Patty A. Kormanik

Prognostic significance of sup 111 Indium-DTPA CSF flow studies in leptomeningeal metastases

We assessed the clinical significance of interruption of CSF flow documented by radionuclide ventriculography (sup 111 Indium-DTPA CSF flow study) in patients with leptomeningeal metastases. Forty patients (25 men and 15 women) ranging in age from 6 to 70 years (median 38.5 years) with cytologically documented leptomeningeal metastases were demonstrated to have interruption of CSF flow by radionuclide ventriculography. All patients were treated with radiotherapy (30 Gy in 10 fractions) to the site of CSF obstruction after which intra-CSF chemotherapy (methotrexate or cytarabine followed by cytarabine or thio-TEPA if clinically indicated) was administered. Twenty patients (group 1) after radiotherapy to the site of CSF flow block demonstrated reestablishment of normal CSF flow. By contrast, 20 patients (group 2) treated in a similar manner had persistent CSF flow obstruction. All patients were treated with intraventricular chemotherapy. Median survival was 6 months in group 1 (range 3 to 15 months) compared with 1.75 months in group 2 (range 1 to 4 months) (p < 0.0001). Cause of death differed between groups with 20% of group 1 patients dying of progressive leptomeningeal disease compared with 70% of group 2 patients (p < 0.0006). In patients with leptomeningeal metastases and CSF flow obstruction,111 Indium-DTPA CSF flow studies predict patient survival and are useful in determining which patients would be candidates for intra-CSF chemotherapy administration. NEUROLOGY 1996;46: 1674-1677

Salvage chemotherapy with paclitaxel for recurrent primary brain tumors.

PURPOSE To assess the safety and efficacy of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) given at a dose of 175 mg/m2 every 3 weeks as a 3- to 4-hour outpatient infusion to patients with recurrent malignant primary brain tumors who had received prior radiotherapy and at least one chemotherapy regimen containing nitrosoureas and who were no longer responding to therapy. PATIENTS AND METHODS Twenty patients (12 men and eight women), ages 19 to 69 years (median, 35), with recurrent primary brain tumors were treated according to a phase II protocol with intravenous Taxol. Tumor histologies included the following: anaplastic astrocytoma (n = 8), glioblastoma multiforme (n = 8), and anaplastic oligodendroglioma (n = 4). All patients had been previously treated with subtotal resection, limited-field radiotherapy (median dose, 60 Gy; range, 54 to 78 Gy), and nitrosourea-based chemotherapy. Taxol was administered intravenously at a dose of 175 mg/m2/d every 3 weeks with neurologic and neuroradiographic evaluation every 8 to 9 weeks. Complete blood cell counts were performed weekly. RESULTS A median of six cycles of Taxol (range, two to 12) were administered to 20 assessable patients. Toxicities included partial alopecia (n = 10), thrombocytopenia (n = 4), rate of Taxol administration-dependent bradycardia (n = 3), and nondisabling peripheral neuropathy (n = 1). No patient developed neutropenic fever or sepsis or required cytokine support. Two patients required blood-product support (platelet transfusions in both). Four patients (20%) demonstrated a partial response (PR) and seven (35%) had stable disease (SD) for a total response plus SD rate of 55%. The median time to tumor progression was 6 months (range, 2 to 20). CONCLUSION Taxol demonstrated modest efficacy with minimal toxicity in this heavily pretreated cohort of young patients with recurrent primary brain tumors.

