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  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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    Editor-in-Chief
    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
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    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
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Letter to the Editor

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Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

Hyung Joon Yim , Young Eun Ahn , Tae Hyung Kim , Young Kul Jung

Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea

Correspondence to: Hyung Joon Yim
ORCID https://orcid.org/0000-0002-6036-2754
E-mail gudwns21@korea.ac.kr

Received: December 12, 2022; Accepted: December 20, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2023;17(2):341-342. https://doi.org/10.5009/gnl220522

Published online February 15, 2023, Published date March 15, 2023

Copyright © Gut and Liver.

Reply:

We appreciate the letter from Deng and colleagues regarding our study.

They raised several questions related to the treatment of hepatocellular carcinoma with sorafenib or hepatic arterial infusion chemotherapy (HAIC).1

First, they were curious about combination therapies. As we described in the combination and second-line therapy section, patients in the HAIC group more frequently (68%) received combination such as transarterial chemolipiodolization (15.3%), radiotherapy (26.3%), or both therapies (23.7%) as well as radiotherapy plus percutaneous ethanol injection (2.6%). Among the patients in the sorafenib group, only 17% received combination therapy using transarterial chemolipiodolization (5.7%) and radiotherapy (11.4%). To prevent ischemic insults to the liver in the presence of portal vein tumor thrombosis, we chose transarterial chemolipiodolization for patients needing local tumor control.2 However, overall survival or time to progression was not different between the monotherapy and combination therapy groups. During the study period, as there was no approved immune-oncologic agent, we did not have a chance to evaluate the combination of HAIC with immunotherapies such as atezolizumab plus bevacizumab. However, this is an interesting topic that has recently yielded favorable data, so further evaluation of HAIC in combination with the newer drugs is warranted.3

Second, treatment-associated adverse events were more common in the HAIC group than in the sorafenib group. Most grade 3 or 4 adverse events were hematologic or port-related events, which are mostly manageable.1 Regarding the underlying liver function and performance, one-third had Child-Pugh class B and another one-third showed Eastern Cooperative Oncology Group grade 2 or 3 status in our study. These patients were associated with worse survival than those with well-preserved liver function and performance status as Deng and colleagues indicated. However, we cannot exclude these patients from the treatment in the real-life setting as their survival is too short with supportive care only. In our study, compared with sorafenib, HAIC showed trends of benefit in overall survival in patients with Child-Pugh B liver function (5.9 months vs 15.3 months for Child-Pugh 7 and 3.4 months vs 5.9 months for Child-Pugh 8 or 9) and performance status 3 (0.8 months vs 6.3 months, respectively).1 However, there were no statistical differences, suggesting further studies with lager number of patients are needed in these subgroups of the population.

Third, although we used cisplatin and 5-fluorouracil for HAIC, there are reports of combining new cytotoxic agents such as oxaliplatin.4,5 We appreciate the suggestion of performing HAIC using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin), which significantly improved overall survival over sorafenib. Furthermore, improved local tumor control with HAIC may lead to listing the patients for liver transplantation with expanding indications.6

In conclusion, we agree with the opinion on further evaluating HAIC plus systemic therapy and considering the switch of the HAIC regimen from cisplatin plus 5-fluorouracil to FOLFOX.

No potential conflict of interest relevant to this article was reported.

  1. Ahn YE, Suh SJ, Yim HJ, et al. Comparison of sorafenib versus hepatic arterial infusion chemotherapy-based treatment for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Gut Liver 2021;15:284-294.
    Pubmed KoreaMed CrossRef
  2. Woo HY, Heo J. New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2015;21:115-121.
    Pubmed KoreaMed CrossRef
  3. Xin Y, Cao F, Yang H, et al. Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Front Immunol 2022;13:929141.
    Pubmed KoreaMed CrossRef
  4. He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol 2019;5:953-960.
    Pubmed KoreaMed CrossRef
  5. Lyu N, Kong Y, Mu L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol 2018;69:60-69.
    Pubmed CrossRef
  6. Chu KK, Wong KH, Chok KS. Expanding indications for liver transplant: tumor and patient factors. Gut Liver 2021;15:19-30.
    Pubmed KoreaMed CrossRef

Article

Letter to the Editor

Gut and Liver 2023; 17(2): 341-342

Published online March 15, 2023 https://doi.org/10.5009/gnl220522

Copyright © Gut and Liver.

Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

Hyung Joon Yim , Young Eun Ahn , Tae Hyung Kim , Young Kul Jung

Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea

Correspondence to:Hyung Joon Yim
ORCID https://orcid.org/0000-0002-6036-2754
E-mail gudwns21@korea.ac.kr

Received: December 12, 2022; Accepted: December 20, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

Reply:

We appreciate the letter from Deng and colleagues regarding our study.

They raised several questions related to the treatment of hepatocellular carcinoma with sorafenib or hepatic arterial infusion chemotherapy (HAIC).1

First, they were curious about combination therapies. As we described in the combination and second-line therapy section, patients in the HAIC group more frequently (68%) received combination such as transarterial chemolipiodolization (15.3%), radiotherapy (26.3%), or both therapies (23.7%) as well as radiotherapy plus percutaneous ethanol injection (2.6%). Among the patients in the sorafenib group, only 17% received combination therapy using transarterial chemolipiodolization (5.7%) and radiotherapy (11.4%). To prevent ischemic insults to the liver in the presence of portal vein tumor thrombosis, we chose transarterial chemolipiodolization for patients needing local tumor control.2 However, overall survival or time to progression was not different between the monotherapy and combination therapy groups. During the study period, as there was no approved immune-oncologic agent, we did not have a chance to evaluate the combination of HAIC with immunotherapies such as atezolizumab plus bevacizumab. However, this is an interesting topic that has recently yielded favorable data, so further evaluation of HAIC in combination with the newer drugs is warranted.3

Second, treatment-associated adverse events were more common in the HAIC group than in the sorafenib group. Most grade 3 or 4 adverse events were hematologic or port-related events, which are mostly manageable.1 Regarding the underlying liver function and performance, one-third had Child-Pugh class B and another one-third showed Eastern Cooperative Oncology Group grade 2 or 3 status in our study. These patients were associated with worse survival than those with well-preserved liver function and performance status as Deng and colleagues indicated. However, we cannot exclude these patients from the treatment in the real-life setting as their survival is too short with supportive care only. In our study, compared with sorafenib, HAIC showed trends of benefit in overall survival in patients with Child-Pugh B liver function (5.9 months vs 15.3 months for Child-Pugh 7 and 3.4 months vs 5.9 months for Child-Pugh 8 or 9) and performance status 3 (0.8 months vs 6.3 months, respectively).1 However, there were no statistical differences, suggesting further studies with lager number of patients are needed in these subgroups of the population.

Third, although we used cisplatin and 5-fluorouracil for HAIC, there are reports of combining new cytotoxic agents such as oxaliplatin.4,5 We appreciate the suggestion of performing HAIC using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin), which significantly improved overall survival over sorafenib. Furthermore, improved local tumor control with HAIC may lead to listing the patients for liver transplantation with expanding indications.6

In conclusion, we agree with the opinion on further evaluating HAIC plus systemic therapy and considering the switch of the HAIC regimen from cisplatin plus 5-fluorouracil to FOLFOX.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References

  1. Ahn YE, Suh SJ, Yim HJ, et al. Comparison of sorafenib versus hepatic arterial infusion chemotherapy-based treatment for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Gut Liver 2021;15:284-294.
    Pubmed KoreaMed CrossRef
  2. Woo HY, Heo J. New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2015;21:115-121.
    Pubmed KoreaMed CrossRef
  3. Xin Y, Cao F, Yang H, et al. Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Front Immunol 2022;13:929141.
    Pubmed KoreaMed CrossRef
  4. He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol 2019;5:953-960.
    Pubmed KoreaMed CrossRef
  5. Lyu N, Kong Y, Mu L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol 2018;69:60-69.
    Pubmed CrossRef
  6. Chu KK, Wong KH, Chok KS. Expanding indications for liver transplant: tumor and patient factors. Gut Liver 2021;15:19-30.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.18 No.3
May, 2024

pISSN 1976-2283
eISSN 2005-1212

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