Abstract Background: Serum NSE, a marker of neuronal injury, may serve as a non-invasive indicator of early CNS involvement in solid tumors. Here, we explore the role of NSE for predicting development of CNS metastases. Methods: The BrainStorm program, is an ongoing international, multicenter prospective initiative, allowing the constitution of a large clinicopathological database and biobank to study CNS metastases. The program is recruiting patients (pts) with newly diagnosed non-CNS metastatic solid tumors at high risk of (Part A) or with CNS metastases (Part B and C). All pts undergo serologic NSE testing at baseline and at regular intervals pre- and post-CNS metastases. Main objective of the present analysis was to assess the role of baseline NSE as a predictive biomarker of CSN development from pts tested in Part A vs B, using Mann-Whitney test for group comparisons and logistic regression models to estimate OR. Results: 124 pts with available NSE results were included in the program from Nov/2020 to Jun/2025 (Part A, n=73; Part B, n=51) - Table 1. NSE levels were significatively higher in Part B than Part A (median 15.0 (IQR 12.8-24.3) vs 13.6 (IQR 11.4-16.4) ng/mL; p=0.017). In Part A, baseline NSE, as a continuous variable, was significantly associated with CNS metastases development (OR per ng/mL increase 1.12; 95% CI 1.02-1.22). Using the upper limit of normal as a categorical cut-off, baseline NSE showed a trend toward higher odds of CNS metastases (OR 2.84; 95%CI 0.60-13.39; 8 CNS events). Conclusions: These findings support a potential role for NSE as a non-invasive predictive biomarkers for the development of CNS metastases although confirmation in the fully accrued BrainStorm program is required. Citation Format: Soraia Lobo-Martins, Diogo Martins-Branco, Luca Arecco, Guilherme Nader-Marta, Andrea Gombos, Anthony Gonçalves, Eleonora Stephane de Maio D’Esposito, Philippe Barthelemy, Vincent Vanhaudenarde, Florian Clatot, Stéphane Holbrechts, Francois P. Duhoux, Edith Borcoman, Elisabeth Pop, Damien Parlier, Claire Cheymol, Joseph Gligorov, Hannelore Denys, Paul Clement, Caroline Duhem, Lore Decoster, Jean-Luc Canon, Nadège Kindt, Françoise Rothé, Ahmad H. Awada, Nuria Kotecki. Serum neuron-specific enolase (NSE) as a biomarker of central nervous system (CNS) metastases: Updated results from the BrainStorm program (Oncodistinct 006) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1063.
Lobo-Martins et al. (Fri,) studied this question.