EP1.01-52 Preferable Intracranial Chemotherapy for Lung Cancer Patients with Meningeal Metastasis Harboring CIN in CSF

Abstract

Brain metastases occur in about half of the NSCLC patients throughout the course of disease, including brain parenchymal metastasis and meningeal metastasis. It has been reported that compared with plasma detection, next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) is capable of more comprehensively characterizing the genomic alterations of brain tumor, so as to identify actionable variants. We conducted a small sample study consisting of 7 patients with brain metastasis, including 3 lung cancer patients with meningeal metastasis (P314, P316, P318), a lung cancer patient with brain parenchymal metastasis (P323), 2 breast cancer patients with meningeal metastasis (P324 and P328) as well as a gastric cancer patient with meningeal metastasis (P326). Profiling of the specimens from CSF, brain parenchyma and plasma of these 7 patients was performed using NGS along with bioinformatics analysis. Among the three patients P314, P316 and P318, high-frequency driver mutations including ERBB2 p.V659E, EGFR p.L858R & MET amplification, EGFR 19del were detected in the CSF respectively, but all of these variants were not observed in the plasma. Notably, these three patients’ brain lesions continued to progress after receiving corresponding targeted agents, while their conditions remained stable in the presence of switching to intracranial chemotherapy. Following bioinformatic analysis revealed the occurrence of chromosome instability (CIN). We wonder if it is a special case or a common phenomenon. To further explore whether there is similar phenomenon in brain parenchymal metastasis, we examined the patient P323. The detection results of his brain parenchyma, CSF and plasma showed that there was no variation of CIN in brain parenchyma and CSF. In view of this, we hypothesized that CIN variants might exist only in lung cancer patients with meningeal metastasis. In addition, our results displayed that no chromosome instability was identified in the CSF of patients P324, P328 and P326. In summary, CIN is likely an important genomic feature of lung cancer with meningeal metastasis and is apt to be detected in the CSF. According to our observation, NGS of CSF specimen rather than plasma sample may be more favorable to the selection of appropriate treatment options for lung cancer patients with meningeal metastasis. For such patients with CIN variation, intracranial chemotherapy possibly offers more significant clinical benefit than other treatments such as targeted therapy. It still requires more investigations to verify above hypothesis.