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Oncology Letters Feb 2023Multifocal dissemination of cancer cells from the primary tumor sites to the subarachnoid, pia mater and cerebrospinal fluid (CSF) of the brain and spinal cord causes...
Multifocal dissemination of cancer cells from the primary tumor sites to the subarachnoid, pia mater and cerebrospinal fluid (CSF) of the brain and spinal cord causes carcinomatous meningitis (CM). CM is rarely observed in patients with gynecological cancer. The present study described a 59-year-old woman who was diagnosed with CM as a recurrence of stage IIIC ovarian cancer, after presenting with headache and decreased level of consciousness. During adjuvant therapy following surgical debulking, she developed nausea and vomiting. The post-contrast fluid-attenuated inversion-recovery magnetic resonance imaging showed leptomeningeal enhancement on all sulci, particularly around the falx cerebri and cerebellar hemisphere. CM was suspected and CSF cytology revealed adenocarcinoma cells, thus confirming the diagnosis. Overall, although CM is rare, clinicians should be aware of this complication when patients with malignancies experience neurological symptoms, including headache, nausea and vomiting. Knowledge of this clinical entity should assist clinicians in ascertaining accurate diagnoses.
PubMed: 36644158
DOI: 10.3892/ol.2022.13652 -
BioMed Research International 2022The diagnosis of tuberculous meningitis (TBM) is difficult and relies on the patient's clinical presentation and initial cerebrospinal fluid testing. Treatment outcomes...
PURPOSE
The diagnosis of tuberculous meningitis (TBM) is difficult and relies on the patient's clinical presentation and initial cerebrospinal fluid testing. Treatment outcomes for some patients with early consideration of TBM meningitis are often poor. . In this study, we retrospectively analyzed 24 non-TBM patients whose early changes of cerebrospinal fluid were similar to those of TBM through the second-generation cerebrospinal fluid sequencing technology.
RESULTS
All patients included in this study had an acute onset, including 5 patients with a history of upper respiratory tract infection, 9 patients with fever, 6 patients with headache, 5 patients with psychiatric symptoms, 6 patients with cognitive impairment, 9 patients with signs of meningeal irritation, and 6 patients with seizures. Sixteen patients presented with altered content and level of consciousness during their admission. The leukocyte counts (median, 124.0 × 10/L) and total protein concentrations (median, 1300 mg/L) were higher than normal reference values in all patients, whereas glucose (median, 1.345 mmol/L) and chloride concentration values (average, 111.7 ± 5.2 mmol/L) were lower than normal reference values. The patients included 2 cases of Liszt's meningitis, 2 cases of Brucella infection in the CNS, 4 cases of Varicella zoster virus encephalitis, 2 cases of human herpes simplex virus type 1, 2 cases of lupus encephalopathy, 2 cases of anti-NMDAR receptor encephalitis, 2 cases of meningeal carcinomatosis, 5 cases of cryptococcal meningitis, 2 cases of CNS sarcoidosis, and a case of invasive Rhizopus oryzae infection. All patients were tested for NGS in cerebrospinal fluid. Eight patients were diagnosed with anti-NMDAR encephalitis, meningeal carcinomatosis, lupus encephalopathy, and CNS sarcoidosis. Nine patients experienced death; 15 patients had a good prognosis and left no significant sequelae.
CONCLUSION
The analysis of patients with TBM-like cerebrospinal fluid changes will help improve the diagnostic accuracy of the disease and reduce misdiagnosis and underdiagnosis.
Topics: Humans; Tuberculosis, Meningeal; Retrospective Studies; Meningeal Carcinomatosis; Sarcoidosis; Brain Diseases; Encephalitis; Cerebrospinal Fluid
PubMed: 36624852
DOI: 10.1155/2022/9692804 -
Clinical Lung Cancer Mar 2023Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to...
Safety, Pharmacokinetic and Clinical Activity of Intrathecal Chemotherapy With Pemetrexed via the Ommaya Reservoir for Leptomeningeal Metastases From Lung Adenocarcinoma: A Prospective Phase I Study.
INTRODUCTION
Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via Ommaya reservoir in LUAD with refractory LM.
METHODS
In this prospective, single-arm, phase I trial (ChiCTR2000028936), LUAD-LM patients who had progressed after at least two prior treatments were recruited. Pemetrexed from 30 mg to 50 mg was administered on Days 1 and 8 every 3 weeks via Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and therapeutic toxicities.
