Neuron - specific enolase predicts the prognosis in advanced small cell lung cancer patients treated with first-line PD-1/PD-L1 inhibitors

Abstract

There has been no effective biomarker for small cell lung cancer (SCLC) patients with first-line immune checkpoint inhibitors (ICIs) treatment. The predictive value of neuron-specific enolase (NSE) in this cohort remains unclear. The medical records of 254 consecutive SCLC patients receiving programmed cell death receptor-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors were compiled from January 2015 to October 2020 in Chinese PLA General Hospital. Survival analysis was performed to explore the prognostic role of NSE at baseline and 3 weeks post treatment. One hundred two advanced SCLC patients treated with first-line PD-1/PD-L1 inhibitors were enrolled in this study. Normal baseline NSE levels were correlated with significantly prolonged progression-free survival (PFS, median: 8.7 vs 4.7 months, P = .006) and overall survival (OS, median: 23.8 vs 15.2 months, P = .014) compared with elevated baseline NSE levels, so as for normal NSE levels at 3 weeks with prolonged PFS (median PFS: 8.4 vs 4.5 months, P = .0002) and OS (median OS: 23.3 vs 7.4 months, P < .0001). Intriguingly, elevated NSE levels at 3 weeks were associated with shorter PFS (median PFS: 4.5 vs 5.8 months, P = .04) and OS (median OS: 5.5 vs 14.7 months, P < .0001) compared with normal NSE levels in the elevated baseline NSE subgroup. Most subgroup analyses stratified by clinical characteristics confirmed the prognostic value of baseline NSE level. Elevated NSE levels at baseline and 3 weeks were associated with worse prognosis in advanced SCLC patients receiving first-line ICIs treatment. NSE level might be applied as a useful prognostic tool for SCLC patients with immunotherapy.

Clinical Efficacy of Anti-programmed Death Ligand 1 Immunotherapy Combined with Chemoradiotherapy in the Treatment of Limited-stage Small Cell Lung Cancer and Its Effect on Serum Tumor Markers and T Lymphocyte Subsets

“…Tumor markers are produced and secreted by human tumor tissues and cells [18] , and their levels are positively correlated with the severity of the patient's condition [19] NSE is a sensitive marker of neuroendocrine tumors, which can re ect the occurrence and progress of tumors; Pro GRP is an important marker for tumor condition and prognosis evaluation. Its expression level is positively correlated with the severity of the disease, which is of great signi cance for disease condition evaluation and prognosis prediction [20][21][22] .…”

Assessment of Specific Tumoral Markers, Inflammatory Status, and Vitamin D Metabolism before and after the First Chemotherapy Cycle in Patients with Lung Cancer

“…While NSE is widely accepted as a biomarker in SCLC, its usefulness in NSCLC is not clearly defined yet. Circulating NSE levels illustrate statistically significant variations in SCLC according to the status of patient: elevated pre-treatment levels will initially increase after chemotherapy (tumor lysis syndrome), followed by a decrease in responder patients (chemotherapy sensitive tumors) [ 45 ]. In SCLC, a recent study by Li et al [ 46 ] showed the prognostic value of NSE levels: elevated baseline and three-week levels were associated with worse prognosis in advanced SCLC patients receiving immunotherapy [ 46 ].…”

“…Moreover, circulating NSE could also represent a useful marker in NSCLC and a significant and independent predictor of survival. According to the studied literature, patients with lower NSE pre-treatment levels have a significantly higher survival rate than those with elevated levels, and the prognostic value of NSE is independent of other prognostic variables [ 45 ].…”

Neuron-Specific Enolase—What Are We Measuring?

“…NSE has also been actively studied in other diseases [4,[34][35][36][37][38]. Increased serum NSE levels have been observed in lung diseases such as tuberculosis, chronic obstructive pulmonary disease, alveolar proteinosis, and acute respiratory distress syndrome [4].…”

“…Patients with severe respiratory failure caused by SARS-CoV-2 infection have been reported to have higher serum NSE levels than those with mild disease and controls [35]. Elevated serum NSE levels have been found in patients with small cell lung cancer [36]. NSE modulation regulates cell proliferation, drug resistance, and tumor growth [37].…”