Reply to the Letters to the Editor regarding the sequential ART-Score
Authors: Florian Hucke, Wolfgang Sieghart, Markus Peck-Radosavljevic
Journal: Journal of Hepatology (2014)

ART score for retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma: Is it really applicable?Journal of HepatologyVol. 61Issue 1PreviewWe read with great interest the work by Hucke et al. published in the Journal of Hepatology [1]. The authors have already developed the ART score, the Assessment for Retreatment with Transarterial Chemoembolization (TACE), to guide the decision on whether re-treating hepatocellular carcinoma (HCC) patients with a further TACE in their last paper published in Hepatology [2]. In their study, ART score differentiated patients into two groups (0–1.5 points; ⩾2.5 points) with distinct prognosis (median OS:23.7 vs. Full-Text PDF Open AccessThe ART-strategy: Sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACEJournal of HepatologyVol. 60Issue 1PreviewRecently, we developed the ART score (assessment for re-treatment with TACE) to guide the decision for a second transarterial chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC). Patients with an ART score of 0–1.5 points gained benefit from a second TACE session, while patients with an ART score ⩾2.5 points did not. Here, we investigated (1) the prognostic significance of the ART score prior to the third (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided re-treatment strategy by sequential assessment of the ART score in HCC patients treated with multiple TACE sessions. Full-Text PDF The ART strategy: Sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACEJournal of HepatologyVol. 61Issue 1PreviewHucke and colleagues are to be congratulated on their work predicting likely response to multiple cycles of transarterial chemoembolization (TACE) [1]. However, there are some issues that need addressing. Full-Text PDF Open Access We would like to thank Yousuf and colleagues for the thoughtful comments on our work regarding the sequential use of the ART score to select patients for retreatment with TACE [[1]Hucke F. Sieghart W. Pinter M. Graziadei I. Vogel W. Muller C. et al.The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE.J Hepatol. 2014; 60: 118-126Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. They are right in commenting that the Child-Pugh score (CPS) consists of 5 variables but the reason why we use the change in CPS was that in our uni- and multivariate analysis from the original ART-score manuscript, the change in composite CPS was a better predictor for survival than the change in the individual variables included in the CPS [[2]Sieghart W. Hucke F. Pinter M. Graziadei I. Vogel W. Muller C. et al.The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma.Hepatology. 2013; 57: 2261-2273Crossref PubMed Scopus (251) Google Scholar]. In addition, from a practical point of view, the CPS has to be calculated to evaluate the patient’s suitability with regards to liver function for the selection for any treatment according to the BCLC staging classification, so this information is always available anyways. We also agree that the greatest weight in the ART-score is put on the aspartate aminotransferase (AST) and not on radiologic response. But this was derived from the hazard ratio in the multivariate analysis giving the greatest weight to the rising AST as opposed to other statistically significant parameters. We acknowledge that the authors developed the HAP score [[3]Kadalayil L. Benini R. Pallan L. O’Beirne J. Marelli L. Yu D. et al.A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer.Ann Oncol. 2013; 24: 2565-2570Crossref PubMed Scopus (215) Google Scholar], but the HAP score serves a different purpose: it is a prognostic score, which helps to subclassify BCLC-stage B patients undergoing chemoembolization into different prognostic groups prior the first TACE treatment. In contrast, the ART-score, aims to detect (1) patients that can tolerate repeated-TACE well and (2) patients, whose liver function and prognosis would be harmed by another occlusion of the arterial blood supply to parts of the liver. So patients might be in a good prognostic group by the HAP score or by the BCLC stage B subclassification at baseline, but a subgroup of these patients may present with an ART of ⩾2.5 points prior to TACE-2 with subsequent dismal prognosis in case of retreatment with TACE. On the other hand, some suboptimal candidates for TACE at baseline may tolerate repeated TACE quite well as outlined by an ART score of 0–1.5 points and therefore have a fairly good outcome with TACE treatment, as detailed in our original ART-score manuscript. Regarding the comments by Han and colleagues we would like to confirm that even if a patient receives 2.5 points in the ART-score through lack of radiologic response and an increase in CPS by 1 point after TACE 1, he still is a poor candidate for further TACE’s. It might be true that he might show a radiologic response after the second TACE but this will lead to further deterioration in his liver function and therefore a dismal prognosis despite radiologic response. This has been clearly shown in our initial art score manuscript. Therefore the recommendations by different authors that patients should undergo at least two TACE-procedures initially – statements made well before the publication of the art score – cannot be supported anymore. Regarding the impact of different TACE or TAE techniques, the authors misunderstood the message we are giving: it might be true that treatment with DC-beads gives a better treatment respond than cTACE (even though not supported by the published literature so far [[4]Lammer J. Malagari K. Vogl T. Pilleul F. Denys A. Watkinson A. et al.Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.Cardiovasc Intervent Radiol. 2010; 33: 41-52Crossref PubMed Scopus (1148) Google Scholar]), but this will be taken into account by the ART-score anyway through the parameter “radiologic response”. Thus, different TACE techniques could have an impact on the ART-sore values; but nevertheless, the ART-score values obtained retain their prognostic significance regardless of the technique used. We disagree with the authors that the response definition is different because we did not evaluate patients with complete response in our initial ART-score manuscript: the definition was the same but the inclusion criteria did not allow inclusion of patients with less than 2 TACE-procedures (which was obviously necessary to evaluate the impact of repeated TACE’s on outcome, since patients with complete response do not receive retreatment with TACE within three months if TACE is applied in a “on demand” fashion). Patients that had a complete response after TACE 2 or TACE 3 did not receive further TACE sessions in our institutions, as outlined very clearly in the methods of our manuscripts. So the validation of the ART-score seems to be very robust but we certainly welcome further evaluation of the ART-score in different patient populations worldwide, in particular when performed prospectively. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.