Circulating cell-free DNA: A potential biomarker to differentiate inflammation and infection during radiochemotherapy

Kerstin Zwirner; Franz J Hilke; German Demidov; Stephan Ossowski; Cihan Gani; Olaf Rieß; Daniel Zips; Stefan Welz; Christopher Schroeder

doi:10.1016/j.radonc.2018.07.016

Circulating cell-free DNA: A potential biomarker to differentiate inflammation and infection during radiochemotherapy

Radiother Oncol. 2018 Dec;129(3):575-581. doi: 10.1016/j.radonc.2018.07.016. Epub 2018 Aug 7.

Authors

Kerstin Zwirner¹, Franz J Hilke², German Demidov², Stephan Ossowski³, Cihan Gani⁴, Olaf Rieß², Daniel Zips⁴, Stefan Welz⁴, Christopher Schroeder²

Affiliations

¹ Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany. Electronic address: Kerstin.Zwirner@med.uni-tuebingen.de.
² Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany.
³ Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Spain.
⁴ Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tübingen, Germany.

PMID: 30097252
DOI: 10.1016/j.radonc.2018.07.016

Abstract

Background and purpose: Radiochemotherapy is a standard treatment option for patients with head and neck cancer (HNSCC). During radiation, local toxicities are common and need to be differentiated from infections. As levels of circulating cell-free DNA (cfDNA) are known to be elevated during infections, cfDNA might complement clinical parameters. The aim of the study was to investigate the dynamics of cfDNA during radiochemotherapy.

Material and methods: In total, 78 blood samples of 20 patients with HNSCC were analysed in this prospective biomarker study. Blood samples were taken before and during treatment. CfDNA levels were quantified fluorometrically and results were compared to laboratory and clinical parameters.

Results: Elevated cfDNA levels were associated with the pre-treatment volumes of lymph node metastases (p = 0.0002), gastrostomy tube placement (20.23 ng/ml vs. 9.04 ng/ml (median), p = 0.025), the application of antibiotics (16.47 ng/ml vs. 9.04 ng/ml, p = 0.006) and manifest infections (16.81 ng/ml vs. 9.04 ng/ml, p = 0.010). Furthermore, a significant difference between moderate inflammation (radiation-induced toxicity RTOG grade 2-3) and manifest infections could be observed (8.97 ng/ml vs. 16.81 ng/ml, p = 0.014), allowing for a more pronounced differentiation than by CRP levels (p = 0.119). There might be an association between the application of G-CSF and elevated cfDNA levels.

Conclusion: CfDNA levels are correlated with infections during radiochemotherapy and could represent an informative complemental biomarker to drive therapeutic decision-making. Estimated levels of circulating cell-free tumour DNA (ctDNA) in plasma should be interpreted cautiously when monitoring tumour outcome by next-generation-sequencing, as confounders like infections or drug application might influence the fraction of ctDNA in total cfDNA.

Keywords: Cell-free nucleic acids; Granulocyte colony-stimulating factor; Infection; Liquid biopsy; Radiotherapy; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers
C-Reactive Protein / analysis
Cell-Free Nucleic Acids / blood*
Chemoradiotherapy*
Female
Head and Neck Neoplasms / therapy*
Humans
Infections / blood
Infections / diagnosis*
Inflammation / blood
Inflammation / diagnosis*
Male
Prospective Studies

Substances

Biomarkers
Cell-Free Nucleic Acids
C-Reactive Protein