PMC7727459_01
Timeline and effect of EGFR-TKI treatments. (A) Treatment timeline; (B) Baseline images of CT and MRI at diagnosis; (C) Brain metastases progressed and original lung mass reduced after seven months of icotinib treatment; (D) Brain metastases progressed and thoracic lesions controlled after eight months of osimertinib treatment; EGFR, epithelial growth factor receptor; TKI, tyrosine kinase inhibitor; CT, computed tomography; MRI, magnetic resonance imaging.
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Computed tomography (CT) scans showed a lung mass of the upper left lobe along with nodules involvement ( Figure 1B ). Brain magnetic resonance imaging (MRI) revealed brain metastases ( Figure 1B ). Variant allele frequencies (VAFs) of the detected EGFR L858R and A859S mutations were 8.7 and 8.41%, respectively ( Figures 1A ,  2 ). Tumors (RECIST v1.1) ( Figure 1C ). These phenomena can be inferred that the patient had developed resistance to icotinib. Plasma ctDNA detection results showed two secondary EGFR T790M and Y891D mutations, and VAFs were 1 and 1.89% respectively, accompanied with decreased VAFs of EGFR L858R and A859S mutations to 6.25 and 5.61%, respectively ( Figures 1A ,  2 ). CT scans showed thoracic lesions were still well controlled, but brain MRI revealed the brain metastases were larger and the edema was more obvious than before ( Figure 1D ). Compared with the VAFs of EGFR mutation sites in the second ctDNA testing, the third gene detection results revealed EGFR T790M disappeared, L858R and A859S decreased to 4.25 and 4.18% respectively, while Y891D increased to 4.38% ( Figures 1A ,  2 ). The patient received afatinib (40 mg per day) and experienced improvements in nausea, vomiting, consciousness and legs movement within two weeks.
Map of clonal evolution. The different colors represent different mutation sites in EGFR gene, as measured by the NGS platform; NGS, next-generation sequencing.
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Variant allele frequencies (VAFs) of the detected EGFR L858R and A859S mutations were 8.7 and 8.41%, respectively ( Figures 1A ,  2 ). Plasma ctDNA detection results showed two secondary EGFR T790M and Y891D mutations, and VAFs were 1 and 1.89% respectively, accompanied with decreased VAFs of EGFR L858R and A859S mutations to 6.25 and 5.61%, respectively ( Figures 1A ,  2 ). T790M disappeared, L858R and A859S decreased to 4.25 and 4.18% respectively, while Y891D increased to 4.38% ( Figures 1A ,  2 ). The patient received afatinib (40 mg per day) and experienced improvements in nausea, vomiting, consciousness and legs movement within two weeks.