Biomedical subjects
Publications and source records attributed to M C Chamberlain.
Eighteen patients (age range, 28 to 62 years; median, 58) with carcinomatous meningitis defined clinically (100%) and neuroradiographically (39%) with negative CSF cytology were evaluated with CSF biochemical markers. In only four patients (22%), CSF biochemical markers corroborated a diagnosis of carcinomatous meningitis.
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.
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.
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BACKGROUND: A long-term regimen of oral etoposide, a type of chemotherapy, is used in oncology and is effective in treating germ-cell tumors, lymphomas, Kaposi sarcoma, and primary brain tumors. OBJECTIVE: To examine the toxic effects and efficacy of long-term salvage chemotherapy using oral etoposide. PATIENTS AND METHODS: Fourteen children (8 boys and 6 girls) with recurrent supratentorial gliomas, ranging in age from 4 to 18 years (median age, 9 years), were treated with etoposide. Tumor histologic grades included Daumas-Duport grade 3 (10 children) and grade 4 astrocytomas (4 children). All children had been treated previously with radiotherapy (median dose, 60 Gy) and nitrosourea-based chemotherapy. Each cycle of therapy consisted of 21 days of etoposide (50 mg/m2 daily) followed by a 14-day period of rest and an additional 21 days of etoposide (50 mg/m2 daily). Measurements of complete blood cell counts were taken biweekly. A neurological examination and a magnetic resonance image of the brain with contrast medium were performed before each cycle of therapy. RESULTS: Treatment-related complications included the following partial alopecia (8 children); diarrhea (6 children); weight loss (4 children); anemia (4 children); neutropenia (4 children) and thrombocytopenia (4 children). Four children required transfusion (4 with packed red blood cells and 3 with platelets) and 2 children received antibiotic therapy for neutropenic fever. There were no treatment-related deaths. All children were examined for response. In 7 children (50%), the results of magnetic resonance imaging indicated either a partial response (3 children) or stable disease (4 children), with a median duration of response of 8 months. CONCLUSION: Oral etoposide is a well tolerated and relatively nontoxic chemotherapeutic agent with demonstrated activity in children with recurrent supratentorial gliomas.
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.
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.
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.
Fifteen children ranging in age from 4 to 18 years with leptomeningeal metastases were evaluated for extent of tumor and treated with radiotherapy or chemotherapy. Histologic diagnosis included: acute lymphoblastic leukemia (4); anaplastic astrocytoma (1); ependymoma (2); nonseminomatous germ cell tumor (1); non-Hodgkin's lymphoma (1); pineoblastoma (1); and primitive neuroectodermal tumor not otherwise specified (2). Pretreatment imaging studies demonstrated recurrent intracranial parenchymal disease in nine, spinal disease in four, and abnormal radioisotope ventriculography in six. Systemic disease was seen in four children (3 leukemia; 1 non-Hodgkin's lymphoma). All children were treated with systemic chemotherapy and intraventricular chemotherapy. Nine children received radiotherapy to bulky or symptomatic leptomeningeal disease. Median survival was 6 months (range, 4-18 months). Children with hematologic malignancies had superior outcomes compared to children with solid tumors. Three children with leukemic or lymphomatous meningitis are alive and disease free whereas all children with carcinomatous meningitis died. In conclusion, leptomeningeal metastases in children portends a limited survival, and therapies at this time remain palliative except in children with hematologic malignancies.
The purpose of this investigation was to assess the toxicity and activity of chronic oral etoposide in the management of children with recurrent juvenile pilocytic cerebellar astrocytomas. Twelve children with recurrent juvenile pilocytic cerebellar astrocytomas, refractory to surgical resection, radiotherapy, and chemotherapy were treated with chronic oral etoposide. Treatment related complications included alopecia, diarrhea, weight loss, and thrombocytopenia. Three children required transfusion and one child developed neutropenic fever. No treatment related deaths occurred. Six children demonstrated either a radiographic response or stable disease with a median duration of 7 months. Oral etoposide was well tolerated, produced modest toxicity, and had apparent activity in this small cohort of children with recurrent juvenile pilocytic cerebellar astrocytomas.
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.
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).
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%).
An 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.
Infantile spasms and the Lennox-Gastaut syndrome are considered to be age-specific pediatric epileptic syndromes and together constitute a significant percentage of medically resistant seizures in childhood. Twenty children, ages 4 to 28 months (median, 12 months), with medically refractory infantile spasms or the Lennox-Gastaut syndrome, were treated with the investigational benzodiazepine nitrazepam in an open-label study. Daily dosage of nitrazepam ranged from 0.5 to 3.5 mg/kg, with a median dosage of 1.5 mg/kg, divided into two doses per day. Side effects included pooling of oral secretions (12 children) and sedation (six children); however, no serious side effects were seen. Responses to nitrazepam were as follows: five complete responses (cessation of all seizures), seven partial responses (greater than 50% reduction of seizures), and eight with no response. Median duration of response was 9 months (range, 4 to 16 months) in children with infantile spasms and 14 months (range, 8 to 26 months) in children with the Lennox-Gastaut syndrome. Nitrazepam is an effective anticonvulsant in this small cohort of children with medically refractory infantile spasms and the Lennox-Gastaut syndrome, resulting in a 25% response rate and only modest side effects.
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.
Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment of these aggressive primary brain tumors. Fourteen patients (eight men, six women), ranging in age from 28 to 61 years (median 51 years), were prospectively treated for primary malignant meningiomas according to an institutional protocol. All patients underwent surgery (gross-total in four and subtotal resection in 10 patients) followed in 2 to 4 weeks by involved-field radiotherapy (range 59-60 Gy, median dose 60 Gy). Two to 4 weeks after radiotherapy all patients were treated with adjuvant chemotherapy that included cyclophosphamide, adriamycin, and vincristine (CAV). Patients who underwent gross-total resection received three cycles, whereas those with subtotal resection received six cycles of CAV. Four patients required CAV dose reduction due to myelosuppression, and in three patients, myelosuppression prevented administration of the planned course of CAV. Four patients required transfusions (four received red blood cells, three received platelets), and two developed neutropenic fever without bacteriological documentation. Neuroradiographic response included three partial responses and 11 with stable disease. The median time to tumor progression was 4.6 years (range 2.2-7.1 years) and median survival was 5.3 years (range 2.6-7.6 years). The author concludes that combined modality therapy for the treatment of malignant meningiomas is associated with acceptable toxicity and a modest improvement in survival when compared to patients treated with surgery alone.