TNF-α Indicates Radiation-induced Liver Injury After Interstitial High Dose-rate Brachytherapy

Abstract

Background/Aim: The aim of the present study was to determine whether the early systemic markers of inflammation, interleukin-6 (IL-6) and tumor necrosis factorα (TNF-α), respond to high dose-rate (HDR) brachytherapy, and their possible correlation with radiation-induced liver injury of patients with liver metastases. Patients and Methods: This prospective study included 20 tumor patients (TP) undergoing irradiation-based interstitial HDR brachytherapy (iBT) of liver metastases, who received total radiation ablative doses to the planning target volume ranging from 15 to 25 Gy, depending on the tumor entity. Hepatobiliary magnetic resonance imaging (MRI) was performed 6 weeks after iBT to assess the maximum extent of focal radiation-induced liver injury (fRILI). Furthermore, blood samples for the pro-inflammatory cytokine response were taken one day prior to and 6 weeks after irradiation. IL-6 and TNF-α were measured by flow cytometry. Ten healthy volunteers (HV) were used as control group. Results: Compared to HV, TNF-α was significantly enhanced in TP before and after therapy (p<0.05 for both comparisons), while IL-6 increase at baseline was not statistically significant. HDR brachytherapy significantly reduced IL-6 levels after 6 weeks in TP (p<0.05). IL-6 levels after 6 weeks have shown a significant negative correlation with the tumor volume (r=-0.5606; p=0.0261), while no significant correlation was observed between baseline IL-6 or followup IL-6 levels with the fRILI. Baseline TNF-α levels positively correlated with the tumor volume (r=0.4342; p=0.0492), and post treatment TNF-α levels showed a significant correlation with the fRILI (r=0.7404; p=0.0022). Conclusion: TNF-α was correlated with both tumor volume and radiation-induced liver injury; thus, representing a promising biomarker for focal radiation-induced liver injury.Locoregional therapies, defined as imaging-guided liver tumor-directed procedures, are emerging treatment options for primary and secondary liver malignancies (1, 2). In the last decades several techniques have been developed including thermal and irradiation-based ablation methods, latter comprising Yttrium 90 radioembolization (Y 90 RE), stereotactic-ablative body radiotherapy and interstitial high dose rate (HDR) brachytherapy (iBT) (3-6). However, the irradiation-based iBT of liver metastases bears a risk for radiation-induced liver disease (RILD), which originates from sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD) (7,8).The development of SOS/VOD, as a potentially lifethreatening complication, has been mostly associated with high-intensity chemotherapies upon allogeneic or autologous hematopoietic stem cell transplantation, thus, not necessarily representing the iBT-induced SOS/VOD (9). It may occur rapidly, and since it remains unpredictable, it is of great importance to identify risk factors and biomarkers to facilitate prompt diagnosis and subsequent timely optimal treatment of this complication. The histopathological 2265

Radioprotective countermeasures for radiation injury (Review)

“…Therefore, blocking or promoting one cytokine may affect the activities of other cytokines. Some cytokines increase sensitivity to IR when used alone, such as tumor growth factor-β, IL-6 and TNF-α (155)(156)(157). These cytokines must be used in combination with other cytokines.…”