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Biomedical subjects

W A Hall

Publications and source records attributed to W A Hall.

At least 55 records · Page 3Linked to original sources
PubMed1999

Brain biopsy using high-field strength interventional magnetic resonance imaging.

OBJECTIVE: Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance imaging (MRI) now allows neurosurgeons to interactively investigate specific regions, with exquisite observational detail. We evaluated the safety and efficacy of this new surgical approach. METHODS: Between January 1997 and June 1998, 35 brain biopsies were performed in a high-field strength interventional MRI unit. All biopsies were performed using MRI-compatible instrumentation. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathological examination of the biopsy specimens was performed to verify the presence of diagnostic tissue, and intra- and postoperative imaging was performed to exclude the presence of intraoperative hemorrhage. Recently, magnetic resonance spectroscopic targeting was used for six patients. RESULTS: Diagnostic tissue was obtained in all 35 brain biopsies and was used in therapeutic decision-making. Histological diagnoses included 28 primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2 anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1 cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis. In all cases, magnetic resonance spectroscopy was accurate in distinguishing recurrent tumors (five cases) from radiation necrosis (one case). No patient sustained clinically or radiologically significant hemorrhage, as determined by intraoperative imaging performed immediately after the biopsy. One patient (3%) suffered transient hemiparesis after a pontine biopsy for investigation of a brain stem glioma. Another patient developed scalp cellulitis, with possible intracranial extension, 3 weeks after the biopsy; this condition was effectively treated with antibiotic therapy. Three patients were discharged on the day of the biopsy. CONCLUSION: Interventional 1.5-T MRI is a safe and effective method for evaluating lesions of the brain. Magnetic resonance spectroscopic targeting is likely to augment the diagnostic yield of brain biopsies.

Adolescent↗
PubMed1999

Comparison of stereotactic brain biopsy to interventional magnetic-resonance-imaging-guided brain biopsy.

Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance (MR) imaging now allows neurosurgeons to interactively investigate specific regions with exquisite visualization. We compared the safety and efficacy of this new surgical approach with stereotaxis. From February 1991 to June 1998, 134 stereotactic and 35 interventional MR-guided brain biopsies were performed. Stereotactic biopsies utilized preoperative scanning. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathologic examination of biopsy material was performed to verify the presence of diagnostic tissue in both biopsy groups. Intra- and postoperative MR imaging was obtained to exclude the presence of intraoperative hemorrhage. Recently, MR spectroscopic targeting has been utilized in 6 patients. In the stereotactic group, 129/134 (96%) biopsies were diagnostic. One patient had a transient hemiparesis after a brain stem biopsy and another suffered a fatal hemorrhage for a morbidity rate of 0.7% and a mortality rate of 0.7%. In reviewing 7,471 stereotactic biopsies, the morbidity was 3.5%, mortality 0.7% and diagnostic yield 91%. All 35 MR-guided brain biopsies were diagnostic (100%). MR spectroscopy was accurate in all cases in distinguishing recurrent tumor (5 cases) from radiation necrosis (1 case). One patient (3%) suffered a transient hemiparesis following a pontine biopsy and another patient (3%) developed a postoperative scalp cellulitis. No patient sustained a clinically or radiologically significant hemorrhage as determined by the immediate postbiopsy, intraoperative MR imaging. Interventional MR-guided brain biopsy is a safe and effective technique for evaluating lesions of the brain with morbidity and mortality rates comparable to those of stereotaxis. MR-guided biopsy appears to have a higher diagnostic yield than stereotaxis, which may reflect the ability to perform interactive, intraoperative scanning with that technique.

Biopsy↗
PubMed1999

Effects of continuous localized infusion of granulocyte-macrophage colony-stimulating factor and inoculations of irradiated glioma cells on tumor regression.

OBJECT: Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats. METHODS: The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF-treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833+/-2284 mm3, 3294+/-1632 mm3, and 1979+/-1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 10(6) gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF-irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging. CONCLUSIONS: These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.

Animals↗
PubMed1998

The safety and efficacy of stereotactic biopsy for intracranial lesions.

