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

PLoS One. 2023 Nov 28;18(11):e0285646. doi: 10.1371/journal.pone.0285646. eCollection 2023.

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.

MeSH terms

  • Brain
  • Brain Injuries* / etiology
  • Brain Injuries* / surgery
  • Brain Neoplasms* / secondary
  • Humans
  • Pilot Projects
  • Radiation Injuries* / etiology
  • Radiosurgery*

Grants and funding

This research is funded by Israel Cancer Research Foundation 2016 (to AZ), The Katz Memorial Fund 2017 (to CM), Prusiner-Abramsky Research Award in clinical and basic Neuroscience 2019 (to CM), Esther Monsa Fund 2018 (to CM), Joint Research Fund of the Hebrew University of Jerusalem and Hadassah Medical Center 2016 (to YC). This work is also supported in part by grants of the Ernest and Bonnie Beutler Research Program of Excellence in Ge-nomic Medicine, The Israel Science Foundation, The Waldholtz/Pakula family, The Robert M. and Marilyn Stern-berg Family Charitable Foundation (to YD). Israel Cancer Research Foundation and the Rothschild Fellowship for Physician- Researchers (AsL) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.