Intraventricular Chemotherapy Research Articles

P14.07 Multi-agent vs. single-agent intra-ventricular chemotherapy for patients with neoplastic meningitis: evidence supporting a new paradigm

P14.07 Multi-agent vs. single-agent intra-ventricular chemotherapy for patients with neoplastic meningitis: evidence supporting a new paradigm

New features placement of the Ommaya reservoir in patients with neuro-oncological and oncohematological diseases

Introduction. The way of placing of Ommaya reservoir for patients with neurooncological and oncohematological diseases by the new gadget Thomale Guide without costly navigation equipment described in this article. Materials and methods. Nineteenth surgeries with usage of Thomale Guide were done from April 2015 to August 2016 in Dmitry Rogachev NRC PHOI. Results. In all 19 cases ventricular catheter was successfully placed to the lateral ventricle that was confirmed by successful functioning of Ommaya reservoir. Conclusion. Simple and easy available Thomale Guide technique allows to implement the concept “to deliver equipment to a patient, but not a patient to equipment”. Nowadays specialist of Dmitry Rogachev NRC PHOI can place Ommaya reservoir in Regions of Russia in the clinics where the intraventricular chemotherapy must be done, but there is no technical possibility to place the Ommaya reservoir.

P13.05 Success Rate and Early Morbidity from Image-Guided Ommaya Reservoir Placement for Intraventricular Chemotherapy: Case Series and Systematic Review

P13.05 Success Rate and Early Morbidity from Image-Guided Ommaya Reservoir Placement for Intraventricular Chemotherapy: Case Series and Systematic Review

P.092 Ommaya reservoir placement for intraventricular chemotherapy: a retrospective case series in the image-guidance era

Background: In 1963, Ayub Ommaya proposed a surgical technique for placement of a subcutaneous reservoir and pump to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion in adults is for patients with hematologic or leptomeningeal disorders who require repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to determine short-term complication rates from Ommaya reservoir placement in the image-guidance era. Methods: We retrospectively evaluated all operative cases of image-guided Ommaya reservoir insertion from 2004-2014 by the senior author (JFM). Patient demographic data and peri-operative complications were collected. Results: We identified 28 patients over the study period (43.3+/-17.3 years; 64.3% male). Indications for placement included acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There was one asymptomatic peri-operative intracranial hemorrhage (3.6%), and one early infection (3.6%). All catheters were well-positioned and functional. Conclusions: In our retrospective single-centre case series, all catheters were placed accurately. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective Ommaya reservoir placement for intraventricular chemotherapy.

Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007.

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU‐RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high‐dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ‐line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6‐year overall and event‐free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment‐related death due to insufficiency of a ventriculo peritoneal shunt (VP‐shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU‐RHAB provides the best available basis for phase I/II clinical trials.

Retrospective Analysis of Cerebrospinal Fluid Profiles in 228 Patients with Leptomeningeal Carcinomatosis : Differences According to the Sampling Site, Symptoms, and Systemic Factors.

ObjectiveElevated cell counts and protein levels in cerebrospinal fluid (CSF) result from disease activity in patients with leptomeningeal carcinomatosis (LMC). Previous studies evaluated the use of CSF profiles to monitor a treatment response or predict prognosis. CSF profiles vary, however, according to the sampling site and the patient's systemic condition. We compared lumbar and ventricular CSF profiles collected before intraventricular chemotherapy for LMC and evaluated the association of these profiles with patients' systemic factors and LMC disease activity.MethodsCSF profiles were retrospectively collected from 228 patients who underwent Ommaya reservoir insertion for intraventricular chemotherapy after a diagnosis of LMC. Lumbar samples taken via lumbar puncture were used for the diagnosis, and ventricular samples were obtained later at the time of Ommaya reservoir insertion. LMC disease activity was defined as the presence of LMC-related symptoms such as increased intracranial pressure, hydrocephalus, cranial neuropathy, and cauda equina syndrome.ResultsCell counts (median : 8 vs. 1 cells/mL) and protein levels (median : 68 vs. 17 mg/dL) significantly higher in lumbar CSF than in ventricular CSF (p<0.001). Among the evaluated systemic factors, concomitant brain metastasis and previous radiation were significantly correlated with higher protein levels in the lumbar CSF (p=0.01 and <0.001, respectively). Among the LMC disease activity, patients presenting with hydrocephalus or cauda equina syndrome showed higher lumbar CSF protein level compared with that in patients without those symptoms (p=0.049 and p<0.001, respectively). The lumbar CSF cell count was significantly lower in patients with cranial neuropathy (p=0.046). The ventricular CSF cell counts and protein levels showed no correlation with LMC symptoms. Carcinoembryonic antigen (CEA), which was measured from ventricular CSF after the diagnosis in 109 patients, showed a significant association with the presence of hydrocephalus (p=0.01).ConclusionThe protein level in lumbar CSF indicated the localized disease activity of hydrocephalus and cauda equina syndrome. In the ventricular CSF, only the CEA level reflected the presence of hydrocephalus. We suggest using more specific biomarkers for the evaluation of ventricular CSF to monitor disease activity and treatment response.

