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Neuro-oncology Practice Dec 2020The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation....
BACKGROUND
The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges.
METHODS
The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis.
RESULTS
We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%).
CONCLUSIONS
LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.
PubMed: 33312678
DOI: 10.1093/nop/npaa041 -
Journal of Applied Physiology... Feb 2021Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe...
Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Owing to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Owing to the coupling of central venous pressure (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32 ± 13 yr) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an impedance threshold device (ITD, -7 cmHO) to generate negative intrathoracic pressure for 5 min, and subsequently, wore bilateral thigh cuffs inflated to 30 mmHg for 2 min. Breathing through an ITD reduced both CVP (6 ± 2 vs. 3 ± 1 mmHg; = 0.02) and ICP (16 ± 3 vs. 12 ± 1 mmHg; = 0.04) compared to baseline, a result that was not observed during the free breathing condition (CVP, 6 ± 2 vs. 6 ± 2 mmHg, = 0.87; ICP, 15 ± 3 vs. 15 ± 4 mmHg, = 0.68). Inflation of the thigh cuffs to 30 mmHg caused no meaningful reduction in CVP in all four individuals (5 ± 4 vs. 5 ± 4 mmHg; = 0.1), coincident with minimal reduction in ICP (15 ± 3 vs. 14 ± 4 mmHg; = 0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading. Spaceflight causes pathological changes in the eye that may be due to the absence of gravitational unloading of intracranial pressure (ICP) under microgravity conditions commonly referred to as spaceflight-associated neuro-ocular syndrome (SANS), whereby countermeasures aimed at lowering ICP are necessary. These data show that impedance threshold breathing acutely reduces ICP via a reduction in central venous pressure (CVP). Whereas, acute thigh cuff inflation, a popular known spaceflight-associated countermeasure, had little effect on ICP and CVP.
Topics: Central Venous Pressure; Humans; Intracranial Pressure; Male; Space Flight; Tonometry, Ocular; Weightlessness
PubMed: 33270516
DOI: 10.1152/japplphysiol.00786.2020 -
The Journal of International Medical... Nov 2020Subdural effusion (SDE) is a common complication secondary to decompressive craniectomy (DC). This current case report describes a patient with contralateral SDE with a... (Review)
Review
Subdural effusion (SDE) is a common complication secondary to decompressive craniectomy (DC). This current case report describes a patient with contralateral SDE with a typical clinical course. Initially, he made a good recovery following a head trauma that caused a loss of consciousness and was treated with decompressive craniectomy. However, he only achieved temporary relief after each percutaneous fluid aspiration from an Ommaya reservoir implanted into the cavity of the SDE. He was eventually transferred to the authors' hospital where he underwent cranioplasty, which finally lead to the reduction and disappearance of his contralateral SDE. Unexpectedly, his clinical condition deteriorated again 2 weeks after the cranioplasty with symptoms of an uncontrolled bladder. A subsequent CT scan found the apparent expansion of the whole cerebral ventricular system, indicating symptomatic communicating hydrocephalus. He then underwent a ventriculoperitoneal shunt procedure, which resulted in a favourable outcome and he was discharged 2 weeks later. A review of the current literature identified only 14 cases of contralateral SDE that were cured by cranioplasty alone. The mechanism of contralateral SDE has been widely discussed. Although the exact mechanism of contralateral SDE and why cranioplasty is effective remain unclear, cranioplasty could be an alternative treatment option for contralateral SDE.
Topics: Decompressive Craniectomy; Humans; Hydrocephalus; Male; Postoperative Complications; Retrospective Studies; Subdural Effusion; Treatment Outcome
PubMed: 33203286
DOI: 10.1177/0300060520966890 -
Therapeutic Advances in Neurological... 2020To investigate outcome and toxicity of high-dose systemic methotrexate (HDMTX)-based polychemotherapy and intracerebroventricular (ICV) chemotherapy an Ommaya reservoir...
BACKGROUND
To investigate outcome and toxicity of high-dose systemic methotrexate (HDMTX)-based polychemotherapy and intracerebroventricular (ICV) chemotherapy an Ommaya reservoir in elderly patients with primary central nervous system lymphoma (PCNSL).
METHODS
We performed a retrospective analysis on patients ⩾65 years with first diagnosis of PCNSL admitted to our center between January 2015 and December 2019. These patients were treated with a standardized chemotherapy protocol in case of absent contraindications for HDMTX-based chemotherapy. The protocol contained induction therapy with systemic rituximab, methotrexate and ifosfamide and consolidation treatment with systemic cytarabine (AraC) and ICV methotrexate, prednisolone and AraC.
