Brain metastases: epidemiology

Ostrom, Quinn T.; Wright, Christina Huang; Barnholtz‐Sloan, Jill S.

doi:10.1016/b978-0-12-811161-1.00002-5

Cited by 238 publications

(198 citation statements)

References 126 publications

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“…Yet, despite advancements in radiosurgery and immunotherapy, the median survival for patients with brain metastases rarely exceeds 12 months. [6][7][8] An improved understanding of the characteristics and pathogenesis of brain metastasis would facilitate the development of more effective therapies to treat and manage cancers that have spread to the brain.…”

Section: Introductionmentioning

confidence: 99%

Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition in Brain Metastasis

Ngo

Kim

Osorio-Vasquez

et al. 2020

Preprint

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A hallmark of metastasis is the adaptation of tumor cells to new environments. Although it is well established that the metabolic milieu of the brain is severely deprived of nutrients, particularly the amino acids serine and its catabolite glycine, how brain metastases rewire their metabolism to survive in the nutrient-limited environment of the brain is poorly understood. Here we demonstrate that cell-intrinsic de novo serine synthesis is a major determinant of brain metastasis. Whole proteome comparison of triple-negative breast cancer (TNBC) cells that differ in their capacity to colonize the brain reveals that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is the most significantly upregulated protein in cells that efficiently metastasize to the brain. Genetic silencing or pharmacological inhibition of PHGDH attenuated brain metastasis and improved overall survival in mice, whereas expression of catalytically active PHGDH in a non-brain trophic cell line promoted brain metastasis. Collectively, these findings indicate that nutrient availability determines serine synthesis pathway dependence in brain metastasis, and suggest that PHGDH inhibitors may be useful in the treatment of patients with cancers that have spread to the brain. Statement of SignificanceOur study highlights how limited serine and glycine availability within the brain microenvironment potentiates tumor cell sensitivity to serine synthesis inhibition. This finding underscores the importance of studying cancer metabolism in physiologically-relevant contexts, and provides a rationale for using PHGDH inhibitors to treat brain metastasis.

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Section: Introductionmentioning

confidence: 99%

Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition in Brain Metastasis

Ngo

Kim

Osorio-Vasquez

et al. 2020

Preprint

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“…Melanoma is the third most frequent cause of brain metastases, after lung and breast cancer, accounting for approximately 6-11% of all metastatic brain lesions 1,2 . Apart from cutaneous melanoma, which is the commonest subtype, melanoma may also arise from other sites containing melanocytes such as the glabrous skin of the palms, soles and nail beds (i.e.…”

Section: Introductionmentioning

confidence: 99%

Primary versus Secondary Central Nervous System Melanoma: a Diagnostic Dilemma and Report of a Case

Lefter¹,

Dumitrescu²,

GOBEJ³

et al. 2019

Rev. Med. Mod.

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Introduction: Malignant melanoma is a cancer of melanocytic origin, typically cutaneous. Despite recent advances, the prognosis is poor. Brain metastases occur in approximately 7-16% of cases and leptomeningeal metastases in 5-7%. Primary central nervous system (CNS) melanoma is rare, accounting for 1% of all melanoma cases and 0.07% of brain tumors. Methods: A 65-year old man presented with haemorrhagic venous infarction of the left temporal lobe, leading to reversible motor aphasia and right-sided hemiparesis. Brain magnetic resonance imaging also revealed peculiar supratentorial cerebral and meningeal lesions suggesting neoplasia or vasculitis. Ancillary tests were unremarkable, a brain biopsy was proposed, but the patient declined. After 1.5 years symptoms recurred and imaging studies found progression of lesions, with necrosis and surrounding vasogenic oedema. The patient fi nally agreed to a brain biopsy for conclusive diagnosis. Results: Histopathological and immunohistochemical assessment was consistent with malignant pigmented melanoma. There were no suspicious primary lesions, but the patient recounted having had a thoracic skin lump excised some years prior, allegedly benign, yet unavailable for second opinion. Conclusion: In suspicious CNS presentations, histopathological reevaluation of previously excised skin lesions is advised, especially if brain biopsy cannot be performed. Albeit rare, primary CNS melanoma should also be considered.

