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Overall survival (OS) of patients who received CSF shunts due to hydrocephalus from leptomeningeal carcinomatosis (a). OS according to preceding disease of brain metastases and primary brain tumors (b) (n = 70)
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Background
Leptomeningeal carcinomatosis (LMC) is frequently associated with hydrocephalus, which quickly devastates the performance of the patient. Cerebrospinal fluid (CSF) shunt is a widely accepted treatment of choice, but the clinical outcomes in patients with LMC are not well studied. This study aimed to examine the efficacy of a CSF shunt in...
Citations
... 18 Over two-thirds of patients with leptomeningeal carcinomatosis, or neoplastic meningitis, develop disturbance in CSF circulation and intracranial compliance, presumably due to obstruction of pathways and malabsorption of CSF. 19 Pressure wave symptoms may occur even in the absence of radiographic evidence of hydrocephalus, 20 and they may manifest as intolerance to quick change in head position, pulsatile tinnitus, headache, blurry vision, papilledema, nausea, projectile vomiting, lethargy, or acute loss of consciousness. Leptomeningeal carcinomatosis is a highly morbid neurologic complication of solid and hematologic malignancies, occurring in approximately 5% of patients with solid tumors 21 and up to 15% of patients with hematologic malignancies. ...
... 20,22 Palliative long-term CSF diversion with ventriculoperitoneal shunt alleviates symptoms and improves quality of life in most patients. 19 Herniation Herniation represents the most common cause of death secondary to CNS tumor progression. 23 FIGURE 11-1 is a schematic diagram of herniation syndromes. ...
OBJECTIVE
Neuro-oncologic emergencies have become more frequent as cancer remains one of the leading causes of death in the United States, second only to heart disease. This article highlights key aspects of epidemiology, diagnosis, and management of acute neurologic complications in primary central nervous system malignancies and systemic cancer, following three thematic classifications: (1) complications that are anatomically or intrinsically tumor-related, (2) complications that are tumor-mediated, and (3) complications that are treatment-related.
LATEST DEVELOPMENTS
The main driver of mortality in patients with brain metastasis is systemic disease progression; however, intracranial hypertension, treatment-resistant seizures, and overall decline due to increased intracranial burden of disease are the main factors underlying neurologic-related deaths. Advances in the understanding of tumor-specific characteristics can better inform risk stratification of neurologic complications. Following standardized grading and management algorithms for neurotoxic syndromes related to newer immunologic therapies is paramount to achieving favorable outcomes.
ESSENTIAL POINTS
Neuro-oncologic emergencies span the boundaries of subspecialties in neurology and require a broad understanding of neuroimmunology, neuronal hyperexcitability, CSF flow dynamics, intracranial compliance, and neuroanatomy.
... Such linear LC might also secondarily cause HC by inhibiting adequate cerebrospinal fluid (CSF) absorption due to the proliferation of metastatic cells in the subarachnoid space [4][5][6]. Symptoms of HC, such as headaches, nausea, vomiting, gait disorders, urinary incontinence, cerebral nerve palsy, and even mental changes might interfere with quality of life as well as systemic cancer treatment by worsening the physical situation of the affected patient [7]. The common neurosurgical treatment of HC consists of surgical release of the obstruction in the area of the CSF drainage pathways (via BM resection) or, if this is not possible, then by establishing a permanent subcutaneous CSF drainage into the abdominal space using a ventriculo-peritoneal shunt (VPS) [8]. ...
... Patients with leptomeningeal seeding due to cancer can experience a broad spectrum of clinical manifestations, ranging from subtle neurological changes to more overt symptoms such as hydrocephalus, which necessitates immediate therapeutic intervention [7]. Hydrocephalus, in this context, often manifests due to the blockage of cerebrospinal fluid pathways by metastatic cells, leading to increased intracranial pressure and a constellation of symptoms including headaches, nausea, and changes in consciousness [8]. ...
Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal chemotherapy (ITC). Ventriculoperitoneal shunts (VPS) equipped with a valve for manual deactivation of shunt function and a concomitant reservoir for application of ITC pose an elegant solution to both problems. The present study evaluates indication, feasibility, and safety of such a modified shunt/reservoir design (mS/R). All patients with LC aged ≥ 18 years who had undergone mS/R implantation between 2013 and 2020 at the authors’ institution were further analyzed. ITC was indicated following the recommendation of the neuro-oncological tumor board and performed according to a standardized protocol. Sixteen patients with LC underwent mS/R implantation for subsequent ITC and concomitant treatment of HC. Regarding HC-related clinical symptoms, 69% of patients preoperatively exhibited lethargy, 38% cognitive impairment, and 38% (additional) visual disturbances. Postoperatively, 86% of patients achieved subjective improvement of HC-related symptoms. Overall, postoperative complications occurred in three patients (19%). No patient encountered cancer treatment-related complications. The present study describes a combination procedure consisting of a standard VPS-system and a standard reservoir for patients suffering from LC and HC. No cancer treatment-related complications occurred, indicating straightforward handling and thus safety.
