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Gene expression-based analysis of extra-cerebral metastases of patients with cerebrotropism (defined here as development of brain metastasis within < 6 months of stage IV disease), compared to patients who did not develop brain metastases for >18 months

ABSTRACT: To test the association between gene expression and cerebrotropism the Wilcoxon rank-sum test was utilized and revealed over 400 genes differentially expressed between thw two patient groups Please note that cerebrotropism is defined here as development of brain metastasis within < 6 months of stage IV disease

ORGANISM(S): Homo sapiens

PROVIDER: GSE60464 | GEO | 2014/08/18

SECONDARY ACCESSION(S): PRJNA258341

REPOSITORIES: GEO

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Gene expression-based analysis of extra-cerebral metastases of patients with cerebrotropism (defined here as development of brain metastasis within < 6 months of stage IV disease), compared to patients who did not develop brain metastases for >18 months

Project description:To test the association between gene expression and cerebrotropism the Wilcoxon rank-sum test was utilized and revealed over 400 genes differentially expressed between thw two patient groups Please note that cerebrotropism is defined here as development of brain metastasis within < 6 months of stage IV disease In this study we utilized a well-annotated cohort of metastatic melanoma cases to acquire expression profiles of a total of 9,829 unique genes Cerebrotropism Status (provided in each sample characteristics field): 1 represents early cerebrotropic patients (patients who developed CNS metastases within 6 months of diagnosis of metastatic disease ) 0 represents non-cerebrotropic patients (patients who did not develop brain metastases for over 18 months.

2014-08-18 | E-GEOD-60464 | biostudies-arrayexpress

Gene expression-based analysis of extra-cerebral metastases of patients with cerebrotropism (defined here as development of brain metastasis within 6 months of stage IV disease), compared to patients who did not develop brain metastases for 18 months

| S-ECPF-GEOD-60464 | biostudies-other

Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery.

Project description:BackgroundTo compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity.MethodsTwenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed.ResultsPatients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively.ConclusionsFollowing BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

| S-EPMC8034660 | biostudies-literature

Detecting Tumor Metastases: The Road to Therapy Starts Here.

Project description:Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process.

| S-EPMC5029857 | biostudies-other

Potential signaling pathways and gene signatures associated with brain metastases in NSCLC patients

Project description:RNA-Seq analyses of various cancers have identified thousands of target genes that help guide clinical treatment. By using RNA-Seq analysis, we examined primary lung tumors from NSCLC patients with and without BM to identify differentially-expressed genes and potential signaling pathways in two groups. A total of 6 patients with histopathologically confirmed NSCLC (against AJCC criteria) were enrolled in the RNA-Seq study, 3 patients with BM and other 3 without BM. All the cancer tissues used in this study were taken from surgical specimens and biopsies, and preserved immediately in liquid nitrogen after surgery. Totally, 566 differentially-expressed genes between BM+ and BM- samples were identified by DESeq2 with log2Fold Change being more than 2 and P value of statistical test less than 0.05, 326 genes were significantly down-regulated and 240 genes were up-regulated in BM+ group.

2019-02-19 | GSE126548 | GEO

Extra cost of brain metastases (BM) in patients with non-squamous non-small cell lung cancer (NSCLC): a French national hospital database analysis.

Project description:To assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis.Data were extracted from the French Hospital medical information database (Programme de Médicalisation des Systèmes d'Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented. Costs were attributed from official French national tariffs and expressed in 2017 euros.The mean number of hospitalisations per patient in the 24-moth follow-up period was 17 in group A and 21 in group B. >99% of patients in both groups received chemotherapy. 58% of patients in group B and 13% in group A were managed by radiotherapy. 37% in group B and 24% in group A received palliative care. The associated cost was €2979 per patient-month for patients in group B and €2426 for patients in group A, representing a differential cost of €553 per month. Radiotherapy (+€164/month) and palliative care (+€130/month) were the principal drivers of the incremental cost.The presence of brain metastases at the time of diagnosis of non-squamous NSCLC carries a significant burden, and ways of lowering this burden are needed.

| S-EPMC6135444 | biostudies-literature

Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases.

Project description:Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes: lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels of inter-lesion diversity. We validate these findings by analyzing 317 multi-region biopsies from an independent cohort of 20 patients. We further demonstrate higher levels of intra-lesion heterogeneity in lymph node than in distant metastases. Our results show that fewer primary tumor lineages seed distant metastases than lymph node metastases, indicating that the two sites are subject to different levels of selection. Thus, lymph node and distant metastases develop through fundamentally different evolutionary mechanisms.

| S-EPMC7343611 | biostudies-literature

Immunotherapy in NSCLC Patients with Brain Metastases.

Project description:Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials. Moreover, the safety and activity of ICIs and radiotherapy combinations compared with single-agent or sequential modalities is still under evaluation to establish the optimal management of these patients. The aim of this review is to summarize the state-of-the-art of clinical evidence of ICIs intracranial activity and the main challenges of incorporating these agents in the treatment armamentarium of NSCLC patients with BMs.

| S-EPMC9267075 | biostudies-literature

Clinical trials in melanoma patients with brain metastases.

Project description: Not available

| S-EPMC4834841 | biostudies-literature

Extra-Neural Metastases From Primary Intracranial Ependymomas: A Systematic Review.

Project description:BackgroundPrimary intracranial ependymomas (IE) are rare brain tumors rarely metastasizing outside the central nervous system. We systematically reviewed the literature on extra-neural metastases from primary IEs.MethodsPubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of extra-neural metastases from primary IEs. Clinical features, management strategies, and survival were analyzed.ResultsWe collected 48 patients from 43 studies. Median age was 13 years (range, 2-65). Primary IEs were frequently located in the parietal (22.9%) and frontal (16.7%) lobes, and mostly treated with resection (95.8%) and/or radiotherapy (62.5%). Most IEs were of grade-III (79.1%), and few of grade-I (6.3%) or grade-II (14.6%). 45 patients experienced intracranial recurrences, mostly treated with resection (86.7%), radiotherapy (60%), and/or chemotherapy (24.4%). Median time-interval from primary IEs was 28 months (range, 0-140). Most extra-neural metastases were diagnosed at imaging (37.5%) or autopsy (35.4%). Extra-neural metastases were multifocal in 38 patients (79.1%), mostly involving cervical or hilar lymph-nodes (66.7%), lung/pleura (47.9%), and/or scalp (29.1%). Surgical resection (31.3%), chemotherapy (31.3%) and locoregional radiotherapy (18.8%) were the most common treatments for extra-neural metastases, but 28 (58.3%) patients were not treated. At last follow-up, 37 patients died with median overall-survivals from primary IEs of 36 months (range, 1-239), and from extra-neural metastases of 3 months (range, 0.1-36). Overall-survival was significantly longer in patients with grade-I and II IEs (P=0.040).ConclusionExtra-neural metastases from primary IEs are rare, but mostly occur at later disease stages. Multidisciplinary management strategies should be intended mostly for palliation.

| S-EPMC9093681 | biostudies-literature

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