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“…Their exact incidence is certainly unknown, but they are estimated to be about ten times more common than primary tumors, they may occur in 9-17% of patients with cancer, and 35-50% of patients with brain metastases presents at least three metastases. The primary tumors that metastasize more frequently to the brain are those originated in lung (≥ 50%), breast (15-25%) and skin (melanoma) (5-20%) [22]- [24].…”

Section: Secondary Brain Tumorsmentioning

confidence: 99%

“…Brain metastases are the most common tumors of the CNS in adults, even more than primary brain tumors [22], [24], [182]. The prognosis of patients diagnosed with metastatic brain tumors is poor: the median survival of these patients is estimated to be limited to months even for patients under treatment [183], [184].…”

Section: Differentiation Between Brain Metastases and Glioblastomas 5mentioning

confidence: 99%

“…As previously stated in Chapter 5, brain metastases (BMs) are the most common neoplasms of the central nervous system (CNS) in adults and constitute a significant cause of morbidity and mortality. The prognosis of patients diagnosed with metastatic brain tumors is poor: the median survival of these patients is estimated to be limited to months even for patients under treatment [22], [24], [184]. The incidence of brain metastases is certainly unknown, although some studies indicate that they occur in nearly 9-17% of patients with cancer.…”

Section: Classification Of Brain Metastases By Their Primary Site Of mentioning

confidence: 99%

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Radiomics for diagnosis and assessing brain diseases: an approach based on texture analysis on magnetic resonance imaging

Ortiz-Ramón¹

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IIIn the third project, we evaluated the hippocampus MRI profile of Alzheimer's disease (AD) patients to identify the different stages of the disease. The current criteria for diagnosing AD require the presence of relevant cognitive deficits, so the underlying neuropathological damage is important by the time the diagnosis is made. With the purpose of establishing new biomarkers to detect AD in its early stages, we evaluated a set of 2D and 3D texture features extracted from MRI scans of the hippocampus of patients with advanced AD, early mild cognitive impairment and cognitive normality. Many 3D texture parameters resulted to be statistically significant to differentiate between AD patients and subjects from the other two populations. When combining these 3D parameters with machine learning techniques, high accuracy was obtained, thus suggesting that texture analysis could at least help identify the presence of AD.In the fourth project, we attempted to characterize the heterogeneity patterns of ischemic stroke in structural MRI. In brain MRI of older individuals, some pathological processes present similar imaging characteristics, like in the case of stroke lesions and white matter hyperintensities (WMH) of diverse natures, thus hindering the study of cerebrovascular diseases by means of imaging. Given that stroke effects are present not only in the affected region, but also in unaffected tissue, we investigated the feasibility of 3D texture features from WMH, normal-appearing white matter and subcortical structures to differentiate individuals who had a lacunar or cortical stroke visible on conventional brain MRI (T1-weighted, T2-weighted and FLAIR images) from subjects who did not. Texture features were not useful to differentiate between post-acute cortical and lacunar strokes, but promising results were achieved for discerning between patients presenting an old stroke and normal-ageing patients who never had a stroke. These results suggest that texture features may help in the detection of stroke lesions.This thesis presents four novel feasibility studies to help clinicians in the evaluation of different brain disorders by means of a radiomics approach based on texture analysis in conventional MRI. The results achieved highlight the potential of this practice for defining and characterizing brain lesions in a fast, reliable and non-invasive way. Abbreviations and Acronyms Brain and DiseasesAD Alzheimer's disease ADNI Alzheimer's Disease Neuroimaging Initiative BM brain metastasis CN cognitively normal, cognitive normality CNS central nervous system CSF cerebrospinal fluid EMCI early mild cognitive impairment GBM glioblastoma multiforme MCI mild cognitive impairment NAWM normal appearing white matter PNS peripheral nervous system SRS stereotactic radiosurgery SS subcortical structures SVD small vessel disease WBRT whole-brain radiotherapy WHO World Health Organization WMH white matter hyperintensities VIII Medical Imaging CAD computer-aided detection and diagnosis CT computed tomography FID free induction dec...

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Brain metastases: epidemiology

Cited by 238 publications

References 126 publications

Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition in Brain Metastasis

Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition in Brain Metastasis

Primary versus Secondary Central Nervous System Melanoma: a Diagnostic Dilemma and Report of a Case

Radiomics for diagnosis and assessing brain diseases: an approach based on texture analysis on magnetic resonance imaging

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