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Journal of Neuro-oncology May 2024Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor...
PURPOSE
Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target.
METHODS
The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma's growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression.
RESULTS
Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results.
CONCLUSIONS
The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.
Topics: Humans; Meningioma; Signal Transduction; Meningeal Neoplasms; Bone Morphogenetic Proteins; Calcinosis; Cell Proliferation; Cellular Senescence; Intercellular Signaling Peptides and Proteins
PubMed: 38446374
DOI: 10.1007/s11060-024-04625-2 -
BMC Medical Imaging Mar 2024This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated...
BACKGROUND
This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery.
MATERIALS
A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built.
RESULTS
The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively.
CONCLUSIONS
The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.
Topics: Humans; Meningioma; Deep Learning; Radiomics; Magnetic Resonance Imaging; Meningeal Neoplasms
PubMed: 38443817
DOI: 10.1186/s12880-024-01218-3 -
Neurology India Jan 2024
Topics: Humans; Meningioma; Meningeal Neoplasms
PubMed: 38442995
DOI: 10.4103/neurol-india.Neurol-India-D-23-00687 -
Asian Journal of Surgery Jun 2024
Topics: Humans; Meningioma; Meningeal Neoplasms; Orbital Neoplasms; Neoplasm Invasiveness; Female; Magnetic Resonance Imaging; Orbit; Middle Aged
PubMed: 38429131
DOI: 10.1016/j.asjsur.2024.01.185 -
Clinical Lung Cancer Jun 2024To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients.
OBJECTIVE
To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients.
MATERIALS AND METHODS
The clinical data of 123 patients with advanced EGFR mutated lung cancer combined with LM treated at Henan Cancer Hospital and confirmed by histology between January 2016 and December 2020 were retrospectively collected, and all patients were followed up until September 2021. Analyze the median overall survival (mOS) time of patients with clinical characteristics and treatment factors to explore the factors influencing the prognosis of lung cancer patients with LM.
RESULTS
A total of 123 patients with EGFR-mutated lung cancer and LM were included in this study. Overall, patients with exon 19 deletion (19del) in the classical mutation of the EGFR gene had a prolonged mOS compared to patients with exon 21 L858R mutation (21L858R) (30.1 months vs. 26.0 months); patients with primary LM (mOS 21.2 months) had a significantly shorter mOS than those with secondary LM (mOS 28.3 months); mOS was also significantly shorter in patients with combined brain metastases (mOS of 25.4 months) than in patients without combined brain metastases (mOS of 33.4 months); Patients treated with tyrosine kinase inhibitors (TKI) combined with antiangiogenic therapy (bevacizumab) experienced delayed onset of LM (mOS1: 19.4 months vs. 13.9 months), and prolonged survival after LM compared with those treated with EGFR-TKI alone (mOS2: 14.5 months vs. 10.0 months); There is no survival benefit to the patients treated with EGFR-TKI combined with chemotherapy compared to the patients treated with EGFR-TKI alone.
CONCLUSION
Among NSCLC-LM patients with EGFR mutation, receiving EGFR-TKI combined with antiangiogenic therapy may result in a better survival benefit. The factors of primary LM, combined brain metastasis may be prognostic factors for poor OS.
Topics: Humans; Male; Retrospective Studies; ErbB Receptors; Female; Lung Neoplasms; Middle Aged; Prognosis; Mutation; Aged; Adult; Survival Rate; Meningeal Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Follow-Up Studies; Brain Neoplasms; Aged, 80 and over; Protein Kinase Inhibitors
PubMed: 38418264
DOI: 10.1016/j.cllc.2024.02.001 -
World Neurosurgery May 2024Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to...
BACKGROUND
Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to recurrence. Our purpose was to identify main factors affecting the time to recurrence to assist preoperative treatment decision-making strategy and to define a tailored clinical and neuroradiological follow-up.
METHODS
Data of 35 patients with intracranial meningioma recurrences have been retrospectively reviewed. Demographic (patient age at initial diagnosis and sex), radiologic (meningioma location, pattern of regrowth and topography of recurrences at first reoperation), pathologic (WHO grade and Ki67-MIB1 at initial surgery and at first reoperation, progesterone receptor [PR] expression), and surgical (extent of resection at initial surgery according to Simpsons grading system, number of reoperations) factors were analyzed.
RESULTS
Time to recurrence ranged from 20 to 120 months. Extent of resection at initial surgery was Simpson grade I in 7 patients (20%), grade II in 10 (28.5%), grade III in 14 (40%), and grade IV in 4 (11.5%). Longer median time to recurrence was observed for skull base localization (P < 0.01), Simpson grades I and II versus grades III (P = 0.01) and IV (P = 0.02), values of Ki67-MIB1 ≤ 4% (P = 0.001), and PR > 60% (P = 0.03); conversely, sex, age, number of reoperations, unchanged/progression of Ki67, and/or World Health Organization grade between first surgery and reoperation did not correlate in statistically significant way with time to recurrence.
