Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 28, 2017; 9(36): 1322-1331
Published online Dec 28, 2017. doi: 10.4254/wjh.v9.i36.1322
Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma
Francesca Romana Ponziani, Irene Spinelli, Emanuele Rinninella, Lucia Cerrito, Antonio Saviano, Alfonso Wolfango Avolio, Michele Basso, Luca Miele, Laura Riccardi, Maria Assunta Zocco, Brigida Eleonora Annicchiarico, Matteo Garcovich, Marco Biolato, Giuseppe Marrone, Anna Maria De Gaetano, Roberto Iezzi, Felice Giuliante, Fabio Maria Vecchio, Salvatore Agnes, Giovanni Addolorato, Massimo Siciliano, Gian Lodovico Rapaccini, Antonio Grieco, Antonio Gasbarrini, Maurizio Pompili
Francesca Romana Ponziani, Irene Spinelli, Emanuele Rinninella, Lucia Cerrito, Antonio Saviano, Luca Miele, Laura Riccardi, Maria Assunta Zocco, Brigida Eleonora Annicchiarico, Matteo Garcovich, Marco Biolato, Giuseppe Marrone, Giovanni Addolorato, Massimo Siciliano, Gian Lodovico Rapaccini, Antonio Grieco, Antonio Gasbarrini, Maurizio Pompili, Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
Alfonso Wolfango Avolio, Salvatore Agnes, Department of Liver Transplant Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
Michele Basso, Department of Oncology, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
Anna Maria De Gaetano, Roberto Iezzi, Department of Bioimaging and Radiological Sciences, Agostino Gemelli Hospital, Rome 00168, Italy
Felice Giuliante, Department of Hepatobiliary Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
Fabio Maria Vecchio, Department of Pathology, Agostino Gemelli Hospital, Rome 00168, Italy
Author contributions: Ponziani FR designed and performed the research, collected data, wrote the paper, performed statistical analysis, revised and approved the final version of the paper; Spinelli I collected data, wrote the paper, revised and approved the final version of the paper; Pompili M, Avolio AW, Siciliano M, Basso M and Miele L contributed to statistical analysis, wrote the paper, revised and approved the final version of the paper; Rinninella E, Cerrito L, Saviano A, Riccardi L, Zocco MA, Annicchiarico BE, Garcovich M, Biolato M, Marrone G, De Gaetano AM, Iezzi R, Giuliante F, Vecchio FM, Agnes S, Addolorato G, Rapaccini GL, Grieco A and Gasbarrini A contributed to this paper.
Institutional review board statement: This is a retrospective study based on the revision of anonymous clinical data; no additional interventional procedures or drug was performed/administered to the study population. Therefore, no institutional review board approval was required.
Informed consent statement: This is a retrospective study based on the revision of anonymous clinical data; no additional interventional procedures or drug was performed/administered to the study population. Therefore, no informed consent was obtained by the patients.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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/
Correspondence to: Dr. Francesca Romana Ponziani, MD, Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Largo Agostino Gemelli 8, Rome 00168, Italy. francesca.ponziani@yahoo.it
Telephone: +39-34-71227242
Received: August 27, 2017
Peer-review started: August 30, 2017
First decision: September 21, 2017
Revised: October 12, 2017
Accepted: November 11, 2017
Article in press: November 12, 2017
Published online: December 28, 2017
Processing time: 121 Days and 18.7 Hours
Abstract
AIM

To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC).

METHODS

The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded.

RESULTS

One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).

CONCLUSION

The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients’ survival confers them as useful predictive tools for treatment management and clinical decisions.

Keywords: Hepatocellular carcinoma; Cirrhosis; Barcelona Clinic Liver Cancer stage C; Alphafetoprotein; Disease control; Performance status; Survival

Core tip: Refining the prognosis of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) is crucial to select patients that can get benefit from and be suitable for locoregional or surgical treatments. This study confirms that high alphafetoprotein serum level and DC are the best predictors of mortality for BCLC C patients, highlighting that the effect of these two variables is reverse and dynamic, in a time dependent manner. Outstandingly, performance status has not been found to be a strong predictor of mortality. According to our results, curative treatments should not be “a priori” excluded in a subset of BCLC stage C patients with favorable prognostic factors.