Validation of the score in three external cohorts of BCLC C patients. Methods: This retrospective study included BCLC C HCC patients (n = 160) at diagnosis or during follow-up, treated by chemoembolization (TACE) 27%, sorafenib 30%, TACE and sorafenib 24% and untreated patients 19%. Determining a score based on prognostic variables of our population. Validation

within three external cohorts of BCLC C HCC patients (Rennes, Nancy, Bordeaux). Results: Cirrhosis was viral 45%, alcohol-related 31%, Child-Pugh A 62%, Child-Pugh B 38%. 50% of HCC were infiltrative tumors. The number of nodules was ≥3 in 44% of Cell Cycle inhibitor cases. Portal vein thrombosis was present in 60% of cases, metastasis in 12% of cases. 45% of the patients had elevated AFP ≥ 200 ng / ml at diagnosis. ECOG grade was ≥1 in 85% of cases. Median survival time of Venetoclax chemical structure patients treated by Sorafenib was 7

months [5–10], by TACE: 10 months [6–15], by TACE then Sorafenib: 13 months [10–15], p = 0.462. Multivariate analysis found five prognostic variables associated with overall survival (AFP ng/ml rate at diagnosis, Child-Pugh score, infiltrative vs. encapsulated tumor, nodule number, ECOG grade). These variables were included in a score (N.I.A.C.E) determined from Beta regression coefficients: 1 x (Nodules: 0 if <3, 1 if ≥ 3) + 1.5 x (Infiltrative 0 if no, 1 if yes) + 1.5 x (AFP: 0 if <200, 1 if ≥ 200) + 1.5 x (Child-Pugh: 0 if A, 1 if B) + 1.5 x (ECOG grade 0 if 0, 1 if ≥ 1). With a threshold value <3, the score found two groups with different survival: <3 (n = 38) 16 months [14–27] vs. ≥3 (n = 122) 7 months [6–9], p < .0001 . Application of the

score to three external BCLC C HCC cohorts treated or not by Sorafenib also found two groups with different DNA ligase survival: <3 (n = 37) 10.6 months [4.1–17.1] vs. ≥3 (n = 46) 5.1 months [2.9–7.4] p < .001 Rennes; Score < 3 (n = 28) 16 months [14–25] vs. ≥3 (n = 55) 6 months [4–8] p < .0001 Nancy; <3 (n = 141) 12 months [10–16] vs. ≥3 (n = 236) 6 months [5–7] p < .0001 Bordeaux. Conclusion: This series confirms that BCLC C HCC are a heterogeneous group. We have determined and validated a simple score which can distinguish a sub-group of better prognosis, regardless of treatment. Current treatments do not appear to alter the natural course of BCLC C HCC with a NIACE score >3. Key Word(s): 1.