scholarly journals CMET-14. BRAIN METASTASES: A NEW PATHOPHYSIOLOGY, A NEW TREATMENT PARADIGM, AND, PERHAPS, A NEW PROGNOSIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi54-vi54
Author(s):  
Richard Dowd ◽  
Tao Ouyang ◽  
Krishnamoorthy Thamburaj ◽  
Dawit Aregawi ◽  
Howard Safran ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Substantial Reduction ◽  
Blood Stream ◽  
Brain Parenchyma ◽  
Neoplastic Meningitis ◽  
Normal Brain ◽  
Malignant Cells ◽  
Therapeutic Implications ◽  
Treatment Paradigm ◽  
Pre Treatment

Abstract INTRODUCTION Brain metastases are widely held to reach the CNS through the blood stream. We provide evidence that the initial site of most CNS metastases is the CSF, with subsequent invasion of brain parenchyma. We also model the therapeutic implications of this novel hypothesis. METHODS Two neuro-radiologists independently assessed whether brain metastases were contiguous with CSF spaces in 200 consecutive patients using pre-treatment MRI. CSF was examined for malignant cells in 66 newly diagnosed, previously untreated patients. We contoured normal brain MRIs of 3 patients to calculate the percentage of brain within 5 mm of a CSF space. We queried an international neoplastic meningitis database to document response of brain metastases to intra-CSF chemotherapy. RESULTS Mean age was 64.2. One hundred patients were male; 143 had lung cancer, 15 melanoma, 12 gastrointestinal, 11 breast, 9 renal, 7 bladder. Mean number of metastases was 4.63. Eighty-five percent of metastases touched a CSF space. In 67% of patients, all metastases touched a CSF space. Neither histology, number or size of metastases, nor patient age predicted contiguity with CSF spaces. In our consecutive subset of patients, 44% (10/23) with one, 46% (5/11) with two, 63% (5/8) with three, and 71% (17/24) with >3 metastases had malignant cells in the CSF (R2=0.93, p=0.037). Five of 7 patients with both brain and CSF metastases receiving only IT chemotherapy experienced a substantial reduction in the size of at least some metastases. Up to 75% of the brain parenchyma lies within 5 mm of CSF spaces. CONCLUSIONS Our data suggest that brain metastases may access the CNS through the CSF rather than the bloodstream. IT chemotherapy may treat brain metastases. We suggest that the CSF should be monitored in all patients with, or at risk for, brain metastases. True cures may require treatment of the CSF space.

scholarly journals RADI-33. DISTRIBUTED FRAMELESS GAMMA KNIFE RADIOSURGERY: A NEW TREATMENT PARADIGM FOR PATIENTS WITH BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
Ankur Patel ◽  
Jameson Mendel ◽  
Aaron Plitt ◽  
Lucien Nedzi ◽  
Robert Timmerman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Treatment Time ◽  
Gamma Knife Radiosurgery ◽  
Median Number ◽  
Treatment Session ◽  
Normal Brain ◽  
Single Session ◽  
Treatment Paradigm ◽  
Number Of Treatment

Abstract INTRODUCTION: Stereotactic radiosurgery (SRS) has excellent efficacy for patients with limited intracranial disease. Its use in patients with >10 brain metastases remains controversial. Nonetheless, cancer patients are living longer due to advancements in systemic therapeutics and avoiding the neurocognitive toxicities of whole brain radiation therapy is critical. Recent reports suggest that SRS may be effective in patients with ≥10 metastases. Treating large numbers of brain metastases in a single Gamma Knife radiosurgery (GKRS) treatment session poses several challenges. Treatment of metastases in close proximity to one another leads to an increased dose to normal brain, potentially increasing the risk of necrosis. Furthermore, single session treatment of multiple metastases may last several hours, causing significant patient discomfort. Here, we describe a novel treatment paradigm to address these issues: distributed frameless GKRS. Patients with ≥6 brain metastases undergo multi-session frameless GKRS with both temporal and spatial distribution over 2–5 sessions, decreasing treatment time per day and not treating adjacent metastases simultaneously. METHODS: We evaluated all patients with brain metastases who underwent distributed frameless SRS, using the Gamma Knife ICON, between January 2017 and November 2018. Fifty-one patients with 1097 unique lesions were included in this analysis. RESULTS: Mean patient age was 58.8 (range 29–89) years. Median follow-up was 4.1 (range: 0–20.4) months. The median number of metastases treated was 5 (range: 1–19) per treatment session and 11.5 (range: 3–82) per treatment course. The median number of treatment sessions per treatment course was 3 (range: 2–10). The median number of treatment courses, per patient, was 1 (range: 1–4). The median margin dose was 15 Gy. The median overall survival was 5.9 (range: 0.2–20.9) months. CONCLUSIONS: Distributed frameless Gamma Knife radiosurgery is technically feasible and should be considered in lieu of single session GKRS for patients with ≥6 brain metastases.