... Among the common LM-related symptoms and signs, increased ICP from CSF flow disturbance is one of the most significant manifestations of LM that affect both quality of life and OS [6,8,16,19]. Furthermore, CSF flow disturbance hinders the normal distribution of intraventricularly or intrathecally injected chemotherapeutics and is thought to increase the toxicity from transependymal drug penetration into the brain parenchyma [1,12,17]. ...
Purpose
This study aimed to evaluate the symptomatic response and side effects of ventriculolumbar perfusion (VLP) methotrexate chemotherapy with a low perfusion rate in patients with leptomeningeal metastasis.
Methods
Patients in a single-arm, two-stage phase II trial based on Simon’s minimax design received VLP with a reduced (15 cc/h) perfusion rate with the purpose of decreasing constitutional side effects such as nausea/vomiting, insomnia, and confusion. The primary outcome was control of increased intracranial pressure (ICP). The secondary outcome was an occurrence of side effects. The results were compared with those of a previous trial of VLP with a 20-cc/h perfusion rate.
Results
Total 90 patients were enrolled. Out of 65 patients with increased ICP, 32 achieved normalized ICP after VLP chemotherapy (bias-adjusted response rate = 51%). The incidence of moderate-to-severe nausea/vomiting was reduced to 46% from 64% in the previous study, and that of sleep disturbance was increased to 13% from 9%, but both failed to reach statistical significance. The incidence of moderate-to-severe confusion was significantly reduced to 12% from 23% in the previous study (p = 0.04). Median overall survival was better among patients with controlled ICP than among those who remained with increased ICP (193 days vs. 94 days, p = 0.013).
Conclusion
Compared with a higher perfusion rate, the low perfusion rate failed to provide non-inferior ICP control or improved side effects, except for confusion. The relationship between VLP perfusion rate and ICP control needs to be evaluated in future trials adjusting for bias from uncompleted protocol due to poor general condition.
... Acetazolamide can also be used to decrease CSF production by the choroid plexus [173], while corticosteroids can also be administered [170]. In select cases, surgical techniques for ICP reduction may be required, such as the use of a ventriculoperitoneal shunt, which improves acute decompensation [174]. ...
Introduction:
Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options.
Areas covered:
This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer.
Expert opinion:
Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease.
... This increased ICP occurs in 40% to 70% of patients with LM during the course of therapy 3) . It necessitates frequent CSF drainage or ventriculoperitoneal shunt use for control 13,14,21,23,27) . The Ommaya reservoir cannot be used for continuous extraventricular drainage (EVD) of CSF due to the lack of a fixed needling system. ...
... We reported on the usefulness of shunt operations in patients with LM, not only based on control of increased ICP without additional intervention but also based on prolonged overall survival of patients 14) . ...
Objective:
To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal fluid (CSF) access in patients with leptomeningeal metastasis (LM).
Methods:
One hundred fifty-two consecutive patients with a diagnosis of LM and who underwent H-port installation between 2015 and 2021 were evaluated. Adverse events associated with installation and intraventricular chemotherapy, and the rate of increased intracranial pressure (ICP) control via the port were evaluated for safety and efficacy. These indices were compared with published data of Ommaya (n=89), from our institution.
Results:
Time-to-install and installation-related complications of intracranial hemorrhage (n=2) and catheter malposition (n=5) were not significantly different between the two groups. Intraventricular chemotherapy-related complications of CSF leakage occurred more frequently in the Ommaya than in the H-port group (13/89 vs. 3/152, respectively, p<0.001). Intracranial hemorrhage during chemotherapy occurred only in the Ommaya group (n=4). The CSF infection rate was not statistically different between groups (14/152 vs. 12/89, respectively). The ICP control rate according to reservoir type revealed a significantly higher ICP control rate with the H-port (40/67), compared with the Ommaya result (12/58, p<0.001). Analyzing the ICP control rate based on the CSF drainage method, continuous extraventricular drainage (implemented only with the H-port), found a significantly higher ICP control rate than with intermittent CSF drainage (33/40 vs. 6/56, respectively, p<0.0001).
Conclusion:
The H-port for intraventricular chemotherapy in patients with LM was superior for ICP control; it had equal or lower complication rates than the Ommaya reservoir.
