Treatment Modalities for Leptomeningeal Metastases (original) (raw)
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Journal of Neuro-Oncology, 2022
Circulating tumor cells (CTC) in cerebrospinal uid (CSF) are a quantitative diagnostic tool for leptomeningeal metastases (LM) from solid tumors, but their prognostic signi cance is unclear. Our objective was to evaluate CSF-CTC quanti cation in predicting outcomes in LM. Methods This is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quanti cation using the CellSearch® platform between 04/2016-06/2019. Information on neuroaxis imaging, CSF results, and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using multivariable Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identi ed through recursive partitioning analysis. Results Out of 290 patients with CNS metastases, we identi ed a cohort of 101 patients with newly diagnosed LM. In this group, CSF-CTC count (median 200 CTCs/3ml) predicted survival continuously (HR = 1.005, 95% CI: 1.002-1.009, p = 0.0027), and the risk of mortality doubled (HR = 2.84, 95% CI: 1.45-5.56, p = 0.0023) at the optimal cutoff of ≥ 61 CSF-CTCs/3ml. Neuroimaging ndings of LM (assessed by 3 independent neuroradiologists) were associated with a higher CSF-CTC count (median CSF-CTCs range 1.5-4 for patients without radiographic LM vs 200 for patients with radiographic LM, p<0.001), but did not predict survival. Conclusion Our data shows that CSF-CTCs quanti cation predicts survival in newly diagnosed LM, and outperforms neuroimaging. CSF-CTC analysis can be used as a prognostic tool in patients with LM and provides quantitative assessment of disease burden in the CNS compartment.
Central neurological complications in critically ill patients with malignancies
Intensive Care Medicine, 2010
Objective To determine outcomes in critically ill patients hospitalized in the ICU for central neurological complications of cancer. Design and setting A 7-year retrospective study. Subject and intervention Observational study in 100 critically ill cancer patients with central neurological complications managed using standardized diagnostic and therapeutic strategies. Measurements and results There were 52 men and 48 women, aged 55 years (IQR, 40–65). Presenting manifestations were coma (56%), epilepsy (48%), focal signs (35%), encephalopathy (31%), and meningitis (7%). Cerebral imaging was abnormal in 61 patients, lumbar puncture in 17, and electroencephalography in 6. Neurosurgical biopsy was performed on four patients. The main etiologies included drug toxicity in 28, malignant brain infiltration in 21 patients, and cerebrovascular disease in 20. Mechanical ventilation was needed for 60 patients. Anticancer chemotherapy was administered during the ICU stay in 15 patients. ICU and hospital mortalities were 28 and 45%, respectively. By multivariate analysis, independent positive predictors of hospital mortality were poor performance status [odds ratio (OR) 2.94, 95% CI, 1.01–8.55, P = 0.047), focal signs at presentation (OR 3.52, 95% CI, 1.14–10.88, P = 0.029), abnormal lumbar puncture (OR 5.49, 95% CI 1.09–27.66, P = 0.038), and need for vasoactive drugs (OR 6.47, 95% CI 1.32–31.66, P = 0.021), whereas remission of the malignancy (OR 0.20, 95% CI 0.04–0.88, P = 0.033) and GCS score at admission (OR 0.81/point, 95% CI, 0.70–0.95, P = 0.009) were negative predictors of hospital mortality. Conclusion In cancer patients, central neurological events are mainly related to malignant brain infiltration and drug-related toxicity. Despite advanced severity, a standardized intensive management strategy yields a 55% hospital survival rate.
Journal of Medical Cases, 2016
When a patient with known brain metastases presents to the emergency department with neurological deterioration, an overt diagnosis exists. However, alternative diagnoses should also be considered in the appropriate clinical context. A correct diagnosis is critical for the appropriate treatment, especially in cases, in which a reversible cause of illness exists. In this report, we describe two cases of cancer patients with known brain metastases in whom the neurological deterioration was due to carcinomatous meningitis and viral menigitis, respectively. A lumbar puncture was performed based on the fact that neurological deterioration was in contrast with the absence of new findings in brain CT scans. As it is emphasized by these two cases, patients with brain metastases, unchanged at CT imaging, and recent neurological deterioration must undergo lumbar puncture before their symptoms are considered a progression of their already existing brain metastases. In some cases, the deterioration might be due to a potentially reversible illness or due to an illness requiring specific treatment.
Novel Therapeutic Approaches in Neoplastic Meningitis
Cancers (Basel), 2022
Neoplastic meningitis (NM), also known as leptomeningeal metastasis or leptomeningeal carcinomatosis, refers to the involvement of the subarachnoid space and leptomeninges- arachnoid and pia mater by primary tumor spread. The incidence of NM ranges from 5–8% in patients with solid tumors to 15% in patients with hematologic malignant spread, and it often accompanies metastases to the brain (BMs) [1]. NM has historically been associated with a dismal prognosis of 2–4 months, and it continues to remain poor, with patients presenting with a wide range of clinical features from simultaneous involvement of multiple locations throughout the neuraxis [1,2]. The diagnosis of NM requires a high index of clinical suspicion and is made by imaging with cerebrospinal fluid (CSF) studies. The management of patients with NM has evolved tremendously over the past decade, improving both the quality of life and survival. This narrative review highlights these advancements in management, focusing on new therapeutic modalities, including targeted and immunotherapies.