Dosimetric comparison of fractionated radiosurgery plans using frameless Gamma Knife ICON and CyberKnife systems with linear accelerator–based radiosurgery plans for multiple large brain metastases

2020 ◽  
Vol 132 (5) ◽  
pp. 1473-1479 ◽  
Author(s):  
Eun Young Han ◽  
He Wang ◽  
Dershan Luo ◽  
Jing Li ◽  
Xin Wang
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Linear Accelerator ◽  
Treatment Time ◽  
Target Volume ◽  
Planning System ◽  
Treatment Planning System ◽  
Normal Brain ◽  
Large Brain ◽  
The Mean

OBJECTIVEFor patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.METHODSTen patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.RESULTSPlans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.CONCLUSIONSAll 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

scholarly journals MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5214
Author(s):  
Inês Figueira ◽  
Joana Godinho-Pereira ◽  
Sofia Galego ◽  
Joana Maia ◽  
János Haskó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Brain Metastases ◽  
Extracellular Vesicles ◽  
Triple Negative ◽  
Survival Rates ◽  
Brain Parenchyma ◽  
Advanced Stages ◽  
Breast Cancer Brain Metastases

Triple negative breast cancer presents higher mortality and poorer survival rates than other breast cancer (BC) types, due to the proneness to brain metastases formation, which are usually diagnosed at advanced stages. Therefore, the discovery of BC brain metastases (BCBM) biomarkers appears pivotal for a timely intervention. With this work, we aimed to disclose microRNAs (miRNAs) and extracellular vesicles (EVs) in the circulation as biomarkers of BCBM formation. Using a BCBM animal model, we analyzed EVs in plasma by nanoparticle tracking analysis and ascertained their blood-brain barrier (BBB) origin by flow cytometry. We further evaluated circulating miRNAs by RT-qPCR and their brain expression by in situ hybridization. In parallel, a cellular model of BCBM formation, combining triple negative BC cells and BBB endothelial cells, was used to differentiate the origin of biomarkers. Established metastases were associated with an increased content of circulating EVs, particularly of BBB origin. Interestingly, deregulated miRNAs in the circulation were observed prior to BCBM detection, and their brain origin was suggested by matching alterations in brain parenchyma. In vitro studies indicated that miR-194-5p and miR-205-5p are expressed and released by BC cells, endothelial cells and during their interaction. These results highlight miRNAs and EVs as biomarkers of BCBM in early and advanced stages, respectively.

scholarly journals Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Andreas M. Stark
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Therapeutic Option ◽  
Contrast Material ◽  
Brain Parenchyma ◽  
Breast Cancer Metastases ◽  
Perilesional Edema ◽  
Cancer Metastases ◽  
Before And After ◽  
Breast Cancer Brain Metastases

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

MRI-based radiomics signature for the prediction of response of lung cancer brain metastases after whole-brain radiotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21096-e21096
Author(s):  
Ruizhe Xu ◽  
Ye Tian ◽  
Bo Zhang
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Gray Level ◽  
Local Response ◽  
Prediction Of Response ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Pre Treatment ◽  
Radiomics Signature

