Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3607
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
Although liver cancer or hepatocellular carcinoma (HCC) is currently the 5th most common cancer and the 2nd cause of death from cancer worldwide, in Argentina represents the sixteenth most frequent cancer. Transarterial chemoembolization (TACE) and systemic treatment with sorafenib are the standards of treatment for patients with intermediate and advanced stage HCC.
The rise of new therapeutic modalities such as radioembolization, the combination of antian-giogenic agents with locoregional therapies and other first and second line systemic options, open up a new paradigm for the treatment of HCC.
Our aim was to describe the treatments performed in the real life setting before the approval of these new systemic options.
This longitudinal observational cohort study was conducted between in 14 different regional hospitals from Argentina between 2009 and 2016. Study data were registered into a web-based electronic system. Patients with intermediate (BCLC-B) or advanced (BCLC C-D) HCC were included. Patients were excluded if (1) clinical baseline data was missing; (2) BCLC stage was either 0 or A, in which potentially curative treatments are recommended such as liver resection (LR), percutaneous ethanol injection (PEI)/radiofrequency ablation (RFA) or liver transpla-ntation (LT); and (3) patients with BCLC-B-D who underwent liver transplantation. Baseline tumor and patients characteristics at HCC diagnosis, as well as treatments performed were registered. Each treatment was discussed at each center on a case-by-case basis. Imaging tumor reassessment after treatments were done according to RECIST 1.1 criteria as recommended by international Western guidelines. Median survival was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. For survival analysis, Cox regression analysis estimating hazard ratios (HR) and 95%CI for baseline variables related with mortality was performed. Kaplan Meier survival curves were compared using the log-rank test (Mantel-Cox).
A total of 327 consecutive adult patients with intermediate and advanced HCC were included, of which 41.3% of the patients were in BCLC stage B (n = 135), 19.9% in stage C (n = 65) and 38.8% in stage D (n = 127). Corresponding median survival for BCLC stages were as follows: Stage B 15 mo (IQR 5-26 mo), stage C 5 mo (IQR 2-13 mo) and stage D 3 mo (IQR 1-13 mo)(Figure 1). TACE was performed in 126 patients (38.5%); 77 were BCLC-B, 22 were BCLC-C and 27 patients were BCLC-C. Among BCLC-B patients (n = 135), 57% received TACE (n = 77) whereas 43% did not (Table 2). Median number of TACEs sessions was 2 (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR 0.29 (CI: 0.21-0.40) with a median survival of 15 mo (IQR 7-25 mo), when compared with BCLC-B without TACE and BCLC-C or D patients treated with TACE. According to tumor reassessment after the first TACE by RECIST 1.1 criteria, patients with complete response (CR) achieved a better overall survival with a HR of 0.15 (CI: 0.04-0.56, P = 0.005). Table 3 describes baseline patient characteristic treated with sorafenib (n = 82). Of these, 43.9% were BCLC-B, 43.9% BCLC-C and 12.2% BCLC-D. Among BCLC-B patients who received sorafenib, 15 were TACE naïve and 21 received a median number of TACEs of 3 (IQR 2-4) until disease progression (n = 7) or no response or un-TACE-able (n = 14). Among BCLC-C patients (n = 65), 55.4% were treated with sorafenib and those not treated with sorafenib received BSC (n = 21) and other treatments (4 patients TACE, 1 TARE and patients 3 LR). Corresponding median survival in all patients treated with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); 5.2 mo (IQR 3.7-12.6 mo) in BCLC-B, 3.8 mo (IQR 1.9-9.9 mo) in BCLC-C and 3.2 mo (IQR 2.0-14.1 mo) in BCLC-D. In BCLC-B patients treated with sorafenib after progression (n = 36), the sequential treatment of sorafenib following TACE presented better survival since systemic treatment when compared to those patients who received sorafenib without prior treatment with TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013].
In conclusion, in this dual cohort study from Argentina, we describe the treatments performed in the real life setting before the approval of new systemic options.
Knowing the real life setting is of interest, in order to assess the most common therapeutic decision making processes and management in these patients. Our results highlights unmet needs and improvement areas in public health among developing regions such as Argentina, particularly to promote early and correct treatments in each stage, prior to the introduction of new treatments for HCC.