Development of a novel prognostic score for 1-year survival in immunotherapy-treated patients with unresectable HCC: The ALIVE-IO score

Spyridon Pantzios¹Orestis Sidiropoulos¹Antonia Syriha¹Nikolaos Ptohis²Ioannis Skouras³Evgenia Mainta³Dimitris P Korkolis⁴Nikolaos Machairas⁵Georgios C. Sotiropoulos⁵Ioannis Elefsiniotis^1*

• ¹Academic Department of Internal Medicine-Hepatogastroenterology Unit, General Oncology Hospital of Kifisia “Agioi Anargyroi”, National and Kapodistrian University of Athens, Athens, Greece, Athens, Greece
• ²Department of Interventional Radiology, “G. Gennimatas” General Hospital of Athens, Athens, Greece, Athens, Greece
• ³Department of Radiology, General Oncology Hospital of Athens “Agioi Anargyroi”, Athens, Greece, Athens, Greece
• ⁴Department of Surgery, “Saint Savvas” Hellenic Anticancer Hospital of Athens, Athens, Greece, Athens, Greece
• ⁵Department of Liver Transplantation and Hepatobiliary Surgery, National and Kapodistrian University of Athens, Athens, Greece, Athens, Greece

Background: There is a lack in reliable and widely used prognostic scores to predict survival in patients with hepatocellular carcinoma (HCC) receiving immunotherapy. The aim of our study was to develop a prognostic score that could predict 1-year OS in patients with unresectable HCC receiving immunotherapy. Methods: We studied 100 patients who received 1 st line immunotherapy. We did a univariate cox regression analysis to assess which of the patients' baseline characteristics was associated with OS. Factors strongly associated with OS were used in the multivariate model and their B coefficients were used to produce a normalized score (ALIVE-IO score) that could predict 1-year OS. Internal validation was done using ROC analysis and 10-fold cross-validation. Then, we separated our patients in three risk groups (low, intermediate, high) based on the new score and studied them for their baseline characteristics, response to immunotherapy and OS. Results: In univariate analysis, significant correlation with OS was found for ALBI grade (p<0.001, HR=2.725), BCLC stage (p=0.031, HR=1.809), macrovascular invasion (p<0.001, HR=2.587), up-to-7 criteria (p<0.001, HR=0.218) and lymphocyte infiltration (p=0.005, HR=0.485). In the multivariate analysis, three factors were significantly correlated with OS; ALBI grade (grade II vs. I, p=0.025, HR=1.946), up-to-7 criteria (beyond vs. within, p=0.001, HR=3.506) and lymphocyte infiltration (no vs. yes, p=0.016, HR=1.889). The ALIVE-IO score was calculated with the contribution of 1 point for ALBI grade II, 2 points for exceeding up-to-7 criteria and 1 point for absence of lymphocyte infiltration. The score had an AUROC of 0.755 for 1-year OS, with 75% sensitivity and 65.4% specificity. We established three risk groups; low (ALIVE-IO: 0-1), intermediate (ALIVE-IO: 2-3) and high (ALIVE-IO: 4). Objective response was reported in 34.8% of patients in the low risk group, compared to 18.5% in intermediate and 4.3% in high risk patients (p=0.031). The median OS of the three groups was 41, 12 and 3 months, respectively (p<0.001). The 1-year OS was 80%, 41% and 16, respectively. Conclusion: The ALIVE-IO score is a promising tool for predicting 1-year OS in HCC patients undergoing immunotherapy using common laboratory, imaging and histological data frequently used in everyday clinical practice.