Individual changes in neurocognitive functioning and health-related quality of life in patients with brain oligometastases treated with stereotactic radiotherapy

Meer, Pim B van der; Habets, Esther J. J.; Wiggenraad, Ruud; Kanter, Antoinette Verbeek-de; Nijeholt, Geert J. Lycklama à; Zwinkels, Hanneke; Klein, Martin; Dirven, Linda; Taphoorn, Martin J.B.

doi:10.1007/s11060-018-2868-7

Cited by 26 publications

(53 citation statements)

References 41 publications

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“…The installation of a cranial imaging window was based on procedures described previously [39]. Mice (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) weeks old; n = 23) were anaesthetised using isoflurane and the head was stabilised in a stereotaxic frame (Kopf Instruments). Cerebral oedema was treated perioperatively with dexamethasone (2 μg/g body weight; intramuscular injection).…”

Section: Cranial Window Installation and Implantation Of Tumour Cellsmentioning

confidence: 99%

“…Treatment options are mainly limited to whole brain radiation, in some cases neurosurgery, and survival is poor [6,7]. Furthermore, patients with metastatic brain tumours present with neurological symptoms including cognitive impairment and epileptic seizures [8,9], and this can have a significant impact on quality of life. However, the pathophysiological mechanisms underlying the cause of neurocognitive impairment and tumour-associated epilepsy are poorly understood [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

Simon

Yang

Marrison

et al. 2020

J Neuroinflammation

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Background: An emerging problem in the treatment of breast cancer is the increasing incidence of metastases to the brain. Metastatic brain tumours are incurable and can cause epileptic seizures and cognitive impairment, so better understanding of this niche, and the cellular mechanisms, is urgently required. Microglia are the resident brain macrophage population, becoming "activated" by neuronal injury, eliciting an inflammatory response. Microglia promote proliferation, angiogenesis and invasion in brain tumours and metastases. However, the mechanisms underlying microglial involvement appear complex and better models are required to improve understanding of function. Methods: Here, we sought to address this need by developing a model to study metastatic breast cancer cellmicroglial interactions using intravital imaging combined with ex vivo electrophysiology. We implanted an optical window on the parietal bone to facilitate observation of cellular behaviour in situ in the outer cortex of heterozygous Cx3cr1 GFP/+ mice. Results: We detected GFP-expressing microglia in Cx3cr1 GFP/+ mice up to 350 μm below the window without significant loss of resolution. When DsRed-expressing metastatic MDA-MB-231 breast cancer cells were implanted in Matrigel under the optical window, significant accumulation of activated microglia around invading tumour cells could be observed. This inflammatory response resulted in significant cortical disorganisation and aberrant spontaneously-occurring local field potential spike events around the metastatic site. Conclusions: These data suggest that peritumoral microglial activation and accumulation may play a critical role in local tissue changes underpinning aberrant cortical activity, which offers a possible mechanism for the disrupted cognitive performance and seizures seen in patients with metastatic breast cancer.

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Section: Cranial Window Installation and Implantation Of Tumour Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

Simon

Yang

Marrison

et al. 2020

J Neuroinflammation

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“…Baseline characteristics of patients with baseline HRQoL scores were not reported in two studies [39,40]. For two studies [33,36], a proportion of patients was also included in a subsequent study (respectively [32,37]). Sample sizes in the 9 selected studies ranged from 15 to 97 patients.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…In most studies, patients were female (range 43.2 to 67.3%), had primary lung cancer (range 37.3 to 100%), and had a median Karnofsky Performance Status (KPS) score of 80 (range < 70 to 100) ( Table 1). In four studies [34][35][36][37], patients with newly diagnosed BM were included; in four other studies [32,33,38,39], patients received prior BM treatment; and in one study [40], it was not reported if patients received prior BM treatment. Reasons for dropout were not reported in 6 studies [32,34,35,[38][39][40], and in two studies [36,37], reasons of dropout were reported, but without the numbers of patients (Table 1).…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…In three [32,33,38] out of nine studies, HRQoL was the primary outcome measure. Four studies [32,33,38,39] evaluated HRQoL both at the group level and at the individual level, two studies [35,36] evaluated HRQoL at the group level only, and two studies [34,37] evaluated HRQoL at the individual level only. In the studies reviewed, HRQoL was measured with 5 different self-report questionnaires.…”

Section: Hrqol Assessmentsmentioning

confidence: 99%

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Health-related quality of life in adult patients with brain metastases after stereotactic radiosurgery: a systematic, narrative review

Verhaak

Gehring

Hanssens

et al. 2019

Support Care Cancer

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Purpose A growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS. Methods We searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately. Results Out of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used. Conclusions In general, SRS does not have significant negative effects on patients' overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review.

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Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy

van Grinsven,

Cialdella,

Verhoeff

et al. 2023

Psycho-Oncology

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ObjectivePatients with brain metastases (BrMs) are a heterogeneous population, with almost 50% experiencing cognitive impairment before brain radiotherapy. Defining pre‐radiotherapy cognitive profiles will aid in understanding of the cognitive vulnerabilities and offer valuable insight and guidance for tailoring interventions.MethodsThe study population consisted of 58 adult patients with BrMs referred for radiotherapy. A semi‐structured interview and comprehensive battery including 10 neuropsychological tests were used to assess subjective and objective cognitive performance prior to radiotherapy.ResultsA majority (69%) of patients report decline in cognitive performance compared to their premorbid level (i.e. pre‐cancer). Objective testing revealed memory (52%), processing speed (33%) and emotion recognition (29%) deficits were most frequent. 21% of patients had no cognitive deficits while 55% had deficits (−1.5SD) in at least two cognitive domains. Hierarchical cluster analysis based on patient deficit profiles identified four clusters: (I) no or limited cognitive deficits selectively restricted to processing speed or executive function, (II) psychomotor speed deficits, (III) memory deficits and (IV) extensive cognitive deficits including memory. No patient or clinical‐related (e.g. age, number of BrMs, previous treatment) differences were found between clusters.ConclusionsPatterns of cognitive performance in patients with BrMs are heterogeneous, with most experiencing at least some degree of neurocognitive dysfunction. We identified four meaningful cognitive clusters. Stability of these clusters over time and in different samples should be assessed to advance understanding of the cognitive vulnerability of this patient population.

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Individual changes in neurocognitive functioning and health-related quality of life in patients with brain oligometastases treated with stereotactic radiotherapy

Cited by 26 publications

References 41 publications

Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

Health-related quality of life in adult patients with brain metastases after stereotactic radiosurgery: a systematic, narrative review

Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy

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