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Biomedical subjects

P Silver

Publications and source records attributed to P Silver.

At least 73 records · Page 4Linked to original sources
PubMed1989

Hyperfractionated radiation therapy for brain-stem glioma: a phase I-II trial.

Fifty-three patients (19 adults and 34 children) harboring brain-stem glioma were treated with hyperfractionated radiation therapy (100 cGy twice a day, 5 days/wk, to a total dose of 7200 cGy). For the entire group, the median time to tumor progression (TTP) was 59 weeks (adults 66 weeks, children 44 weeks) and the median survival time was 74 weeks (adults 92 weeks, children 64 weeks). Statistically significant prognostic factors associated with a decrease in TTP and median survival times (adults less than children) were: patient's age, a clinical history of less than 2 months, widespread brain-stem dysfunction, and a diffuse tumor as seen on magnetic resonance imaging. A finding of glioblastoma multiforme at histological analysis was associated with a statistical trend toward poorer survival, but in general tumor histology was not predictive of outcome. No evidence of an increase in acute or delayed radiation toxicity was seen with this fractionation schedule and total dose. This study suggests that hyperfractionation prolongs the TTP and survival time for many patients with brain-stem glioma. However, there remains a group of patients who are only moderately helped by this technique and for whom more aggressive treatment is warranted.

Adult↗
PubMed1988

A phase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors.

This study was undertaken to determine the maximum tolerated dose of aziridinylbenzoquinone (AZQ) given as a 24-hour intravenous infusion every 21-28 days. Thirty-four patients with recurrent or progressive gliomas received AZQ at a dose of 25, 30, 35, 40, or 45 mg/m2. At a dose of 45 mg/m2, leukopenia and thrombocytopenia of grade 3 or greater was observed in 42% and 25% of patients respectively; no patient required transfusion or antibiotics for fever. For administration of AZQ at a 24-hour intravenous infusion, we recommend a starting dose of 40 mg/m2 for patients without previous exposure to cytotoxic agents, and 35 mg/m2 for patients treated with such agents. In 14 patients with glioblastoma, tumor regression was observed in 1 patient (14%) and stabilization of disease was demonstrated in 7 patients (50%). In 17 patients with anaplastic astrocytomas there were no responses, but 8 patients (47%) stabilized. Of two patients with an oligodendroglioma, one continues without progression at 34 weeks after initial response. One patient with malignant ependymoma stabilized and had not progressed at 39 weeks. The median time to tumor progression in patients who stabilized and responded was 18 weeks for those with glioblastoma multiforme and 16 weeks in those with anaplastic astrocytomas.

Antineoplastic Agents↗
PubMed1988

A phase II trial of oral melphalan in recurrent primary brain tumors.

Thirty-seven patients with recurrent primary brain tumors were treated with oral melphalan at a dose of 8 mg/m2/day for 5 days every 4-6 weeks. All patients had failed prior nitrosourea-based chemotherapy. Oral melphalan had no activity against glioblastoma, and minimal activity against other anaplastic astrocytomas. One recurrent medulloblastoma did have a clinical and radiographically sustained response that continued for greater than 14 months. We concluded that oral melphalan was not effective in the treatment of recurrent astrocytomas, but might have efficacy in medulloblastoma.

Administration, Oral↗
PubMed1988

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine.

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

Adolescent↗
PubMed1988

Treatment of extraneural metastatic medulloblastoma with a combination of cyclophosphamide, adriamycin, and vincristine.

Seven patients with extraneural metastases from medulloblastoma were treated with a combination of cytoxan, adriamycin, and vincristine (CAV). None of the patients had evidence of active neural axis disease. All patients with bone metastases responded with a reduction in bone pain and improvement on the radionuclide bone scan. One patient presenting with lymph node metastases showed initial reduction in the size of the palpable nodes. In this group, the median time to the development of extraneural metastasis was 18 months from the time of original diagnosis of central nervous system medulloblastoma. The median duration of response to CAV, after extraneural metastasis, was 17 months (4-65 months). Four of seven patients died of disease-related causes, one patient presumed well was lost to follow-up, and two of seven are still without evidence of active disease at 37 and 65 months. The combination of CAV is well tolerated and provides reasonably good palliation for extraneural medulloblastoma.

Adolescent↗
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

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↗
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

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

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↗
PubMed1984

Influence of suspension hypokinesia on rat soleus muscle.

Hindlimb hypokinesia was induced in rats by the Morey method to characterize the response of the soleus muscle. Rats suspended for 1-4 wk exhibited continuous and significant declines in soleus mass, function, and contractile duration. Soleus speeding was in part explained by an alteration in fiber type. The normal incidence of 70-90% type I fibers in the soleus muscle was reduced after 4 wk of suspension to 50% or less in 9 of 11 rats. A significant decline in type I myosin isozyme content occurred without a change in that of type II. Other observed histochemical changes were characteristic of denervation. Consistent with soleus atrophy, there was a significant increase in lysosomal (acid) protease activity. One week of recovery after a 2-wk suspension was characterized by a return to values not significantly different from control for muscle wet weights, peak contraction force, one-half relaxation time, and type I myosin. Persistent differences from control were observed in maximal rate of tension development, contraction time, and denervation-like changes.

Animals↗