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Biomedical subjects

V A Levin

Publications and source records attributed to V A Levin.

At least 127 records · Page 7Linked to original sources
PubMed1988

Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine.

Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

Adolescent↗
PubMed1988

Pineal region tumors in children.

The authors believe that the preferred treatment for pineal region tumors in children requires definitive surgery with a histological diagnosis and that a conservative approach consisting of shunting and radiation therapy no longer seems to be appropriate. The results are reported of a retrospective review of the presentation, treatment, and outcome of 36 children under the age of 18 years treated between 1974 and 1986. Eleven children had germinomas (two-cell type), seven had astrocytomas, and the remaining 18 had 15 histologically different tumor types. Surgery was performed on 30 patients; there were no deaths, but a 10% rate of persistent morbidity was found. The median follow-up period was 4 years. Nine (82%) of 11 patients with germinomas are alive without evidence of recurrence; one child died from recurrent tumor in the pineal region and another is presently being treated for recurrent tumor of the spinal cord. Six (86%) of the seven patients with astrocytoma are well after biopsy and radiation therapy. Of the remaining 18 children, five (28%) died from tumor progression. The cerebrospinal fluid (CSF) tumor markers alpha-fetoprotein and beta-human chorionic gonadotropin were helpful in determining the presence of malignant germ-cell tumors, particularly those with a poor prognosis. Magnetic resonance imaging was useful for diagnosis and for planning the operative approach. Magnetic resonance images showed the presence of pineal region tumors in four children with hydrocephalus who had no evidence of tumor on computerized tomography scans. Because the great variety of tumor types found in the pineal region must be treated in different ways and because improved microsurgical and stereotaxic surgical techniques have made mortality and morbidity rates acceptably low, a biopsy diagnosis should be obtained in all patients. Preoperative assessment of CSF tumor markers and cytology is useful for the identification of patients who have a poor prognosis.

Adolescent↗
PubMed1988

PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome.

Positron emission tomography (PET) with rubidium-82 (82Rb) and fluorine-18-fluorodeoxyglucose (18F-FDG) was used to diagnose active tumor recurrence and to differentiate this from radiation injury after interstitial irradiation of malignant gliomas. Patients were studied when they presented with radiological or clinical deterioration after an initial period of posttreatment stabilization. Forty studies were performed in 34 patients. The 82Rb was used as a blood-brain barrier tracer to localize the lesion. Uptake of 18F-FDG by the lesion was then compared to uptake by adjacent brain in order to make a diagnosis of active tumor recurrence (higher or equal lesion uptake) or no active tumor (lower uptake). Radiation injury was diagnosed by the exclusion of active tumor. A retrospective clinical diagnosis was established in 38 cases by following the patients' progress for 8 to 142 weeks after the PET study. In two cases, no follow-up diagnosis could be determined. The PET results agreed with the follow-up diagnosis in 15 of 17 cases of active tumor and 17 of 21 cases of radiation injury. Histological examination of surgically resected tissue obtained after the PET study was performed in 18 patients (nine with tumor regrowth and nine with radiation injury). This showed apparently viable tumor as well as necrosis in all cases, regardless of eventual clinical outcome. Some cells from the irradiated volume may appear morphologically intact, but have little or no metabolic or clinical activity. The functional nature of the PET-FDG technique allows diagnosis of tumor activity, which cannot be demonstrated by anatomic imaging studies or by histological examination. The addition of a blood-brain barrier tracer to the 18F-FDG study aids in differentiating normal brain uptake from tumor activity and improves the accuracy of the technique.

Astrocytoma↗
PubMed1988

Prognostic implications of the proliferative potential of low-grade astrocytomas.

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.

Astrocytoma↗
PubMed1987

Reoperation for recurrent glioblastoma and anaplastic astrocytoma.

