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Breast Cancer Research and Treatment Aug 2024Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and...
PURPOSE
Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort.
METHODS
In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data.
RESULTS
We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30).
CONCLUSION
This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.
Topics: Humans; Female; Middle Aged; Retrospective Studies; Aged; Adult; Breast Neoplasms; Meningeal Neoplasms; Aged, 80 and over; Meningeal Carcinomatosis; Receptor, ErbB-2; Prognosis
PubMed: 38888796
DOI: 10.1007/s10549-024-07339-1 -
Medical Oncology (Northwood, London,... Jun 2024Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal... (Review)
Review
Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.
Topics: Humans; Thiotepa; Injections, Spinal; Central Nervous System Neoplasms; Antineoplastic Agents, Alkylating; Hematologic Neoplasms; Meningeal Neoplasms
PubMed: 38884819
DOI: 10.1007/s12032-024-02401-w -
Neurosurgical Review Jun 2024This letter provides a critical assessment of a previous study on the utility of whole tumor apparent diffusion coefficient (ADC) histogram characteristics in predicting...
This letter provides a critical assessment of a previous study on the utility of whole tumor apparent diffusion coefficient (ADC) histogram characteristics in predicting meningioma progesterone receptor expression. While acknowledging the benefits of employing classical diffusion-weighted imaging (DWI) for non-invasive tumor evaluation, it also emphasizes significant drawbacks. Advanced imaging techniques such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) were not used in the study, which could have provided a more comprehensive understanding of tumor microstructure and heterogeneity. Furthermore, the inclusion of necrotic and cystic areas in ADC analysis may distort results due to their different diffusion properties. While focusing on first-order ADC histogram characteristics is useful, it ignores the potential insights gained from higher-order features and texture analysis. These limitations indicate that future research should combine improved imaging modalities with thorough analytical methodologies to increase the predictive value of imaging biomarkers for meningioma features and progesterone receptor expression.
Topics: Meningioma; Humans; Receptors, Progesterone; Meningeal Neoplasms; Diffusion Magnetic Resonance Imaging; Female
PubMed: 38884687
DOI: 10.1007/s10143-024-02508-8 -
Behavioural Neurology 2024The most common and aggressive tumor is brain malignancy, which has a short life span in the fourth grade of the disease. As a result, the medical plan may be a crucial...
The most common and aggressive tumor is brain malignancy, which has a short life span in the fourth grade of the disease. As a result, the medical plan may be a crucial step toward improving the well-being of a patient. Both diagnosis and therapy are part of the medical plan. Brain tumors are commonly imaged with magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). In this paper, multimodal fused imaging with classification and segmentation for brain tumors was proposed using the deep learning method. The MRI and CT brain tumor images of the same slices (308 slices of meningioma and sarcoma) are combined using three different types of pixel-level fusion methods. The presence/absence of a tumor is classified using the proposed Tumnet technique, and the tumor area is found accordingly. In the other case, Tumnet is also applied for single-modal MRI/CT (561 image slices) for classification. The proposed Tumnet was modeled with 5 convolutional layers, 3 pooling layers with ReLU activation function, and 3 fully connected layers. The first-order statistical fusion metrics for an average method of MRI-CT images are obtained as SSIM tissue at 83%, SSIM bone at 84%, accuracy at 90%, sensitivity at 96%, and specificity at 95%, and the second-order statistical fusion metrics are obtained as the standard deviation of fused images at 79% and entropy at 0.99. The entropy value confirms the presence of additional features in the fused image. The proposed Tumnet yields a sensitivity of 96%, an accuracy of 98%, a specificity of 99%, normalized values of the mean of 0.75, a standard deviation of 0.4, a variance of 0.16, and an entropy of 0.90.
Topics: Humans; Brain Neoplasms; Magnetic Resonance Imaging; Meningioma; Multimodal Imaging; Tomography, X-Ray Computed; Deep Learning; Sarcoma; Image Processing, Computer-Assisted; Brain; Neural Networks, Computer; Meningeal Neoplasms
PubMed: 38882177
DOI: 10.1155/2024/4678554 -
Gan To Kagaku Ryoho. Cancer &... May 2024A 72-year-old male was referred with a 2-week history of diplopia. Following magnetic resonance imaging, an area of abnormal signal intensity was observed along the...
A 72-year-old male was referred with a 2-week history of diplopia. Following magnetic resonance imaging, an area of abnormal signal intensity was observed along the lateral ventricle, without any unusual findings at other sites. Cerebrospinal fluid cytology revealed abnormal lymphocytes with atypia, which were positive for CD20 and light-chain restriction, as detected by surface marker analysis, leading to a diagnosis of primary meningeal B-cell lymphoma. The patient underwent chemoradiotherapy and achieved a remission. While meningeal lymphoma is a rare occurrence, pathological tissue biopsy is considered the gold-standard diagnostic method. However, obtaining a biopsy sample from the tumor site can be challenging. In this case report, cytology and flow cytometry played a vital role in the diagnosis of meningeal lymphoma.
