Neutrophil-to-Lymphocyte Ratio and Extrahepatic Spread Predict Response and Survival in Unresectable Hepatocellular
Dong Yun Kim1, Heechul Nam2,3, Jun Yong Park1
1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Purpose:
Identifying nonresponders to atezolizumab plus bevacizumab (AB) remains challenging in unresectable hepatocellular carcinoma (uHCC). We aimed to develop and externally validate a simple risk scoring system using baseline neutrophil-to-lymphocyte ratio (NLR) and extrahepatic spread (EHS) to predict treatment outcomes.
Materials And Methods:
We included 304 patients with uHCC receiving first-line AB from multiple Korean centers (discovery, n = 220; validation, n = 84). Study outcomes included objective response rate (ORR) assessed by modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression-free survival (PFS). Multivariable analysis identified high NLR (>4.575) and EHS as independent predictors of nonresponse. The NLR-EHS score assigned 2 points for high NLR and 1 point for EHS (range, 0-3).
Results:
In the discovery cohort, the score predicted nonresponse with an area under the receiver operating characteristic curve (AUC) of 0.749 (95% CI, 0.688-0.810); ORR fell across low- (0), moderate- (1-2), and high-risk (3) groups (67.3%, 47.7%, and 8.2%; p < 0.001). Validation confirmed comparable discrimination (AUC, 0.705; 95% CI, 0.603-0.806) and a consistent ORR gradient (77.8%, 54.2%, and 22.2%; p < 0.001). The score was prognostic for OS in discovery (HR, 1.28; p = 0.003) and validation cohorts (HR, 1.45; p = 0.007), remaining significant after adjustment (adjusted HR, 1.25 and 1.61, respectively). High-risk patients had inferior median OS (6.9 vs. 17.1 months in validation).
Conclusion:
The NLR-EHS score is a practical tool for stratifying nonresponse risk and survival in uHCC patients receiving AB, facilitating early identification of high-risk patients who may benefit from alternative strategies.