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M D Prados

Publications and source records attributed to M D Prados.

107 records · Page 6Linked to original sources

Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole.

Positron emission tomography (PET) with the hypoxic-cell tracer [18F]fluoromisonidazole presents a possible means of noninvasively demonstrating tumor hypoxia. PET studies using this tracer were performed in three patients with malignant glioma, and in all patients the tumor was clearly seen at 5 min postinjection and initial tumor activity exceeded cortical activity. In one patient, there was no tumor retention of [18F] fluoromisonidazole and tumor activity fell while cortical activity increased, with the two tissues reaching equality at 40-50 min. The tumor-to-plasma ratio was 0.71 at 3 hr. The other two patients showed variable tumor retention of [18F]fluoromisonidazole, with tumor-to-plasma ratios of 1.10 and 1.49 at 2 and 3 hr. These results demonstrate the feasibility of using [18F]fluoromisonidazole PET to detect hypoxia in human gliomas in vivo. Clinical trials are needed to determine whether a relationship exists between [18F]fluoromisonidazole uptake and tumor radiation response.

Adult↗

A comparison of CT contrast enhancement and BUDR labeling indices in moderately and highly anaplastic astrocytomas of the cerebral hemispheres.

Contrast enhancement on computerized tomography (CT) scans has been used in directing therapy for presumed intracranial gliomas. However, for moderately anaplastic astrocytomas (MOAAS) and highly anaplastic astrocytomas (HAAS), it provides no information about proliferative potential. The bromodeoxyuridine (BUDR) labeling index (LI), however, indicates proliferative potential, correlating with histologic malignancy and survival. An LI less than 1% is a favorable indicator; LI greater than 5% suggests more aggressiveness. To determine the correlation, if any, between BUDR LI and contrast enhancement, CT scans of 71 patients with cerebral hemisphere tumors labeled with BUDR were retrospectively reviewed. Among 36 MOAAS, the BUDR LI was less than 1% in 77% of enhanced tumors and 61% of unenhanced tumors. Among 35 HAAS, it was less than 5% in 56% of enhanced tumors and 90% of unenhanced tumors. Therefore, contrast enhancement on CT scans does not always correctly predict proliferative potential in these tumors, and biopsy and labeling studies are recommended before therapy.

Adolescent↗

External irradiation followed by an interstitial high activity iodine-125 implant "boost" in the initial treatment of malignant gliomas: NCOG study 6G-82-2.

Between January 1982 and January 1990, 107 patients with unifocal, circumscribed malignant gliomas participated in a non-randomized trial testing brachytherapy in their initial treatment. Focal external irradiation (6000 cGy) was combined with an implant of high-activity iodine-125 (5000-6000 cGy) and six courses of procarbazine, lomustine, and vincristine. Of the 101 evaluable patients, 63 received implants. Of these, 29 had non-glioblastoma anaplastic gliomas, and 34 had glioblastoma multiforme. The other 38 did not receive implants, in most cases because radiation therapy failed to reduce the size of the tumor. The median survival was 165 weeks for all evaluable patients with non-glioblastoma anaplastic gliomas, 157 weeks for those with implants, 67 weeks for all evaluable glioblastoma patients, and 88 weeks for those with implants. Of the glioblastoma patients with implants, nine were alive after 2 years, and three were alive after 3 years. In each of the groups, nearly half the patients underwent reoperation for clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site after 46.1 weeks (median) for glioblastoma multiforme and 41.3 weeks for non-glioblastoma patients. Karnofsky Performance Scores showed only a small decline in performance after brachytherapy. Patients receiving implants for non-glioblastoma anaplastic gliomas had a mean Karnofsky Performance Score of 91% (range 90-100%) after 1 month and 78% (range 60-100%) 30 months after brachytherapy. Those treated for glioblastoma multiforme had a mean Karnofsky Performance Score of 86% (range 60-100%) at 1 month and 75% (range 60-100%) at 24 months. The quality of life of treated patients appears to be satisfactory. On the basis of comparisons with previous studies, we conclude that a brachytherapy "boost" after external irradiation may be valuable for some patients with glioblastoma multiforme but not for those with non-glioblastoma anaplastic gliomas.

Adult↗

Evaluation of bromodeoxyuridine in glioblastoma multiforme: a Northern California Cancer Center Phase II study.

In a study activated in 1983 and closed in 1987, the Brain Tumor Research Center of the University of California and the Northern California Cancer Center evaluated the effect of bromodeoxyuridine in the treatment of glioblastoma multiforme. A total of 160 patients were evaluable of 173 entered. Patients were to receive a bromodeoxyuridine infusion of 0.8 g/m2 daily over 24 hours for 4 days of each of 6 weeks of radiotherapy directed to the tumor plus a margin delivering a total of 60 Gy. Eligibility requirements included Karnofsky performance status greater than or equal to 70, biopsy or resection and central pathology review by one of the authors. Following radiotherapy patients were to receive chemotherapy with procarbazine, CCNU, and vincristine for 1 year. Median survival was 55.7 weeks and time to failure, 34.5 weeks for the evaluable group of 160 patients. In a univariate analysis the variables that influence survival and time to failure were: age, Karnofsky performance status, bromodeoxyuridine dose and the delivery of at least one procarbazine, CCNU, and vincristine cycle following radiotherapy. In multivariate analysis, age, Karnofsky performance status, and bromodeoxyuridine dose remain significant for time to failure; age and Karnofsky performance status remain significant for survival.

Adult↗

Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.

Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

Adenocarcinoma↗

Desmoplastic medulloblastoma metastatic to the pancreas: case report.

