Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib

Rimini M, Kudo M, Tada T, Shigeo S, Kang W, Suda G, Jefremow A, Burgio V, Iavarone M, Tortora R, Marra F, Lonardi S, Tamburini E, Piscaglia F, Masi G, Cabibbo G, Foschi FG, Silletta M, Kumada T, Iwamoto H, Aoki T, Goh MJ, Sakamoto N, Siebler J, Hiraoka A, Niizeki T, Ueshima K, Sho T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T, Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N, Shibata H, Ochi H, Yasuda S, Toyoda H, Fukunishi S, Ohama H, Kawata K, Tani J, Nakamura S, Nouso K, Tsutsui A, Nagano T, Takaaki T, Itokawa N, Okubo T, Arai T, Imai M, Joko K, Koizumi Y, Hiasa Y, Cucchetti A, Ratti F, Aldrighetti L, Cascinu S, Casadei-Gardini A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 6

Article Number: 100330

Journal Issue: 6

DOI: 10.1016/j.esmoop.2021.100330

Abstract

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.

Authors with CRIS profile

Involved external institutions

Saiseikai Niigata Daini Hospital Japan (JP) Ehime Prefectural Central Hospital Japan (JP) Sapporo Medical University / 札幌医科大学 Japan (JP) Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation) Italy (IT) Kindai University / 近畿大学 Japan (JP) Sungkyunkwan University (SKKU) Korea, Republic of (KR) Nippon Medical School Japan (JP) Ehime University / 愛媛大学 Japan (JP) Teine Keijinkai Hospital Japan (JP) Kagawa Prefectural Central Hospital Japan (JP) Okayama University Hospital Japan (JP) Asahi General Hospital Japan (JP) Toyama University Hospital Japan (JP) Otakanomori Hospital Japan (JP) Tokushima Prefectural Central Hospital Japan (JP) Matsuyama Red Cross Hospital Japan (JP) Ogaki Municipal Hospital Japan (JP) Osaka Medical and Pharmaceutical University Japan (JP) Kagawa University Japan (JP) Himeji Red Cross Hospital / 姫路赤十字病院 Japan (JP) Hamamatsu University / 浜松大学 Japan (JP) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Italy (IT) University of Bologna / Università di Bologna Italy (IT) Università degli Studi di Modena e Reggio Emilia (UNIMORE) Italy (IT) L'Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli Italy (IT) Università degli Studi di Firenze / University of Florence Italy (IT) Istituto Oncologico Veneto (IOV), IRCCS Italy (IT) Hospital "Card. G. Panico" Italy (IT) Ospedaliero Universitaria di Bologna Policlinico S.Orsola-Malpighi Italy (IT) Azienda Ospedaliero-Universitaria Pisana Italy (IT) Università degli Studi di Palermo Italy (IT) Azienda Unità Sanitaria della Romagna, Biella, Italy Italy (IT) Campus Bio-Medico University of Rome Italy (IT) Gifu Kyoritsu University Japan (JP)

How to cite

APA:

Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G.,... Casadei-Gardini, A. (2021). Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib. ESMO Open, 6(6). https://doi.org/10.1016/j.esmoop.2021.100330

MLA:

Rimini, M., et al. "Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib." ESMO Open 6.6 (2021).

BibTeX: Download