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.

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-Hodgkin's 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 x time (C x 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 > or =60, no evidence of disseminated PCNSL, a CD4 count >200, no concurrent opportunistic infection and a patient's 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/ 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.

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.

Salvage chemotherapy with tamoxifen for recurrent anaplastic astrocytomas.

BACKGROUND: A prospective phase 2 study of daily oral tamoxifen citrate in young adults with recurrent anaplastic astrocytomas. METHODS: Twenty-four patients (15 men; 9 women) aged 19 to 45 years (median age, 31.5 years) with recurrent anaplastic astrocytomas were treated. All patients had been treated previously with surgery and involved-field radiotherapy (median dose, 60 Gy; range, 59-61 Gy). In addition, 22 patients were treated adjuvantly with nitrosourea-based chemotherapy (combined procarbazine hydrochloride, lomustine, and vincristine sulfate in 16; carmustine in 6). All patients were treated with salvage chemotherapy at first recurrence, with 1 to 4 chemotherapy regimens (median, 1 regimen). Tamoxifen citrate was administered orally at a fixed dosage of 80 mg/m2 as a single or a twice-daily dosage. Neurologic and neuroradiographic evaluation were performed every 12 weeks, operationally defined as a single cycle of tamoxifen. RESULTS: All patients were able to undergo evaluation. A median of 4 cycles of tamoxifen (range, 1-8 cycles) were administered. No tamoxifen-related toxic effects were seen, nor were there any treatment-related deaths. Four patients (17%) demonstrated a neuroradiographic partial response; 11 patients (46%), stable disease; and 9 patients (38%), progressive disease following a single cycle of tamoxifen. Time to tumor progression ranged from 3 to 25 months (median, 12 months). Survival ranged from 3 to 27 months (median, 13 months). Five patients are alive, with 3 receiving alternative chemotherapy regimens and 2 continuing to receive tamoxifen. In the group with responding and stable disease, median survival was 15 months (range, 8-27 months). CONCLUSION: Tamoxifen demonstrated modest efficacy with no apparent toxic effects in this heavily pretreated cohort of young adults with recurrent anaplastic astrocytomas.

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 Diego's 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.

Leptomeningeal metastasis: pathophysiology, treatment, and nursing management.

PURPOSE/OBJECTIVES: To review the pathophysiology, diagnosis, and clinical treatment of leptomeningeal metastasis. DATA SOURCES: Published articles, abstracts, and book chapters. DATA SYNTHESIS: Leptomeningeal metastasis is an increasingly seen complication of cancer. Treatment is intensive and may increase survival from four to five weeks without treatment to an average of six months. Clinical management and treatment of these patients is complex and best accomplished by a multi-disciplinary healthcare team. CONCLUSIONS: Information regarding the anatomy, pathophysiology, treatment, and treatment complications can facilitate the care of patients with leptomeningeal metastasis. IMPLICATIONS FOR NURSING PRACTICE: Nursing interventions should focus on patient and family education about the disease process, side-effects of treatment, and early identification of disease progression.

Recurrent primary central nervous system lymphoma complicated by lymphomatous meningitis.

