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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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Clinical Parameters Work Well as Predictive Factors for Atezolizumab and Bevacizumab Treatment in Hepatocellular Carcinoma

Ji Yeon Lee1,2 , Pil Soo Sung1,2

1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Internal Medicine, Seoul St. Mary’s Hospital, Seoul, Korea

Correspondence to: Pil Soo Sung
ORCID https://orcid.org/0000-0002-5780-9607
E-mail pssung@catholic.ac.kr

See “ Analysis of Factors Predicting the Real-World Efficacy of Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma” by Byeong Geun Song, et al. on page 709, Vol. 18, No. 4, 2024

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 2024;18(4):558-559. https://doi.org/10.5009/gnl240274

Published online July 15, 2024, Published date July 15, 2024

Copyright © Gut and Liver.

More than half of patients are diagnosed with hepatocellular carcinoma (HCC) that is unresectable and requires chemoembolization or systemic treatment.1 The IMbrave150 trial established a combination treatment of atezolizumab and bevacizumab as the first-line treatment for advanced HCC, showing significantly improved overall survival and progression-free survival (PFS) compared with sorafenib in patients with unresectable HCC.2

Research to identify biomarkers for the screening, diagnosis, and prediction of unresectable HCC is ongoing. For example, alpha-fetoprotein (AFP) has been studied extensively in relation to prognosis, with increased AFP values associated with poor prognosis in advanced HCC; however, controversy exists regarding the optimal cutoff value for AFP to predict poor prognosis.3 The ability to make a definitive diagnosis of HCC through radiographic evaluation alone, without histological confirmation, limits the need to obtain tumor tissue, resulting in a smaller sample size for tissue-based biomarkers and potentially reducing their reliability.4 Circulating tumor DNA, microRNA, and circulating tumor cells, which are obtained through liquid biopsy, have demonstrated potential as prognostic and predictive biomarkers for HCC.5,6 However, much of the evidence is derived from observational studies, and further validation is needed through additional research. Radiomics, an emerging concept that proposes the discovery of new associations between clinical data and quantitative data extracted from medical images using artificial intelligence, aims to provide guidance in clinical decision-making by predicting the phenotype and genotype of the underlying tissue.7 However, the reproducibility and repeatability of radiomic models are often poor owing to insufficient reporting and a lack of effective means to interpret extensive datasets. In summary, biopsy- and radiomics-based biomarkers have not shown a clear and consistent performance in daily clinical practice.

In this issue of Gut and Liver, Song et al.8 evaluated the real-world efficacy and safety of atezolizumab plus bevacizumab in advanced HCC patients. Their analysis showed that the albumin-bilirubin grade, age, C-reactive protein (CRP) and AFP in immunotherapy CRAFITY score, macrovascular invasion, lung metastases, and combined radiotherapy were significant predictors of PFS. The CRAFITY score, which assigns points based on the AFP (≥100 ng/mL)and CRP (≥1 ng/mL) levels, is known to predict overall survival and the radiological response in HCC patients undergoing immunotherapy with immune checkpoint inhibitors.9 It was also shown in Song et al.’s study to be an independent prognostic factor in the multivariate analysis; patients with higher CRAFITY scores showed a significantly shorter PFS than those with HCC undergoing atezolizumab plus bevacizumab treatment. The researchers also found that AFP levels were higher in the progressive disease group, but protein induced by vitamin K absence-II and CRP levels showed no significant differences across the best-response categories. Patients with peritoneal seeding demonstrated a higher likelihood of complete remission, and those receiving combined radiotherapy showed significantly better objective responses.

Overall, the study of Song et al.8 confirmed the efficacy of atezolizumab and bevacizumab for the treatment of advanced HCC in domestic clinical settings. Through a logistic regression analysis, the CRAFITY score emerged as a valuable tool for predicting PFS and overall prognosis in immunotherapy without invasive measures. Clinical parameters such as the Glasgow Prognosis Score, reflecting systemic inflammatory response and nutritional status, have shown similar prognostic utility across various types of cancers. It is a scoring tool based on serum concentrations of CRP and albumin and has been identified as a prognostic factor for inoperable gastroesophageal, pancreatic, and colorectal cancer.10

Clinical parameters work well as predictive and prognostic factors in various types of cancers treated with immune-based therapy, including advanced HCC. Further research is needed to refine these clinical parameters and validate their role in guiding personalized treatment decisions according to individual patient conditions.

