotherapy for advanced hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036568/
https://www.ncbi.nlm.nih.gov/pubmed/33807219
http://dx.doi.org/10.3390/cancers13071607
work_keys_str_mv AT hunghaochien responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT leejinchiao responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT wangyuchao responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT chengchihhsien responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT wutsunghan responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT leechenfang responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT wutingjung responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT chouhongshiue responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT chankunming responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma
AT leeweichen responsepredictioninimmunecheckpointinhibitorimmunotherapyforadvancedhepatocellularcarcinoma