A case of different gene mutations in primary and metastatic lesions after EGFR-TKI treatment of lung cancer.
BACKGROUND
It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment.


CASE REPORT
We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis.


CONCLUSION
Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.
['Xie|Shaonan|S|https://orcid.org/0000-0002-0400-1348', 'Deng|Huiyan|H|', 'Liu|Guangjie|G|', 'Liu|Qingyi|Q|https://orcid.org/0000-0002-6797-6783']
D000328:Adult D066246:ErbB Receptors D005091:Exons D006801:Humans D008175:Lung Neoplasms D008279:Magnetic Resonance Imaging D008297:Male D009154:Mutation D009362:Neoplasm Metastasis D009367:Neoplasm Staging D047428:Protein Kinase Inhibitors D017384:Sequence Deletion D014057:Tomography, X-Ray Computed
EGFR-TKI Lung adenocarcinoma spatial heterogeneity acquired resistance genetic mutation