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (grant number RS-2024-00337298 to P.S.S.).

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

  1. Cho Y, Kim BH, Park JW. Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: an Asian perspective comparison. Clin Mol Hepatol 2023;29:252-262.
    Pubmed KoreaMed CrossRef
  2. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.
    Pubmed CrossRef
  3. Kim DY, Toan BN, Tan CK, et al. Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region. Clin Mol Hepatol 2023;29:277-292.
    Pubmed KoreaMed CrossRef
  4. Park JG, Roh PR, Kang MW, et al. Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC. Hepatology. Epub 2024 Feb 15. https://doi.org/10.1097/HEP.0000000000000772
    CrossRef
  5. Sogbe M, Bilbao I, Marchese FP, et al. Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment. Clin Mol Hepatol 2024;30:177-190.
    Pubmed KoreaMed CrossRef
  6. Han JW, Jang JW. Predicting outcomes of atezolizumab and bevacizumab treatment in patients with hepatocellular carcinoma. Int J Mol Sci 2023;24:11799.
    Pubmed KoreaMed CrossRef
  7. Hwang SH, Rhee H. Radiologic features of hepatocellular carcinoma related to prognosis. J Liver Cancer 2023;23:143-156.
    Pubmed KoreaMed CrossRef
  8. Song BG, Goh MJ, Kang W, et al. Analysis of factors predicting the real-world efficacy of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. Gut Liver 2024;18:709-718.
    Pubmed CrossRef
  9. Scheiner B, Pomej K, Kirstein MM, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy: development and validation of the CRAFITY score. J Hepatol 2022;76:353-363.
    Pubmed CrossRef
  10. McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 2013;39:534-540.
    Pubmed CrossRef

Article

Editorial

Gut and Liver 2024; 18(4): 558-559

Published online July 15, 2024 https://doi.org/10.5009/gnl240274

Copyright © Gut and Liver.

Clinical Parameters Work Well as Predictive Factors for Atezolizumab and Bevacizumab Treatment in Hepatocellular Carcinoma

Ji Yeon Lee1,2 , Pil Soo Sung1,2

1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Internal Medicine, Seoul St. Mary’s Hospital, Seoul, Korea

Correspondence to:Pil Soo Sung
ORCID https://orcid.org/0000-0002-5780-9607
E-mail pssung@catholic.ac.kr

See “ Analysis of Factors Predicting the Real-World Efficacy of Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma” by Byeong Geun Song, et al. on page 709, Vol. 18, No. 4, 2024

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

More than half of patients are diagnosed with hepatocellular carcinoma (HCC) that is unresectable and requires chemoembolization or systemic treatment.1 The IMbrave150 trial established a combination treatment of atezolizumab and bevacizumab as the first-line treatment for advanced HCC, showing significantly improved overall survival and progression-free survival (PFS) compared with sorafenib in patients with unresectable HCC.2

Research to identify biomarkers for the screening, diagnosis, and prediction of unresectable HCC is ongoing. For example, alpha-fetoprotein (AFP) has been studied extensively in relation to prognosis, with increased AFP values associated with poor prognosis in advanced HCC; however, controversy exists regarding the optimal cutoff value for AFP to predict poor prognosis.3 The ability to make a definitive diagnosis of HCC through radiographic evaluation alone, without histological confirmation, limits the need to obtain tumor tissue, resulting in a smaller sample size for tissue-based biomarkers and potentially reducing their reliability.4 Circulating tumor DNA, microRNA, and circulating tumor cells, which are obtained through liquid biopsy, have demonstrated potential as prognostic and predictive biomarkers for HCC.5,6 However, much of the evidence is derived from observational studies, and further validation is needed through additional research. Radiomics, an emerging concept that proposes the discovery of new associations between clinical data and quantitative data extracted from medical images using artificial intelligence, aims to provide guidance in clinical decision-making by predicting the phenotype and genotype of the underlying tissue.7 However, the reproducibility and repeatability of radiomic models are often poor owing to insufficient reporting and a lack of effective means to interpret extensive datasets. In summary, biopsy- and radiomics-based biomarkers have not shown a clear and consistent performance in daily clinical practice.