AIDS-related Central Nervous System Lymphomas

Purpose: To evaluate combined radio-chemotherapy in patients with AIDS-related lymphomatous meningitis (LM) or primary central nervous system lymphoma (PCNSL).Patients and methods: Eighteen men and 2 women with AIDS had cytologically documented LM. Fifteen patients had systemic non-Hodgkins lymphoma with LM and 5 patients had PCNSL with CSF dissemination. Standardized pre-treatment evaluations included contrast cranial MRI, placement of an intraventricular reservoir, contrast spine MRI, ophthalmologic evaluation and 111Indium-DTPA CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field irradiation. Concurrent systemic chemotherapy was administered in 18 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) according to a concentration×time (C×T) drug schedule. In cytologic or clinical failures, patients were treated with salvage therapy using intraventricular ara-C and in a similar manner, patients were treated with intraventricular thio-TEPA following cytologic relapse or clinical failure intraventricular following intraventricular ara-C.Sixty-seven patients (63 men; 4 women) with PCNSL underwent a standardized pre-treatment evaluation as in patients with LM and were treated according to 3 schedules. In the first group (n=15), comfort care was offered. In the second group (n=45), whole brain radiotherapy was administered. In the third group (n=7), patients were treated with combined radio- and chemotherapy using systemic procarbazine, CCNU and vincristine (PCV-3). The third group was selected based on a Karnofsky performance status ≥60, no evidence of disseminated PCNSL, a CD4 count ≥200, no concurrent opportunistic infection and a patients desire for aggressive therapy.Results: In the LM patient group, 16 patients were evaluable as 4 patients subsequently withdrew consent for treatment. Median time to tumor progression/survival were as follows: not-treated (n=4) 12 days/1 month; treated non-responding (n=6) 30 days/2 months; and treated responding (n=10) 130 days/6 months. In the PCNSL patient group, median range survival were as follows: comfort care (n=15) 1.5/0.5–3 months; whole brain radiotherapy (n=45) 4/1.5–5 months; and combined radio-chemotherapy (n=7) 13/10–18 months.Conclusions: Combined radio- and chemotherapy is appropriate for a small subset of patients with AIDS and either LM or PCNSL. This approach results in meaningful palliation not strikingly dissimilar from that seen in non-AIDS patients.

Epidural spinal cord compression: a single institution's retrospective experience.

Epidural spinal cord compression (ESCC) is a common metastatic complication occurring in 5% of patients with cancer. We sought to determine retrospectively the frequency of multiple sites of ESCC at presentation and the risk of recurrence of ESCC. Of the cancer patients seen by the University of California San Diegos Neuro-Oncology Service between August 1986 and January 1997, 108 developed ESCC that was documented both clinically and by MRI of the spine. In 77 patients (71%), a single site of ESCC was seen; 31 patients (29%) had multiple sites of ESCC. All sites of ESCC were irradiated. In 7% of patients with single-site ESCC and in 9% of patients with multiple-site ESCC, the disease recurred. Length of survival was similar for patients with single- or multiple-site ESCC (median, 4.5 months) versus patients with recurrent ESCC (median, 7 months). An MRI of the entire spine in patients with suspected ESCC demonstrated multiple sites of ESCC in nearly one-third of patients. In 8% of patients with ESCC, symptomatic ESCC recurred.

A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases.

Leptomeningeal metastases (LMs) are common metastatic complications, occurring in at least 5% of patients with disseminated cancer. Cerebrospinal fluid (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 flow 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% confidence 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% confidence 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.

Salvage chemotherapy with paclitaxel for recurrent oligodendrogliomas.

PURPOSE A prospective phase II study of paclitaxel was performed in adult patients with recurrent hemispheric oligodendrogliomas. PATIENTS AND METHODS Twenty adult patients (14 men and six women), ages 18 to 52 years (median, 40.5), with recurrent supratentorial hemispheric oligodendrogliomas were treated. All patients had previously been treated with surgery, involved-field radiotherapy (median dose, 55 Gy; range 54 to 55 Gy) and nitrosourea-based (procarbazine, lomustine [CCNU], and vincristine [PCV-3 regimen]) chemotherapy (median number of cycles, five; range, four to six). Fourteen patients were treated adjuvantly with radiotherapy and nitrosourea-based chemotherapy; six were treated at recurrence following initial gross total resection with reoperation (subtotal resection in all), radiotherapy, and nitrosourea-based chemotherapy. Paclitaxel was administered intravenously at a dose of 175 mg/m2 every 3 to 4 weeks with neurologic and neuroradiographic evaluation every 8 weeks. RESULTS A median of three cycles of paclitaxel (range, two to 10) were administered. All patients were assessable. Toxicity included partial alopecia (12 patients), thrombocytopenia (six), neutropenia (three), and anemia (one). One patient developed neutropenic fever without bacteriologic documentation and four required transfusion of blood products (RBCs, n = 2; platelet, n = 2). No treatment-related deaths occurred. Ten patients (50%) demonstrated either a neuroradiographic partial response (n = 3) or stable disease (n = 7), with a median response and stable disease duration of 10 months (range, 5 to 14). CONCLUSION Paclitaxel demonstrated modest efficacy with minimal toxicity in this pretreated cohort of adult patients with recurrent hemispheric oligodendrogliomas.

