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      Cognitive effects of stereotactic radiosurgery in adult patients with brain metastases: A systematic review

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          Abstract

          Purpose

          Stereotactic radiation surgery (SRS) is increasingly applied in patients with brain metastases (BM) and is expected to have fewer adverse effects on cognitive functioning than whole brain radiation therapy (WBRT). Patients with BM are often confronted with a relatively short life expectancy, and the prevention or delay of cognitive decline to maintain quality of life is a clinically and highly relevant treatment goal. This review systematically and specifically evaluates the current literature on the cognitive effects of SRS in patients with BM.

          Methods and materials

          Published trials on SRS alone or in combination with WBRT, including objective assessment of cognitive functioning, were identified through a systematic search of the PubMed database up to March 2018.

          Results

          Of the 241 records screened, 14 studies matched the selection criteria: 2 pilot studies, 7 single-group/observational trials (1 study update), and 5 randomized trials (1 secondary analysis).

          Conclusions

          In general, the results show little to no objective cognitive decline up to 4 months after SRS compared with WBRT. However, most trials suffered from methodologic limitations that hindered reliable conclusions. Most importantly, few studies investigated the specific cognitive effects of SRS alone or versus WBRT. Furthermore, disentangling the cognitive effects of SRS from the effects of the disease itself and from the effects of other treatments remains very difficult. By presenting this comprehensive review, we aim to encourage researchers to probe deeper into this area and to do so in a standardized and methodologically optimal manner. The ultimate objective of this line of research is to inform both doctors and patients more precisely about the cognitive effects they can expect from treatment. This study is expected to improve the quality of decision-making and maximize clinical outcomes for each individual patient.

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          Most cited references55

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          Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

          Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.
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            Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

            Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series. © 2014 by American Society of Clinical Oncology.
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              Hopkins Verbal Learning Test ? Revised: Normative Data and Analysis of Inter-Form and Test-Retest Reliability

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                Author and article information

                Contributors
                Journal
                Adv Radiat Oncol
                Adv Radiat Oncol
                Advances in Radiation Oncology
                Elsevier
                2452-1094
                11 July 2018
                Oct-Dec 2018
                11 July 2018
                : 3
                : 4
                : 568-581
                Affiliations
                [a ]Gamma Knife Center, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
                [b ]Department of Cognitive Neuropsychology, Tilburg University, Tilburg, the Netherlands
                [c ]Department of Neurosurgery, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
                [d ]Department of Radiation Oncology, GROW–School for Oncology and Developmental Biology, Maastricht University Medical Centre, the Netherlands
                Author notes
                []Corresponding author. Tilburg University, Department of Cognitive Neuropsychology, Simon Building, Room S221, P.O. Box 90153, Warandelaan 2, 5000 LE Tilburg, The Netherlands. Phone: +31(0)657641948. w.schimmel@ 123456tilburguniversity.edu
                Article
                S2452-1094(18)30118-0
                10.1016/j.adro.2018.06.003
                6200877
                2d02e9fa-5598-4871-a253-7549ee76fd4f
                © 2018 The Authors on behalf of the American Society for Radiation Oncology

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 23 November 2017
                : 20 March 2018
                : 25 June 2018
                Categories
                Central Nervous System

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