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[This article belongs to Volume - 71, Issue - 3]
Published on : 2026-03-29 18:46:43
Article Code: AMJ-29-03-2026-12371
Title : Integrating liquid biopsy and multimodal management in a patient with EGFR-mutant NSCLC and leptomeningeal carcinomatosis: A case-based review
Author(s) : Sarah Chen, MD, PhD, Robert Thompson, MD, Jennifer Williams, NP
Abstract :
This case report presents a 52-year-old woman with EGFR exon 19 deletion-mutant lung adenocarcinoma who
developed symptomatic leptomeningeal carcinomatosis (LC) following progression on first-line osimertinib,
manifesting with headaches, diplopia, and cerebellar ataxia. Liquid biopsy of cerebrospinal fluid (CSF) revealed an
EGFR C797S resistance mutation in trans configuration with concurrent plasma ctDNA negativity, confirming the CNS
sanctuary site hypothesis and clonal evolution distinct from systemic disease. Through a multidisciplinary approach
integrating neurosurgical placement of an Ommaya reservoir, intrathecal pemetrexed chemotherapy (50 mg twice
weekly), and pulse-dose osimertinib (560 mg twice weekly), the patient achieved rapid symptomatic resolution,
cytologic clearance of malignant cells, and undetectable CSF ctDNA within eight weeks. Subsequent craniospinal
proton irradiation was employed for nodular progression, yet despite initial disease control, MET amplification
emerged as a bypass resistance mechanism, necessitating the addition of crizotinib and ultimately transition to
hospice care 34 months from LC diagnosis. This case illustrates the critical role of CSF liquid biopsy in guiding targeted
therapy decisions for TKI-resistant LC, demonstrates the efficacy of intrathecal pemetrexed combined with high-dose
osimertinib as a salvage strategy, and underscores the imperative for fourth-generation EGFR inhibitors and MET
targeted combinations to address spatial heterogeneity and acquired resistance in this historically refractory
condition.