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Notably, compared with serum, continuous monitoring in patients with recurrent GBM (n=4) undergoing a specific biochemotherapy regimen (irinotecan, thalidomide and doxycycline) revealed that MMP-9 levels in the cerebrospinal fluid (CSF) significantly and continuously increased over the treatment period (P=0.001), and this elevation preceded magnetic resonance imaging (MRI) detection of tumor progression signs, suggesting that CSF-derived MMP-9 could serve as an early biomarker for GBM recurrence or progression (63)