A case is reported in which a desmoplastic medulloblastoma metastasized to the pancreas and to the surrounding soft tissues but did not recur locally or disseminate within the central nervous system. Multidrug chemotherapy and local radiation therapy resulted in a complete remission. In all four previously reported cases of medulloblastoma metastasizing to the pancreas, the diagnosis was not made until the postmortem examination, and all of these patients also had extensive metastases in other organ systems. Modification of the Weiss criteria defining extraneural metastases from tumors of the central nervous system is suggested.

Cerebellar Neoplasms↗

Intradural chordoma of the tentorium cerebelli. Case report.

A rare case of intradural chordoma is described. The literature contains seven examples of intradural extraosseous chordoma, all reported in a ventral location. This is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra- and infratentorial compartments.

Cerebellum↗

Severe community-acquired pneumonia. Etiology, prognosis, and treatment.

The frequency of community-acquired pneumonia coupled with its mortality rate of 10 to 25% is of growing concern to clinicians. A prospective study of 67 patients with severe community-acquired pneumonia was carried out to determine the causative agents, the impact fore-knowledge of the etiology has on the outcome, the value of clinical and radiologic criteria in predicting the evolution, and the efficacy of empirical therapy. The study group included 45 men and 22 women (mean age: 56.8 +/- 16.6 yr), and 46.2% suffered from a concurrent debilitating disease. The cause of pneumonia was diagnosed in 32 cases, and the most common pathogens were Streptococcus pneumoniae (37.5%), Legionella pneumophila (21.8%), and gram-negative bacilli (25.0%). The fact that fungal infections were present in three patients and Pneumocystis carinii in one are worthy of note. The overall death rate was 20.8%. A fatal outcome was related to the age of the patient (p less than 0.05), the presence of debilitating disease (p = 0.026), and septic shock (p = 0.0009). Diagnosis of the causative agents did not aid in increasing the survival rate, but it did allow for better patient management. Most of the patients (85.1%) initiated on treatment with erythromycin plus tobramycin recovered, but only 68.4% of the subjects commenced on treatment with other therapeutics survived. Furthermore, it was necessary to modify the therapy of a greater percentage of the latter group (p less than 0.025). Gram-negative bacillary pneumonia was a frequent finding among the patients who did not recover, making empirical treatment with erythromycin plus third generation cephalosporins most advisable for severe cases of community-acquired pneumonia.

Age Factors↗

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↗

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↗

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↗

Chemotherapy of brain tumors.

For many years, chemotherapy has been utilized for the treatment of malignant brain tumors with minimal success. This particularly true with chemotherapy in adult malignant gliomas for which no new drug has been approved for use since the initial studies using nitrosoureas and procarbazine in the early 1960s. However, the results of more recent clinical trials research using newer agents appear to show improved outcome in some tumor types. Better understanding of the basic biology of these diverse tumors also have given rise to new treatment strategies, especially to drug development. A large number of new antineoplastic agents are now being tested in Phase I and II trials; they are very promising and soon may lead to new drug approvals. This review will discuss the results of completed trials for newly diagnosed and recurrent glioma in adults, as well as ongoing, new drug studies with these patients. A discussion of the more common pediatric brain tumors and the use of chemotherapy in that age group is also presented. Chemotherapy is often the primary treatment modality used to control tumor growth in newly diagnosed infants and young children, and it is in this setting that chemotherapy is particularly beneficial in reducing morbidity and increasing survival. As part of a multimodality approach that includes surgery and radiotherapy, chemotherapy has a significant role to play in the treatment of both adults and children with brain neoplasms.

Adult↗

Alignment of volume MR images and high resolution [18F]fluorodeoxyglucose PET images for the evaluation of patients with brain tumors.

PURPOSE: The goal of the study was to investigate the use of automated registration techniques for interpretation of volume MR and high resolution FDG-PET images that were obtained from patients with brain tumors. METHOD: Twenty-one patients with brain tumors were studied on one or more occasions using MRI and high resolution FDG-PET. The data were aligned using automated volume- and surface-matching algorithms. Composite images comprising the resliced pre- and postgadolinium spoiled GRE, T2-weighted SE, and PET data were constructed to correlate intensities of regions on the PET images with regions that corresponded to normal gray matter, white matter, and gadolinium enhancement. RESULTS: The accuracy of registration between the MR and PET images was estimated to be within 1-2 mm based upon the distance between surfaces of the outside of the head. In 12 of the 24 examinations, there were diagnoses of recurrent tumor, with only 5 of these exhibiting regions of higher FDG uptake than normal gray matter. For 19 of the 24 studies, the anatomic context provided by the registered MR images was found to be important in distinguishing recurrent tumor from necrosis based upon FDG uptake. CONCLUSION: The automated alignment was found to be an important factor in interpreting the high resolution PET images. This was particularly true for small lesions close to the cortex and for situations where FDG uptake had been reduced by prior treatment with radiation therapy.

Adult↗

Primary central nervous system tumors: advances in knowledge and treatment.

The ability to diagnose, monitor, and treat CNS tumors has been improved by new imaging techniques such as positron emission tomography (PET) scanning and functional MR imaging, stereotactic surgery, delivery of radiotherapy with brachytherapy and radiosurgery, and novel methods for delivering chemotherapy. These innovations combined with the new information about tumor pathogenesis and behavior revealed by molecular research give hope that more specific treatments for malignant CNS tumors will be developed in the future.

Cell Transformation, Neoplastic↗

Adult medulloblastoma: an analysis of survival and prognostic factors.

PURPOSE: This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control. PATIENTS AND METHODS: We performed a retrospective review of 34 adult patients, age > or = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis. RESULTS: The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease. DISCUSSION: Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.

Adolescent↗