A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1

Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3– 4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1– 3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability. Plain Language Summary: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti‑PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3– 4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation demonstrated good reliability. Keywords: hepatocellular carcinoma, advanced, intensity-modulated radiotherapy, antibody against programmed cell death 1, nomogram