BMET-13CSF PROFILES AS PROGNOSTIC MARKER OR PREDICTIVE MARKER FOR INTRAVENTRICULAR CHEMOTHERAPY IN PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS FROM SOLID CANCERS

One of difficulties in intra-CSF chemotherapy for leptomeningeal carcinomatosis (LMC) is a lack of quantitative measure for the treatment response. Previous studies evaluated CSF profiles to predict treatment response or to correlate with prognosis. However, the results were inconsistent mainly due to small number of patients and heterogeneous treatment. We analyzed 283 patients with LMC from solid cancer, who underwent intraventricular chemotherapy at National Cancer Center from 2003 to 2013. CSF parameters were cytology, cell count and protein level. Control of intracranial pressure (ICP) was reviewed as an objective indicator of symptom improvement. CSF profiles before the treatment were significantly different according to sample sites (p < 0.001) in both cell count (lumbar vs. ventricular is mean 23 ± 44 vs. 8 ± 30) and protein level (mean 124 ± 168 vs. 33 ± 66 mg/dL). Initial lumbar CSF protein level was correlated with development of increased ICP (p = 0.059), hydrocephalus (HCP) (p = 0.049), and cauda equine syndrome (CES) (p< 0.001). But, initial ventricular CSF profiles did not reflect LMC disease activity. Decrease of CSF protein level after treatment was associated with increased ICP control (p = 0.017) while cell count change or cytology conversion is not predictive. Patients with low initial protein level (≤ 50mg/dL), or cell count (≤15) show prolonged survival (p = 0.001 and 0.015, respectively). But, decrease of either protein level or cell count after the treatment and cytology response did not significantly affect the patients OS. We suggest that CSF cell count is too low to reflect disease activity or treatment response especially those from ventricle. Initial CSF protein is in accordance with LMC symptoms and the decrease of protein level after the treatment is predictive of treatment response. We need new quantitative pharmacodynamic markers for LMC treatment to improve efficacy of intraventricular chemotherapy.

Survival following Ommaya reservoir placement for neoplastic meningitis

The objective of this study was to evaluate the outcomes of patients with neoplastic meningitis (NM) following Ommaya reservoir placement in order to determine whether any patient factors are associated with longer survival. NM is a devastating late manifestation of cancer, and given its dismal prognosis, identifying appropriate patients for Ommaya reservoir placement is difficult. The authors performed a retrospective review of 80 patients who underwent Ommaya reservoir placement at three medical centers from September 2001 through September 2012. The primary outcome was death. Differences in survival were assessed with Kaplan–Meier survival analyses. The Cox proportional hazards and logistic regression modeling were performed to identify factors associated with survival. The primary diagnoses were solid organ, hematologic, and primary central nervous system tumors in 53.8%, 41.3%, and 5%, respectively. The median overall survival was 72.5days (95% confidence interval 36–122) with 30% expiring within 30days and only 13.8% surviving more than 1year. There were no differences in median overall survival between sites (p=0.37) despite differences in time from diagnosis of NM to Ommaya reservoir placement (p<0.001). Diagnosis of hematologic malignancy was inversely associated with death within 90days (p=0.04; odds ratio 0.34), older age was associated with death within 90days (p=0.05; odds ratio 1.5, per 10year increase in age). The prognosis of NM remains poor despite the available treatment with intraventricular chemotherapy. There exists significant variability in treatment algorithms among medical centers and consideration of this variability is crucial when interpreting existing series of Ommaya reservoir use in the treatment of patients with NM.

Recent Advancements of Treatment for Leptomeningeal Carcinomatosis.