Topics: Humans; Male; Aged; Meningeal Neoplasms; Flow Cytometry; Lymphoma, B-Cell; Chemoradiotherapy; Antineoplastic Combined Chemotherapy Protocols; Magnetic Resonance Imaging; Cytology
PubMed: 38881073
DOI: No ID Found -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Meningiomas arising from accessory nerve sheath without dural attachment are rare. To date, only 5 cases are described in the literature. A 53-year-old male presented... (Review)
Review
Meningiomas arising from accessory nerve sheath without dural attachment are rare. To date, only 5 cases are described in the literature. A 53-year-old male presented with long history of occipital pain and headaches. Magnetic resonance imaging revealed a small intradural extramedullary contrast enhanced tumor at the level of foramen magnum. The patient underwent microsurgical resection through minimally invasive midline suboccipital approach. According to intraoperative findings, cystic tumor arose from the left accessory nerve without dural attachment. Gross total resection was achieved without damage to the nerve. Histological analysis revealed angiomatous meningioma. Postoperative period was uneventful without new neurological symptoms. Meningiomas can rarely arise from accessory nerve sheath and mimic schwannoma. These tumors may be totally resected without damage to accessory nerve using minimally invasive surgical approaches.
Topics: Humans; Male; Meningioma; Middle Aged; Meningeal Neoplasms; Magnetic Resonance Imaging; Cranial Nerve Neoplasms
PubMed: 38881021
DOI: 10.17116/neiro20248803190 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these...
UNLABELLED
Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.
OBJECTIVE
To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer.
MATERIAL AND METHODS
Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity).
RESULTS
The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months.
CONCLUSION
Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Injections, Spinal; Adult; Meningeal Neoplasms; Methotrexate; Aged; Meningeal Carcinomatosis; Antimetabolites, Antineoplastic
PubMed: 38881013
DOI: 10.17116/neiro20248803131 -
Zhongguo Fei Ai Za Zhi = Chinese... May 2024Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM... (Review)
Review
Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM poses significant challenges in diagnosis, has poor prognosis, limited treatment options, and lacks standardized criteria for evaluating therapeutic efficacy, making it a difficult aspect of NSCLC management. Circulating tumor DNA (ctDNA), shed from tumor cells and carrying cancer-related information, holds significant value in precision oncology. Cerebrospinal fluid (CSF), present in the subarachnoid space of the brain, the spinal cord, and the central canal, and in direct contact with meningeal tissues, serves as the fluid medium that best reflects the genetic characteristics of LM. In recent years, CSF ctDNA has become a focal point due to its multi-omics features, playing a crucial role in the management of central nervous system (CNS) metastatic tumors. Its applications span the entire continuum of care, including aiding in diagnosis, assessing treatment response, predicting prognosis, and analyzing resistance mechanisms. This article provides a concise overview of CSF ctDNA detection techniques and their clinical applications in patients with NSCLC-LM. .
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Lung Neoplasms; Meningeal Neoplasms
PubMed: 38880925
DOI: 10.3779/j.issn.1009-3419.2024.102.16 -
Turkish Neurosurgery Aug 2023Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive...
AIM
Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive bony invasion. Two main critical decisions need to be taken: the timing for cranial vault reconstruction and the choice of the adequate material for cranioplasty. We believe that this case underscores the complexity of such lesions, the importance of a prompt devascularization, and the pivotal role of an immediate reconstruction to avoid the additional morbidity of a re-do surgery.
MATERIAL AND METHODS
We report a case of 68-year-old men who presented with slow growing right parietal bone swelling he noted many years before, but for which he didn't seek medical attentions, associated with mild contralateral hemiparesis. Neuroradiological examinations revealed a giant extradural intradiploic tumor affecting the right temporo-parietal bone and conditioning significant compression of the underlying brain. We planned a surgical strategy to deafferent the tumor and to reduce the intraoperative bleeding. At first, a circumferential craniectomy centered upon the lesion was performed, then it was devascularized by means of surgical ligation of the ipsilateral superficial temporal artery (STA) and middle meningeal artery (MMA); these steps allowed a subsequent en block tumor excision, despite its large size, without significant blood loss and respecting the oncological principles. At the end, a contextual calvarial reconstruction was performed using a precurved titanium mesh.
RESULTS
Was discharged seven days after surgery with complete recovery of the left-sided motor deficit. Thereafter, he underwent scheduled outpatient evaluations and radiological exams. After 1 year, the Modified Rankin Scale (MRS) was 1, with no evidence of recurrent disease.
CONCLUSION
Surgical complications can be reduced adopting an optimal preoperative work-up and a tailored surgical strategy focused on early tumor deafferentation. Moreover, an immediate cranial vault reconstruction avoids the risks related to a second procedure.
PubMed: 38874243
DOI: 10.5137/1019-5149.JTN.43641-23.2 -
Nature Reviews. Cancer Jul 2024The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation... (Review)
Review
The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5-10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system.
Topics: Humans; Meningeal Neoplasms; Tumor Microenvironment; Animals
PubMed: 38871881
DOI: 10.1038/s41568-024-00700-y