Circulating tumor DNA accurately predicts disease progression and genotype alterations in postoperative adjuvant EGFR-TKI resistance: a case report

Background: Circulating tumor DNA (ctDNA) is receiving more and more attention for its role in tumor screening and disease surveillance in cancer patients. However, it is unclear whether ctDNA can be used to predict recurrence and metastasis in patients after radical resection due to the resulting lower tumor burden. The published literature on postoperative ctDNA levels is also currently limited.

Case description: In this article, we report a rare case in which ctDNA accurately predicted relapse, disease progression and mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in adjuvant setting in an EGFR-mutated lung adenocarcinoma patient. The 49-year-old male patient was a current smoker and denied any family history. Chest computed tomography (CT) scans revealed a 5.7×4.3 mass in the left upper lobe. He received adjuvant gefitinib after surgery for a stage IIIB (pT3N2M0) pulmonary adenocarcinoma. The ctDNA detection showed that the EGFR exon 19 deletion (EGFR del19) gene mutation frequencies decreased gradually and even disappeared. However, 8 months after the operation, the EGFR del19 mutation re-emerged in the blood, accompanied by a newly emerged solitary nodule (2 mm) that was later confirmed to be metastatic. Soon afterward, ctDNA detection revealed the EGFR T790M mutation, and the mediastinal lymph nodes rapidly enlarged. The patient's treatment was switched to Osimertinib and the ctDNA detection results showed the EGFR T790M gene mutation frequencies steadily decreased to zero. During the treatment period, ctDNA detection accurately predicted each change in disease burden and revealed genotype alterations. The patient ultimately developed severe metastases in the liver after developing resistance to Osimertinib.

Conclusions: This report suggests that ctDNA help monitor disease recurrence and identify genotypes in patients undergoing postoperative adjuvant EGFR-TKI therapy. More clinical researches are needed to support ctDNA is a promising tool for predicting disease progressive.