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

Robert Damm; Maciej Pech; Florian Haag; Paola Cavalli; Severin Gylstorff; Jazan Omari; Ricarda Seidensticker; Jens Ricke; Max Seidensticker; Borna Relja

doi:10.21873/invivo.12955

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

In Vivo. 2022 Sep-Oct;36(5):2265-2274. doi: 10.21873/invivo.12955.

Authors

Robert Damm^{1

2}, Maciej Pech^{1

3}, Florian Haag^{1

3

4}, Paola Cavalli^{1

3

4}, Severin Gylstorff^{1

3

4}, Jazan Omari^{1

3}, Ricarda Seidensticker⁵, Jens Ricke⁵, Max Seidensticker⁵, Borna Relja^{6

3

4}

Affiliations

¹ Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
² Radiology Practice, Dessau, Germany.
³ Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany.
⁴ Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
⁵ Department of Radiology, Ludwig-Maximilian-University, Munich, Germany.
⁶ Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany; info@bornarelja.com.

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 factor-α (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 follow-up 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.

Keywords: Tumor necrosis factor; biomarker; interleukin; liquid biopsy; liver.

MeSH terms

Brachytherapy* / adverse effects
Chemical and Drug Induced Liver Injury, Chronic*
Humans
Interleukin-6
Liver Neoplasms* / radiotherapy
Liver Neoplasms* / secondary
Prospective Studies
Radiation Injuries* / diagnosis
Radiation Injuries* / etiology
Tumor Necrosis Factor-alpha

Substances

Interleukin-6
Tumor Necrosis Factor-alpha