Chronic Oral VP-16 for Recurrent Medulloblastoma

Chronic oral VP-16 (Etoposide) is a chemotherapy regimen with wide application in oncology and documented efficacy against germ cell tumors, lymphomas, Kaposi sarcoma, and glial brain tumors. Eight patients ranging in age from 4 to 36 years (median 7.5 years) with locally recurrent medulloblastoma were treated with VP-16. No patient displayed evidence of cerebrospinal fluid dissemination, distant brain or spine parenchymal metastases, or extraneural metastatic disease. All patients had previously been treated with surgery (gross total resection, 5; subtotal resection, 3), craniospinal radiotherapy, and platinum-based chemotherapy (adjuvant, 3; salvage, 8). Each cycle of therapy consisted of 21 days of VP-16 (50 mg/m2/day) followed by a 7 to 14 day rest followed by an additional 21 days of VP-16 (50 mg/m2/day). Complete blood counts were obtained weekly. Neurologic examination and brain magnetic resonance imaging scan with contrast were performed prior to each cycle of therapy. Treatment-related complications included: partial alopecia (5 patients); diarrhea (4); weight loss (3); anemia (2); neutropenia (4); and thrombocytopenia (4). Two patients required transfusion and 1 patient received antibiotics for neutropenic fever. All patients were evaluable for response: 3 demonstrated progressive disease after the first cycle of VP-16, 3 had stable disease (range 4 to 6 months) and 2 had partial neuroradiographic responses (8 and 10 months). Median duration of response and stable disease was 6 months (range: 4 to 10 months) in 5 of 8 (62.5%) patients. Chronic oral VP-16 is a well-tolerated and relatively non-toxic chemotherapeutic agent with demonstrated activity in locally recurrent medulloblastoma.

Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas.

Background: A prospective Phase II study of Taxol in young adult patients with recurrent anaplastic astrocytomas.Methods: Twenty-four patients (15 men; 9 women) ages 19–45 years (median 31.5), with recurrent anaplastic astrocytomas were treated. All patients had previously been treated with surgery and involved-field radiotherapy (median dose 60 Gy; range 51–61 Gy). Additionally, 22 patients were treated adjuvantly with nitrosourea-based chemotherapy (PCV in 17; BCNU in 5). Fourteen patients were treated with salvage chemotherapy at first recurrence with 1–2 chemotherapy regimens (median 1). Taxol was administered at a fixed dose of 175 mg/m2 given as a 3 h intravenous infusion monthly. Neurological and neuroradiographic evaluation were performed every 8 weeks after 2 courses of Taxol, operationally defined as a single cycle of Taxol.Results: All patients were evaluable. A median of 3.5 cycles of Taxol (range 1–13) were administered. Taxol-related toxicity included: partial alopecia (13 patients); non-disabling peripheral neuropathy (4); neutropenia (4); anemia (3); and thrombocytopenia (2). Four patients required transfusions (2 packed red blood cell; 2 platelet) and one patient was treated for culture negative neutropenic fever. No treatment-related deaths were observed. Three patients (13%) demonstrated a neuroradiographic partial response, 16 patients (67%) demonstrated stable disease and 5 patients (21%) had progressive disease following a single cycle of Taxol. Time to tumor progression ranged from 2–26 months (median 7.5 months). Nineteen patients were offered alternative chemotherapy after failing Taxol of whom 13 clinically responded. Survival ranged from 3–56 months (median 18.5 months). Four patients are alive, all are on alternative chemotherapy regimens.Conclusions: Taxol demonstrated modest efficacy with manageable toxicity in this heavily pre-treated cohort of young adult patients with recurrent anaplastic astrocytomas.

Non-AIDS-related lymphomatous meningitis: Combined modality therapy

Twenty-two patients (age range, 38 to 69 years; median, 60 years) with lymphomatous meningitis due to metastatic non-AIDS-related non-Hodgkins lymphoma were treated. Cytologic responses were seen in 16 patients (73%) to first-line chemotherapy, 7 patients (58%) to second-line chemotherapy, and 2 patients (40%) to third-line chemotherapy. Median survival was 10 months(range, 3 to 24 months).

Spindle cell hemangioendothelioma of the spinal cord

SummaryAn intradural extramedullary spinal cord hemangioendothelioma at T10, T11 recurred twice and was irradiated after the third resection. This first reported case prompted a review of the neuropathology and natural history of this unusual tumor.