Primary central nervous system lymphomas (PCNSL) are chemosensitive primary brain tumors and are treated primarily with adjuvant chemotherapy. Nonetheless, therapy is palliative with the majority of tumors recurring in brain parenchyma. A common pattern of PCNSL recurrence is that of cerebrospinal fluid (CSF) dissemination manifested as lymphomatous meningitis (LM). Fourteen patients (8 men; 6 women) 34-76 years of age (median 56 years) with recurrent PCNSL manifested as either lymphomatous meningitis (8 patients) or combined parenchymal and CSF disseminated tumor (5) were retrospectively evaluated. All patients had received prior adjuvant therapy including surgery (gross total resection in 3; biopsy in 11), radiotherapy (whole brain in 11; craniospinal in 1; and orbital in 1) and chemotherapy (systemic in 13; intraventricular in 4). At recurrence, documented by either positive CSF cytology (14 patients) or neuroradiographic evidence of disease progression (6 patients), all patients were evaluated for extent of central nervous system disease. Two patients not previously irradiated were treated with whole brain radiotherapy. Eight patients received systemic chemotherapy including 7 patients (Brown University; Group A) treated with either high dose methotrexate (n=4) or cytosine arabinoside (n=3). Seven patients (UCSD: Group B) received intraventricular chemotherapy (methotrexate 5; cytosine arabinoside 4; thio-TEPA 4) without concomitant high dose systemic chemotherapy. Four of 14 patients (28.6%) are disease-free and have durable responses (median 36 months, range 22-56 months). Ten patients (71.4%) have died of disease progression (5 due to combined PCNSL and LM; 4 due to LM; and 1 due to PCNSL). Median survival was 5.5 months with a range of 3-12 months. Grade III/IV myelosuppression was seen in 5 patients, all as a result of systemic chemotherapy (Group A patients). Aseptic meningitis due to intraventricular chemotherapy was seen in 7 patients (Group B patients). No treatment-related deaths occurred. Four patients are disease-free and manifest leukoencephalopathy of whom 2 are symptomatic. Outcome was comparable in Group A and B patients. Recurrent PCNSL complicated by LM may be palliated by combined modality therapy and in this small series, approximately one-quarter of patients (two from each treatment group) are long-term survivors and disease-free. Outcome is similar in patients treated with intraventricular chemotherapy as compared to patients treated with high dose systemic methotrexate or cytosine arabinoside. Treatment-related toxicity was manageable however delayed neurotoxicity is seen in disease-free survivors.

Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy.

BACKGROUND: Leptomeningeal metastases (LM) are increasingly diagnosed as anticancer therapies become more effective and result in prolonged patient survival. OBJECTIVE: To evaluate survival, cause of death, and treatment-related toxic effects in patients undergoing combined modality therapy for LM of non-small cell lung cancer. PATIENTS AND METHODS: Thirty-two patients (age range, 48-73 years; median, 57 years) with LM attributable to metastatic non-small cell lung cancer were treated prospectively. Neurologic presentation included headache (11 patients), cranial neuropathies (9), ataxia (5), cauda equina syndrome (3), myelopathy (3), meningismus (2), radiculopathy (2), and confusion (1). All patients underwent radiographic evaluation to determine the extent of central nervous system disease followed by radiotherapy (16 patients) and sequential and intraventricular chemotherapy (methotrexate in 32 patients; cytarabine in 16; and thiotepa in 6). Twelve patients received concurrent systemic chemotherapy. RESULTS: Central nervous system imaging demonstrated interrupted cerebrospinal fluid flow (13 patients), parenchymal brain metastases (9), subarachnoid nodules (8), hydrocephalus (5), and epidural spinal cord compression (2). Cytological responses were seen in 17 patients to first-line chemotherapy, 8 to second-line chemotherapy, and 2 to third-line chemotherapy. Treatment-related toxic effects included 20 patients with aseptic meningitis (grade 2 in 16; grade 3 in 4) and 12 patients with grade 3 or 5 thrombocytopenia or neutropenia (4 related to intraventricular chemotherapy). Median survival was 5 months (range, 1-12 months). Nineteen patients died of progressive LM or combined LM and systemic disease progression. Patients with persistent interruption of cerebrospinal fluid flow fared worse than patients with normal cerebrospinal fluid flow (median survival, 4 vs 6 months; P<.05). CONCLUSIONS: Leptomeningeal metastases in patients with non-small cell lung cancer may be palliated with combined modality therapy; however, therapy and survival is based on the extent of central nervous system disease present at pretreatment evaluation.

Practical guidelines for the treatment of malignant gliomas.

