PMC8727519_01
Computed tomography scans show (A) lung lesions and mediastinal lymph node metastasis before icotinib therapy; (B) partial response in lung lesions after icotinib treatment; (C) pericardial effusion development; and (D) pericardial effusion was well controlled after osimertinib treatment.
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However, liver, lung, and bone metastases appeared twenty months later ( Figure 1A ). No progression of metastatic foci was identified ( Figure 1B ); however, neoplastic pericardial effusion ( Figure 2 ) developed with signs of disease progression after 6 months of icotinib treatment ( Figure 1C ). Chest computed tomography showed a small pericardial effusion after osimertinib treatment and the patient achieved a progression-free survival interval of more than 11 months ( Figure 1D ). The timeline of the clinical course is summarized in  Figure S1 .
Pericardiocentesis indicated positive cytology of pericardial effusion (hematoxylin-eosin stain; original magnification x400).
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No progression of metastatic foci was identified ( Figure 1B ); however, neoplastic pericardial effusion ( Figure 2 ) developed with signs of disease progression after 6 months of icotinib treatment ( Figure 1C ).
Next-generation sequencing analysis showed VOPP1-EGFR fusion mutations by repeat liquid biopsy of pericardial effusion and blood samples. (A) Integrative Genomics Viewer snapshot of VOPP1-EGFR fusion; (B) a schematic map of the VOPP1-EGFR fusion protein domain structure *indicates that termination codons cannot encode any amino acids.
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A repeat liquid biopsy of pericardial effusion and blood samples was performed for NGS to explore the mechanism(s) of acquired resistance and showed an emerging acquired VOPP1-EGFR fusion gene coexistent with T790M ( Figure 3 ).