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Thorac Cancer. 2019 Apr;10(4):957-965. doi: 10.1111/1759-7714.13035. Epub 2019 Mar 18.

Re-biopsy and liquid biopsy for patients with non-small cell lung cancer after EGFR-tyrosine kinase inhibitor failure.

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Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.



Re-biopsy is important for exploring resistance mechanisms, especially for non-small cell lung cancer (NSCLC) patients who develop resistance to EGFR-tyrosine kinase inhibitors (TKIs). Liquid biopsy using circulating tumor DNA has come into use for this purpose. This retrospective study investigated the status of re-biopsy and liquid biopsy in NSCLC patients with EGFR mutations and evaluated their effect on clinical strategies and prognosis.


Five hundred fifty-five NSCLC patients with resistance to EGFR-TKIs were included and divided into three groups: re-biopsy, liquid biopsy, and no re-biopsy. Amplification refractory mutation system (ARMS) PCR or super ARMS PCR was used to detect EGFR mutations.


Three hundred eight (55.5%) patients underwent re-biopsy; 45.5% (140/308) were positive for T790M. The most common re-biopsy procedure was computed tomography-guided percutaneous core needle biopsy (60.1%), followed by effusion drainage (29.5%) and superficial lymph node biopsy (6.5%). One hundred eighteen (21.3%) patients underwent liquid biopsy; the T790M detection rate was 41.5% (49/118.) Of the 308 patients who underwent re-biopsy, 69 were examined for EGFR mutations with plasma. The concordance rate of T790M detection between tissue and plasma was 66.7%. A statistical difference in further treatment after EGFR-TKI failure was observed among all groups (P = 0.014). Patients in the biopsy groups were more likely to receive third-generation EGFR-TKIs. Multivariate analysis showed that re-biopsy had a significant impact on overall survival (P < 0.001).


Re-biopsy plays a pivotal role in the management of patients with NSCLC and resistance to EGFR-TKIs. Liquid biopsy may be an alternative if difficulties performing re-biopsy exist.


EGFR-TKI resistance; liquid biopsy; non-small cell lung cancer; re-biopsy

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