NCMP-24. BRAIN-DERIVED CIRCULATING DNA AS A BIOMARKER FOR RADIOTHERAPY-INDUCED BRAIN DAMAGE

Abstract INTRODUCTION Radiotherapy is a common treatment for brain metastases. However, it is commonly associated with central nervous system (CNS) toxicity. There are no biomarkers for early detection of radiotoxicity. Here we explore the utility of cell-free circulating DNA (cfDNA) for detection of brain cells death in the context of brain metastases. Using comparative methylome analysis we have previously identified 12 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes and astrocytes. These brain-specific methylation markers were identified in plasma of patients suffering from multiple sclerosis, as well as traumatic and ischemic brain damage. We hypothesize that brain-derived cell-free DNA (bncfDNA) can be identified in patients suffering from brain metastases receiving radiotherapy, and can potentially be used as a biomarker to help guide treatment. MATERIALS AND METHODS We recruit oncological patients treated by brain radiotherapy for brain metastases. We serially assess each patient before, during and after treatment by neurological examination and MRI studies. In each study visit a blood sample is collected for bncfDNA measurement. RESULTS Preliminary results on samples from 22 patients show elevation of bncfDNA in patients suffering from brain metastases (average 8501 copies/ml; range 0-112336 copies/ml) compared with an extremely low background in healthy individuals (average 6 copies/ml; range 0–33 copies/ml); p < 0.0001). We observed elevation of cfDNA derived from neurons, oligodendrocytes and astrocytes. Next, we studied bncDNA levels following brain radiotherapy. Preliminary results from a patient suffering from an acute central facial paralysis during radiotherapy show clinical correlation of bncfDNA levels with neurological impairment related to acute radiotoxicity. Other patients are still followed-up with bncfDNA measurement during and after radiotherapy. CONCLUSION BncfDNA reflects brain cells death incurred by metastases, as well as damage associated with radiotherapy, and may serve as circulating biomarker for neurotoxicity in patients suffering from brain metastases.