RESULTS
Twenty-three patients were enrolled and analyzed, revealing an ORR of 43.5% (95% CI, 23.2%-63.8%) and DCR of 82.6% (95% CI, 61.2%-95.0%). The median PFS and OS were 6.3 and 9.5 months, respectively. Dose-limiting toxicity was only observed in 2 patients (2/23, 8.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP).
CONCLUSIONS
Intrathecal pemetrexed at a dose of 30 mg via Ommaya reservoirs on Days 1 and 8 every 21 days achieved promising disease control and satisfactory survival with moderate toxicities in resistant LUAD-LM, providing a feasible and effective option, especially for the patients who cannot tolerate LP.
Topics: Humans; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Adenocarcinoma of Lung; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36588048
DOI: 10.1016/j.cllc.2022.11.011 -
Arquivos de Neuro-psiquiatria Nov 2022Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the... (Review)
Review
BACKGROUND
Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce.
OBJECTIVE
To critically review the literature on CM and propose a rational approach in the Brazilian scenario.
METHODS
Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil.
RESULTS
In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data.
CONCLUSION
We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.
Topics: Humans; Brazil; Meningitis; Syndrome; Neurocysticercosis; Neurosyphilis
PubMed: 36577417
DOI: 10.1055/s-0042-1758645 -
Scientific Reports Dec 2022Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and...
Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p < 0.0001). The median time to the onset of PM and LM from the diagnosis of advanced NSCLC was 0 months and 8.3 months, respectively. Patients with LM had a statistically shorter over survival (OS) compared to either No-BM or PM patients (p < 0.0001). Based on independent predictive variables, two nomogram models were constructed to predict the development of PM and LM in advanced NSCLC patients, and the C-indexes were 0.656 and 0.767, respectively. Although both considered as BM, PM and LM had different clinical characteristics. And the nomogram showed good performance in predicting LM development, but not PM.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Meningeal Carcinomatosis; Brain Neoplasms; Brain; Mutation
PubMed: 36572759
DOI: 10.1038/s41598-022-26131-z -
Clinical Nuclear Medicine Feb 2023Nasopharyngeal carcinoma (NC) is an epithelial tumor with distinctive prevalence in East and Southeast Asia. Most patients with NC only experience regional metastasis....
Nasopharyngeal carcinoma (NC) is an epithelial tumor with distinctive prevalence in East and Southeast Asia. Most patients with NC only experience regional metastasis. In cases of distant metastasis, prognosis is grim. Leptomeningeal spread of the disease is a rare occurrence, which is sparsely described in the literature. We present a case of a 33-year-old man with a history of high-grade NC with leptomeningeal metastasis. Initial MRI lumbar spine demonstrated subtle findings consistent with leptomeningeal disease. These findings are easily discernible on 18 F-FDG PET/CT.
Topics: Male; Humans; Adult; Nasopharyngeal Carcinoma; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Positron-Emission Tomography; Meningeal Carcinomatosis; Nasopharyngeal Neoplasms
PubMed: 36562736
DOI: 10.1097/RLU.0000000000004499 -
Neuro-oncology Feb 2023
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Meningeal Carcinomatosis; Methotrexate
PubMed: 36534954
DOI: 10.1093/neuonc/noac225 -
CNS Drugs Jan 2023Leptomeningeal metastases represent an aggressive stage of cancer with few durable treatment options. Improved understanding of cancer biology, neoplastic reliance on... (Review)
Review
Leptomeningeal metastases represent an aggressive stage of cancer with few durable treatment options. Improved understanding of cancer biology, neoplastic reliance on oncogenic driver mutations, and complex immune system interactions have resulted in an explosion in cancer-directed therapy in the last two decades to include small molecule inhibitors and immune checkpoint inhibitors. Most of these therapeutics are underexplored in patients with leptomeningeal metastases, limiting extrapolation of extracranial and even intracranial efficacy outcomes to the unique leptomeningeal space. Further confounding our interpretation of drug activity in the leptomeninges is an incomplete understanding of drug penetration through the blood-cerebrospinal fluid barrier of the choroid plexus. Nevertheless, a number of retrospective studies and promising prospective trials provide evidence of leptomeningeal activity of several small molecule and immune checkpoint inhibitors and underscore potential areas of further therapeutic development for patients harboring leptomeningeal disease.
