Genotyping of Cerebrospinal Fluid Associated With Osimertinib Response and Resistance for Leptomeningeal Metastases in EGFR-Mutated NSCLC

Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer

“…In those patients, cerebrospinal fluid is emerging as an alternative source of ctDNA to detect gene alterations and clonal heterogeneity. [66][67][68] Recommendation: Plasma ctDNA can now be considered a valid tool for genotyping of newly diagnosed patients with advanced NSCLC, and results are often complementary to those of tissue analysis. At the time of acquired resistance after tyrosine kinase inhibitor (TKI) therapy in an oncogene-driven NSCLC, initial use of ctDNA is preferred for evaluation of mechanisms of resistance ("plasma-first"), with repeat tissue biopsy if plasma ctDNA is uninformative.…”

Detecting ALK Rearrangement with RT-PCR: A Reliable Approach Compared with Next-Generation Sequencing in Patients with NSCLC

“…Information about the therapeutic response to ALK -TKIs of these patients was not included for analysis because of a lack of therapeutic information about ALK inhibition, but treatment information for these patients is provided in Table 2 in the ESM. It is reported that the median progression-free survival of osimertinib should be much longer than 3 months, even where EGFR and TP53 mutations co-exist [ 22 ]. Thus, for one patient (ID: 1902861), the resistance mechanism should be ALK fusion, which was not detected with NGS.…”

Molecular Profiling of the Cerebrospinal Fluid in Leptomeningeal NSCLC: The Shape of Things to Come?

“…Some of the conclusions made in the study of Zheng et al 1 do fall short of this logic. Yet they do offer insights into some of the questions we may ask of CSF cfDNA analyses in the future.…”

“…However, unless the initial assessment of the driver oncogene status is derived from a resected central nervous system (CNS) metastasis, personalized medicine has largely steered clear of the CNS in NSCLC. In this issue of the Journal of Thoracic Oncology, Zheng et al 1 report on using next-generation sequencing of cfDNA in the cerebral spinal fluid (CSF) to interrogate the molecular status of leptomeningeal disease (LMD) in patients with EGFR-mutant NSCLC and hint at both the potential value and the challenges in interpreting such data for the future. 2 In their study, LMD was diagnosed on the basis of CSF cytology or "typical" leptomeningeal enhancement on brain magnetic resonance imaging and the data set comprised two separate cohorts.…”

“…The study of Zheng et al 1 then explored which baseline molecular characteristics in the CSF influenced intracranial progression-free survival (iPFS) and intracranial response (per Response Assessment in Neuro-Oncology-Leptomeninges criteria) in cohort 1 and whether the analyses in cohort 2 could offer insights into the later mechanisms of CNS resistance. 3 Many of the lessons learned from interpreting bloodbased cfDNA analyses will have to be equally applied to CSF-based cfDNA analyses.…”