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      Recent advances in managing brain metastasis

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          Abstract

          Brain metastases are the most common malignancy encountered in the central nervous system (CNS), with up to 30-40% of cancer patients developing brain metastases at some point during the course of their disease. The management of brain metastasis is rapidly evolving and the roles of local therapies such as whole-brain radiation therapy, stereotactic radiosurgery, and resection along with systemic therapies are in flux. An emphasis on the neurocognitive side effects associated with treatment has gained prominence. Novel molecular studies have demonstrated important evolutionary patterns underpinning the development of brain metastasis and leptomeningeal disease, which may be key to unlocking new therapeutic strategies. This article provides a framework for incorporating the results of recent randomized radiotherapy clinical trials into practice, expounds upon the emphasis on cognition being an important driver in therapeutic selection, describes the importance of CNS-penetrating systemic therapies, and provides an overview of the novel molecular insights that will likely set the stage for future developments in this field.

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          Most cited references50

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          Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft

          Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.
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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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              Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer

              Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.
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                Author and article information

                Contributors
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: SupervisionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                9 November 2018
                2018
                : 7
                : F1000 Faculty Rev-1772
                Affiliations
                [1 ]Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA
                [2 ]Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
                [3 ]Northwestern Medicine Cancer Center Warrenville, Warrenville, IL, USA
                [4 ]Northwestern University Feinberg School of Medicine, Chicago, IL, USA
                [5 ]Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
                [6 ]Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
                [7 ]Divisions of Hematology/Oncology and Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA
                [8 ]Harvard Medical School, Boston, MA, USA
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-4812-5713
                Article
                10.12688/f1000research.15903.1
                6234720
                30473769
                6c20f2d5-06cd-4047-be9e-a1aa94df4e33
                Copyright: © 2018 Kotecha R et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 November 2018
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles

                brain metastasis,whole brain radiation therapy,stereotactic radiosurgery,neurocognition,targeted therapy,genomic

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