Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2019; 25(27): 3607-3618
Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3607
Intermediate-advanced hepatocellular carcinoma in Argentina: Treatment and survival analysis
Federico Piñero, Sebastián Marciano, Nora Fernández, Jorge Silva, Margarita Anders, Alina Zerega, Ezequiel Ridruejo, Gustavo Romero, Beatriz Ameigeiras, Claudia D’Amico, Luis Gaite, Carla Bermúdez, Virginia Reggiardo, Luis Colombato, Adrián Gadano, Marcelo Silva
Federico Piñero, Ezequiel Ridruejo, Marcelo Silva, Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
Federico Piñero, Margarita Anders, Ezequiel Ridruejo, Marcelo Silva, Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires B1629HJ, Argentina
Sebastián Marciano, Carla Bermúdez, Adrián Gadano, Hospital Italiano de Buenos, Cuidad Autónoma de Buenos Aires, Buenos Aires C1424BYE, Argentina
Nora Fernández, Luis Colombato, Hospital Británico, Cuidad Autonoma de Buenos Aires, Buenos Aires C1280AEB, Argentina
Jorge Silva, Hospital G Rawson, San Juan 5400, Argentina
Margarita Anders, Hospital Aleman, Cuidad Autonoma de Buenos Aires, Buenos Aires C1280AEB, Argentina
Alina Zerega, Sanatorio Allende from Córdoba, Córdoba 5016, Argentina
Ezequiel Ridruejo, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Ciudad de Buenos Aires 1431, Argentina
Gustavo Romero, Hospital Udaondo, Cuidad Autonoma de Buenos Aires C1264AAA, Argentina
Beatriz Ameigeiras, Hospital Ramos Mejía, Ciudad de Buenos Aires C1221ADC, Argentina
Claudia D’Amico, Centro Especialidades Medicas Ambulatorias (CEMA), Mar del Plata, Buenos Aires 7600, Argentina
Luis Gaite, Clínica de Nefrología, Santa Fe 3000, Argentina
Virginia Reggiardo, Hospital del Centenario, Rosario, Santa Fe S2002KDT, Argentina
Author contributions: Piñero F, Silva M contributed to concept and design, writing of article; Marciano S, Fernández N, Silva J, Anders M, Zerega A, Ridruejo E, Ameigeiras B, D’amico C, Gaite L, Bermúdez C, Romero G, Reggiardo V, Colombato L and Gadano A contributed to data recording, critical review of the manuscript; Piñero F contributed to statistical analysis.
Institutional review board statement: The study was reviewed and approved by the Austral University, School of Medicine and the Bioethics Institutional Committee of the Austral University Hospital (CIE approval study protocol number 14-039) and from each Bioethics Institutional Committee from all participating centers.
Informed consent statement: All study participants from the prospective cohort, or their legal guardian, provided informed written consent prior to the study enrollment. From the retrospective cohort, all study investigators signed a confidential agreement. We submit the informed consent (IC) and it’s Spanish version approved by the Austral University, School of Medicine and the Bioethics Institutional Committee of the Austral University Hospital (CIE approval study protocol number 14-039).
Conflict-of-interest statement: Piñero F has received Advisory Board and speaker honoraria and he is consultant for BAYER Cono Sur; research grants from the Argentinean National Institute of Cancer (INC ID-190), Argentinean National Ministry of Science and Technology Development (PICT 2017, FONCYT) and from the Latin American Liver Research Educational and Awareness Network (LALREAN). Silva M has received has received speaker honoraria and is a consultant for Abvie, Gador, Bristol-Myers Squibb, Merck, BAYER and research grants from the Argentinean National Institute of Cancer (INC ID-190), Argentinean National Ministry of Science and Technology Development (PICT 2017, FONCYT).
STROBE statement: All procedures followed were in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Federico Piñero, MD, MSc, Academic Research, Doctor, Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Av. Presidente Perón 1500, Pilar, Buenos Aires B1629HJ, Argentina. fpinerof@cas.austral.edu.ar
Telephone: +54-230-4482000 Fax: +54-230-4482236
Received: March 19, 2019
Peer-review started: March 19, 2019
First decision: April 30, 2019
Revised: May 5, 2019
Accepted: June 25, 2019
Article in press: June 26, 2019
Published online: July 21, 2019
Processing time: 122 Days and 10.6 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.

AIM

To describe real-life treatments performed in patients with intermediate-advanced HCC before the approval of new systemic options.

METHODS

This longitudinal observational cohort study was conducted between 2009 and 2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer (BCLC) HCC stages (BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios (HR) calculations and 95% confidence intervals (95%CI).

RESULTS

From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D. Corresponding median survival were 15 mo (IQR 5-26 mo), 5 mo (IQR 2-13 mo) and 3 mo (IQR 1-13 mo) (P < 0.0001), respectively. Among BCLC-B patients (n = 135), 57% received TACE with a median number of 2 sessions (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR = 0.29 (CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15 (CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C (87.8%). However, 12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo (IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients, treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013].

CONCLUSION

In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.

Keywords: Hepatocellular carcinoma; Therapeutics; Survival; Real-life

Core tip: Trans-arterial chemoembolization and systemic treatment with sorafenib or lenvatinib are the standards of treatment for patients with intermediate and advanced stage hepatocellular carcinoma (HCC). The rise of new current therapeutic modalities such as radioembolization, the combination of antiangiogenic agents with locoregional therapies and other first and second line systemic options, open up a new paradigm for the treatment of HCC. In this dual cohort study, we describe the treatments performed in the real life setting before the approval of these new systemic options. Our real-data outcomes, lower than expected, highlight unmet needs and improvement areas in the daily practice prior to the introduction of new treatments for HCC.