gms | German Medical Science

Objective: Neuron-specific enolase (NSE) is an enzyme that is found in many cells of neural origin, including neuroendocrine cells. Blood levels of NSE can be increased in diseases of brain, lung or liver. It can serve as a tumor marker in small cell lung cancer, neuroendocrine tumors and neuroblastoma. Despite modern neurosurgical treatments, brain metastases are a harbinger of reduced survival and have a risk of in-brain recurrence. It is unknown whether pre- and immediately postoperative NSE levels could serve as a blood biomarker for local in- brain tumor recurrence and survival. Therefore, we assessed the value of NSE based on our prospective Metastasys trial data.

Methods: According to the Metastasys trial protocol, blood samples were obtained prior and three days following resection of a suspected metastasis to the brain using the Diasorin-method (LIAISON®NSE, LNSE) with a normal value of 18.3ug/ml. Patients with possible causes of false positive NSE-values (proton pump inhibitor treatment, hemolytic anemia, liver and end stage kidney failure) were excluded. To analyze the predictive value of NSE levels, we employed descriptive statistic methods, paired t-test, survival function (Kaplan-Meier; log-rank) and a cutoff p-value <0.05.

Results: Out of 117 patients, 66 (56.4%) were male, 103 (88%) aged >50y. Pulmonary neoplasia was the primary tumor of origin in 60 cases (51.3%). Seventeen (14.5%) were small cell lung cancers (SCLC) and 43 (36.8%) were non-small cell lung cancers (NSCLC). Elevated NSE was seen in 39 (33.3%) patients and was in normal range in 78 (66.7%). NSE values increased significantly from a mean of 20.072 (standard deviation [SD] 18.178) preoperatively to 22.574 (SD 26.243) postoperatively (p<0.001). No significant difference was observed with regard to tumor diameter (cutoff>30mm; p=0.429). Local in-brain recurrence was seen in 3 (7.7%) patients with elevated NSE, and in 11 patients with initially normal NSE (p=0.314), yielding no significant difference. Normal preoperative NSE levels were associated with significantly longer survival than elevated NSE levels (12 (95%CI 6.9-17.1) months vs. 7 (95%CI 5.0-9.0; p= 0.015).

Conclusion: In metastatic brain disease treated surgically, NSE levels were not associated with the risk of in-brain tumor recurrence.However, elevated NSE levels were associated with shorter survival, indicating the potential for blood NSE as prognostic marker of outcome.