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

Recurrent encephaloclastic cyst induced by intraventricular topotecan

ObjectiveTo report two rare cases of encephaloclastic cyst induced by intraventricular topotecan. To share our experience in diagnosing and treating this rare disease. BackgroundOmmaya reservoirs provide fast access and reliable drug delivery to cerebral spinal fluid. They are routinely utilized for the administration of intrathecal chemotherapy accounting for greater than 80% of cases for which they are used. Complications of Ommaya reservoir placement and its use consist of infectious and other late noninfectious causes. Encephaloclastic cysts provoked by intraventricular chemotherapy are very uncommon. The pathogenesis may result from alterations in CSF pulsations with retrograde flow of intraventricular chemotherapy into the brain parenchyma and subsequent development of a local chemical encephalopathy. It has been previously reported with methotrexate use but never with topotecan administration. MethodsWe report two rare cases of encephaloclastic cyst with intraventricular topotecan use. The patients were diagnosed and treated at The University of Texas MD Anderson Cancer Center. They consented to the publication of their laboratory results and imaging studies for educational purposes. ResultThe patients presented with metastatic cancers (breast/lung) complicated by leptomeningeal disease. Ommaya reservoirs were placed in both cases and patients were initiated on intraventricular topotecan at 0.4mg twice weekly. After approximately 12 intraventricular treatments, both patients developed confusion, seizures and headaches. MRI of the brain demonstrated cystic dilatation of the brain parenchyma around the catheter that connects to the reservoir dome and delivers the drug to the intraventricular space. The catheter was surrounded by vasogenic edema. Catheters were removed and analyzed and were found to be intact. CSF analyses showed no evidence of infection or malignancy. Intraventricular topotecan was discontinued and both patients demonstrated sustained clinical and radiological responses. ConclusionThese cases highlight an atypical complication of intraventricular use of topotecan with successful management.

Diagnosis and treatment of primary CNS lymphoma

Primary CNS lymphoma (PCNSL) is a rare lymphoma that is confined to the CNS, with low tendency for systemic dissemination and a relatively aggressive course. Outcome in patients with PCNSL is often poor. Owing to its low incidence, current knowledge about optimal treatment of PCNSL is fragmentary. Chemotherapy regimens based on high-dose methotrexate are currently standard treatment for all patients with PCNSL who can tolerate such drugs. Whole-brain radiotherapy alone can lead to remission in up to 90% of patients, but often results in poor long-term disease control when given alone, and in delayed neurotoxicity when given after high-dose methotrexate. In this Review, we describe current approaches to diagnosis and treatment of PCNSL, and discuss novel therapeutic approaches that are currently in development, such as the use of rituximab and high-dose chemotherapy followed by autologous stem-cell transplantation. The possible use of intrathecal and intraventricular chemotherapy, optimal salvage treatment, and specific treatment approaches in elderly, paediatric and immunocompromised patients, are also considered.

Analysis of Treatment Outcomes of Intraventricular Chemotherapy in 105 Patients for Leptomeningeal Carcinomatosis from Non–Small-Cell Lung Cancer

Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non-small-cell lung cancer. Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients' survival and symptom responses, including intracranial pressure (ICP) control. There were 44 men and 61 women, with a median age of 56 years (range, 31-75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1-49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5-21.5 months). Age (≥ 60 years), poor Karnofsky performance score (< 70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis. Intraventricular chemotherapy for patients with LMC from non-small-cell lung cancer could palliate associated symptoms and prolong patients' survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.

GRP-120 Multidisciplinary Intervention: Intrathecal and Intraventricular Chemotherapy in Paediatrics

BackgroundA communications system was designed after notification of two errors in two months, in intrathecal and intraventricular chemotherapy in paediatric oncohaematology: prescribing by protocol, consultation sheet standardised and computerised; transcription...

Intraventricular rituximab and systemic chemotherapy for treatment of central nervous system post‐transplant lymphoproliferative disorder after kidney transplantation

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.

Chemoport with a non-collapsible chamber as a replacement for an Ommaya reservoir in the treatment of leptomeningeal carcinomatosis