... LMS is considered one of the rare and serious complications, with a median OS of 2-5 months after LMS diagnosis [9]. Some previous reports have revealed various incidence of LMS from 4.0% to 23.4%, which is increasing annually [7,10,12]. More frequent LMS testing, MRI resolution improvement, and OS improvement may contribute to the increased incidence of LMS [7,10,13]. ...
... This study diagnosed 27 cases with hydrocephalus, and all patients underwent V-P shunt. Kim et al. reported that the hydrocephalus treatment with a V-P shunt in patients with LMS could improve symptoms and prolong OS [23]. However, our study found no significant difference in PLS between patients with or without hydrocephalus. ...
Purpose
This study aimed to identify prognostic factors associated with survival in patients with high-grade glioma (HGG) after leptomeningeal spread (LMS) and to clarify the behavior and treatment response.
Methods
This retrospective study included 114 patients with HGGs diagnosed with LMS from August 1, 2014, to July 30, 2021, at our institution. Clinical, radiological, pathological, and outcome data were collected. Univariable and multivariable Cox regression were used for overall survival (OS) and post-LMS survival (PLS) analysis.
Results
The median OS was 17.0 months and the median PLS was 6.0 months. Gross total resection (GTR) after LMS diagnosis and pathology grade III were statistically significantly associated with longer OS in all patients. GTR after LMS diagnosis and nodular LMS were independent favorable prognostic factors on PLS. Non-adjuvant therapy after LMS diagnosis was associated with shorter OS and PLS. In glioblastoma (GBM) subgroup analysis, GTR after LMS diagnosis and secondary LMS were independent favorable prognostic factors on OS. Karnofsky Performance Status (KPS) of ≥80 at LMS diagnosis, chemotherapy after LMS and intrathecal methotrexate (MTX) treatment were statistically significantly associated with longer PLS. MRI type II was a predictor of shorter PLS.
Conclusion
The treatment of patients with glioma after LMS diagnosis is very challenging and limited. Safe GTR of tumor and subsequent adjuvant therapy after LMS remains a powerful weapon to improve survival for HGG patients with LMS. Chemotherapy and Intrathecal MTX treatment are feasible treatments after LMS. The extent of tumor dissemination may affect the survival after LMS.
... Even so, we do not have any evidence to suspect that there were peritoneal metastases, as the patient underwent a CT abdomen without any lesions, and never presented ascites or any abdominal symptoms. Although no clinical trials have been conducted, multiple studies, including systematic reviews and meta-analyses consider ventriculoperitoneal shunt and other CSF diversion techniques to treat hydrocephalus in patients with leptomeningeal disease due to systemic cancer [18][19][20]. Although multiple complications can occur in ventriculoperitoneal shunts in patients with leptomeningeal disease (from a systemic cancer like breast or lung, or primary brain tumors like gliomas and medulloblastoma), new or worsening metastases are not common complications of the procedure [18][19][20]. ...
... Although no clinical trials have been conducted, multiple studies, including systematic reviews and meta-analyses consider ventriculoperitoneal shunt and other CSF diversion techniques to treat hydrocephalus in patients with leptomeningeal disease due to systemic cancer [18][19][20]. Although multiple complications can occur in ventriculoperitoneal shunts in patients with leptomeningeal disease (from a systemic cancer like breast or lung, or primary brain tumors like gliomas and medulloblastoma), new or worsening metastases are not common complications of the procedure [18][19][20]. In fact, ventriculoperitoneal shunts can improve symptoms and can prolong overall survivorship in patients with hydrocephalus due to leptomeningeal carcinomatosis [18][19][20]. ...
... Although multiple complications can occur in ventriculoperitoneal shunts in patients with leptomeningeal disease (from a systemic cancer like breast or lung, or primary brain tumors like gliomas and medulloblastoma), new or worsening metastases are not common complications of the procedure [18][19][20]. In fact, ventriculoperitoneal shunts can improve symptoms and can prolong overall survivorship in patients with hydrocephalus due to leptomeningeal carcinomatosis [18][19][20]. ...
Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare neoplasm of the central nervous system (CNS) that primarily affects the leptomeninges. However, it can also involve the brain parenchyma and spinal cord. We report the first case of metastasis of this primary CNS tumor to the lung and bone marrow. An 18-year-old male was diagnosed with DLGNT through meningeal biopsy after multiple events of transient neurologic signs and symptoms that included recurrent episodes of encephalopathy, seizures, cerebral vasospasms, cranial nerve palsy, and urinary dysfunction. Five months after diagnosis, the patient presented with pancytopenia and pulmonary effusion. At that time, he was being treated with temozolomide, after radiation treatment to the brain and spinal cord. Bone marrow biopsy and pleural cytology revealed systemic metastases from the primary CNS tumor. He was then treated with chemotherapy with carboplatin and vincristine which improved his condition for two and a half months. Unfortunately, the patient died of a high systemic metastatic burden. Primary CNS tumors rarely produce systemic metastases, and this is the first report of DLGNT with bone marrow and pulmonary metastases. Chemotherapy with carboplatin and vincristine should be considered as a treatment for patients with DLGNT, as the patient presented a systemic response with clinical and radiological improvement.
