Hippocampal sparing in brain radiotherapy

Abstract

Radiotherapy is one of the principal methods for treating brain cancer. Over recent years, a decline in patient quality of life has increasingly been observed in those undergoing brain irradiation, where hippocampal-dependent cognitive function has become impaired. The hippocampus is a paired structure of the limbic system situated in the medial temporal lobes of the telencephalon. Preliminary findings suggest that irradiation damaged neural stem cells in the hippocampus undergo apoptosis, resulting in deteriorating cognitive function. Despite the technical aspects for affording hippocampal avoidance during irradiation, much controversy still surrounds the techniques that shield the hippocampus without reducing the benefits of the intended radiotherapy for a given clinical condition. Furthermore, a tolerated radiation dose sufficient for preserving neural stem cell function has not been yet established. Delivering a method for an unequivocal assessment of cognitive function, post-irradiation, is also fraught with difficulty. Hitherto, only subjective psychological testing have been applied such as MMSE, HVLT or AVLT methods. Objective methods for optimally determining radiation-induced injury to the hippocampal region are still being investigated.

The Learning Curve and Inter-Observer Variability in Contouring the Hippocampus under the Hippocampal Sparing Guidelines of Radiation Therapy Oncology Group 0933

“…Brain irradiation (BI) is an essential treatment modality in a variety of oncological disorders and includes whole brain radiotherapy (WBRT) or stereotactic radiotherapy (SRT) for brain metastases (BM), prophylactic cranial irradiation (PCI) for small cell lung cancer patients, cranial irradiation or SRT in primary brain tumors (PBT) and other cerebral pathologies [1][2][3]. Despite many benefits of cranial irradiation, e.g., improved local control (LC) and overall survival (OS) [4,5], focus has recently shifted to the adverse events associated with the treatment, particularly neurocognitive decline and a decreased quality of life (QoL) in irradiated patients [6,7]. Clinical evidence indicates that three months after BI, patients suffer from impairment in memory function, in particular immediate and delayed recall [8], which is the result of radiation-induced injury to the brain neurogenic zones including the hippocampus [4].…”

“…The hippocampus is a paired brain structure, situated in the ventromedial section of the temporal lobe, located laterally to the temporal horn of the lateral ventricle. The bodies of the hippocampi consist of the dentate gyrus and the cornu ammonis areas, and their parts of the limbic system [6]. The hippocampus plays an essential role in learning, spatial processing, memory formation, retrieval and consolidation of information [11].…”

“…The hippocampus contains active neural stem cells (NSCs) in two "niches": the subgranular zone of the dentate gyrus (SGZ)-a crucial center for learning and memory function-and the subventricular zone (SVZ) [12]. NSCs are very sensitive to ionizing radiation which causes their apoptosis (reaching a peak as early as 12 h after irradiation) followed by a decrease in the number of proliferating cells in SGZ [6,13]. Finally, bilateral or unilateral radiation-induced injury to NSC niches results in deterioration of neurocognitive function [14].…”