case_images: PMC11015836_01
case_images: Schematic of treatment history of the patient. (A) The timeline of treatment (red arrow indicates the primary tumor and red circles indicate metastatic tumors). (B-E) Chest CT images and brain MRI throughout the disease course.
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case_images: A 71-year-old Chinese female was diagnosed with stage IV adenocarcinoma of the right lung in July 2020 (Figure 1A). TKI which is approved by National Medical Products Administration (NMPA) for use in China as first-line monotherapy in patients with NSCLC with somatic EGFR mutations. The patient received three cycles of icotinib treatment, and reexamination via computed tomography (CT) indicated clinical benefit (Figure 1B). T790M mutation was identified. The administration of osimertinib was initiated for the patient in June 2021 and demonstrated favorable tolerability (Figure 1C). However, a CT scan after one year of treatment revealed the presence of progressive lesions in the right lung (Figure 1D). T790M, TP53 R156Afs*14 and acquired BRAF V600E mutations (Figure 2B). Consequently, in August 2022, the patient underwent a combination therapy comprising furmonertinib, dabrafenib, and trametinib. The CT scans after 2 months of treatment showed obvious shrinkage in the pulmonary lesions, which contributed to a partial response (PR) in February 2023 (Figure 1D). Subsequent CT scans revealed the presence of secondary malignant tumors in both the brain and bone (Figure 1E).
case_images: Serial tumor tissue or ctDNA NGS analysis. (A) Presumed clonal evolution of our case. The horizontal axis suggests the clinical history, and the vertical axis represents tumor volume. NGS analysis assessed at the time of diagnosis revealed a high allelic fraction of EGFR, which decreased at the time of resistance. An BRAF V600E mutation had emerged when the patient resistant to osimertinib. After 8 months of treatment with furmonertinib, dabrafenib, and trametinib, the BRAF V600E was undetectable, but a new MAP2K1 K57N mutation had emerged. (B) Detected alterations and its' mutation frequency trend. Solid blue circles represent the mutation frequencies which tested from tissue samples. Filled red triangles represent the mutation frequencies which tested from ctDNA.
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case_images: T790M, TP53 R156Afs*14 and acquired BRAF V600E mutations (Figure 2B). Consequently, in August 2022, the patient underwent a combination therapy comprising furmonertinib, dabrafenib, and trametinib. The CT scans after 2 months of treatment showed obvious shrinkage in the pulmonary lesions, which contributed to a partial response (PR) in February 2023 (Figure 1D). However, progressive tumor progression was observed on follow-up images in March 2023, and a puncture genetic test of the right lower lung mass revealed the disappearance of the BRAF V600E and the presence of the MAP2K1 K57N (Figure 2). TP53 R156Afs*14 mutations in May 2023 (Figure 2). The patient was subsequently treated with anlotinib.