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Non-small cell lung cancer (NSCLC) is a profoundly devastating disease that is the leading cause of cancer-related death worldwide. With the rapid development of next-generation sequencing (NGS), which has supplied the ability to decode tumors at the DNA level, so that targeted therapy plays a crucial role in improving NSCLC survival. We first reported a 32-year-old Chinese female patient received the ninth-line treatment, who was initially diagnosed with advanced NSCLC with EGFR 19 deletion. The patient had a satisfactory clinical response to initial gefitinib treatment. Subsequently, an EGFR T790M mutation was detected from plasma-derived circulating tumor DNA (ctDNA) by ddPCR after disease progression, while NGS did not. Osimertinib was still tried but had no therapeutic effect. Then the disease even progressed on the administration of chemotherapy and gefitinib in succession. Rebiopsy for NGS detection was performed, and gefitinib plus anlotinib/vemurafenib were tried. And then, gefitinib plus crizotinib were administrated for MET amplification after the third biopsy. Furthermore, chemotherapy combined with immunotherapy was performed due to the PD-L1 positive expression. Up to now, osimertinib treatment was undertaken to base on an EGFR exon 20 T790M mutation using NGS-based genotyping in cerebrospinal fluid (CSF) ctDNA. Tumor genome dynamic monitoring can identify tumor driving genes and drug resistance mechanisms to guide tumor treatment. This study found that the total survival time of advanced NSCLC patients was more than four years after chemoradiotherapy and targeted therapy, indicating the significance of dynamic monitoring of gene alterations for cancer treatment.

Long-term survival with targeted therapy in an advanced non-small cell lung cancer patient based on genetic profiling