The CRAFITY score: A new guidepost for prognosis prediction in patients with hepatocellular carcinoma undergoing immunotherapy

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – development and validation of the CRAFITY scoreJournal of HepatologyVol. 76Issue 2PreviewImmunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need. Full-Text PDF Open AccessReply to: “The CRAFITY score: A new guidepost for prognosis prediction in patients with hepatocellular carcinoma undergoing immunotherapy”Journal of HepatologyVol. 76Issue 5PreviewWe thank Drs. Zhou, Yang, and Zhou for their great interest in our paper1 and for complimenting the design and presentation of our study published in Journal of Hepatology.2 We are happy to reply to the authors’ comments. Full-Text PDF We read with interest the study by Scheiner and colleagues, who developed a simple and easy score based on serum alpha-fetoprotein (AFP ≥100 ng/ml) and C-reactive protein (CRP ≥1 mg/dl) to predict the prognosis in patients with hepatocellular carcinoma (HCC) undergoing immunotherapy with immune checkpoint blockers (ICBs), which is named “CRAFITY”.[1]Scheiner B. Pomej K. Kirstein M.M. Hucke F. Finkelmeier F. Waidmann O. et al.Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – development and validation of the CRAFITY score.J Hepatol. 2022; 76: 353-363Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar The CRAFITY score showed simplified and satisfactory stratification: patients with no criterion (0 points) had significantly longer overall survival (OS) and superior radiological response, followed by those fulfilling one criterion (1 point) and patients meeting both criteria (2 points). This study was well designed and clearly presented, and the CRAFITY score was easy to acquire and simple to use. Nevertheless, several vital aspects still need to be sufficiently demonstrated, considering that the CRAFITY score may serve as a guidepost for prognosis prediction in patients with HCC undergoing immunotherapy. First, it remains unknown whether the CRAFITY score outperforms existing prognostic models in patients with HCC undergoing immunotherapy. Moreover, discrimination and calibration should emphasize evaluating model performance rather than the difference in risk stratification.[2]Moons K.G.M. Kengne A.P. Woodward M. Royston P. Vergouwe Y. Altman D.G. et al.Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (Bio)marker.Heart. 2012; 98: 683-690Crossref PubMed Scopus (629) Google Scholar,[3]Steyerberg E.W. Vickers A.J. Cook N.R. Gerds T. Gonen M. Obuchowski N. et al.Assessing the performance of prediction models.Epidemiology. 2010; 21: 128-138Crossref PubMed Scopus (3015) Google Scholar Second, although both histological and radiological diagnoses are available, histological diagnosis is recommended for patients with HCC receiving immunotherapy.4NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers, Version 5. 2021https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdfDate accessed: November 16, 2021Google Scholar, 5Vogel A. Cervantes A. Chau I. Daniele B. Llovet J.M. Meyer T. et al.Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2018; 29: v238-v255Abstract Full Text Full Text PDF Scopus (588) Google Scholar, 6Llovet J.M. Kelley R.K. Villanueva A. Singal A.G. Pikarsky E. Roayaie S. et al.Hepatocellular carcinoma.Nat Rev Dis Primers. 2021; 7: 6Crossref PubMed Scopus (2259) Google Scholar, 7Greten T.F. Abou-Alfa G.K. Cheng A. Duffy A.G. El-Khoueiry A.B. Finn R.S. et al.Society for immunotherapy of cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma.J Immunother Cancer. 2021; 9e2794Crossref PubMed Scopus (37) Google Scholar Too many patients diagnosed radiologically may have misdiagnoses that will increase the selection bias. In addition, considering all missing values as disease progression may overstate the poor prognosis, which may misestimate the performance of the predictive model. It is better to show the proportion of radiological diagnosis and missing values. Third, CRP is an acute-phase protein that is synthesized by the liver and may increase following tissue injury or infection. Some diseases increasing CRP levels that are not related to HCC should be considered. Therefore, adjusting CRP points can optimize and improve the model performance. On the other hand, the additional inflammatory indices that are easily acquired should be integrated into the survival prediction model, such as neutrophil-to-lymphocyte ratio.[8]Hung H. Lee J. Wang Y. Cheng C. Wu T. Lee C. et al.Response prediction in immune checkpoint inhibitor immunotherapy for advanced hepatocellular carcinoma.Cancers. 2021; 13: 1607Crossref PubMed Scopus (18) Google Scholar,[9]Nakano M. Kuromatsu R. Niizeki T. Okamura S. Iwamoto H. Shimose S. et al.Immunological inflammatory biomarkers as prognostic predictors for advanced hepatocellular carcinoma.ESMO Open. 2021; 6: 100020Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Moreover, some indices reflecting liver function are important predictors of prognosis for patients with HCC, which help to build a more comprehensive and accurate prediction model. Last, but not least, since the characteristics of patients with HCC are heterogeneous in terms of liver function, treatment line and type of immunotherapy, subgroup analysis should be generally conducted to evaluate the effectiveness of using the CRAFITY score. The results of subgroup analysis will adequately reflect the predictive performance in different subgroups. In conclusion, the flaws do not detract from the jade's essential beauty. The CRAFITY score cannot be regarded as a simple “one-size-fits-all” approach. It has set a novel landmark for prognosis prediction in patients with HCC undergoing immunotherapy. Futural prospective studies need to further validate and compare the CRAFITY score with real-world big data. This study was supported by the Jiangsu Provincial Innovative and Entrepreneurial Doctor Program (303073543ER21). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. HFZ, WY and WZZ contributed equally to concept and writing of this article. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The authors thank Pro. Hai-Bin Shi and Pro. Sheng Liu from Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, for their comprehensive support. The following are the supplementary data to this article: Download .pdf (.22 MB) Help with pdf files Multimedia component 1