Serum NSE is Early Marker of Transformed Neuroendocrine Tumor After EGFR-TKI Treatment of Lung Adenocarcinoma

BACKGROUND: Transformation to a lung neuroendocrine tumor (LNET) is a mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). Serum neuron-specific enolase (NSE) is a useful marker in the detection of LNET. Therefore, we explored the clinical significance of serum NSE levels in the detection of transformed neuroendocrine tumors after EGFR-TKI therapy. METHODS: We report a cohort of 5 cases in our treatment group. The characteristics of the patients, pathological diagnoses, immunohistochemistry with molecular detection, laboratory examination, and treatment histories are analyzed. The tumor markers of serum NSE were analyzed. Additionally, we reviewed the publications reporting the tumor markers before and after LNET transformation during EGFR-TKI therapy. RESULTS: Most patients are female (3/5), aged <60 years old (4/5), nonsmokers (4/5) and harbor the EGFR 19 exon deletion (4/5). The median time of LNET transformation was 19 months (range: 12–31 months). The clinical characteristics were similar to those reported in previous studies. Laboratory examination revealed an increased NSE level before the LNET is defined. Sixteen publications were reviewed. Of those, 86.67% (13/15) publications showed an increased level of NSE when the LNET transformation was defined. CONCLUSION: Adenocarcinoma tumors in non-smokers, young patients harboring the EGFR 19 exon deletion tended to transform to LNETs after EGFR-TKI therapy. Combining our findings and a review of the literature, we suggest that serum NSE may be a useful tumor marker to predict neuroendocrine tumor transformation.