Short report: Plasma based biomarkers detect radiation induced brain injury in cancer patients treated for brain metastasis: A pilot study

Chen Makranz, Asael Lubotzky, Hai Zemmour, Ruth Shemer, Benjamin Glaser, Jonathan Cohen, Myriam Maoz, Eli Sapir, Marc Wygoda, Tamar Peretz, Noam Weizman, Jon Feldman, Ross A. Abrams, Alexander Lossos, Yuval Dor, Aviad Zick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background Radiotherapy has an important role in the treatment of brain metastases but carries risk of short and/or long-term toxicity, termed radiation-induced brain injury (RBI). As the diagnosis of RBI is crucial for correct patient management, there is an unmet need for reliable biomarkers for RBI. The aim of this proof-of concept study is to determine the utility of brain-derived circulating free DNA (BncfDNA), identified by specific methylation patterns for neurons, astrocytes, and oligodendrocytes, as biomarkers brain injury induced by radiotherapy. Methods Twenty-four patients with brain metastases were monitored clinically and radiologically before, during and after brain radiotherapy, and blood for BncfDNA analysis (98 samples) was concurrently collected. Sixteen patients were treated with whole brain radiotherapy and eight patients with stereotactic radiosurgery. Results During follow-up nine RBI events were detected, and all correlated with significant increase in BncfDNA levels compared to baseline. Additionally, resolution of RBI correlated with a decrease in BncfDNA. Changes in BncfDNA were independent of tumor response. Conclusions Elevated BncfDNA levels reflects brain cell injury incurred by radiotherapy. further research is needed to establish BncfDNA as a novel plasma-based biomarker for brain injury induced by radiotherapy.

Original languageAmerican English
Article numbere0285646
JournalPLoS ONE
Volume18
Issue number11 November
DOIs
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
Copyright: © 2023 Makranz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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