In this issue of Gut and Liver, Song et al.8 evaluated the real-world efficacy and safety of atezolizumab plus bevacizumab in advanced HCC patients. Their analysis showed that the albumin-bilirubin grade, age, C-reactive protein (CRP) and AFP in immunotherapy CRAFITY score, macrovascular invasion, lung metastases, and combined radiotherapy were significant predictors of PFS. The CRAFITY score, which assigns points based on the AFP (≥100 ng/mL)and CRP (≥1 ng/mL) levels, is known to predict overall survival and the radiological response in HCC patients undergoing immunotherapy with immune checkpoint inhibitors.9 It was also shown in Song et al.’s study to be an independent prognostic factor in the multivariate analysis; patients with higher CRAFITY scores showed a significantly shorter PFS than those with HCC undergoing atezolizumab plus bevacizumab treatment. The researchers also found that AFP levels were higher in the progressive disease group, but protein induced by vitamin K absence-II and CRP levels showed no significant differences across the best-response categories. Patients with peritoneal seeding demonstrated a higher likelihood of complete remission, and those receiving combined radiotherapy showed significantly better objective responses.

Overall, the study of Song et al.8 confirmed the efficacy of atezolizumab and bevacizumab for the treatment of advanced HCC in domestic clinical settings. Through a logistic regression analysis, the CRAFITY score emerged as a valuable tool for predicting PFS and overall prognosis in immunotherapy without invasive measures. Clinical parameters such as the Glasgow Prognosis Score, reflecting systemic inflammatory response and nutritional status, have shown similar prognostic utility across various types of cancers. It is a scoring tool based on serum concentrations of CRP and albumin and has been identified as a prognostic factor for inoperable gastroesophageal, pancreatic, and colorectal cancer.10

Clinical parameters work well as predictive and prognostic factors in various types of cancers treated with immune-based therapy, including advanced HCC. Further research is needed to refine these clinical parameters and validate their role in guiding personalized treatment decisions according to individual patient conditions.

ACKNOWLEDGEMENTS

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (grant number RS-2024-00337298 to P.S.S.).

CONFLICTS OF INTEREST

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

References

  1. Cho Y, Kim BH, Park JW. Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: an Asian perspective comparison. Clin Mol Hepatol 2023;29:252-262.
    Pubmed KoreaMed CrossRef
  2. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.
    Pubmed CrossRef
  3. Kim DY, Toan BN, Tan CK, et al. Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region. Clin Mol Hepatol 2023;29:277-292.
    Pubmed KoreaMed CrossRef
  4. Park JG, Roh PR, Kang MW, et al. Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC. Hepatology. Epub 2024 Feb 15. https://doi.org/10.1097/HEP.0000000000000772
    CrossRef
  5. Sogbe M, Bilbao I, Marchese FP, et al. Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment. Clin Mol Hepatol 2024;30:177-190.
    Pubmed KoreaMed CrossRef
  6. Han JW, Jang JW. Predicting outcomes of atezolizumab and bevacizumab treatment in patients with hepatocellular carcinoma. Int J Mol Sci 2023;24:11799.
    Pubmed KoreaMed CrossRef
  7. Hwang SH, Rhee H. Radiologic features of hepatocellular carcinoma related to prognosis. J Liver Cancer 2023;23:143-156.
    Pubmed KoreaMed CrossRef
  8. Song BG, Goh MJ, Kang W, et al. Analysis of factors predicting the real-world efficacy of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. Gut Liver 2024;18:709-718.
    Pubmed CrossRef
  9. Scheiner B, Pomej K, Kirstein MM, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy: development and validation of the CRAFITY score. J Hepatol 2022;76:353-363.
    Pubmed CrossRef
  10. McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 2013;39:534-540.
    Pubmed CrossRef
Gut and Liver

Vol.19 No.1
January, 2025

pISSN 1976-2283
eISSN 2005-1212

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