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

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.

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

“…A divergent activity of pro-inflammatory cytokines, such as tumor necrosis factor α, was noted between HCC patients of different CTP scores at baseline and early during liver SBRT. 35,36 This variable cytokine profile by liver function was suggested to mediate the differential radiation sensitivity of the liver and the development of liver toxicity, thereby affecting survival. In this cohort, the baseline CTP class was identified as the only predictor of dNLR after SBRT, and the difference in dNLR between CTP groups mainly arises from the post-SBRT change.…”

Cytokine Profiles of Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy with Regards to Radiation Pneumonitis Severity

“…The authors suggested that in prostate cancer, cytokine changes during RT had a predictive role in gastrointestinal and genitourinary toxicity. Ng et al [ 25 ] assessed the changes of pro-inflammatory cytokine receptors in patients with hepatocellular carcinoma treated with stereotactic radiotherapy. The patients who developed chronic liver toxicity showed significantly higher levels of sTNFRII, and lower levels of sCD40L and CXCL1 early during stereotactic body radiation therapy (SBRT); in addition, early death after SBRT was significantly related to high levels of sTNFRII and sIL-6R after one to two fractions of SBRT.…”

Toxicity After Stereotactic Body Radiation Therapy for Prostate Cancer in Patients With Inflammatory Bowel Disease: A Multi-institutional Matched Case-Control Series

“…The greater likelihood of developing acute grade  2 GI and GU toxicities after SBRT in the IBD cohort may be associated to the underlying processes causing chronic inflammation in IBD patients and an immunomodulatory response from radiotherapy 16,17 . Pre-clinical data suggests that SBRT-induced tumor cell death triggers the release of tumor antigens and inflammatory cytokines 18 , which could increase the risk of developing both GI and GU toxicity. This is supported by the delayed occurrence of urinary symptoms after SBRT and rapid symptomatic response to oral steroids 19 .…”