PMID- 35596772 OWN - NLM STAT- MEDLINE DCOM- 20220915 LR - 20220923 IS - 1432-1335 (Electronic) IS - 0171-5216 (Print) IS - 0171-5216 (Linking) VI - 148 IP - 10 DP - 2022 Oct TI - Correlation of chemokines and growth factors with radiation-induced liver injury after interstitial high dose rate (HDR) brachytherapy of liver metastases. PG - 2815-2826 LID - 10.1007/s00432-022-04041-x [doi] AB - BACKGROUND: Locoregional therapies, as imaging-guided tumor-directed procedures, are emerging treatment strategies in the management of primary and secondary liver malignancies such as e.g. colorectal cancer liver metastases. As one of those, irradiation-based interstitial high dose rate brachytherapy (iBT) of liver metastases bears a risk of developing focal radiation-induced liver injury (fRILI). Since little is known about biological factors involved in hepatic dysfunction after irradiation, the aim of this study was to identify factors, that may play a role in the underlying mechanism of fRILI, and that potentially may serve as biomarkers for post-therapeutic fRILI to improve specific management and treatment of patients. METHODS: Twenty-two patients with hepatic malignancies (tumor patients, TP) underwent iBT with total ablative doses of radiation to the target volume ranging from e.g. 15 to 25 Gy. Hepatobiliary magnetic resonance imaging (MRI) was performed 6 weeks after iBT to quanitify fRILI. Blood samples were taken before (pre) and 6 weeks after (post) iBT from TP, and from ten healthy volunteers (HV controls) for the analyses of humoral mediators: monocyte chemoattractant protein-1 (MCP-1), chemokine (C-X3-C motif) ligand 1 (CX3CL1), vascular endothelial growth factor (VEGF) and beta-nerve growth factor (beta-NGF) using the Multi-Analyte Flow Assay via flow cytometry. Correlation analyses between the humoral mediators (pre and post iBT) with the tumor volume and fRILI were performed. RESULTS: While MCP-1 and CX3CL1 tended to decrease in TP vs. HV, VEGF was significantly decreased in TP vs. HV pre and post iBT (p < 0.05). Beta-NGF levels were significantly increased in TP vs. HV pre and post iBT (p < 0.05). Baseline circulating levels of MCP-1, VEGF and beta-NGF have shown significant positive correlations with the hepatic tumor volume (p < 0.05). Circulating levels of humoral mediators before treatment did not correlate with fRILI, while CX3CL1 and VEGF after iBT have shown significant positive correlations with fRILI (p < 0.05). CONCLUSION: Tumor volume and threshold dose of irradiation damage correlated positively with MCP-1 and VEGF as well as NGF and CX3CL, respectively. Thus, investigation of biological mediators in blood samples from tumor patients may provide an appropriate tool to predict fRILI after interstitial HDR brachytherapy of liver metastases. CI - (c) 2022. The Author(s). FAU - Damm, Robert AU - Damm R AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Radiology Practice, Dessau, Germany. FAU - Pech, Maciej AU - Pech M AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. FAU - Cavalli, Paola AU - Cavalli P AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. AD - Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 30120, Magdeburg, Germany. FAU - Haag, Florian AU - Haag F AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. AD - Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 30120, Magdeburg, Germany. FAU - Gylstorff, Severin AU - Gylstorff S AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. AD - Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 30120, Magdeburg, Germany. FAU - Omari, Jazan AU - Omari J AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. FAU - Thormann, Maximilian AU - Thormann M AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. FAU - Seidensticker, Ricarda AU - Seidensticker R AD - Department of Radiology, Ludwig-Maximilians-University, Munich, Germany. FAU - Ricke, Jens AU - Ricke J AD - Department of Radiology, Ludwig-Maximilians-University, Munich, Germany. FAU - Seidensticker, Max AU - Seidensticker M AD - Department of Radiology, Ludwig-Maximilians-University, Munich, Germany. FAU - Relja, Borna AU - Relja B AUID- ORCID: 0000-0002-5625-8823 AD - Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Magdeburg, Germany. info@bornarelja.com. AD - Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany. info@bornarelja.com. AD - Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 30120, Magdeburg, Germany. info@bornarelja.com. LA - eng GR - 13GW0473A/Bundesministerium fur Bildung und Forschung/ PT - Journal Article DEP - 20220521 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Chemokines) RN - 0 (Vascular Endothelial Growth Factor A) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - *Brachytherapy/adverse effects MH - Chemokines MH - Humans MH - *Liver/pathology/radiation effects MH - *Liver Neoplasms/secondary MH - Nerve Growth Factor MH - *Radiation Injuries/etiology MH - Radiotherapy Dosage MH - Vascular Endothelial Growth Factor A PMC - PMC9470622 OTO - NOTNLM OT - Biomarker OT - CX3CL1 OT - Liquid biopsy OT - MCP-1 OT - NGF OT - VEGF COIS- The authors declare no conflict of interest. EDAT- 2022/05/22 06:00 MHDA- 2022/09/16 06:00 PMCR- 2022/05/21 CRDT- 2022/05/21 11:13 PHST- 2022/02/07 00:00 [received] PHST- 2022/04/25 00:00 [accepted] PHST- 2022/05/22 06:00 [pubmed] PHST- 2022/09/16 06:00 [medline] PHST- 2022/05/21 11:13 [entrez] PHST- 2022/05/21 00:00 [pmc-release] AID - 10.1007/s00432-022-04041-x [pii] AID - 4041 [pii] AID - 10.1007/s00432-022-04041-x [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2022 Oct;148(10):2815-2826. doi: 10.1007/s00432-022-04041-x. Epub 2022 May 21.