The fact that almost a third of the patients in either group received further TACE sessions after they went off protocol further outlines the danger of inadequate retreatment criteria for protocol compliance and consequently the success of multicenter

TACE studies. The ART score developed here is able to identify patients with good prognosis despite the presence of Child-Pugh stage B 7-9 points (Fig. 4B,C) or ascites (Fig. 4D) and would therefore provide a robust and objective evidence based tool to guide retreatment with TACE in future clinical trials. Finally, regarding the association of higher ART score values with SAEs and unplanned admissions (Table 4) and poorer OS (Figs. 3, 4), the application of this score may spare patient suffering see more and consequential costs by avoiding treatment-related side effects. The retrospective nature and the heterogeneous TACE types (TAE, cTACE, DEB-TACE) in the training cohort may be potential limitations of this study. However, we confirmed the results in all three TACE types in the training cohort (Fig. 3C-E) and in a completely independent external (Table 1, Figs. 3F, 4) patient GSI-IX cohort in

which most patients received conventional TACE. Additionally, the outcome of our patient population within the different Child-Pugh stages (Table 2) matches the published survival data reported in prospective clinical trials tuclazepam and meta-analysis3 and, thus,

further confirms the validity of our data. Another limitation may be the ART score assessment at heterogeneous timepoints between the first and second TACE (13-90 days), since the ART score is composed of laboratory changes that may be potentially reversible over time. However, time-related sensitivity analysis (Supporting Table 1-2) revealed no significant hint that the time of the ART score assessment influenced the results of this study. Finally, the ART score was developed by using the radiologic EASL-response criteria. Although the prognostic performance of EASL criteria in the setting of TACE seems to be equal to the performance of mRECIST criteria,25 the latter may be more adequate to dissect the prognosis of patients with partial response from that of subjects with stable disease.26 This could rely on a different definition of partial response in the two models: greater than 50% tumor reduction for EASL and greater than 30% for mRECIST criteria. Given that radiologic response is a parameter of the ART score, there is a need for prospective studies validating the ART score which include mRECIST criteria to the study design. In summary, we developed a novel and externally validated, noninvasive, objective, widely applicable prognostic (ART) score for patients with HCC allocated to retreatment with TACE. Patients with 2.