PMC9403890_01
(A) Treatment timeline of the patient, histological morphology, and genetic results of three tissue biopsies (primary lesion in March 2017, lung metastasis in November 2019, and liver metastasis in November 2020). Dynamic monitoring of radiological results (B) and circulating tumor DNA using next-generation sequencing (NGS) (C).
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The patient underwent tissue biopsy through a bronchoscope and was diagnosed with stage IV LUAD ( Figure 1A ). After 16 months of erlotinib treatment, CT scans showed progressed disease (PD) due to the enlargement of lung metastatic nodules ( Figure 1B ). T790M along with L858R mutation, as well as EGFR amplification ( Figure 1C ). The patient started osimertinib treatment at 80 mg once daily as second-line therapy, and liquid biopsy monitoring only detected L858R and EGFR amplification 2 months after osimertinib, with no T790M retained. Osimertinib treatment lasted for 7 months before the resistance occurred ( Figure 1B ). Moreover, AKT1 E17K and a large fragment deletion of RB1 (exon18-27) were also detected ( Figure 1C ). CT scans showed rapid growth of the primary lesion in September 2019 ( Figure 1B ). Tissue biopsy guided by CT of metastatic lung lesion showed LUAD with sarcomatoid differentiation ( Figure 1A ). In November 2020, a new liver metastatic lesion was found and was confirmed to be adenocarcinoma with neuroendocrine differentiation via tissue biopsy ( Figure 1A ). FISH signal accounts (copy number) were recorded for a total of 50 nuclei, and the tumor was considered EGFR amplification when EGFR/CEP7 ratio was greater than or equal to 2 in 15% of recorded cells.  Figure 1A  shows that FISH revealed EGFR amplification in the metastatic lesions of both lung and liver, while no EGFR amplification was observed in the primary lesion. Dynamic monitoring of radiological results and liquid biopsy NGS results are shown in  Figures 1B, C .
The images of CT scans with different treatments. (A) CT scan of basic examination before first-line erlotinib. (B) CT scan during the first-line erlotinib treatment. (C) CT scan at the progression of first-line erlotinib. (D) CT scan at progression of second-line osimertinib. (E) CT scan at the progression of chemotherapy. (F) CT scan at progression of afatinib plus nimotuzumab. (G) CT scan at the progression of immunotherapy. (H) CT scan during combination therapy of irinotecan, nimotuzumab, and dacomitinib.
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The images of chest CT scans at different timepoints are shown in  Figure 2 .