Sequencing of cerebrospinal fluid in non‐small‐cell lung cancer patients with leptomeningeal metastasis: A systematic review

Abstract

Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells in the subarachnoid space, pia, and arachnoid mater and is a severe condition associated with metastatic solid tumors. The most common solid tumor that develops into LM is lung cancer and the incidence increased in patients with advanced non‐small‐cell lung cancer (NSCLC) with targetable mutations. However, tissue biopsy of LM is inaccessible, leading to the paucity of genomic profiles of LM to guide targeted treatments and explore biological mechanisms. In recent years, liquid biopsy is considered a minimally invasive and dynamic method to trace the genomic alterations of cancer cells and some studies started to perform sequencing of cerebrospinal fluid (CSF) in patients with LM to reveal the targeted mutations and genomic profiles. In this review, we focused on studies performed sequencing of CSF in NSCLC patients with LM and summarized the sequencing results and their commonality. As the only way to reveal the genomic landscapes of LM, our review provided evidence that sequencing of CSF is a promising management method in LM patients to dynamically guide target therapy and monitor intracranial tumor response. Furthermore, it reveals a unique genomic profile of LM including driver genes, drug‐resistant mutations, and a number of copy number variations. Sequencing of CSF in LM patients seems to provide more comprehensive genomic information than we expected and the biological significance behind the genomic alternations needs further study.

Quantification of Cerebrospinal Fluid Tumor DNA in Lung Cancer Patients with Suspected Leptomeningeal Carcinomatosis

“…Additionally, beyond the dynamic heterogeneity in tumor genotype over time, spatial heterogeneity may also help direct therapy. 48…”

“…46,47 In the selection of patients most likely to benefit from TKI re-challenge, plasma ctDNA and CSF-tDNA could allow personalized surveillance of resistance mechanisms within and outside of the CNS. 27,[31][32][33]48 Early changes in clonal composition, particularly those conferring therapeutic resistance, could aid clinical decision-making in identifying drugs most likely to be effective. Additionally, beyond the dynamic heterogeneity in tumor genotype over time, spatial heterogeneity may also help direct therapy.…”

Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis

“…EGFR-TKI re-challenge remains promising, with multiple studies evaluating re-administration of EGFR-targeted therapy after salvage cytotoxic chemotherapy 46 , 47 . In the selection of patients most likely to benefit from TKI re-challenge, plasma ctDNA, and CSF-tDNA could allow personalized surveillance of resistance mechanisms within and outside of the CNS 27 , 31 – 33 , 48 . Early changes in clonal composition, particularly those conferring therapeutic resistance, could aid clinical decision-making in identifying drugs most likely to be effective.…”

Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer

“… 39 To evaluate acquired resistance to EGFR‐TKI, a single test for EGFR mutation is not sufficient and NGS is the preferred method for genetic testing after EGFR‐TKI resistance. Besides tissue and liquid NGS from blood, there are increasing evidence that liquid NGS from pleural effusion, 40 , 41 , 42 ascites, 43 and cerebrospinal fluid 44 can provide information for tumor genetics and subsequent treatments. Body fluid NGS is particularly of value, especially in patients with only peritoneal or pleural metastases or leptomeningeal carcinomatosis.…”