Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2021; 27(24): 3630-3642
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3630
High rate of complete histopathological response in hepatocellular carcinoma patients after combined transarterial chemoembolization and stereotactic body radiation therapy
Ulrike Bauer, Sabine Gerum, Falk Roeder, Stefan Münch, Stephanie E Combs, Alexander B Philipp, Enrico N De Toni, Martha M Kirstein, Arndt Vogel, Carolin Mogler, Bernhard Haller, Jens Neumann, Rickmer F Braren, Marcus R Makowski, Philipp Paprottka, Markus Guba, Fabian Geisler, Roland M Schmid, Andreas Umgelter, Ursula Ehmer
Ulrike Bauer, Fabian Geisler, Roland M Schmid, Andreas Umgelter, Ursula Ehmer, Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany
Sabine Gerum, Falk Roeder, Department of Radiotherapy and Radiation Oncology, University of Salzburg, Salzburg 5020, Austria
Sabine Gerum, Falk Roeder, Department of Radiation Oncology, University Hospital of Munich, Campus Großhadern, LMU Munich, Munich 81377, Germany
Stefan Münch, Stephanie E Combs, Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany
Alexander B Philipp, Enrico N De Toni, Department of Medicine II, Liver Centre, University Hospital, LMU Munich, Munich 81377, Germany
Martha M Kirstein, Arndt Vogel, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, Germany
Carolin Mogler, Institute of Pathology, Technical University of Munich, Munich 81675, Germany
Bernhard Haller, Institute of Medical Informatics, Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany
Jens Neumann, Institute of Pathology, Faculty of Medicine, University Hospital of Munich, Munich 81377, Germany
Rickmer F Braren, Marcus R Makowski, Institute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany
Philipp Paprottka, Institute of Diagnostic and Interventional Radiology, Section for Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany
Markus Guba, Department of General-, Visceral-, Vascular- and Transplant-Surgery, University hospital of Munich, Campus Großhadern, LMU Munich, Munich 81377, Germany
Andreas Umgelter, Emergency Department, Vivantes hospital group, Humboldt hospital, Berlin 13509, Germany
Author contributions: Bauer U, Gerum S, Roeder F, Münch S, Combs SE, Philipp AB, De Toni EN, Kirstein MM, Vogel A, Paprottka P, Guba M, Geisler F, Schmid RM, Umgelter A, and Ehmer U analyzed data; Bauer U, Gerum S, Münch S, Mogler C, Neumann J, Braren RF, Makowski MR, and Ehmer U designed and reviewed figures; Combs SE, De Toni EN, Vogel A, Haller B, Braren RF, Makowski MR, Geisler F, Schmid RM, and Umgelter A critically revised the manuscript; Bauer U, Gerum S, Schmid RM, Umgelter A and Ehmer U concepted the study; Bauer U and Ehmer U wrote the manuscript.
Institutional review board statement: This study was reviewed and approved by the local Ethics Committee of each participating center.
Informed consent statement: We performed a retrospective analysis and all data were completely anonymized for analysis and storage. In addition, there was no risk for the subjects as our study was a retrospective analysis of patients treated with standard of care procedures. According to local ethics committees there is no informed consent required given the retrospective study design, anonymous data analysis, and lack of any risks for the subjects in this study.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available as they could compromise the privacy of research participants.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Ursula Ehmer, MD, PhD, Doctor, Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 21, Munich 81675, Germany. ursula.ehmer@tum.de
Received: February 5, 2021
Peer-review started: February 5, 2021
First decision: March 6, 2021
Revised: March 20, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: June 28, 2021
Abstract
BACKGROUND

Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology.

AIM

To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone.

METHODS

In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests.

RESULTS

Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001).

CONCLUSION

Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.

Keywords: Hepatocellular carcinoma, Transarterial chemoembolization, Stereotactic body radiation therapy, Bridging therapy, Liver transplantation

Core Tip: In patients with early-stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation, liver transplantation presents a curative treatment option. To halt tumor growth during waiting time, bridging therapies such as transarterial chemoembolization (TACE), ablation, and stereotactic body radiation therapy (SBRT) are used prior to liver transplantation. In a multicenter retrospective trial with 27 HCC patients who received either TACE or SBRT alone, or a combination of TACE and SBRT, explant histopathology was analyzed to assess treatment response. Strikingly, almost all patients in the combination group exhibited no residual vital tumor by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response.