The treatment of patients with malignant gliomas is palliative and encompasses surgery, radiotherapy, and chemotherapy. Outcome measures have demonstrated improvement in both survival and neurologic performance in patients undergoing complete or near-complete tumor resection. After surgery, involved-field radiotherapy (radiotherapy administered to the tumor and to the tissue in a 3-cm radius surrounding the tumor) has been shown to further improve survival rates when given in a total dose of 6000-6500 cGy. Survival is further improved by the coadministration of the chemoradiopotentiator hydroxycarbamide (hydroxyurea). The role of adjuvant or boost stereotactic radiotherapy is unclear, despite its frequent use. In addition, adjuvant chemotherapy has been shown to improve survival rates in approximately one-quarter of patients with glioblastoma multiforme and in the majority of patients with anaplastic astrocytoma. No a priori method exists, however, to predict which patient will benefit from adjuvant chemotherapy. As a consequence, all physiological young patients with good performance status or limited neurologic disability are treated with chemotherapy. The best results of adjuvant chemotherapy are achieved with a nitrosourea chemotherapy, either carmustine (BCNU) or a combination of procarbazine and lomustine (CCNU) and vincristine, known as PCV-3 therapy. Salvage chemotherapy is reserved for patients with tumor progression, some of whom benefit from a re-operation. Occasional patients with recurrent gliomas may be palliated by stereotactic radiotherapy.

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 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.

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-Hodgkin's 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).

Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases.

The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM). One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system. The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42). Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two). Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome. Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10). Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient. Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one). There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five). Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system. The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy. Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning. In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).

Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases.

OBJECTIVE: To assess the clinical significance of bulky metastatic central nervous system disease in patients with leptomeningeal metastases. PATIENTS AND METHODS: Forty patients (24 women and 16 men) ranging in age from 32 to 74 years (median, 56.5 years) with cytologically documented leptomeningeal metastases were demonstrated by cranial or spinal magnetic resonance imaging to have either no bulky central nervous system metastatic disease (group A; 20 patients) or bulky central nervous system metastatic disease (group B; 20 patients). Twenty-nine patients were treated with involved-field radiotherapy, and all patients were treated with sequential intraventricular chemotherapy. RESULTS: Median survival was 7 months in group A (range, 5-12 months) as compared with 4 months in group B (range, 2-12 months) (P < .01; Mantel-Cox log rank analysis). Cause of death was similar in both patient groups. CONCLUSIONS: In patients with leptomeningeal metastases, neuroradiographic demonstration of bulky metastatic central nervous system disease independently predicts survival and is useful in determining which patients are candidates for intraventricular chemotherapy.

Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy.

PURPOSE: To identify the factors predictive of response and increased survival in patients with leptomeningeal metastases (LM) from breast cancer receiving multi-modal therapy. BACKGROUND: Leptomeningeal metastases (LM) are being diagnosed with increasing frequency as anti-cancer therapies become more effective and result in prolonged patient survival. PATIENTS AND METHODS: 32 women (range 28 to 74 years; median 49) with LM due to metastatic breast cancer were treated. Neurologic presentation included: cranial neuropathies (10 patients); headache (10); cauda equina syndrome (6); ataxia (6); meningismus (3); radioculopathy (2); myelopathy (2); confusion (2); and seizure (1). All patients underwent radiographic evaluation of the extent of CNS disease followed by radiotherapy (21 women) and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22; thio-TEPA 11). RESULTS: CNS imaging (cranial MR, spine MR and radionuclide ventriculography) demonstrated: interrupted CSF flow (21); subarachnoid nodules (8); parenchymal brain metastases (6); hydrocephalus (4); and epidural spinal cord compression (1). Cytologic responses were seen in 14 women to first-, 7 to second- and 3 to third-line chemotherapy. Treatment-related toxicity included 21 women with aseptic meningitis and 10 women with thrombocytopenia or neutropenia (5 related to intraventricular chemotherapy). Median survival was 7.5 months (range 1.5 to 16), 18 women died of progressive LM or combined LM and systemic disease progression. Women with persistent interruption of CSF flow fared worse than women with normal CSF flow (median survival 3 versus 10 months; p < 0.0001). CONCLUSION: LM in women with metastatic breast cancer may be palliated with combined modality therapy, however, success of therapy and survival is based upon pre-treatment CNS extent of disease evaluation.

