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

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

doi:10.21873/invivo.12955

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

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\textless0.05 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\textless0.05). 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.

Reference:

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), In In vivo (Athens, Greece), volume 36, 2022.

Bibtex Entry:

@article{damm_tnf-_2022,
	title = {{TNF}-α {Indicates} {Radiation}-induced {Liver} {Injury} {After} {Interstitial} {High} {Dose}-rate  {Brachytherapy}},
	volume = {36},
	copyright = {Copyright © 2022, International Institute of Anticancer Research (Dr. George J.  Delinasios), All rights reserved.},
	issn = {1791-7549 0258-851X 0258-851X},
	doi = {10.21873/invivo.12955},
	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{\textless}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{\textless}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.},
	language = {eng},
	number = {5},
	journal = {In vivo (Athens, Greece)},
	author = {Damm, Robert and Pech, Maciej and Haag, Florian and Cavalli, Paola and Gylstorff, Severin and Omari, Jazan and Seidensticker, Ricarda and Ricke, Jens and Seidensticker, Max and Relja, Borna},
	month = oct,
	year = {2022},
	pmid = {36099091},
	pmcid = {PMC9463893},
	keywords = {*Brachytherapy/adverse effects, *Chemical and Drug Induced Liver Injury, Chronic, *Liver Neoplasms/radiotherapy/secondary, *Radiation Injuries/diagnosis/etiology, biomarker, Humans, interleukin, Interleukin-6, liquid biopsy, liver, Prospective Studies, Tumor necrosis factor, Tumor Necrosis Factor-alpha},
	pages = {2265--2274}
}