BACKGROUND: Stereotactic brain biopsy is considered by many physicians to have significant morbidity and mortality rates with a high risk of sampling error resulting in misdiagnosis. The technical aspects necessary to perform the procedure safely and effectively are unfamiliar to most physicians. METHODS: After reporting his initial results with stereotactic brain biopsy, several modifications were implemented by the author to improve the morbidity, mortality, and diagnostic yield rates, including complex surgical planning with regard to patient selection, biopsy trajectory, imaging technique, target choice, and intraoperative pathologic review. The results of implementing these modifications were examined retrospectively in 134 consecutive brain biopsies. RESULTS: One hundred and thirty-four stereotactic brain biopsies were performed in 122 patients. Computed tomography guidance was used in 85 patients (63%) and magnetic resonance imaging was used in 49 patients (37%). Sixty-four lesions (48%) were located in the right hemisphere, 61 (45%) in the left, and 9 (7%) in the midline. The most common diagnoses included 62 malignant brain tumors (46%), 24 benign brain tumors (18%), 23 neurologic disorders (17%), and 20 infections (15%). Five biopsies (4%) did not demonstrate a pathologic process for an overall diagnostic yield of 96%. Reasons for diagnostic failure included lesion location adjacent to the ventricular system, inaccurate targeting, and the inability to penetrate the tumor. One patient sustained a neurologic deficit after the biopsy for a morbidity rate of 0.7% and one sustained a fatal hemorrhage during the biopsy of a vascular tumor for a mortality rate of 0.7%. These results are comparable to those reported in 7471 biopsies (current series included) in which the morbidity rate was 3.5%, the mortality rate was 0.7%, and the diagnostic yield was 91%. CONCLUSIONS: Stereotactic brain biopsy is an extremely safe and effective procedure for evaluating intracranial lesions. Complex surgical planning can decrease the risk of potential complications and the use of intraoperative pathologic examination can improve the diagnostic yield for this procedure.

Adolescent↗
PubMed1998

Complications of subcutaneous low-dose heparin therapy in neurosurgical patients.

BACKGROUND: Venous thromboembolism is a major cause of postoperative morbidity and mortality in neurosurgery. The use of low-dose unfractionated heparin therapy perioperatively for prophylaxis against deep vein thromboses and pulmonary embolism has been well demonstrated in many other surgical specialties but is less commonly used in neurosurgery because of fears of devastating postoperative hematomas. METHODS: The safety of such therapy has been analyzed in 950 patients undergoing an inpatient neurosurgical procedure. 872 patients (152 cranial procedures) completed treatment with 5000 U sodium heparin subcutaneously twice a day, commencing before surgery and continuing till patients were ambulatory. RESULTS: There were three minor hemorrhagic complications-two superficial wound hematomas (one requiring treatment) and one gastrointestinal hemorrhage-identified. Three clinically significant major complications developed, two epidural hematomas after spinal surgery requiring evacuation and one intraventricular hemorrhage after brain biopsy. CONCLUSION: This report, along with an analysis of previously published reports of low-dose perioperative heparin therapy in neurosurgical patients, suggests that such therapy is unlikely to be associated with increased morbidity. Given the known efficacy of low-dose heparin in reducing venous thromboembolism in other surgical patients, such therapy may reduce mortality and morbidity from thromboembolic complications in neurosurgical patients with minimal risk.

Anticoagulants↗
PubMed1998

Malignant gliomas of the cerebellum: an analytic review.

Using an analytical review, the demographic data on malignant cerebellar gliomas such as length of survival, and those factors associated with prolonged survival were examined. Seventy-one cases of malignant cerebellar glioma reported since 1975 were combined and reviewed with the seven cases treated at our institution since that time. Thirty-seven patients (47%) had grade III tumors and 41 (53%) had grade IV tumors. Fifty-nine percent of the tumors were located in the hemispheres and 41% were found in the vermis. Median survival for patients with grade III anaplastic astrocytomas was 32 months compared to 11 months for those with grade IV glioblastomas multiforme (P = 0.0257). For the entire cohort, patients with grade III tumors, those who had a surgical resection, and those that had received radiation therapy for treatment of their tumor had prolonged survival on multivariable analysis. Radiation therapy was associated with extended survival for patients with grade III tumors by uni- and multivariate analysis. For grade IV tumors, univariate analysis revealed prolonged survival for those patients who had surgical resection compared to those who had biopsy alone (P = 0.0036) and for those who received external beam radiation therapy (P = 0.0001). Patients with malignant gliomas of the cerebellum had length of survival comparable to their supratentorial counterparts. Prompt diagnosis and treatment may explain the similarity in survival found between supra- and infratentorial malignant gliomas despite an expected shorter survival because of treatment limitations. Surgical resection followed by radiation therapy is recommended for patients with malignant gliomas of the cerebellum.

Adolescent↗
PubMed1998

Patient selection criteria for the treatment of brain metastases with stereotactic radiosurgery.