RESULTS
Of a total of 46 patients seen in this period, 3 did not qualify for HDMTX. Thus, 43 patients were included in this analysis. Median age was 74 years (range 65-86), median Karnofsky performance score was 50 (range 20-90). Of the 43 patients, 32 (74.4%) completed treatment including ICV therapy. Complete remission/complete remission unconfirmed was achieved in 26 of 43 patients (60.5%), partial response (PR) in 3 (7%); 5 (11.6%) had progressive disease, and 3 (7.0%) died due to treatment-related complications; in the remaining 6 (14.0%) therapy could not be completed. Median progression free survival was 16 months (95% confidence interval 8-24 months) and median overall survival had not been reached after a median follow up of 23 months (range 1-52 months); the 75th percentile survival time was 12 months. No Ommaya reservoir infection was observed. Complications of ICV treatment were pericatheter leucencephalopathy in two patients and surgical scar dehiscence with cerebrospinal fluid leak in one patient.
CONCLUSION
Toxicity of HDMTX plus ICV chemotherapy for elderly patients with PCNSL was manageable and outcome was excellent for patients treated with this protocol.
PubMed: 33101460
DOI: 10.1177/1756286420951087 -
AJP Reports Jul 2020Cerebellar hemorrhage is rare in term newborns and is most often seen after traumatic birth. Lifelong sequelae include motor and cognitive impairment. We report the...
Cerebellar hemorrhage is rare in term newborns and is most often seen after traumatic birth. Lifelong sequelae include motor and cognitive impairment. We report the uncommon case of a late preterm infant born by spontaneous delivery who showed right peripheral facial palsy at 24 hours of life. Cranial ultrasound showed lateral ventricles dilatation and a diffuse hyperechoic round lesion in the right cerebellar hemisphere. The computed tomography scan confirmed a hemorrhagic lesion in the right cerebellar hemisphere and in the vermis with midline shift and intraventricular bleeding. Ommaya reservoir was inserted and used for a few days. The facial palsy gradually recovered to a complete remission after 6 weeks. Follow-up examinations at 12 and 18 months evidenced infant's delayed motor function, hyperreflexia, tremors, and speech delay.
PubMed: 33094015
DOI: 10.1055/s-0040-1715162 -
Journal of Neurology Feb 2021To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.
METHODS
Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.
RESULTS
Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.
CONCLUSIONS
IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.
CLASSIFICATION OF EVIDENCE
This study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression.
EU CLINICAL TRIAL REGISTER
EudraCT; 2008-002626-11 and 2012-000721-53.
Topics: Disease Progression; Humans; Immunologic Factors; Multiple Sclerosis, Chronic Progressive; Rituximab
PubMed: 32901316
DOI: 10.1007/s00415-020-10210-0 -
Journal of Biomedical Research Aug 2019Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular...
Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular metastasis from rectal cancer. A 72-year-old male presented with a new diagnosis of multiple intraventricular lesions, an anterior mediastinal mass and a rectal mass. His workup revealed rectal adenocarcinoma with intraventricular metastases and an incidental thymoma. Ommaya reservoir placement was performed an awake procedure rather than under general anesthesia due to airway concerns. Cerebrospinal fluid (CSF) cytology was positive for malignancy and consistent with adenocarcinoma. Two weeks postoperatively, the patient underwent whole brain radiation. Although rare, this diagnosis should always be considered in the differential for solitary or multiple intraventricular lesions. CSF sampling is a useful alternative to intraventricular biopsy for diagnosis of intraventricular metastases. Awake placement of Ommaya reservoir is a safe option in the management of patients with intraventricular metastases, especially those who cannot undergo general anesthesia.
PubMed: 32701070
DOI: 10.7555/JBR.33.20180133 -
Annals of Palliative Medicine Jul 2020Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC), and it lacks standard treatment guidelines and is always...
Treatment response to intrathecal chemotherapy with pemetrexed via an Ommaya reservoir in EGFR-mutated leptomeningeal metastases from non-small cell lung cancer: a case report.
Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC), and it lacks standard treatment guidelines and is always accompanied by poor prognosis. We report a patient who was definitively diagnosed as LM from NSCLC with a targeted mutation of epidermal growth factor receptor (EGFR) via magnetic resonance imaging (MRI) and positive cerebrospinal fluid (CSF) cytology. Tyrosine kinase inhibitors (TKIs) were implemented but ineffective. Then the patient received the installation of an intraventricular Ommaya reservoir. Thirty mg of pemetrexed and other adjuvant treatments were implemented on days 1 and 8 every 3 weeks via the Ommaya reservoir. This treatment regimen resulted in the alleviation of the neurological symptoms, the clearing of CSF cytology and a reduced lesion of LM without notable side effects. At recent follow-ups, MRI examinations revealed the sustained stable LM lesion. We report the first successful example of administering intrathecal chemotherapy with pemetrexed via an Ommaya reservoir, providing a new therapeutic approach against LM from NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Meningeal Carcinomatosis; Pemetrexed
PubMed: 32648459
DOI: 10.21037/apm-19-521 -
Neuro-oncology Advances 2019Glioblastoma (GBM) is the most common primary brain neoplasm with median overall survival (OS) around 15 months. There is a dearth of effective monitoring strategies for... (Review)
Review
Glioblastoma (GBM) is the most common primary brain neoplasm with median overall survival (OS) around 15 months. There is a dearth of effective monitoring strategies for patients with high-grade gliomas. Relying on magnetic resonance images of brain has its challenges, and repeated brain biopsies add significant morbidity. Hence, it is imperative to establish a less invasive way to diagnose, monitor, and guide management of patients with high-grade gliomas. Currently, multiple biomarkers are in various phases of development and include tissue, serum, cerebrospinal fluid (CSF), and imaging biomarkers. Here we review and summarize the potential biomarkers found in blood and CSF, including extracellular macromolecules, extracellular vesicles, circulating tumor cells, immune cells, endothelial cells, and endothelial progenitor cells. The ability to detect tumor-specific biomarkers in blood and CSF will potentially not only reduce the need for repeated brain biopsies but also provide valuable information about the heterogeneity of tumor, response to current treatment, and identify disease resistance. This review also details the status and potential scope of brain tumor-related cranial devices and implants including Ommaya reservoir, microelectromechanical systems-based depot device, Alzet mini-osmotic pump, Metronomic Biofeedback Pump (MBP), ipsum G1 implant, ultra-thin needle implant, and putative devices. An ideal smart cranial implant will overcome the blood-brain barrier, deliver various drugs, provide access to brain tissue, and potentially measure and monitor levels of various biomarkers.
PubMed: 32642651
DOI: 10.1093/noajnl/vdz013 -
Acta Neuropathologica Communications Jun 2020Treatment with small-molecule inhibitors, guided by precision medicine has improved patient outcomes in multiple cancer types. However, these compounds are often not...
Treatment with small-molecule inhibitors, guided by precision medicine has improved patient outcomes in multiple cancer types. However, these compounds are often not effective against central nervous system (CNS) tumors. The failure of precision medicine approaches for CNS tumors is frequently attributed to the inability of these compounds to cross the blood-brain barrier (BBB), which impedes intratumoral target engagement. This is complicated by the fact that information on CNS penetration in CNS-tumor patients is still very limited. Herein, we evaluated cerebrospinal fluid (CSF) drug penetration, a well-established surrogate for CNS-penetration, in pediatric brain tumor patients. We analyzed 7 different oral anti-cancer drugs and their metabolites by high performance liquid chromatography mass spectrometry (HPLC-MS) in 42 CSF samples obtained via Ommaya reservoirs of 9 different patients. Moreover, we related the resulting data to commonly applied predictors of BBB-penetration including ABCB1 substrate-character, physicochemical properties and in silico algorithms. First, the measured CSF drug concentrations depicted good intra- and interpatient precision. Interestingly, ribociclib, vorinostat and imatinib showed high (> 10 nM), regorafenib and dasatinib moderate (1-10 nM) penetrance. In contrast, panobinostat und nintedanib were not detected. In addition, we identified active metabolites of imatinib and ribociclib. Comparison to well-established BBB-penetrance predictors confirmed low molecular weight, high proportion of free-drug and low ABCB1-mediated efflux as central factors. However, evaluation of diverse in silico algorithms showed poor correlation within our dataset. In summary, our study proves the feasibility of measuring CSF concentration via Ommaya reservoirs thus setting the ground for utilization of this method in future clinical trials. Moreover, we demonstrate CNS presence of certain small-molecule inhibitors and even active metabolites in CSF of CNS-tumor patients and provide a potential guidance for physicochemical and biological factors favoring CNS-penetration.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adolescent; Adult; Antineoplastic Agents; Biological Transport; Blood-Brain Barrier; Brain Neoplasms; Child; Drug Delivery Systems; Female; Humans; Male; Young Adult
PubMed: 32493453
DOI: 10.1186/s40478-020-00953-2