Abstract
Introduction: Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI.Methods: A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0 Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects.Results: At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white mater of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks.Conclusion: As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.
Highlights
Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited
As implied from the network structure of the brain, the inter-network resting-state functional connectivity (RSFC) was generally lower than the within-network connectivity in the healthy subjects, and was significantly further reduced in the patient for the visual, somato-motor, dorsal attention, and ventral attention networks
A nonsmall cell cancer (NSCLC) long-term survivor with metastatic brain disease who had WBRT developed extended white matter damage expressed by T2/FLAIR hyperintensities mainly covering the dorsal bilateral frontal and parietal lobes
Summary
Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Modern concepts of brain function suggest that cognitive performance in different domains does not rely solely on the function of specialized single cortical regions but rather depends on the interaction of multiple cortical regions organized in distributed functional networks. Several of these functional networks have been identified using resting-state functional MRI (rs-fMRI), and a set of cognitive functions have been assigned to them (Yeo et al, 2011; Schaefer et al, 2018). Because WBRT, as chemotherapy, potentially affects multiple cortical regions and networks, it can be hypothesized that cognitive deficits after WBRT affect functional connectivity both within and between multiple networks and may result in deficits in multiple cognitive domains
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
