TY - JOUR
T1 - Nonalcoholic steatohepatitis in hepatocarcinoma
T2 - new insights about its prognostic role in patients treated with lenvatinib
AU - Rimini, M.
AU - Kudo, M.
AU - Tada, T.
AU - Shigeo, S.
AU - Kang, W.
AU - Suda, G.
AU - Jefremow, A.
AU - Burgio, V.
AU - Iavarone, M.
AU - Tortora, R.
AU - Marra, F.
AU - Lonardi, S.
AU - Tamburini, E.
AU - Piscaglia, F.
AU - Masi, G.
AU - Cabibbo, G.
AU - Foschi, F. G.
AU - Silletta, M.
AU - Kumada, T.
AU - Iwamoto, H.
AU - Aoki, T.
AU - Goh, M. J.
AU - Sakamoto, N.
AU - Siebler, J.
AU - Hiraoka, A.
AU - Niizeki, T.
AU - Ueshima, K.
AU - Sho, T.
AU - Atsukawa, M.
AU - Hirooka, M.
AU - Tsuji, K.
AU - Ishikawa, T.
AU - Takaguchi, K.
AU - Kariyama, K.
AU - Itobayashi, E.
AU - Tajiri, K.
AU - Shimada, N.
AU - Shibata, H.
AU - Ochi, H.
AU - Yasuda, S.
AU - Toyoda, H.
AU - Fukunishi, S.
AU - Ohama, H.
AU - Kawata, K.
AU - Tani, J.
AU - Nakamura, S.
AU - Ratti, F.
AU - Aldrighetti, L.
AU - Cascinu, S.
AU - Casadei-Gardini, A.
N1 - Funding Information:
None declared. AC-G has received grants and personal fees from MSD, Eisai and Bayer; and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca and GSK. MK has received grants from Taiho Pharmaceuticals, Chugai Pharmaceuticals, Otsuka, Takeda, Sumitomo Dainippon-Sumitomo, Daiichi Sankyo, AbbVie, Astellas Pharma and Bristol-Myers Squibb; has received grants and personal fees from MSD, Eisai and Bayer; and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, Eli Lilly and ONO Pharmaceutical. AJ reports personal fees from Eisai. All other authors have declared no conflicts of interest. Data available on request from the authors.
Publisher Copyright:
© 2021 The Authors
PY - 2021/12
Y1 - 2021/12
N2 - Background: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
AB - Background: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
KW - advanced hepatocarcinoma
KW - atezolizumab
KW - bevacizumab
KW - hepatitis C
KW - hepatocellular carcinoma
KW - immunotherapy
KW - lenvatinib
KW - nonalcoholic steatohepatitis
KW - sorafenib
UR - http://www.scopus.com/inward/record.url?scp=85120063634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120063634&partnerID=8YFLogxK
U2 - 10.1016/j.esmoop.2021.100330
DO - 10.1016/j.esmoop.2021.100330
M3 - Article
AN - SCOPUS:85120063634
VL - 6
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
IS - 6
M1 - 100330
ER -