The advisability of a second operation for recurrent glioblastoma multiforme or anaplastic astrocytoma depends on the expected duration and quality of subsequent survival. We reviewed the results in 70 consecutive patients who underwent reoperation for supratentorial glioblastoma multiforme (n = 39) or anaplastic astrocytoma (n = 31) between 1975 and 1984. The operative morbidity rate was 5.7% (4 of 70 patients); the 6-week postoperative mortality rate was 4.3% (3 of 70 patients). The median duration of survival after reoperation was 36 weeks in patients with glioblastoma multiforme and 88 weeks in those with anaplastic astrocytoma. The median duration of high quality survival (defined as the period during which the patient had a Karnofsky performance score of at least 70) after reoperation was 10 weeks for patients with glioblastoma multiforme and 83 weeks for patients with anaplastic astrocytoma. Age and preoperative Karnofsky score in patients with glioblastoma multiforme and age in patients with anaplastic astrocytoma had statistically significant effects on the duration of high quality survival after reoperation, but not on postoperative survival independent of quality. Although age and functional status do not significantly affect the duration of survival after reoperation, they do have a significant effect on the quality of life after reoperation. Frequently, a patient can expect to spend a greater portion of his life at a higher level of function than he would have without reoperation. As adjunctive forms of therapy improve, reoperation will play an increasingly prominent role in the management of recurrent malignant astrocytic tumors.

Adult↗
PubMed1987

Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism.

To determine the risk of intracranial hemorrhage in patients with malignant gliomas who are treated with anticoagulant drugs for late postoperative venous thromboembolism, the authors retrospectively reviewed the computerized data base of all patients with primary brain tumors seen at the University of California, San Francisco, over a 9-year period. Of 915 patients 18 years of age or older who had a pathological diagnosis of malignant glioma and an initial Karnofsky performance scale score of 60% or higher, 36 (4%) developed venous thromboembolism 6 to 246 weeks postoperatively and 22 were treated with anticoagulant drugs. Anticoagulant therapy usually consisted of intravenous heparin for 7 to 10 days, followed for at least 3 to 6 months by either subcutaneous heparin (5000 to 8000 U twice daily) or oral warfarin. All patients were closely monitored to ensure control of hypertension, compliance with therapy, maintenance of prothrombin time within the therapeutic range, and early recognition of adverse side effects. No patient had an intracranial hemorrhage. Thus, anticoagulant agents can be safely administered after intracranial operations for malignant gliomas without increased risk of morbidity or mortality if the patients are carefully monitored according to established guidelines.

Adolescent↗
PubMed1987

Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources.

The authors report survival data for the first 41 patients treated for recurrent malignant gliomas with interstitial brachytherapy at the University of California, San Francisco (1980-1984). Iodine-125 (125I) sources were temporarily implanted using stereotaxic techniques. The median survival period for 18 patients with recurrent glioblastomas was 52 weeks after brachytherapy; two patients are alive more than 5 years after brachytherapy. The median survival period for 23 patients with recurrent anaplastic astrocytomas is 153 weeks after brachytherapy, with 10 patients alive more than 3 years and four patients alive more than 4 years after brachytherapy. Both groups did significantly better (p less than 0.01) than groups of patients with the same diagnoses and similar general characteristics who were treated at recurrence with chemotherapy alone. Because of deterioration of their clinical condition and evidence of recurrence from computerized tomographic scans, 17 (41%) of 41 patients required reoperation 20 to 72 weeks after brachytherapy. Despite the invariable presence of apparently viable tumor cells mixed with necrotic tissue in the resected specimen, nine patients have survived more than 2 years after reoperation and two of the nine are still alive 4 years after reoperation. The authors conclude that brachytherapy with temporarily implanted 125I sources for well-circumscribed, hemispheric, recurrent malignant gliomas is effective and offers a chance for long-term survival even though focal radiation necrosis can seriously degrade the quality of survival in a minority of patients.

Adolescent↗
PubMed1987

Does chemotherapy benefit the patient with a central nervous system glioma?

The authors discuss the results of clinical trials assessing the value of chemotherapy for brain tumors in the adjuvant setting as well as at recurrence. Adjuvant chemotherapy does benefit some patients with malignant brain gliomas. Improved survival rates seem to be related to an increased number of long-term survivors. The most effective chemotherapy is BCNU or a combination of CCNU, procarbazine, and vincristine (PCV). Drugs that potentiate radiation therapy, such as hydroxyurea and BUdR, are also useful in some patients.

Antineoplastic Agents↗
PubMed1987

Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors.

Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing.

Adolescent↗
PubMed1986

Retreatment of pediatric brain tumors with radiation and misonidazole. Results of a CCSG/RTOG phase I/II study.