In this study we evaluate prognostic factors that predict local-regional control and survival following stereotactic radiosurgery (SRS) in patients with brain metastasis and establish guidelines for patient selection. Our evaluation is based on 73 patients with brain metastasis treated with SRS at the University of Minnesota between March 1991 and November 1995. The ability of stereotactic radiosurgery to improve local control in patients with brain metastases is confirmed in our study in which only 6 of 62 patients failed locally after SRS, with an actuarial local progression-free survival of 80% at 2 years. Variables that predicted worse prognosis were larger tumor size (p = 0.05) for local progression-free survival and multiplicity of metastasis (p = 0.03) and infratentorial location of metastases (p = 0.006) for regional progression-free survival. Absence of extracranial disease, KPS > or = 70, and single intracranial metastasis were significant predictors of longer survival. Patients who fulfill all three criteria will survive longer after SRS (MS = 17.7 months) and will most likely benefit from the increase local control in the brain achieved by SRS. Survival in patients who do not meet any of these criteria is very poor (MS = 1.5 months), and these patients are less likely to benefit from this treatment. Careful selection of patients for SRS is warranted.

Adult↗
PubMed1998

Interleukin-12-based immunotherapy against rat 9L glioma.

OBJECTIVE: Interleukin-12 (IL-12) may be useful for immunotherapy against gliomas because it can reverse the glioma-induced suppression of T-cell proliferation and interferon-gamma production. We postulated that peripheral infusion of IL-12 along with irradiated tumor cells can lead to immunological rejection of 9L glioma. METHODS: 9L gliosarcoma flank tumors were established in syngeneic Fischer 344 rats. Osmotic minipumps delivered IL-12 subcutaneously, and irradiated 9L cells were injected on Days 0, 3, 7, 14, and 21. Tumor volumes were measured by a blinded observer. For tumor rechallenge, animals initially cured of 9L flank tumors received either another implantation of flank tumor or a stereotactic injection of 10(6) 9L cells into the right striatum. Delayed-type hypersensitivity was measured after injecting 10(6) irradiated 9L tumor cells into the right pinnae. RESULTS: Tumor growth curves were significantly different between treated and control animals. Among the animals that received 1 ng per day of IL-12, 40% did not develop any measurable tumors at all. A combination of irradiated 9L cells and IL-12 was necessary for optimal effect. Cured animals rejected future flank tumors. All animals rechallenged with intraparenchymal brain tumors survived, whereas control animals all died by Day 22. Delayed-type hypersensitivity measurements showed a specific and long-lasting response against 9L cells. CONCLUSION: Continuous administration of the lymphokine IL-12, in the presence of irradiated tumor cells for antigen presentation, circumvents the need for gene transfection for generating tumor cell vaccines. We have demonstrated that the combination of IL-12 and irradiated tumor cells can lead to regression of 9L flank tumors and resistance to future flank and central nervous system tumor challenges.

Animals↗
PubMed1998

Investigation of intraoperative brain deformation using a 1.5-T interventional MR system: preliminary results.

All image-guided neurosurgical systems that we are aware of assume that the head and its contents behave as a rigid body. It is important to measure intraoperative brain deformation (brain shift) to provide some indication of the application accuracy of image-guided surgical systems, and also to provide data to develop and validate nonrigid registration algorithms to correct for such deformation. We are collecting data from patients undergoing neurosurgery in a high-field (1.5 T) interventional magnetic resonance (MR) scanner. High-contrast and high-resolution gradient-echo MR image volumes are collected immediately prior to surgery, during surgery, and at the end of surgery, with the patient intubated and lying on the operating table in the operative position. In this paper we report initial results from six patients: one freehand biopsy, one stereotactic functional procedure, and four resections. We investigate intraoperative brain deformation by examining threshold boundary overlays and difference images and by measuring ventricular volume. We also present preliminary results obtained using a nonrigid registration algorithm to quantify deformation. We found that some cases had much greater deformation than others, and also that, regardless of the procedure, there was very little deformation of the midline, the tentorium, the hemisphere contralateral to the procedure, and ipsilateral structures except those that are within 1 cm of the lesion or are gravitationally above the surgical site.

Adult↗
PubMed1998

High-field strength interventional magnetic resonance imaging for pediatric neurosurgery.

