Department of Neurology and Oncology, The Gaffin Center for Neurooncology, Sharett Institute for Oncology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
PLoS One. 2023 Nov 28;18(11):e0285646. doi: 10.1371/journal.pone.0285646. eCollection 2023.
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.
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.
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.
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.
放射疗法在治疗脑转移瘤方面具有重要作用，但存在短期和/或长期毒性的风险，称为放射性脑损伤（RBI）。由于 RBI 的诊断对于正确的患者管理至关重要，因此迫切需要 RBI 的可靠生物标志物。本概念验证研究的目的是确定通过神经元、星形胶质细胞和少突胶质细胞的特定甲基化模式鉴定的脑源性循环游离 DNA（BncfDNA）作为放射治疗引起的脑损伤的生物标志物的效用。
24 例脑转移患者在脑放射治疗前、期间和后进行临床和影像学监测，并同时采集血液进行 BncfDNA 分析（98 个样本）。16 例患者接受全脑放射治疗，8 例患者接受立体定向放射外科手术。
在随访期间发现了 9 例 RBI 事件，与基线相比，所有 RBI 事件均与 BncfDNA 水平的显著升高相关。此外，RBI 的缓解与 BncfDNA 的降低相关。BncfDNA 的变化独立于肿瘤反应。
升高的 BncfDNA 水平反映了放射治疗引起的脑细胞损伤。需要进一步的研究来确立 BncfDNA 作为放射治疗引起的脑损伤的新型血浆生物标志物。
