In conclusion, the data obtained from the present study demonstrates the following: (1) ctDNA is detectable in all CSF samples; (2) gene mutations are detectable in all CSF samples; (3) the gene copy number varies in all CSF samples; (4) the PI3K-Akt and ERK1/2 signaling pathways are the most altered signaling pathways for these mutated genes; (5) novel gene mutations are induced by intrathecal chemotherapy and systemic therapy in NM patients; (6) lung cancer (especially lung adenocarcinoma) is the major primary tumor in the present cohort of NM patients. Here, PIK3CA is linked to lung adenocarcinoma.