Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity

Sylvia S W Ng,Laura A Dawson,Lisa Wang,Deborah Citrin,Hong Zhang

doi:10.1038/s41698-020-0124-z

Abstract

Plasma levels of soluble factors early during hepatocellular carcinoma (HCC) stereotactic body radiotherapy (SBRT) were evaluated in relation to radiation liver injury, tumor response, and risk of early death. No significant differences were found in baseline plasma levels of AFP, CXCL1, and HGF amongst HCC patients with different Child Pugh scores. Higher levels of sTNFRII (P < 0.001), and lower levels of sCD40L (P < 0.001) and CXCL1 (P = 0.01) following one to two fractions of SBRT were noted in patients who developed liver toxicity vs. those who did not. High circulating levels of AFP (HR 2.16, P = 0.04), sTNFRII (HR 2.27, P = 0.01), and sIL-6R (HR 1.99, P = 0.03) early during SBRT were associated with increased risk of death 3 months post treatment. Plasma levels of the studied factors early during SBRT were not associated with tumor response. A pro-inflammatory systemic environment is associated with development of liver toxicity and increased risk of early death following SBRT.

Highlights

Stereotactic body radiotherapy (SBRT) refers to the use of high doses of radiation per fraction in fewer fractions with high precision and accuracy to achieve local tumor control
The present study demonstrated that hepatocellular carcinoma (HCC) patients with worse baseline liver function have elevated sTNFRII, ANGPTL4, and sgp[130] levels, and lower sCD40L levels in the circulation at baseline and early during SBRT
Ellsworth et al.[18] reported that early stage non-small cell lung cancer patients undergoing hypofractionated SBRT (50–60 Gy in 10–20 fractions) have a more limited repertoire of circulating cytokines and less variability in cytokine levels at baseline and during treatment compared those receiving conventional fractionation RT, and that sCD40L is identified as one of three cytokines (CXCL10 and macrophage inflammatory protein-1 being the remaining two cytokines) that accounts for the majority of the variability in cytokine levels seen during lung SBRT

Summary

Introduction

Stereotactic body radiotherapy (SBRT) refers to the use of high doses of radiation per fraction in fewer fractions with high precision and accuracy to achieve local tumor control. For advanced hepatocellular carcinoma (HCC) patients who are not candidates for local therapies, such as surgery, radiofrequency ablation, or transcatheter arterial chemoembolization, liver SBRT is a treatment option. Prior clinical studies have demonstrated that liver SBRT is well tolerated and efficacious, with 1-year and 3-year local control rates of 95% and 85%, respectively, in Child Pugh A HCC patients[1,2,3,4]. Child Pugh B HCC patients have been treated effectively with liver SBRT, with an increased risk of toxicity[5]. Albumin-bilirubin (ALBI) grade has been shown to be a more objective and discriminatory metric for the assessment of liver function in HCC patients[7]

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