BACKGROUND: Interventional magnetic resonance (MR) imaging allows neurosurgeons to interactively perform surgery using MR guidance. High-field (1.5-Tesla) strength imaging provides exceptional visualization of intracranial and spinal pathology. The full capabilities of this technology for pediatric neurosurgery have not been defined or determined. MATERIALS AND METHODS: From January 1997 through June 1998, 10 of 85 cases performed in the interventional MR unit were in the pediatric population (mean age 8.3, median 8, range 2-15 years). Procedures included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The biopsies and reservoir placement were performed using MR-compatible equipment. Craniotomies and spinal surgery were performed with conventional instrumentation outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging was performed to assess the goals of surgery. RESULTS: Both brain biopsies were diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was optimally placed within the tumor cyst. Of the 5 tumor resections, all were considered radiographically complete. One biopsy patient and 1 tumor resection patient experienced transient neurological deficits after surgery. The patient with the thoracic syrinx required reoperation when the syringosubarachnoid shunt migrated into the syrinx 3 months after initial placement. No patient sustained a postoperative hemorrhage. Tumor histologies found at craniotomy were craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor progression has been seen in any of these patients at a mean follow-up of 5.3 (range 4-8) months. The goals of the procedure were achieved in all 10 cases. There were no untoward events experienced related to MR-compatible instrumentation or intraoperative patient monitoring, despite the present inability to monitor core body temperature. CONCLUSIONS: 1.5-Tesla interventional MR is a safe and effective technology for assisting neurosurgeons to achieve the goals of pediatric neurosurgery. Preliminary results suggest that surgical resection of histologically benign tumors is enhanced in the interventional MR unit. The incidence of surgically related morbidity is low.

Adolescent↗
PubMed1998

Long-term survival in rhinocerebral mucormycosis. Case report.

Mucormycosis refers to a group of rapidly progressive infections caused by fungi belonging to the order Mucorales. Infection most often develops in individuals with immunological or metabolic compromise, although patients without underlying abnormalities have been affected. Specific clinical manifestations are associated with various predisposing factors. Rhinocerebral mucormycosis is the most common form and most frequently develops in individuals with poorly controlled diabetes mellitus. The extent of anatomical involvement and clinical course are unpredictable, depending on the intrinsic factors of the host. Over the past 20 years the prognosis for patients with rhinocerebral mucormycosis, once considered to be a uniformly fatal disease, has improved. Coordinated medical and surgical treatment, including rapid diagnosis, the advent of systemic antifungal agents, aggressive surgical debridement, and control of the underlying disease process, have been credited with its successful management. The range of survival rates recorded with the regimen of combined therapies is wide because the number of patients reported is limited and anatomical involvement is diverse. Survival with intracerebral abscess is rare. The authors describe the successful management of a patient who developed a bifrontal fungal abscess during treatment for rhinocerebral mucormycosis associated with ketoacidosis and diabetes mellitus. The patient remains without radiographic or clinical evidence of infection more than 2 years after treatment. The authors review the characteristic clinical, radiographic, and pathological features of previously reported infections and emphasize the importance of early detection and aggressive treatment in the management of this frequently fulminant and fatal disease.

Adult↗
PubMed1997

Comparison of confidence between mothers who breastfed and formula fed their preterm infants.

Mothers develop confidence to care for their preterm infants in challenging situations. To date no studies have explored the effects of choice of feeding method on the development of maternal confidence in the preterm population. A descriptive, longitudinal design was used to explore the demographic characteristics of a convenience sample of 173 maternal-preterm infant dyads to examine whether confidence increased over time and to compare levels of confidence between mothers who formula fed and mothers who breastfed their preterm infants. There were no significant differences between feeding groups in maternal confidence; however, maternal confidence within each group increased significantly over time.

Bottle Feeding↗
PubMed1997

The use of stereotactic radiosurgery to treat neurological tumors.

Stereotactic radiosurgery is the precise delivery of a single dose of radiation to a well-defined intracranial volume. The radiation field is contoured to encompass the entire pathologic entity. Radiosurgery is used to treat a wide variety of neurological diseases as either primary or adjuvant therapy. It is a noninvasive and sometimes curative treatment for some brain tumors and inoperable arteriovenous malformations. Radiosurgery can also be used for inaccessible benign neoplasms or in medically unstable patients unable to withstand surgery. This article reviews the literature pertaining to stereotactic radiosurgery and includes our preliminary data from radiosurgery treatments at the University of Minnesota Hospital and Clinic (now Fairview-University Medical Center).

Brain Neoplasms↗
PubMed1996

Brain metastases. Histology, multiplicity, surgery, and survival.