Treatment of central nervous system metastases from small cell lung cancer with chemotherapy
Lung Cancer, 1993
Central nervous sytem (CNS) metastases are frequently seen in patients with small cell lung cancer (SCLC) [l]. The group of CNS metastases includes brain metastases, spinal cord metastases and meningeal carcinomatosis (MC). Sometimes the brain metastases are subdivided for therapeutic reasons into metastases of the cerebral hemispheres, the cerebellum and the brain stem. Epidural metastasis is in essence a dissemination to a non-CNS localization. The vast majority of CNS metastases are brain metastases [2]. In most cases they are multiple, quite often very numerous [3]. A single metastatic brain lesion is rather rare in patients with SCLC. Brain metastases may develop at any point in the clinical course of SCLC. They are present in about 10% of the patients at the time of diagnosis [2,4,5], while in about l-2% of the patients this is the sole site of documented extrathoracic disease [2]. An additional 3&40% of the patients develop clinically overt CNS metastases prior to death [2,6]. The rate at autopsy is even higher [4]. The probability at 2 years is 80% [2]. Direct metastasis to the spinal cord has been described in rare instances, nearly always in the setting of widespread disease [2,7]. Meningeal carcinomatosis (MC) may originate from metastases in the neural parenchyma, either adjacent to the ependyma of the cerebral ventricles or underlying the leptomeninges covering the surface of the brain and the spinal cord. However, it can also evolve from hematogenous seeding to the leptomeninges. In that situation it has often a multifocal distribution [S]. In only 0.5% of the patients MC is present at the time of diagnosis [9], the incidence was in a number of studies between 5 and 18% [9-131. The actuarial probability rises rapidly up to 25% at 3 years [2]. Epidural dissemination occurs for the greater part at the spinal level, in most cases originating from vertebral metastases. This concerns a localization outside the blood-brain
Current and Future Management of Brain Metastasis
Progress in Neurological Surgery, 2012
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Management of paraneoplastic neurological syndromes: report of an EFNS Task Force
European Journal of Neurology, 2006
Paraneoplastic neurological syndromes (PNS) are remote effects of cancer on the nervous system. An overview of the management of classical PNS, i.e. paraneoplastic limbic encephalitis, subacute sensory neuronopathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome and paraneoplastic peripheral nerve hyperexcitability is given. Myasthenia gravis and paraproteinemic neuropathies are not included in this report. No evidence-based recommendations were possible, but good practice points were agreed by consensus. Urgent investigation is indicated, especially in central nervous system (CNS) syndromes, to allow tumour therapy to be started early and prevent progressive neuronal death and irreversible disability. Onconeural antibodies are of great importance in the investigation of PNS and can be used to focus tumour search. PDG-PET is useful if the initial radiological tumour screen is negative. Early detection and treatment of the tumour is the approach that seems to offer the greatest chance for PNS stabilization. Immune therapy usually has no or modest effect on the CNS syndromes, whereas such therapy is beneficial for PNS affecting the neuromuscular junction. Symptomatic therapy should be offered to all patients with PNS.
Management and outcomes of malignant posterior reversible encephalopathy syndrome
Clinical Neurology and Neurosurgery, 2014
Introduction: Recognition of severe forms of posterior reversible encephalopathy syndrome (PRES) has improved. Management of these patients remains challenging, particularly in patients with the combination of edema and hemorrhage. Methods: A prospective inpatient neuro-intensive care database was queried for patients with PRES. Malignant PRES was diagnosed by clinical assessments (GCS less than 8 and clinical decline despite standard medical management for elevated intracranial pressure) and radiographic criteria (edema with associated mass effect; brain hemorrhage exerting mass effect; effacement of basal cisterns, transtentorial, tonsillar, or uncal herniation). Malignant PRES was defined as: radiology studies consistent with PRES; GCS less than 8; and clinical decline despite standard elevated intracranial pressure management. Results: Five cases were identified over a 4 year interval. The following contributing conditions were also present: chemotherapy (1), systemic lupus erythematosis (2), pregnancy (1), and methamphetamines (1). Neurocritical care interventions included: hyperosmolar therapy (5), anticonvulsants (5), management of coagulopathy (5), and ventilatory support (5). Neurosurgical interventions included: craniectomy (5), hematoma evacuation (3), and external ventricular drain (4). Brain biopsy was performed in 5 patients and was negative for vasculitis, demyelinating disease, tumor, or infection. Cyclophosphamide was administered to the two patients with SLE. With long-term follow up, all patients achieved good functional outcomes (modified Rankin score 1-2). Conclusion: In contrast to historical reports of high mortality rates (16-29%) for severe and hemorrhagic PRES variants, we had no fatalities and observed favorable functional outcomes with intracranial pressure monitoring and craniectomy for malignant PRES cases who fail medical ICP management.