New Considerations in Radiation Treatment Planning for Brain Tumors: Neural Progenitor Cell–Containing Niches

Abstract

The purpose of this critical review is to explore the controversy regarding the relationship between radiation dose to the neural progenitor cell (NPC) niches and patient outcomes, in terms of both toxicity and tumor control. NPCs in the subventricular zone (SVZ) and hippocampus are paradoxically associated with long-term neurocognitive sequelae of brain irradiation, as well as resistance to therapy and tumor recurrence. The reconciliation of these somewhat opposing functions is challenging. Current literature suggests that radiation and other treatments against the NPC in the hippocampus and the SVZ may influence patient outcome. As a result, both the SVZ and the hippocampus could have important implications on radiation treatment planning strategies, and future laboratory and clinical evaluations will be critical in designing studies to optimize treatment outcome, effectiveness, and safety.

Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma

“…The advantages become even more relevant in children, where declines in IQ, processing speed, and fine motor skills have been reported after CRT [33][34][35]. The hippocampus and the bilateral SVZ are known to harbor NPCs [36,37], which are assumed to contribute to neurogenesis and injury repair with their self-renewing capacities [38,39], and could thereby play a major role in the initiation of neurocognitive impairment. However, the role of the dose to stem-cell niches is still under debate [40].…”

Glioblastoma recurrence patterns near neural stem cell regions

“…However, the contribution of these neurogenic regions as potential sources of cancer stem cells as well as their role in GBM recurrence is controversial [15]. Stem cells within the SVZ and SGZ are thought to play functional roles in memory, neurocognition, and neuro-regeneration [9,16,17].…”

Dosimetric advantages of proton therapy over conventional radiotherapy with photons in young patients and adults with low-grade glioma

“…The reason for radiation-induced neurocognitive impairment is most likely multifactorial [13, 39]; however, there is growing evidence that supports the idea that neural progenitor cells (NPCs) in stem cell niches play an important role. The hippocampus and the SVZ are known areas of origin for NPCs [11, 12]. Although their role has not yet been fully elucidated, it is hypothesized that their capability for self-renewal and injury repair is of central importance to the genesis of long-term neurocognitive effects [41, 42].…”

“…In view of the dosimetric superiority of PRT compared to 3D-CRT, this study was conducted to present in detail the influence on structures that are essential for neurocognitive function, in addition to specific OAR that are responsible for neurologic side effects or impairment of quality of life. In the world of radiation oncology, sparing of the hippocampus and other stem cell niches has become a topic of particular interest [11, 12]. However, there are several risk factors for the development of neurocognitive dysfunction: in addition to radiotherapy, tumor localization, the extent of resection, and concomitant chemotherapy are recognized risk factors [13].…”