Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

Abstract

Glioblastoma (GB) is the most frequent and aggressive type of primary brain tumor. Recurrences are mostly located at the margin of the resection cavity in the peritumoral brain zone (PBZ). Although it is widely believed that infiltrative tumor cells in this zone are responsible for GB recurrence, few studies have examined this zone. In this study, we analyzed PBZ left after surgery with a variety of techniques including radiology, histopathology, flow cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The resulting PBZ profiles were compared with those of the GB tumor zone and normal brain samples to identify characteristics specific to the PBZ. We found that tumor cell infiltration detected by standard histological analysis was present in almost one third of PBZ taken from an area that was considered normal both on standard MRI and by the neurosurgeon under an operating microscope. The panel of techniques used in this study show that the PBZ, similar to the tumor zone itself, is characterized by substantial inter-patient heterogeneity, which makes it difficult to identify representative markers. Nevertheless, we identified specific alterations in the PBZ such as the presence of selected tumor clones and stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is a growing field of interest and this region needs to be characterized further. This will facilitate the development of new, targeted therapies for patients with GB and the development of approaches to refine the per-operative evaluation of the PBZ to optimize the surgical resection of the tumor.

Radiomic features from the peritumoral brain parenchyma on treatment-naïve multi-parametric MR imaging predict long versus short-term survival in glioblastoma multiforme: Preliminary findings

“…Multiple studies 4,5,6 have demonstrated that GBM heterogeneity is not limited to the tumour margins but also involves the peritumoral brain parenchymal zone (PBZ), with roughly 90% of GBM recurrences occurring in the PBZ. 7 Few studies 8 have investigated the PBZ and its microenvironment suggesting that interaction of specific cells (i.e. glioma cells, vascular endothelial, neuroglial, and microglial cells 9,10 ) and molecular events in PBZ contribute to tumour infiltration, blood brain barrier compromise, and micro vascularity, ultimately leading to poor survival in GBM.…”

Quantitative MRI for analysis of peritumoral edema in malignant gliomas

“…If radical resection is impossible due to tumor location near eloquent regions of the brain, the aim is maximal tumor resection with preservation of brain function. The extent of resection influences the prognosis, and it is known that malignant gliomas extend beyond their contrast-enhancing border with a diffuse, non-enhancing infiltration into the peritumoral edema, which complicates the assessment of the remaining tumor burden [18,19]. These diffuse, non-enhancing tissue changes are not easily detected visually on conventional MR images, but can to some extent be identified with diffusion and perfusion imaging, which correlates with histopathological features of the tumors [20].…”

Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma

“…Usually, this area shows hyper-intensity on T 2 WI and FLAIR images due to vasogenic edema [40]; as the blood-brain barrier breaks down, capillary permeability increases, a pressure gradient from the vasculature to the extracellular environment is formed, and many intravascular proteins penetrate into the extra-cellular space [41]. In this study, the APTw value in the PBZ of SBMs and GBMs was significantly higher than in the CNAWM ( P <0.001).…”

“…In metastases brain tumors, PBZ T 2 hyperintensity mainly reflects vasogenic edema [7; 35]. In the GBMs, it is hypothesized that specific cells and inflammatory cells infiltrate into the PBZ [40; 42–44], and that the PBZ T 2 hyperintensity reflects more than vasogenic edema. Technically, the APTw effect is due to the shift of amide proton from mobile proteins and peptides to water proton [12].…”