Concurrent carboplatin and iodine-125 brachytherapy for recurrent glioblastoma multiforme.

Toxicity and safety study of concurrent carboplatin chemotherapy and iodine-125 (I-125) brachytherapy. I-125 brachy therapy has an established albeit limited role in surgically accessible recurrent gliomas. Carboplatin has anti-tumoral; activity against gliomas and demonstrated sensitization of tumor to radiotherapy. In 15 patients (age range 30-77 years; median 53) with recurrent glioblastoma multiforme, stereotactically placed catheters were afterloaded with I-125 sources. A median 50 Gy minimum treatment volume dose was delivered during a 100 h period in conjunction with continuous infusion carboplatin (100 mg/m(2)/20 h x 5). Tumor volumes ranged from 13 to 63 cm(3) (median, 32 cm(3)). Early complications included: headache (n=7), transient exacerbations of pre existing neurologic deficits (n=5), seizures (n=2), nausea/vomiting (n=2), myelosuppression (n=2) and a catheter site wound CSF leak (n=1). Late complications included: steroid dependency (n=10), carcinomatous meningitis in association with hydrocephalus (n=1) and radiation-induced necrosis requiring reoperation (n=6). All patients were evaluable with a median survival of 10 months. In 12 patients, best clinical and neuroradiographic response was stable disease all of whom died of recurrent tumor (local recurrence in 11; CSF dissemination in 1). In 3 patients best response was either complete (n=2) or partial (n=1) all of whom are alive with a median follow-up of 31 months. I-125 brachytherapy with concurrent carboplatin chemotherapy is associated with an acceptable level of toxicity, has anti-tumoral activity and warrants further investigation in carefully selected patients with recurrent gliomas.

Lymphomatous meningitis in immunocompetent patients.

A prospective study of combined modality therapy of non-AIDS related lymphomatous meningitis was carried out. Lymphomatous meningitis is diagnosed increasingly as anti-lymphoma therapies become more effective and result in prolonged patient survival. Twenty-two patients (range 38-69 years; median 60) with lymphomatous meningitis due to metastatic non-AIDS related non-Hodgkins lymphoma were treated. Neurologic presentation included: headache (n=13); cranial neuropathies (n=9); ataxia (n=5); cauda equina syndrome (n=3); myelopathy (n=1); and meningismus (n=1). All patients underwent radiographic evaluation of the extent of central nervous system disease (CNS) followed by radiotherapy (n=8) and sequential intraventricular chemotherapy (methotrexate in 22 patients; cytarabine in 12; thio-TEPA in 5). CNS imaging demonstrated: interrupted CSF now (n=8); intra-cranial subarachnoid nodules (n=2); hydrocephalus (n=2); spinal subarachnoid nodules (2); nerve root enhancement (n=2); and epidural spinal cord compression (n=1). Cytologic responses were seen in 16 patients (73%) to first-, 7 (58%) to second- and 2 (40%) to third-line chemotherapy. Treatment-related toxicity included 14 patients (64%) with aseptic meningitis and 12 patients (55%) with thrombocytopenia or neutropenia (all unrelated to intraventricular chemotherapy). Median survival was 10 months (range: 3-24 months). Fourteen patients (64%) died of their systemic disease, 3 patients (14%) died of progressive lymphomatous meningitis, 4 patients (19%) died of progressive combined systemic disease in lymphomatous meningitis and 1 patient (5%) is disease-free. Fourteen patients (64%) received concurrent systemic chemotherapy and no differences were seen in outcome within this group of patients including 6 patients treated with dose intensive chemotherapy and autologous bone marrow transplantation. Lymphomatous meningitis in patients with non-AIDS related non-Hodgkin's lymphoma may be palliated with combined modality therapy, however, despite the application of standard or dose intensive systemic chemotherapy, therapy remains non-curative.

Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases.

We assessed the clinical significance of interruption of CSF flow documented by radionuclide ventriculography (111Indium-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, 111Indium-DTPA CSF flow studies predict patient survival and are useful in determining which patients would be candidates for intra-CSF chemotherapy administration.