Dose-dependent volume loss in subcortical deep grey matter structures after cranial radiotherapy

Abstract

Background and purpose The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms. Materials and methods We selected 31 patients treated with RT for glioma. Pre-RT and post-RT 3D T1 MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age. Results A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16-1.37 %/Gy, corresponding to 4.9-41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years. Conclusion Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with more volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.

The Impact of Stereotactic or Whole Brain Radiotherapy on Neurocognitive Functioning in Adult Patients with Brain Metastases: A Systematic Review and Meta-Analysis

“…Rather, change in cognitive performance was observed across several cognitive constructs, including, but not limited to verbal L&M, EF, information processing speed, and fine motor coordination, which have been linked to a wide range of neuroanatomical substrates involving both cortical areas and white matter networks [50-54]. This is supported by previous research indicating morphological changes after brain irradiation in both cortical structures (cortical thickness, gray matter volume, and gray matter density) as well as white matter networks [55-61]. Additionally, the amount of microstructural damage to white matter fibers has been shown to be directly associated with cognitive deterioration in cancer patients [62].…”

Morphological changes after cranial fractionated photon radiotherapy: localized loss of white matter and grey matter volume with increasing dose

“…Subcortical structures such as hippocampus, amygdala, have also been shown to be vulnerable to volume changes after RT (9, 10). We have repeated these analyses, and observed comparable results (8). Furthermore, we found that in addition to these two structures, the thalamus, globus pallidus, nucleus accumbens, and putamen also show an association between radiotherapy dose and post RT volume loss.…”

“…Advances in imaging techniques have allowed the examination of the precise morphological changes in the brain after RT. Changes of white matter (WM) (3), cerebral cortex (4–7), and subcortical grey matter (GM) structures (8–10) have already been linked to received dose in several studies. However, these investigations have focused on specific parts or structures of the brain, which may limit the generalizability of the acquired knowledge.…”

The ROCOCO performance scoring system translates dosimetric differences into clinically relevant endpoints: Comparing IMPT to VMAT in an example pilocytic astrocytoma dataset

“…One could argue to score only the untreatable toxicity for example resulting in cognitive decline. Radiation therapy can cause late cognitive decline caused by damaging the brain by several mechanisms such as inducing vascular damage, demyelination and white matter changes to certain parts of the brain [18] , [19] , [20] , [21] . Although recently the OARs identified as possibly being relevant to cognition are expanded, future research needs to show if other areas in the brain should be taken into account and delineated when treating a CNS tumour [20] .…”