CONCLUSIONS
The extent of resection and the Ki67-MIB1 represent the most important factors predicting shorter recurrence time of intracranial meningiomas. Patients with incomplete (Simpson grades III and IV) resection and high Ki67-MIB1 values, especially at non-skull base localization and with low PR values, require a closer short-term clinical and radiologic follow-up in the first years after surgery.
Topics: Humans; Meningioma; Female; Male; Middle Aged; Neoplasm Recurrence, Local; Meningeal Neoplasms; Aged; Retrospective Studies; Adult; Time Factors; Reoperation; Neurosurgical Procedures; Aged, 80 and over; Follow-Up Studies; Young Adult; Ki-67 Antigen
PubMed: 38417623
DOI: 10.1016/j.wneu.2024.02.087 -
ESMO Open Apr 2024This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung...
BACKGROUND
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615).
PATIENTS AND METHODS
Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria.
RESULTS
The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS.
CONCLUSIONS
This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.
Topics: Humans; Female; Male; Middle Aged; Aged; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Lung Neoplasms; Adult; ErbB Receptors; Injections, Spinal; Prospective Studies; Meningeal Neoplasms; Protein Kinase Inhibitors; Meningeal Carcinomatosis; Treatment Outcome
PubMed: 38377785
DOI: 10.1016/j.esmoop.2024.102384 -
Acta Neuropathologica Feb 2024
Topics: Humans; Animals; Dogs; DNA Methylation; Meningioma; Meningeal Neoplasms
PubMed: 38376604
DOI: 10.1007/s00401-024-02693-2 -
Journal of Cancer Research and... Oct 2023Fifty-two years, NID type-2 diabetic female was admitted with progressive headache, enlarging, pulsatile midline mass, dizziness, and numbness of extremities. Physical...
Fifty-two years, NID type-2 diabetic female was admitted with progressive headache, enlarging, pulsatile midline mass, dizziness, and numbness of extremities. Physical examination revealed only hypoesthesia in the upper left extremity C7-dermatome. Preoperative computed tomography revealed eroded parafalcian dural mass and caused a round 7 cm calvarial defect over the superior sagittal sinus (SSS) and another left parietal 1.2 cm satellite mass. Magnetic resonance imaging revealed an extra-axial, diffuse heterogeneous gadolinium-enhanced, well-circumscribed lesion invading the SSS and Trolard veins (bilaterally). Supratotal resection 1 cm from the tumor borders was performed, histopathology suggested papillary thyroid carcinoma follicular variant. The euthyroid patient underwent total thyroidectomy, and final pathology revealed invasive TFC. 5-year follow-up was uneventful without recurrence or new metastasis. Parafalcian meningioma classification was reviewed for the best surgical approach. The definitive diagnosis of meningioma should be established with histopathological analysis. TFC should be included in the differential diagnosis in cases of extra-axial tumors.
Topics: Female; Humans; Meningioma; Adenocarcinoma, Follicular; Thyroid Neoplasms; Meningeal Neoplasms
PubMed: 38376330
DOI: 10.4103/jcrt.jcrt_2017_21 -
Journal of Neuro-oncology Mar 2024Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor...
BACKGROUND
Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients.
METHODS
single-center retrospective study of GEC treated from 2007 to 2021. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of CNS diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used.
RESULTS
Of 3283 GEC patients, 100 (3.04%) were diagnosed with BrM and 20 with LMC (0.61%). Patients with known human epidermal growth factor receptor 2 (HER2) status (N = 48), 60% were HER2 positive (defined as IHC 3 + or IHC 2+/FISH+). Among LMC patients most were signet-ring subtype (85%), and only 15% (2/13) were HER2 positive. Median survival was 0.7; 3.8; and 7.7 months in BrM patients treated with best supportive care, radiation, and surgery, respectively (p < 0.001). In LMC, median survival was 0.7 month in patients who had best supportive care (7/19) and 2.8 months for those who had whole brain radiation therapy (p = 0.015). Multivariate analysis showed worse outcomes in ECOG ≥ 2 (p = 0.002), number of BrM ≥ 4 (p < 0.001) and number of metastatic sites (p = 0.009).
CONCLUSION
HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.
Topics: Humans; Meningeal Carcinomatosis; Retrospective Studies; Brain Neoplasms; Proportional Hazards Models; Carcinoma
PubMed: 38372902
DOI: 10.1007/s11060-024-04576-8