Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Vitale, Alessandro; Farinati, Fabio; Noaro, Giulia; Burra, Patrizia; Pawlik, Timothy M.; Bucci, Laura; Giannini, Edoardo G.; Faggiano, Chiara; Ciccarese, Francesca; Rapaccini, Gian Lodovico; Marco, Maria Di; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Sacco, Rodolfo; Cabibbo, Giuseppe; Virdone, Roberto; Marra, Fabio; Felder, Martina; Morisco, Filomena; Benvegnù, Luisa; Gasbarrini, Antonio; Svegliati‐Baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Colecchia, Antonio; Fornari, Fabio; Marignani, Massimo; Vicari, Susanna; Bortolini, Emanuela; Cozzolongo, Raffaele; Grasso, Alessandro; Aliberti, Camillo; Bernardi, Mauro; Frigo, Anna Chiara; Borzio, Mauro; Trevisani, Franco; Cillo, Umberto

doi:10.1002/hep.30185

Cited by 32 publications

(34 citation statements)

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“…First, the need to connect prognostic stages to specific therapeutic choices limits the prognostic power of the staging systems (prognostic problem). Further, the prognostic scores (such as ITA.LI.CA, MESIAH and CLIP), in fact, usually show a better discriminatory and predictive ability than the staging‐treatment schemes (ie BCLC, HKLC).…”

Section: Discussionmentioning

confidence: 99%

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The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

Vitale

Farinati

Pawlik

et al. 2019

Liver International

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Alessandro Vitale and Fabio Farinati equally contributed to this work.Prognosis and designing a treatment modality in patients with hepatocellular carcinoma (HCC) are extremely complex because, in most cases, this neoplasm is accompanied by the cirrhotic liver and other comorbidities. 1 Thus in such cases, tumour stage, the degree of liver function and general conditions of patients are the major deterministic factors. 2,3 A common and promising approach linking prognostic variables with therapeutic choice is to analyse large patient cohorts and, using treatment selection as the main endpoint, identify the fundamental treatment rules. An example of such a data-based approach is the HCC treatment schedule recently proposed by the Hong Kong Liver Cancer (HKLC) group. In this approach, Yau et al 4 applied an algorithm based on classification and regression tree statistical methodology to link the main treatment decision rules with HKLC tumour stages. The main limitation of this approach, however, was that the Key points• Using a large consecutive cohort of patients with hepatocellular carcinoma from Italy (n = 4,867), we showed that a clear therapeutic hierarchy exists irrespective of tumour stage, live function, patient general conditions and treatment period.• This therapeutic hierarchy, in order of survival benefit gain, follows liver transplantation, liver resection, ablation, intra-arterial therapies, systemic therapy and best supportive care.• The results of this study suggest that a personalized approach based on the therapeutic hierarchy concept should be pursued in the context of a multidisciplinary evaluation, for each patient with hepatocellular carcinoma, irrespective of the stage of the disease. AbstractBackground: The Italian Liver Cancer (ITA.LI.CA) prognostic system for patients with hepatocellular carcinoma (HCC) has recently been proposed and validated. We sought to explore the relationship among the ITA.LI.CA prognostic variables (ie tumour stage, functional score based on performance status and Child-Pugh score, and alpha-fetoprotein), treatment selection and survival outcome in HCC patients. Patients and Methods:We analysed 4,867 consecutive HCC patients undergoing six main treatment strategies (liver transplantation, LT; liver resection, LR; ablation, ABL; intra-arterial therapy, IAT; Sorafenib, SOR; and best supportive care, BSC) and enrolled during 2002-2015 in a multicenter Italian database. In order to control pretreatment imbalances in observed variables, a machine learning methodology was used and inverse probability of treatment weights (IPTW) was calculated. An IPTWadjusted multivariate survival model that included ITA.LI.CA prognostic variables, treatment period and treatment strategy was then developed. The survival benefit of HCC treatments was described as a hazard ratio (95% confidence interval), using BSC as a reference value and as predicted median survival.Results: After the IPTW, the six treatment groups became well balanced for most baseline characteristics. In the IPTW-adjust...

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Section: Discussionmentioning

confidence: 99%

“…Moreover, the ITA.LI.CA score showed the best prognostic performance compared with other available HCC prognostic systems and its superiority was confirmed by an independent study group . It also showed better performance in complex restaging after an HCC treatment …”

Section: Introductionmentioning

confidence: 99%

The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

Vitale

Farinati

Pawlik

et al. 2019

Liver International

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“…There is growing evidence about the potential synergistic effect of RT and ICI in clinical and preclinical studies . Local RT induces the release of tumor‐specific antigens as in situ individualized tumor vaccines that can result in anticancer immune responses that mediate abscopal effects .…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of radiotherapy before and/or during nivolumab treatment in hepatocellular carcinoma

Lee

et al. 2019

Cancer Medicine

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Background This study aimed to investigate the clinical significance of previous and/or concurrent application of radiotherapy (RT) in the course of nivolumab treatment for advanced hepatocellular carcinoma (HCC). Methods Patients with advanced HCC who received nivolumab treatment between March 2017 and May 2018. were included. Nivolumab treatment was indicated in patients who did not respond to conventional therapy including locoregional therapy and/or sorafenib. RT was performed when necessary for curative/palliative purpose. Results Among the 76 HCC patients who received nivolumab, 54 (71.1%) had received RT for HCC before and/or during the treatment. The period from initial HCC diagnosis to nivolumab treatment was significantly longer (P = .007) and the rate of undergoing transarterial chemoembolization (TACE; P = .006) and sorafenib treatment (P = .007) was significantly higher in patients who received previous/concurrent RT than in those who did not. Nivolumab‐related toxicities were generally tolerable regardless of the history of RT. During the follow‐up, 39 (51.3%) patients died and 54 (71.1%) patients experienced disease progression according to the RECIST v1.1. Patients who had received previous/concurrent RT had a significantly longer progression‐free survival (PFS; P = .008) and overall survival (OS; P = .007) than those who did not receive RT; however, this trend was not observed in patients with a history of radiofrequency ablation or TACE (all P > .05). Conclusion Previous and/or concurrent application of RT in the course of nivolumab treatment was related with longer PFS and OS in advanced HCC patients. Nonetheless, further clinical studies are warranted to confirm our findings.

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“…We read with great interest the comment letter by Huo et al, because this letter gives us the possibility to better explain some aspects of the ITA.LI.CA prognostic system that were probably unclear in our previous studies …”

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confidence: 97%

“…First, the ITA.LI.CA system is a score based on 14 prognostic subgroups and not only 4: The lowest score (ITA.LI.CA score = 0) of the model corresponded to the best prognosis, and the highest score (ITA.LI.CA score = 13) was associated with the worst prognosis. In the original paper in which the ITA.LI.CA score was developed and externally validated, and in this paper focused on restaging, we stratified our score in quartiles only to clearly and legibly represent the discrimination and calibration abilities of the ITA.LI.CA system by Kaplan‐Meier survival curves.…”

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confidence: 99%

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et al. 2019

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Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Abstract: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Cited by 32 publications

References 25 publications

The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

Clinical significance of radiotherapy before and/or during nivolumab treatment in hepatocellular carcinoma

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