BACKGROUND: With the advent of new therapies for metastatic carcinoma to the brain, patterns of intracranial disease and factors influencing survival become important considerations when examining potential treatment options. METHODS: The records of 729 patients with metastases to the brain treated during the period between 1973 to 1993 were reviewed. RESULTS: Primary tumor histologic type in order of descending frequency included nonsmall cell lung carcinoma (NSCLC), breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown primary carcinoma. There were 384 patients (53%) with a single brain metastasis, which was encountered most commonly in patients with prostate carcinoma and least often in patients with SCLC. Multiple metastases were present in 345 patients (47%). The median duration from diagnosis to presentation with a brain metastasis was 12 months, ranging from 3 months for patients with NSCLC to 53 months for patients with breast carcinoma. The median duration from presentation with brain metastases to death was 4 months, ranging from 3 months for patients with SCLC to 13 months for patients with prostate carcinoma. Median survival from presentation with brain metastases to death was 5 months for patients with single lesions and 3 months for patients with multifocal disease (P = 0.0001). Median survival for patients with a single lesion was 11 months with surgery and 3 months without surgery (P = 0.0001). Surgery did not significantly influence survival in patients with multiple metastases. CONCLUSIONS: Dissemination of systemic carcinoma to the brain continues to carry a poor prognosis. Knowledge of the metastatic patterns and limited survival associated with specific tumor types may be useful for guiding future therapeutic intervention.

Brain Neoplasms↗
PubMed1996

Stereotactic radiosurgery in pediatric patients.

Although stereotactic radiosurgery has been studied extensively in adults, the data demonstrating its efficacy in children is limited. Medical records were reviewed to identify the indications for and outcomes of patients treated with this modality. Linear accelerator-based radiosurgery was used to treat 11 recurrent brain tumors and one posterior fossa arteriovenous malformation over 3 years. The mean and median age of those treated was 10 and 8 years, respectively (range 1-20 years). Patients received 700 to 3,000 cGy delivered to the 50-90% isodose line in a single fraction. The mean and median follow-up was 15 and 17 months, respectively. Three of the four children with malignant disease died 6 to 9 months after treatment. One patient died of recurrence outside the treatment field. Another child died of complications related to radiation injury, and the third died of disease progression. All children with low-grade tumors remain alive without complications. Six of eight (75%) children exhibit substantial radiographic reductions in tumor size. The child with a vascular malformation has been followed for 26 months, without hemorrhage and with a radiographically proved decrease in size. Our series suggests that radiosurgery has limited usefulness in malignant disease. Therapeutic response is influenced by lesion size and/or location. Stereotactic radiosurgery appears to be effective in children with low-grade intracranial tumors or arteriovenous malformations. Further experience is required to establish the role and long term side effects of radiosurgery in pediatric patients.

Adolescent↗
PubMed1996

Antisense oligonucleotides for central nervous system tumors.

The poor prognosis associated with malignant primary brain tumors has led investigators to seek and develop new, innovative treatment modalities. Current adjuvant therapies lack tumor specificity, which can lead to toxic central nervous system side effects. Advances in molecular biology now allow specific gene sequences to be inserted or targeted in the malignant cell genome. Antisense oligodeoxynucleotides represent complementary nucleic acid sequences that can recognize and bind to target genes, resulting in the arrest of deoxyribonucleic acid transcription or the translation of messenger ribonucleic acid. Although the use of antisense oligodeoxynucleotides is still in the experimental stages, these molecules enter cells in tissue culture by simple diffusion or active endocytosis and temporarily inhibit cell proliferation in a time- and dose-dependent fashion. The ability of antisense oligodeoxynucleotides to recognize specific gene sequences and to down-regulate gene expression make them ideal agents for use in targeting oncogenes, such as c-myb, that are expressed in central nervous system neoplasms.

Central Nervous System Neoplasms↗
PubMed1996

Immunotoxin therapy.

Immunotoxins are extremely potent agents that recognize specific antigens located on metastatic tumor cells and cause cytotoxicity after cell entry by inhibiting protein synthesis. These agents have considerable in vitro efficacy against numerous metastatic tumor cell lines. In vivo studies have shown complete tumor regression in athymic animals bearing flank tumors or with leptomeningeal neoplasia. Phase I clinical trials have demonstrated therapeutic efficacy in patients with carcinomatous meningitis or with intraparenchymal brain metastases. These agents may be particularly appropriate for patients with widespread intracranial metastatic disease or with radioresistant tumor histology.

Animals↗