Dataset Information

Palliative cerebrospinal fluid shunting for leptomeningeal metastasis-related hydrocephalus in patients with lung adenocarcinoma: A single-center retrospective study.

ABSTRACT:

Purpose

Management of leptomeningeal metastasis-related hydrocephalus (LM-H) is particularly challenging regarding the control of severe headache, nausea, and vomiting due to intracranial hypertension. To investigate the improvements of performance status and outcome with cerebrospinal fluid (CSF) shunt surgery for LM-H in patients with lung adenocarcinoma.

Methods

Data on patients with leptomeningeal metastasis-related hydrocephalus from lung adenocarcinoma diagnosed by MR imaging and/or cytological examination were retrospectively analyzed. Between August 2008 and July 2017, the authors reviewed 31 patients requiring CSF shunt, who underwent ventriculo-peritoneal or lumbo-peritoneal shunt.

Results

The patients consisted of 11 men and 20 women with a median age of 59 years. Twenty-six patients received EGFR-tyrosine kinase inhibitors (TKIs). CSF shunt surgery yielded rapid improvement in the performance status of 90.3% of patients. Median overall survival from the diagnosis of LM in patients with ECOG performance status less than 2 was 7.7 months, and this was significantly longer than those in patients with PS 3 or 4 (4.4 or 1.5 months; p<0.001). Multivariate analysis by Cox regression revealed survival differences according to PS at diagnosis of LM [PS 1-3 vs. PS4, hazard ratio (HR) 0.201, p = 0.034], controlled extracranial disease (HR 0.248, p = 0.005), and post-shunt EGFR-TKI for LM treatment (HR 0.193, p = 0.008). Postoperative symptomatic peritoneal carcinomatosis was observed in one patient (3.2%).

Conclusion

CSF shunting may be a safe and effective strategy in patients with LM-H from lung adenocarcinoma. A prospective study is needed to establish the effectiveness and safety of palliative CSF shunt for LM-H.

SUBMITTER: Mitsuya K

PROVIDER: S-EPMC6328154 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Palliative cerebrospinal fluid shunting for leptomeningeal metastasis-related hydrocephalus in patients with lung adenocarcinoma: A single-center retrospective study.

Mitsuya Koichi K Nakasu Yoko Y Hayashi Nakamasa N Deguchi Shoichi S Takahashi Toshiaki T Murakami Haruyasu H Naito Tateaki T Kenmotsu Hirotsugu H Ono Akira A Wakuda Kazushige K Harada Hideyuki H

PloS one 20190110 1

<h4>Purpose</h4>Management of leptomeningeal metastasis-related hydrocephalus (LM-H) is particularly challenging regarding the control of severe headache, nausea, and vomiting due to intracranial hypertension. To investigate the improvements of performance status and outcome with cerebrospinal fluid (CSF) shunt surgery for LM-H in patients with lung adenocarcinoma.<h4>Methods</h4>Data on patients with leptomeningeal metastasis-related hydrocephalus from lung adenocarcinoma diagnosed by MR imagin ...[more]

PMID: 30629621

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Project description:Background: Leptomeningeal metastasis (LM) has frequently been observed in patients with lung adenocarcinoma. So far, its diagnosis and disease course monitoring are still extremely difficult. Moreover, there is no effective treatment regimen for LM due to a lack knowledge on the molecular mechanism of LM. This study aimed to identify LM-related cerebrospinal fluid (CSF) miRNAs, which have potential value for diagnosing and monitoring LM and exploring the molecular mechanism. Methods: CSF miRNAs were screened and verified by microarray analysis and quantitative real-time PCR (qRT-PCR) in LM patients with lung adenocarcinoma and non-LM controls, and the diagnostic performance of candidate miRNAs was evaluated. Then, candidate miRNAs in matched CSF samples from LM patients at diagnosis, after initial therapy, at relapse, and after salvage therapy, were analyzed to assess the relationship between CSF miRNAs and LM disease course. The effect of candidate miRNAs on proliferation, invasion, and migration of lung adenocarcinoma cell lines was assessed. The targeted genes of the candidate miRNA were predicted by TargetScan, miRDB, and miRTarbase online analysis tools. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functional categories of predicted target genes. Results: CSF miR-7975, miR-7977, and miR-7641 were screened and verified to be statistically significantly up-regulated in LM patients compared to non-LM controls. The three miRNAs, when combined, exhibited optimal diagnostic performance. Longitudinal data of CSF miR-7975 and miR-7977 correlated well with clinical courses of LM. Overexpression of miR-7977 promoted proliferation, migration, and invasion of lung adenocarcinoma cells. Moreover, 385 targeted genes of miR-7977 were predicted and were involved in various pathways related to cancer metastasis. Conclusions: This study offers insights for future research of CSF miRNAs as robust tools for diagnosing and monitoring LM. It also reveals a novel pathway for exploration of underlying mechanisms of LM.

Project description:IntroductionHydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value.MethodsCSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPP?, sAPP?, A?42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC.ResultsCSF levels of APP, sAPP?, sAPP?, A?42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPP?, especially in subjects ?12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPP? (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ?12 months, a normalized CSF sAPP? cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC.ConclusionsCSF proteins such as sAPP? and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.

Dataset Information

Palliative cerebrospinal fluid shunting for leptomeningeal metastasis-related hydrocephalus in patients with lung adenocarcinoma: A single-center retrospective study.

Purpose

Methods

Results

Conclusion

Publications

Palliative cerebrospinal fluid shunting for leptomeningeal metastasis-related hydrocephalus in patients with lung adenocarcinoma: A single-center retrospective study.

Similar Datasets

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