Prognostic value of cell-free DNA in cerebrospinal fluid from lung cancer patients with brain metastases during radiotherapy

Abstract

Background: During the last decades, radiotherapy (RT) for non-small cell lung cancer (NSCLC) with brain metastases (BM) has been developed. However, the lack of predictive biomarkers for therapeutic responses has limited the precision treatment in NSCLC-BM. Patients and methods: In order to find the predictive biomarkers for RT, we investigated the influence of RT on the cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and the frequency of T cell subsets of NSCLC patients with BM. A total of 19 patients diagnosed as NSCLC with BM were enrolled. The CSF from 19 patients and matched plasma samples from 11 patients were collected before RT, during RT, and after RT. The cfDNA from CSF and plasma were extracted, and the cerebrospinal fluid tumor mutation burden (cTMB) was calculated after through next-generation sequencing. The frequency of T cell subsets in peripheral blood was using flow cytometry. Results: The detection rate of cfDNA was higher in CSF compared to plasma in the matched samples. The mutation abundance of cfDNA in CSF was decreased after RT. However, no significant difference was observed in cTMB before and after RT. Although the median intracranial progression-free survival (iPFS) has not yet been reached in patients with decreased or undetectable cTMB, there was a trend that these patients possessed longer iPFS compared to those with stable or increased cTMB (HR 0.28, 95% CI 0.07–1.18, P = 0.067). The proportion of CD4+T cells in peripheral blood was decreased after RT. Conclusion: Our study indicates that cTMB can serve as a prognostic biomarker in NSCLC patients with BMs.