Leptomeningeal metastases (LMs) are common metastatic complications, occurring in at least 5% of patients with disseminated cancer. Cerebrospinal uid (CSF) cytology remains the standard for diagnosis and assessment of treatment response, but may be inadequate. Our objective was to compare ventricular and lumbar CSF cytology in patients who had cytologically proven LM and were receiving intra-CSF chemotherapy. Sixty patients with LM, positive lumbar CSF cytology documented at diagnosis, limited extent of CNS disease, and no evidence of CSF ow obstruction were treated with a variety of intra-CSF chemotherapies. All patients underwent a single simultaneous ventricular and lumbar CSF sampling (mean volume of CSF per site examined, 10 ml) to assess response to therapy at either 1 or 2 months after treatment initiation. Ventricular CSF cytology was positive in 44 patients (73%), 35 of whom were also positive by lumbar CSF cytology. Lumbar CSF cytology was positive in 45 patients (75%), of which 35 were also positive by ventricular CSF cytology. Samples were negative at both ventricular and lumbar sites in 6 patients (10%). Paired CSF cytologies were discordant in 19 (32%) patients. The lumbar cytology was negative in 9, whereas the ventricular cytology was positive (lumbar false-negative rate of 17%); the ventricular cytology was negative in 10, whereas the lumbar cytology was positive (ventricular false-negative rate of 20%). In the presence of spinal signs or symptoms of LM, the lumbar CSF cytology was more likely to be positive than was the ventricular (odds ratio = 2.86; 95% con dence interval, 0.86-9.56). Conversely, in the presence of cranial signs or symptoms, the ventricular CSF cytology was more likely to be positive than was the lumbar (odds ratio = 2.71; 95% con dence interval, 0.76-9.71). In this cohort of patients, whose LM was documented initially by positive lumbar CSF cytology, ventricular and lumbar CSF samples obtained during treatment had similar false-negative rates, depending on the site of clinical or radiologic disease. This suggests that both lumbar and ventricular sites must be sampled when assessing treatment response. If clinical or radiographic disease is present only at 1 site, then CSF from that site is more likely to be positive than is CSF obtained from the more distant site. Neuro-Oncology 3, 42-45, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-033, October 19, 2000

Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemiaElias Jabbour and colleagues reported on the novel use of intralumbar liposomal extended-release ara-C (DepoCyt; SkyePharma, San Diego, CA) administered in lieu of standard central nervous system (CNS) prophylaxis for adult patients with acute lymphocytic leukemia (ALL). 1 Concerningly, 5 of the 31 patients receiving DepoCyt (16%) developed neurologic complications attributed by the investigators to intralumbar DepoCyt. We would like to comment on the neurologic syndromes observed in this patient cohort and attributed to DepoCyt.In one instance, an unprovoked, uncomplicated seizure was reported. Seizures occasionally occur (more than 1%) with intracerebrospinal fluid (intra-CSF) chemotherapy and in particular following intraventricular drug instillation. However, in the authors' experience, seizures occur in relation to acute drug administration (ie, either at time of drug injection or as a complication of drug-induced chemical meningitis). 2 A seizure occurring 10 days after intralumbar therapy seems unlikely to be related to intra-CSF chemotherapy and more likely metabolic in etiology or cryptogenic and occurring in a genetically predisposed patient.Patient 2 developed "pseudotumor cerebri" characterized by progressive visual loss and increased opening pressure on lumbar puncture. 3 Treatment with ventriculoperitoneal (VP) shunting resulted in partial visual restoration. Intra-CSF chemotherapy often produces transient chemical meningitis, which, rarely, gives rise to an adhesive arachnoiditis and, as a result, CSF flow disturbances. This sequence of events, culminating in communicating hydrocephalus, has only previously been described following intraventricular drug administration. The risk factors for this poorly understood disorder likely include female sex and corticosteroid administration.The third patient was described as having a cauda equina syndrome with isolated incontinence and saddle anesthesia. Cauda equina syndromes are characterized by lower motor neuron asymmetric paraparesis and dermatomal lower-extremity sensory loss with the late appearance of incontinence. The symptoms in this patient suggest instead a conus medullaris syndrome typified by early incontinence and sacral sensory disturbance. Unfortunately, this is a rare complication of intralumbar chemotherapy regardless of drug administered.The fourth patient was also described as having a cauda equina syndrome though the clinical findings were incontinence only. Incontinence as the sole manifestation of spinal cord dysfunction is rarely seen. The fact that this symptom did not progress (or new symptoms develop) despite continued intralumbar DepoCyt seems unusual and unlikely to represent spinal cord injury.The final patient developed what was characterized as encephalitis; however, encephalopathy seems more precise. Again, a relation between the ...

In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classified as good risk and 12 were classified as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% confidence interval, >26 months to infinity). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% confidence interval, 27 to infinity) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% confidence interval, 0 to infinity). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 microl) in 6, thrombocytopenia (<50,000 microl) in 6, nephrotoxicity (>25% decrease by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide decrease >40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing deficit (>20 dB) or tinnitus. The POG and Packer protocols...

<p>PDF file - 338KB, Figure S1. COX-2 is overexpressed in MDA-MB-231 cells. Figure S2. Celecoxib inhibits the invasion and migration capacity of breast cancer cells in vitro. Figure S3. Celecoxib inhibits the migration of breast cancer cells into the cerebrospinal fluid. Figure S4. Enumerating human breast cancer cells in mouse blood using the CellSearch system. Figure S5. Changes in CTC and CSFTC counts as a function of changes in neurological or systemic clinical symptoms of disease. Table S1. Receptor status of enrolled breast cancer patients.</p>

<p>PDF file - 338KB, Figure S1. COX-2 is overexpressed in MDA-MB-231 cells. Figure S2. Celecoxib inhibits the invasion and migration capacity of breast cancer cells in vitro. Figure S3. Celecoxib inhibits the migration of breast cancer cells into the cerebrospinal fluid. Figure S4. Enumerating human breast cancer cells in mouse blood using the CellSearch system. Figure S5. Changes in CTC and CSFTC counts as a function of changes in neurological or systemic clinical symptoms of disease. Table S1. Receptor status of enrolled breast cancer patients.</p>