Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy

Bernhard Scheiner^{1

2}, Beodeul Kang³, Lorenz Balcar^{1

2}, Iuliana-Pompilia Radu⁴, Florian P Reiter⁵, Gordan Adžić⁶, Jiang Guo⁷, Xu Gao^{8

9}, Xiao Yuan⁸, Long Cheng⁷, Joao Gorgulho¹⁰, Michael Schultheiss¹¹, Frederik Peeters¹², Florian Hucke¹³, Najib Ben Khaled¹⁴, Ignazio Piseddu¹⁴, Alexander Philipp¹⁴, Friedrich Sinner¹⁵, Antonio D'Alessio^{16

17}, Katharina Pomej^{1

2}, Anna Saborowski¹⁸, Melanie Bathon¹⁸, Birgit Schwacha-Eipper⁴, Valentina Zarka⁵, Katharina Lampichler¹⁹, Naoshi Nishida²⁰, Pei-Chang Lee²¹, Anja Krall²², Anwaar Saeed²³, Vera Himmelsbach²⁴, Giulia Tesini^{25

26}, Yi-Hsiang Huang^{27

28}, Caterina Vivaldi^{29

30}, Gianluca Masi³⁰, Arndt Vogel^{31

32

33}, Kornelius Schulze³⁴, Michael Trauner¹, Angela Djanani³⁵, Rudolf Stauber²², Masatoshi Kudo²⁰, Neehar D Parikh³⁶, Jean-François Dufour³⁷, Juraj Prejac^{6

38}, Andreas Geier⁵, Bertram Bengsch^{11

39}, Johann von Felden³⁴, Marino Venerito¹⁵, Arndt Weinmann⁴⁰, Markus Peck-Radosavljevic¹³, Fabian Finkelmeier²⁴, Jeroen Dekervel¹², Fanpu Ji^{8

41}, Hung-Wei Wang⁴², Lorenza Rimassa^{25

26}, David J Pinato^{16

17}, Mohamed Bouattour⁴³, Hong Jae Chon³, Matthias Pinter^{1

2}

Affiliations

¹ Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
² Liver Cancer (HCC) Study Group Vienna, Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
³ Department of Internal Medicine, Division of Medical Oncology, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea.
⁴ Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵ Department of Medicine II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany.
⁶ Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia.
⁷ Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁸ Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁹ Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁰ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany.
¹¹ Department of Medicine II, Medical Center-University of Freiburg, Germany, Faculty of Medicine, University of Freiburg, Germany.
¹² Department of Gastroenterology and Hepatology, University Hospitals Leuven, Herestraat, Leuven, Belgium.
¹³ Internal Medicine and Gastroenterology (IMuG), including Centralized Emergency Service (ZAE), Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
¹⁴ Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.
¹⁵ Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von Guericke University Hospital, Magdeburg, Germany.
¹⁶ Department of Surgery and Cancer, Division of Cancer, Imperial College London, London, United Kingdom.
¹⁷ Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy.
¹⁸ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
¹⁹ Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
²⁰ Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka, Japan.
²¹ Department of Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
²² Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
²³ Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh (UPMC), Pittsburgh, Pennsylvania, USA.
²⁴ Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/Main, Germany.
²⁵ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy.
²⁶ Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
²⁷ Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
²⁸ Healthcare and Services Center, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
²⁹ Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
³⁰ Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
³¹ Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Canada.
³² Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
³³ Hannover Medical School, Hannover, Germany.
³⁴ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁵ Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
³⁶ Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
³⁷ Centre for Digestive Diseases, Lausanne, Switzerland.
³⁸ University of Zagreb, School of Dental Medicine, Zagreb, Croatia.
³⁹ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
⁴⁰ Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁴¹ Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, China.
⁴² Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan.
⁴³ Liver Cancer and Innovative Therapy, AP-HP, Hôpital Beaujon, Clichy, France.

PMID: 39643944
DOI: 10.1097/HEP.0000000000001163

Multicenter Study

Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy

Bernhard Scheiner et al. Hepatology. 2025.

. 2025 Jun 1;81(6):1714-1727.

doi: 10.1097/HEP.0000000000001163. Epub 2024 Nov 21.

Authors

Affiliations

¹ Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
² Liver Cancer (HCC) Study Group Vienna, Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
³ Department of Internal Medicine, Division of Medical Oncology, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea.
⁴ Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵ Department of Medicine II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany.
⁶ Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia.
⁷ Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁸ Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁹ Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁰ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany.
¹¹ Department of Medicine II, Medical Center-University of Freiburg, Germany, Faculty of Medicine, University of Freiburg, Germany.
¹² Department of Gastroenterology and Hepatology, University Hospitals Leuven, Herestraat, Leuven, Belgium.
¹³ Internal Medicine and Gastroenterology (IMuG), including Centralized Emergency Service (ZAE), Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
¹⁴ Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.
¹⁵ Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von Guericke University Hospital, Magdeburg, Germany.
¹⁶ Department of Surgery and Cancer, Division of Cancer, Imperial College London, London, United Kingdom.
¹⁷ Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy.
¹⁸ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
¹⁹ Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
²⁰ Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka, Japan.
²¹ Department of Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
²² Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
²³ Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh (UPMC), Pittsburgh, Pennsylvania, USA.
²⁴ Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt/Main, Germany.
²⁵ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy.
²⁶ Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
²⁷ Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
²⁸ Healthcare and Services Center, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
²⁹ Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
³⁰ Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
³¹ Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Canada.
³² Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
³³ Hannover Medical School, Hannover, Germany.
³⁴ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁵ Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
³⁶ Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
³⁷ Centre for Digestive Diseases, Lausanne, Switzerland.
³⁸ University of Zagreb, School of Dental Medicine, Zagreb, Croatia.
³⁹ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
⁴⁰ Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁴¹ Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, China.
⁴² Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan.
⁴³ Liver Cancer and Innovative Therapy, AP-HP, Hôpital Beaujon, Clichy, France.

PMID: 39643944
DOI: 10.1097/HEP.0000000000001163

Abstract

Background and aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)-based systemic therapies is unclear.

Approach and results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.4%) achieved CR-mRECIST, and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; Barcelona-Clinic Liver Cancer-C, 70%) was 65.9±9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95% CI: 29.9-34.4) months. One- and 3-year overall survival rates were 98% and 86%. One- and 3-year recurrence-free survival rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥6 months after the first mRECIST CR had a longer recurrence-free survival than those who discontinued immunotherapy earlier ( p =0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n= 2/2; CR-mRECIST-only, n= 6/7).

Conclusions: Overall survival and recurrence-free survival of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable.

Keywords: RECIST; immune checkpoint inhibitor; liver cancer; systemic therapy.

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References

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Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy

Affiliations

Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy

Authors

Affiliations

Abstract

References

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LinkOut - more resources

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Medical