Intratumoral heterogeneity in glioblastoma: don't forget the peritumoral brain zone

Abstract

Glioblastoma (GB) is the most frequent and aggressive primary tumor of the central nervous system. Prognosis remains poor despite ongoing progress. In cases where the gadolinium-enhanced portion of the GB is completely resected, 90% of recurrences occur at the margin of surgical resection in the macroscopically normal peritumoral brain zone (PBZ). Intratumoral heterogeneity in GB is currently a hot topic in neuro-oncology, and the GB PBZ may be involved in this phenomenon. Indeed, this region, which possesses specific properties, has been less studied than the core of the GB tumor. The high rate of local recurrence in the PBZ and the limited success of targeted therapies against GB demonstrate the need for a better understanding of the PBZ. We present here a review of the literature on the GB PBZ, focusing on its radiological, cellular, and molecular characteristics. We discuss how intraoperative analysis of the PBZ is important for the optimization of surgical resection and the development of targeted therapies against GB.

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

“…3 Interestingly, studies 4,6 have suggested that heterogeneity extends beyond the tumour margins into the peritumoral brain parenchyma, and ultimately affects overall survival in GBM. In this work, we investigated the role of “peritumoral” radiomic features computed from the PBZ region on routine multi-parametric MRI protocols (T 1w , T 2w , FLAIR), in predicting long-term versus short-term survivors of GBM.…”

“…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.…”

“…This region is often hyper-intense in T2-weighted (T 2w ), and FLAIR acquisition, which reflects vasogenic oedema in the vicinity of the tumour and suggests tumour infiltration. 4 While several studies have shown the association of pre-operative MRI features from within and around the tumor with patient survival in GBM, 12,13 the contribution of imaging features from the PBZ in patient survival is poorly understood. This is largely due to the challenges in capturing tumour infiltration and the subtle differences in intra-tumoral heterogeneity in PBZ on MRI.…”

Frequent occurrence of therapeutically reversible cmv-associated encephalopathy during radiotherapy of the brain.

“…Especially in the outer zone of high-grade gliomas there are many histopathological differences from the typical "core" histology of gliomas, 11 leading to the hypothesis that "surrounding low-grade tumor," as can often be found on MRI, might actually be surrounding CMV infection.…”

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

“…brain, high resistance to apoptosis [4], robust angiogenesis [5], tumor cell heterogeneity [6], proliferation of cancer stem-like cells [7], and an inflammatory state that results in recruitment of circulating lymphocytes and monocytes. GBM tumors consist of a heterogeneous population of tumor cells and contain immune cells that, with tumor vasculature and the extracellular matrix, constitute the tumor microenvironment.…”