The Ommaya reservoir for intraventricular chemotherapy of leptomeningeal carcinomatosis (LMC) patients has been reported to have some complications. We introduced a Chemoport reservoir, with a solid non-collapsible, high-profile chamber as a the replacement for the Ommaya reservoir in LMC patients. To evaluate the usefulness of Chemoport as an alternative to Ommaya for the intraventricular chemotherapy of LMC. The medical records of 155 patients (89 Ommaya and 66 Chemoport) who underwent intraventricular chemotherapy via a subgaleal reservoir were reviewed. Chemoport was secured with engraving of skull. Reservoir malfunction, including one intracranial hemorrhage (ICH) under the burr hole occurred, in six patients. During the course of therapy, cerebrospinal fluid (CSF) infection was diagnosed in 19 patients and intraventricular hemorrhage with ICH was evident in three patients of the Ommaya group. Incidence of the above-mentioned complications showed no difference between the two groups. CSF leakage under a galeal flap or through a wound edge occurred more frequently in the Ommaya group (12 patients) than in the Chemoport group (two patients) and the difference was statistically significant (p = 0.03). One-hundred and four patients showed increased intracranial pressure (ICP) and 74 of them received additional CSF drainage to control increased ICP by either intermittent CSF drainage in both groups or continuous extraventricular drainage (EVD) of CSF using designated hooked needle only in the Chemoport group. Among the factors related to the control ICP, the number of chemotherapies, type of reservoir in favor of Chemoport, and EVD showed significantly improved control of ICP (p < 0.05). Chemoport, as a reservoir for intraventricular chemotherapy, has superior ICP control at an equal or lower rate of complications compared with the Ommaya reservoir.

Benefit of ventriculoperitoneal cerebrospinal fluid shunting and intrathecal chemotherapy in neoplastic meningitis: a retrospective, case-controlled study

Neoplastic meningitis (NM) is a debilitating and increasingly frequent neurological complication of cancer characterized by infiltration of tumor cells into the leptomeninges and the subarachnoid space. Although NM is rarely curable, combined intrathecal chemotherapy and focal radiation can improve disease-related symptoms and survival. Hydrocephalus occurs in a significant proportion of patients, is associated with poor prognosis and reduced quality of life, and usually precludes the use of intrathecal therapy. Since January of 2005, the authors have used a combined treatment approach for patients with both NM and hydrocephalus that employs a subcutaneously placed reservoir connected in series to an on/off valve and a ventriculoperitoneal shunt for both diversion of CSF and injection of intrathecal chemotherapy. They conducted a retrospective, case-controlled study from 2 independent institutions to review their experience. Twenty-four patients with NM and hydrocephalus underwent placement of a CSF reservoir-on/off valve-ventriculoperitoneal shunt (RO-VPS) construct. There was no perioperative mortality, and there were only 2 minor complications. One shunt failure and no shunt-associated infections were observed over a median of 28 weeks of follow-up. Symptomatic improvement and improved performance status were seen in 20 patients (83.3%) and were sustained over 6 months. Eighteen patients received intraventricular chemotherapy without unexpected toxicity, and cytological responses were found in 11 patients (61.1%). Median progression-free and overall survival was 14 and 31 weeks, respectively. Compared with a contemporaneous comparison group of 24 demographically matched patients with NM who underwent CSF reservoir placement only, those who received RO-VPS constructs (p = 0.02) and had primary diagnosis of breast cancer (p = 0.04) had significant advantage in overall survival. A combined RO-VPS system is safe and practical to install, results in symptomatic improvement in most patients, and allows uncomplicated and effective administration of intrathecal chemotherapy in patients with NM. Cerebrospinal fluid diversion surgery should be considered in NM patients in conjunction with intrathecal and systemic treatments.

Complications related to the placement of an intraventricular chemotherapy device

Leptomeningeal meningitis occurs in 4-15% of patients with solid tumors. It is a severe disease which seriously affects patients' neurological status and quality of life. Intrathecal chemotherapy increases survival and improves quality of life. Administration of drugs by lumbar puncture causes pain and discomfort, reducing therapeutic compliance. Implantation of an intraventricular catheter fixed to a subcutaneous reservoir overcomes these drawbacks. To evaluate complications compared with implantation of an intraventricular chemotherapy device, between June 2006 and December 2009, 50 patients with a solid tumor underwent implantation of a catheter to treat leptomeningeal metastases. Clinical evaluation of all patients was performed every two weeks and magnetic resonance imaging at one month then every three months. Surgical data (operative time, blood loss) and all clinical and radiological complications were prospectively monitored. All patients underwent surgery with local anesthesia. The mean operative time was 15 min, with no complication during surgery. We report five complications (10%) during the follow-up; three required the removal of the device and another was lethal. There was no case of misplacement or obstruction of the catheter. Intraventricular chemotherapy is an effective treatment procedure which improves therapeutic compliance with acceptable morbidity.