... However, as the presence of increased ICP is usually indicative of more advanced leptomeningeal metastases and high neurologic symptom burden, survival after extracranial shunt placement is generally only 3-5 months. If within a patient's goals of care, shunting should be considered in all patients with symptomatic elevations in ICP, with symptom improvement or resolution in approximately 80% of patients [44,45]. In patients with asymptomatic modest elevations in ICP, a period of close observation may be considered however with a low threshold to consider surgical intervention given risk of rapid neurologic decompensation, particularly in those soon to undergo cranial irradiation. ...
Purpose of Review
Headaches are a common, oftentimes debilitating symptom in patients with leptomeningeal metastases.
Recent Findings
The third edition of the International Classification of Headache Disorders provides a useful diagnostic framework for headaches secondary to leptomeningeal metastases based on the temporal relationship of headache with disease onset, change in headache severity in correlation with leptomeningeal disease burden, and accompanying neurologic signs such as cranial nerve palsies and encephalopathy. However, headaches in patients with leptomeningeal metastases can be further defined by a wide range of varying cancer- and treatment-related pathophysiologies, each requiring a tailored approach.
Summary
A thorough review of the literature and expert opinion on five observed headache sub-classifications in patients with leptomeningeal metastases is provided, with attention to necessary diagnostic testing, recommended first-line treatments, and prevention strategies.
... 3,4 The most common symptoms include headache, nausea, and vomiting. 5 Some cases may also include fever, relative devascularization, signs of meningeal irritation, increased stiffness, and alteration of the cranial nerves; furthermore, in more severe cases, convulsions and changes in the level of consciousness may occur. 3 It is well known that the majority of symptoms presented by patients are a consequence of increased intracranial pressure (ICP) and the presence of hydrocephalus (HCP). ...
... Moreover, the increase in ICP and HCP reduces the effectiveness of treatment (uneven distribution of drugs given via intrathecal or intraventricular administration) and contributes to a poor prognosis in patients with leptomeningeal carcinomatosis. 5 The most important diagnostic measures are clinical evaluation, magnetic resonance imaging (MRI), and analysis of the cerebrospinal fluid (CSF), as it is extremely important to perform a full neurological examination to correctly identify the pathology. 6,7 Disease progression can be well demonstrated through MRI, which is considered useful for the diagnosis of this disease. ...
... The VPS, on the other hand, does not possess so many restrictions and may be used regardless of whether the HCP is communicating or noncommunicating. 5 Accordingly, the aim of this study is to perform a literature review on the role of neurosurgery in the treatment of leptomeningeal carcinomatosis, to explain the advances and new possibilities that have been emerging for the treatment of the disease in the surgical setting. ...
Introduction Leptomeningeal carcinomatosis results from metastatic neoplastic cells that reach the leptomeninges through the cerebrospinal fluid. The presentation of the disease is variable, making prognosis challenging. However, the presence of intracranial hypertension is common, which has prompted new treatments to mitigate this effect.
Objective To report the role of neurosurgery in the treatment of leptomeningeal carcinomatosis, as well as its advances.
Methodology Literature review with a search of the PubMed database, between 2011 and 2021, using the following descriptors: Neurosurgery , Leptomeningeal Carcinomatosis , Cerebrospinal and Treatment . A total of 42 articles were found, 16 of which were selected.
Results The shunt insertion considerably improved the effects of cranial hypertension, increasing the average survival time of patients by 3.5 months after surgery. The Ommaya reservoir is also a viable option due to its convenience and safety. The V-Port, on the other hand, has overcome the challenges of conventional devices, with shorter operating times (42 minutes), smaller skin incisions, and no reports of postoperative infection.
Conclusion Devices for the treatment of leptomeningeal carcinomatosis have been steadily improving, simplifying surgical procedures and benefiting patients.
... It can also present with communicating hydrocephalus, typically secondary to leptomeningeal metastasis. This may lead to impaired cerebrospinal fluid (CSF) absorption at the subarachnoid level due to the tumor's high aggressiveness [4,5]. Although tumor removal can theoretically restore cerebrospinal fluid circulation, postoperative hydrocephalus occurs in approximately 10% − 40% of medulloblastoma patients [6][7][8][9]. ...
Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.
