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Abstract
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.
Abbreviations
Anti‑PD1, monoclonal antibodies against programmed cell death 1 pathway; Alb, albumin; AFP, alpha-fetoprotein; AEs, adverse reactions; BCLC, Barcelona Clinic Liver Cancer; CT, computed tomography; CR, complete response; GTV, Gross tumor volume; HCC, Hepatocellular carcinoma; IMRT, intensity-modulated radiotherapy; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; ORR, overall response rate; PFS, progression-free survival; PR, partial response; PLR, platelet-to-lymphocyte ratio; PTV, planned target volume; RT, radiotherapy; RECIST 1.1, Response Evaluation Criteria in Solid Tumors, version 1.1; SII, systemic immune-inflammation index.
Data Sharing Statement
The data underlying this article will be shared on reasonable request to the corresponding author.
Ethics Approval
The protocol of this retrospective study conformed to the Declaration of Helsinki (1975) and its amendments and was approved by the Ethics Review Committee of the Guangxi Medical University Cancer Hospital (LW2023043), which waived the requirement for written informed consent because patients or their legal guardians had consented, upon admission, to analysis and publication of anonymized medical data for research purposes.
Acknowledgments
We wish to thank all patients involved in this research and our colleagues at Guangxi Medical University Cancer Hospital.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.