Fig. 1.

Recurrence of GBM. A–C: Contrast-enhanced MRI of a patient with GBM in the right frontal lobe obtained before surgery (A), after treatment with TMZ and radiotherapy (B), and at recurrence (C). D: Schematic drawing of GBM cell invasion into the deep brain. Although the GBM tumor mass is removed, invaded cells remain in the brain. Clusters of GSCs and non-GSCs form specific environments (GBM niches) with some extracellular matrix and secreting molecules. GBM recurs in the periphery of the removal cavity (marginal area) where some GSCs in GBM niches are resistant to chemo-radiotherapy and survive. GSCs without GBM niches in the invasive area die, stop growing, or grow below the detection level on MRI. GBM: glioblastoma multiforme, GSCs: glioblastoma stem cells, MRI: magnetic resonance imaging, TMZ: temozolomide.