Topics: Humans; Retrospective Studies; Immune Checkpoint Inhibitors; Prospective Studies; Meningeal Carcinomatosis; Blood-Brain Barrier
PubMed: 36474108
DOI: 10.1007/s40263-022-00975-5 -
Clinical Cancer Research : An Official... Feb 2023Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics...
PURPOSE
Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response.
EXPERIMENTAL DESIGN
We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival.
RESULTS
The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05).
CONCLUSIONS
In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
Topics: Humans; Circulating Tumor DNA; Protons; Craniospinal Irradiation; Biomarkers, Tumor; Mutation; Lung Neoplasms; Meningeal Carcinomatosis
PubMed: 36449664
DOI: 10.1158/1078-0432.CCR-22-2434 -
Zhongguo Fei Ai Za Zhi = Chinese... Nov 2022In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3%...
[Investigation of Methods and Influencing Factors to Increase the Positive Rate of Cytological Pathology of Cerebrospinal Fluid from Lung Cancer Leptomeningeal Metastases].
BACKGROUND
In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM. The fixation treatment of cerebrospinal fluid samples has a significant impact on the positive cytology detection rate, and how to improve the positive cytopathology detection rate of cerebrospinal fluid is a hot topic in clinical research.
METHODS
From June 2019 to November 2021, 105 cases diagnosed with LM based on clinical symptoms and positive imaging were collected and retrospectively evaluated in the second ward of the Department of Oncology of The Second Affiliated Hospital of Harbin Medical University. The effect of different fixation methods on the positive rate of cerebrospinal fluid cytopathology was investigated, and specimens of cerebrospinal fluid were collected and sent for examination using different delivery methods, including the application of the TIB cell preservation solution kit (experimental group) and the routine application of sterile plastic tubes in lumbar puncture bags (control group). Biochemical assays (glucose and total protein) were performed on the cerebrospinal fluid fluid, and Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the supplementary diagnostic value for LM patients with lung cancer. The relevance of chemical indexes in the assessment of therapeutic efficacy was examined, and biochemical (glucose, total protein) indices and cytological changes in cerebrospinal fluid fluid after pemetrexed intrathecal injection therapy were dynamically monitored.
RESULTS
In the control group, 24 (45.28%) patients were positive for the first time, while 42 (80.77%) patients were positive for the first time and 10 (19.23%) patients were negative for the first time in the experimental group. Significant differences existed between the two groups (P<0.001). The results of Logistic regression analysis of patients with the first cerebrospinal fluid biochemical test showed that the risk of positive cerebrospinal fluid biochemical pathology with less than 2.5 mmol/L was 2.456 times greater than 2.5 mmol/L of cerebrospinal fluid glucose (OR=2.456, P<0.05), and total cerebrospinal fluid biochemical protein greater than 430 mg/L was 2.647 times less than 430 mg/L (OR=2.647, P>0.05). The ROC curve showed glucose sensitivity of 76.9% in cerebrospinal fluid, the specificity of 54.5%, Youden index of 0.315 and area under the curve (AUC) of 0.620, total protein sensitivity in cerebrospinal fluid of 44.4%, 90.6%, Youden index of 0.350 and AUC of 0.671. After 2 cycles of pemetrexed intrathecal treatment with complete cerebrospinal fluid cytology and cerebrospinal fluid biochemical (glucose, total protein) tests in 73 and 50 patients, respectively, the rate of cerebrospinal fluid cytology turning negative was gradually increased. Cerebrospinal fluid glucose levels increased after 2 cycles of treatment compared with the first time, with a statistically significant difference (P<0.001).
CONCLUSIONS
The use of a cell preservation solution kit to immediately fix cerebrospinal fluid samples following isolation in patients with clinical symptoms and positive imaging greatly enhances the rate of positive cerebrospinal fluid cytology detection. The effect of treatment can be assessed and predicted by continuous dynamic monitoring of cerebrospinal fluid biochemistry and cytology.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Retrospective Studies; Meningeal Carcinomatosis; Glucose
PubMed: 36419392
DOI: 10.3779/j.issn.1009-3419.2022.102.42