Twenty-nine patients with recurrent pediatric brain tumors after full-dose treatment with radiation were retreated with misonidazole (9 gm/m2) and whole-brain irradiation (300 rad X 10). Seventeen of 29 patients (59%) experienced nausea and vomiting with misonidazole administration and 6 patients (21%) developed peripheral neuropathy. Serum levels of misonidazole were similar to those reported for adults. One patient died of trauma shortly after retreatment. For the remaining 28 patients, the median time-to-progression was 5.5 months. Median survival was 13 months. Six patients (21%) developed radiation toxicity, two of whom died from the toxicity. Whereas the results on this study are similar to reported series of patients receiving salvage chemotherapy for recurrent pediatric brain tumors, more effective treatment clearly is needed.

Adolescent↗
PubMed1986

L-fucose labeling of brain tumors in rats.

These studies used L-[14C]fucose to identify 9L brain tumors in rats. Ten days after intracranial implantation of 9L tumor cells, labeled L-fucose was injected intravenously. Autoradiography demonstrated high levels of radioactive L-fucose in the resultant 9L tumors but very little L-fucose in normal brain tissue. In vitro studies comparing uptake of labeled fucose into 9L cells, normal rat fibroblasts and transformed rat fibroblasts, rat astrocytes, and human brain tissue suggest that fucose is not preferentially transported into the 9L cells. These data imply that a permissive blood-brain barrier rather than differences in fucose metabolism underlie 9L tumor labeling.

Animals↗
PubMed1986

Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas.

To determine the percentage of patients who developed multiple central nervous system (CNS) gliomas during postoperative radiation therapy and chemotherapy, the authors reviewed the records of 1047 patients treated between December 2, 1976, and August 16, 1985, who had an original diagnosis of supratentorial glioblastoma multiforme or other anaplastic glioma. The occurrence of multiple lesions was verified by neurodiagnostic studies (computerized tomography or myelography) or by findings at operation or autopsy. Twelve patients (1.1%) who presented with multiple lesions were excluded from this analysis. There were 405 patients with glioblastoma multiforme; their median age was 46.5 years (range 22 to 70 years). Eighteen (5%) of these patients had multiple CNS lesions, five of which were in the spinal cord. The median time from diagnosis to detection of the second lesion in this group was 59.5 weeks (range 10 to 182 weeks). There were 630 patients with anaplastic glioma (which included mixed malignant glioma and highly anaplastic, gemistocytic, moderately anaplastic, and anaplastic astrocytomas); their median age was 30 years (range 2 to 62 years). Fifty-four (8.6%) of these patients had multiple lesions, 10 of which were in the spinal cord; only one case of extraneural metastasis was found. The median time from diagnosis to detection of the second lesion in this group was 101 weeks (range 14 to 459 weeks). These results show that more than 90% of CNS gliomas recur at the site of the original tumor. Considering the high frequency of intellectual dysfunction after whole-brain radiation therapy, the use of focal radiation fields appears to be the most judicious approach to the treatment of patients with gliomas.

Adult↗
PubMed1986

Northern California Oncology Group protocol 6G91: response to treatment with radiation therapy and seven-drug chemotherapy in patients with glioblastoma multiforme.

The Northern California Oncology Group (NCOG) conducted a nonrandomized phase II study to evaluate the benefit of a seven-drug chemotherapy protocol (NCOG 6G91) in patients with glioblastoma multiforme (GM). Time to tumor progression was the primary end point of the study. The treatment consisted of 5-FU and lomustine administered after surgery and before radiation therapy, hydroxyurea and misonidazole during radiation therapy, and procarbazine and vincristine alternated with carmustine and 5-FU after radiation therapy. Ninety patients entered the study; data from the 64 patients with GM who completed radiation therapy and at least started the postradiation chemotherapy regimen and returned for follow-up examination are analyzed in this report. The median time to tumor progression in the 64 adequately treated patients was 42 weeks; the 25th percentile value was 60 weeks. A Cox multivariate analysis showed that age and extent of surgical resection were important prognostic variables in patients with GM. The results of this treatment regimen were similar to those of a previous NCOG protocol (6G61), which consisted of hydroxyurea during radiation therapy followed by chemotherapy with carmustine or a combination of lomustine, procarbazine, and vincristine.

Adult↗
PubMed1986

Phase II study of combined carmustine, 5-fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas.