e21096 MRI-based Radiomics signature for the Prediction of Response of Lung Cancer Brain Metastases After Whole-Brain Radiotherapy Background: Local response prediction for brain metastases (BMs) from lung cancer after Whole-Brain Radiotherapy (WBRT) is challenging, as existing criteria are based solely on unidimensional measurements. This study sought to determine whether radiomic features of lung cancer BMs derived from pre-treatment magnetic resonance imaging (MRI) could be used to predict local response following WBRT. Methods: A total of 88 Lung Cancer patients with BMs treated with WBRT were analyzed. After volumes of interest were drawn, 944 radiomic features including first-order, shape, Gray Level Co-occurrence Matrix (GLCM), Gray Level Dependence Matrix (GLDM), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), Neighborhood Gray Tone Difference Matrix (NGTDM), and Laplacian of Gaussian (LoG) features were extracted, using the baseline pre-treatment post-contrast T1 (T1c) and T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences, respectively. Local response status was determined by contrasting the baseline and follow-up MRI according to the RANO-BM criteria. The independent samples t test or Mann-Whitney U test, and then least absolute shrinkage and selection operator (LASSO) were used for dimensionality reduction and feature selection. An adaboost classifier was trained using the selected radiomic features and evaluated using the area under the receiver operating characteristic curve (AUC) in both the training and testing sets. Other discrimination metrics, including classification accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, were also calculated. Results: The optimal radiomics signature was developed based on a multivariable logistic regression with 4, 5, 6 radiomic features on T1c, T2 FLAIR and T1c+T2 FLAIR, respectively. The radiomics model based on T1c features presented the AUC of (0.920 vs. 0.805, respectively) for both the training and testing sets, followed by T2 FLAIR features (0.893 vs. 0.701, respectively), and T1c+T2 FLAIR features (0.971 vs. 0.857, respectively). The classification accuracy of the radiomics model also well predicted the local response of BMs for both the the training and testing sets (T1c: 82.9% vs. 77.8%, T2 FLAIR: 82.9% vs. 77.8%, T1c+T2 FLAIR: 90.0% vs. 77.8%, respectively). Conclusions: Radiomics holds promise for predicting local tumor response following WBRT in patients with lung cancer and brain metastases. A predictive model built on radiomic features from an institutional cohort performed well on cross-validation testing. These results warrant further validation in independent datasets. Such work could prove invaluable for guiding management of individual patients and assessing outcomes of novel interventions.

Brain Metastases and Neoplastic Meningitis

2014 ◽  
pp. 725-738.e4
Author(s):  
Penny K. Sneed ◽  
Norbert Kased ◽  
James L. Rubenstein
Keyword(s):  
Brain Metastases ◽  
Neoplastic Meningitis

scholarly journals Metabolic Plasticity of Astrocytes and Aging of the Brain

2019 ◽  
Vol 20 (4) ◽  
pp. 941 ◽  
Author(s):  
Mitsuhiro Morita ◽  
Hiroko Ikeshima-Kataoka ◽  
Marko Kreft ◽  
Nina Vardjan ◽  
Robert Zorec ◽  
...  
Keyword(s):  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Acid Oxidation ◽  
Normal Brain ◽  
Atp Production ◽  
Metabolic Plasticity ◽  
Neuronal Synapses ◽  
Age Related ◽  
Pathologic Processes ◽  
The Brain

As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions. In astrocytes, glycolysis and glycogenesis are regulated by noradrenaline and insulin, respectively, while mitochondrial ATP production and fatty acid oxidation are influenced by the thyroid hormone. These regulations are essential for maintaining normal brain activities, and impairments of these processes may lead to neurodegeneration and cognitive decline. Metabolic plasticity is also associated with (re)activation of astrocytes, a process associated with pathologic events. It is likely that the recently described neurodegenerative and neuroprotective subpopulations of reactive astrocytes metabolize distinct energy substrates, and that this preference is supposed to explain some of their impacts on pathologic processes. Importantly, physiologic and pathologic properties of astrocytic metabolic plasticity bear translational potential in defining new potential diagnostic biomarkers and novel therapeutic targets to mitigate neurodegeneration and age-related brain dysfunctions.

scholarly journals A Rare Case of Diffuse Subependymal Periventricular Metastases from Small Cell Lung Carcinoma

2020 ◽  
Vol 13 (3) ◽  
pp. 1304-1310
Author(s):  
Cong Thao Trinh ◽  
Thanh Tam Thi Nguyen ◽  
Hoang Anh Thi Van ◽  
Van Trung Hoang
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Brain Parenchyma ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Small cell lung cancer, whose essence is neuroendocrine tumors, makes up proximately 14–20% of all lung cancer circumstances. Compared to non-small cell lung cancer, its clinical manifestation seems more positive and has a tendency to disseminate earlier in the process of its natural past. About 10% of patients present with brain metastases at the time of provisional diagnosis and sometimes all along the course of their disease, there will be 40–50% of developed brain metastases in addition. Although metastases in the brain parenchyma are often found in patients with advanced lung cancer, periventricular metastases are rare. We report one case of diffuse subependymal periventricular metastases from small cell carcinoma of the lung.

scholarly journals Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma

2011 ◽  
Vol 208 (13) ◽  
pp. 2657-2673 ◽  
Author(s):  
Ming Li ◽  
Akitake Mukasa ◽  
Maria del-Mar Inda ◽  
Jianhua Zhang ◽  
Lynda Chin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Binding Protein ◽  
Brain Parenchyma ◽  
Normal Brain ◽  
Matrix Metalloproteinase 1 ◽  
Egfr Expression ◽  
Egfr Activation ◽  
Guanylate Binding Protein

Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.

Sign in / Sign up

Export Citation Format

Share Document