Dynamic Changes in Neutrophil-to-Lymphocyte Ratio are Associated with Survival and Liver Toxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma

Abstract

Chih-Weim Hsiang,1 Wen-Yen Huang,2,3 Jen-Fu Yang,2 Po-Chien Shen,2 Yang-Hong Dai,2 Ying-Fu Wang,2 Chun-Shu Lin,2 Wei-Chou Chang,1 Cheng-Hsiang Lo2 1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 3Institute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanCorrespondence: Cheng-Hsiang LoDepartment of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec 2, Cheng-Gong Road, Neihu, Taipei, 114, TaiwanTel [phone]Fax [phone]Email [email protected]: Immune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).Methods: Data on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined.Results: The study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p< 0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p< 0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child–Turcotte–Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥ 1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002).Conclusion: Baseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.Keywords: hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, stereotactic body radiotherapy, liver toxicity

Keywords

• hepatocellular carcinoma
• neutrophil-to-lymphocyte ratio
• platelet-to-lymphocyte ratio
• stereotactic body radiotherapy
• liver toxicity