Neues in der Neuroonkologie

Die Standardtherapie des Glioblastoms für erwachsene Patienten ist operative Resektion, Bestrahlung und Temozolomid-Chemotherapie. Therapiestudien mit dem Ziel, dies zu verbessern, werden mit Substanzen durchgeführt, welche Neoangiogenese hemmen, und / oder intrazelluläre Signalübertragung als „small molecules” blockieren, oder auf anderem Wege in Prozesse eingreifen, die Zellproliferation, Migration und / oder Apoptose steuern. Zum Glioblastom des älteren Menschen wurden 2010 aus 2 großen europäischen Studien widersprüchliche Befunde zum Vergleich der Wirksamkeit einer postoperativen alleinigen Bestrahlung mit einer postoperativen alleinigen Chemotherapie vorgelegt, wobei die Unterschiede zwischen den Modalitäten jedoch marginal sind. Beim Rezidiv eines malignen Glioms kommen Re-Operation, Re-Bestrahlung und medikamentöse Therapien zum Einsatz. Zur Therapie des primären ZNS-Lymphoms ist bislang kein „Standard” definiert. Eine Chemotherapie unter Einschluss von Methotrexat (MTX) ist die Basis jeder erfolgreichen Primärtherapie; die Indikation für eine zusätzliche „konsolidierende” Strahlentherapie muss nach den Ergebnissen der größten Therapiestudie bei Primären ZNS-Lymphomen (G-PCNSL-SG1-Studie) bezweifelt werden. Danach besteht im randomisierten Vergleich einer kombinierten Methotrexat(MTX)-basierten Chemo- / Strahlentherapie mit einer alleinigen MTX-basierten Chemotherapie in der Primärbehandlung (und Bestrahlung erst im Rezidiv) kein Überlebensvorteil für eine der beiden Gruppen. Ermutigende Langzeittherapieergebnisse für Patienten bis zum 65. Lebensjahr konnten in einer einarmigen Phase-II-Studie mit einer kombinierten systemischen und intraventrikulären Chemotherapie ohne Bestrahlung erzielt werden: Bei guter Lebensqualität waren etwa die Hälfte der Patienten nach mehr als 8 Jahren noch am Leben.

Case studies of patients receiving intraventricular topotecan for treatment of neoplastic meningitis.

e12540 Background: As cancer patients experience longer survival times, the leptomeningies increasingly play host to metastatic disease from a variety of primary sources. The disease is known as lymphomatous meningitis, or carcinomatous meningitis, depending on the site of origin of the tumor. Generically, the disease can be called neoplastic meningitis (NM) or leptomeningeal metastasis. Sadly, NM frequently results in neurological and functional devastation in afflicted patients. Research into effective and well tolerated treatments is on the rise as the incidence of NM increases. Intrathecal and intraventricular (IVt) chemotherapy via an implanted ventricular reservoir is often administered in order to circumvent the blood-brain-barrier and blood-CSF-barrier, and to provide direct contact of drug with tumor cells. The use of IVt topotecan in the treatment of NM results in progression-free survival outcomes similar to other IVt chemotherapies, while being particularly well tolerated by most patients. Methods: We present case studies from 5 patients who received IVt topotecan for NM. Primary tumors in these patients were as follows: 2 patients with primary breast cancer, 1 patient with multiple myeloma, 1 patient with medulloblastoma and 1 patient with melanoma. Results: In this series of patients, 5 months was the minimum length of treatment with IVt topotecan and maximum length of treatment was 10 months. One patient continues to receive treatment after 7 months. One patient experienced fatigue which was well controlled with dexamethasone. One patient consistently experienced nausea the day after treatment which was well controlled with compazine. There were no other adverse effects. Reasons for stopping treatment were as follows. One patient had progressive systemic disease, 2 patients experienced progression of NM, 1 patient stopped due to progressive neurological and physical decline, one patient continues treatment at this time. Conclusions: Overall, we find IVt topotecan a well tolerated and viable treatment for patients with NM originating from a variety of primary malignancies. No significant financial relationships to disclose.

Medulloblastoma in young children

In early childhood medulloblastoma, three distinct treatment strategies are currently used by different national groups to improve survival rates and to delay or avoid craniospinal radiotherapy: (1) systemic chemotherapy and high-dose chemotherapy, followed by radiotherapy at relapse; (2) systemic and intraventricular chemotherapy; (3) systemic chemotherapy and local conformal radiotherapy. A role for high-dose chemotherapy to delay or avoid craniospinal radiotherapy as a part of multimodal treatment strategies, especially in young children with metastatic or postoperative residual disease, has been recognized by different co-operative groups. Clinical and histological factors such as nodular-desmoplastic variants are considered as important prognostic factors for risk-adapted treatment recommendations.