The Neuro-oncology Service of the University of California Brain Tumor Research Center conducted a nonrandomized phase II study to evaluate, in patients with recurrent malignant glioma, the benefit of a four-drug combination (BFHM) consisting of carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea), 5-fluorouracil, hydroxyurea, and 6-mercaptopurine. There were 29 evaluable glioblastoma multiforme patients and 45 nonglioblastoma anaplastic glioma patients available for analysis. Tumor progression was analyzed as the primary study endpoint. Of the glioblastoma patients, 16 of 29 (55%) responded or stabilized on therapy; of the other anaplastic gliomas, 32 of 45 (71%) responded or stabilized. For patients who stabilized or responded to treatment, BFHM achieved a median time to tumor progression of 46 weeks with a 25th percentile time to tumor progression of 68 weeks for anaplastic gliomas and a median time to tumor progression of 23 weeks with a 25th percentile time to tumor progression of 36 weeks for glioblastoma multiforme patients. A Cox multivariate analysis demonstrated that age and Karnofsky score were important prognostic variables for these patients.

Adolescent↗
PubMed1985

Cell kinetic studies of in situ human brain tumors with bromodeoxyuridine.

At the time of surgery, 18 patients with various brain tumors were given a 1-h i.v. infusion of bromodeoxyuridine (BrdUrd), 150-200 mg/m2. At an infusion rate of 200 mg/m2/h, serum BrdUrd levels of 8 microM were achieved. After the infusion, tumor tissue was obtained and divided into two portions. One portion was fixed in 70% ethanol, embedded in paraffin, and sectioned; the sections were deparaffinized, denatured with 2 N HCl, and reacted with monoclonal antibodies against BrdUrd (anti-BrdUrd MAb). BrdUrd-labeled nuclei were demonstrated satisfactorily by an indirect peroxidase method. The other portion was dissociated into single cells with a DNase enzyme cocktail and reacted with FITC-conjugated anti-BrdUrd MAb to determine the percentage of BrdUrd-labeled cells or with chromomycin A3 for DNA analysis. The single-cell suspensions were analyzed by flow cytometry. The fraction of S-phase cells in the tissue sections was similar to both the percentage of BrdUrd-labeled nuclei and the S-phase fraction determined by flow cytometric analysis. The results obtained with BrdUrd-labeled nuclei were similar to those obtained from previous autoradiographic studies of various brain tumors exposed to a pulse of 3H-thymidine. Since BrdUrd is not radioactive and is nontoxic at the dosage used, these techniques, together with the histopathological diagnosis, may help to predict the biological malignancy of individual tumors.

Antibodies, Monoclonal↗
PubMed1985

Pharmacokinetic approaches to drug distribution in the cerebrospinal fluid based on ventricular administration in beagle dogs.

Two mathematical approaches are described to approximate the distribution of compounds (e.g., drugs) in the cerebrospinal fluid (CSF) downstream of or distal to both the ventricular injection site and the cisterna magna sampling site. The first approach uses a graphic representation and is, in essence, model independent; the second approach considers the geometry and physiology of CSF distribution and clearance. In all studies, radiolabeled inulin was used as an "internal standard" since it is not metabolized and is eliminated from the CSF primarily by bulk flow. Temporal comparison of the study compound to radiolabeled inulin in the cisternal CSF allowed testing of these models in beagle dogs. One use of this data is in the estimation of the drug exposure integral for antineoplastic drugs administered in the CSF to treat leptomeningeal neoplasia.

Animals↗
PubMed1985

Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas.

The authors report the results of a randomized study conducted to evaluate the relative benefit of treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or the combination of procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine (PCV) administered after radiation therapy with hydroxyurea to 76 evaluable patients with glioblastoma multiforme and 72 patients with other anaplastic gliomas. The primary end-point of the study was time to tumor progression. For better-risk patients with Karnofsky performance scores of 70 to 100, results suggest that PCV was of greater benefit than BCNU (p = 0.15 for glioblastoma multiforme; p = 0.13 for other anaplastic gliomas). Median times to tumor progression were 31 and 32 weeks for patients with glioblastoma multiforme; 25th percentile times to progression were 70 and 40 weeks for patients treated with PCV and BCNU, respectively. For patients with other anaplastic gliomas treated with PCV and BCNU, median times to progression were 123 and 77 weeks, respectively. Multivariate analysis showed that the prognostic variables of age and Karnofsky scores were important for patients with glioblastoma multiforme and other anaplastic gliomas, and that the extent of surgical resection was important for those with other anaplastic gliomas.

Adult↗