Abstract
Cytophenotypic transformation from adenocarcinoma to SCLC raises much attention as a mechanism of drug resistance in NSCLC patients treated with EGFR-TKI therapy. However, there’s no noninvasive way to predict and monitor the occurrence of cell transformation. We collected 362 cases of transformation from adenocarcinoma to SCLC to analyze the relationship among cancer development, tumor cell transformation and specific serum tumor marker of SCLC (NSE). The associations among the tumor medications, therapeutic effect and serum NSE were analyzed by chi-square test and Kaplan-Meier survival analysis was conducted by log-rank analysis in adenocarcinoma patients. All 362 adenocarcinoma patients were collected from 2013 to 2015 in Shanghai Pulmonary Hospital and accepted EGFR mutation test. 79 patients accepted the repeat biopsy and 4 patients showed the cytophenotypic transformation. In the cytophenotypic transformation cases, NSE was normal at first and increased remarkably during the treatment. The peculiar rising pattern of serum NSE matched the SCLC pathological confirmation in repeat biopsy. Then we further found that in 362 cases, 66 (18.2%) patients experienced the peculiar rising pattern of serum NSE. Notably, this kind of NSE changing pattern is associated with drug resistance (p=0.026), but has no relationship with EGFR mutation or targeted therapy. What’s more, the peculiar rising pattern of serum NSE during the first-line treatment led to a shortened PFS of the second-line treatment (p=0.042). Cytophenotypic transformation from adenocarcinoma to SCLC develops no matter the EGFR mutation positive or not, targeted therapy taken or not. For adenocarcinoma patients, serum tumor markers, especially NSE, need highly attention in clinical practice. A repeat biopsy is strongly recommended when adenocarcinoma patients’ NSE level shows the remarkable rise in case of cytophenotypic transformation to SCLC.
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