YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==VASCULAR BRAIN TUMORS== 13 AUTHOR Roman-Goldstein S AUTHOR Mitchell P AUTHOR Crossen JR AUTHOR Williams PC AUTHOR Tindall A AUTHOR Neuwelt EA TITLE MR and cognitive testing of patients undergoing osmotic blood-brain barrier disruption with intraarterial chemotherapy. SOURCE AJNR Am J Neuroradiol; VOL 16, ISS 3, 1995, P543-53 ABSTRACT PURPOSE: To determine whether osmotic blood-brain barrier disruption is associated with MR abnormalities or cognitive deterioration and, if so, whether the MR findings correlate with cognitive test results. METHODS: Fifteen brain tumor patients who had a complete tumor response (nine central nervous system lymphoma, three germ cell and two astrocytoma, and one primitive neuroectodermal tumor) treated with blood-brain barrier disruption procedures (318 total procedures) with intraarterial chemotherapy were included. MR images were evaluated for the development of white matter hyperintensity, vascular lesions, or atrophy. Cognitive testing was performed to assess deterioration caused by this therapy. RESULTS: In two patients white matter hyperintensity developed, in two small vascular lesions developed, and in one mild atrophy developed. One infarct was asymptomatic and the second one resulted in mild dysesthesia in one upper extremity. No patient showed diminished cognitive function on the posttherapy evaluation. CONCLUSION: In patients undergoing blood-brain barrier disruption with intraarterial chemotherapy, new abnormalities on MR imaging may develop. These patients maintain the same level of cognitive and neurologic function and MR findings do not correlate with the results of cognitive testing. 18 AUTHOR Serova NK TITLE [The ophthalmological symptoms of craniopharyngiomas] SOURCE Vestn Oftalmol; VOL 109, ISS 4, 1993, P23-6 ABSTRACT Clinical symptoms of craniopharyngioma, a benign tumor, are determined by its effects on the adjacent structures, the optic route being one of them. Ophthalmologic symptoms of craniopharyngiomas reflect the tumor localization and predominant growth and depend on patient's age. Visual disturbances are among the first symptoms of the disease, particularly so in adult patients. The pathogenesis of visual disturbances in craniopharyngiomas is determined by several components: vascular factor, mechanic influence of a volumic formation and brain base major vessels on the optic route structures, toxic effects, and the presence of an optic route nervous tissue edema. It should be noted that visual disturbances may not manifest up to a certain moment because of a high resistance of the optic route nervous tissue. 30 AUTHOR WANIBUCHI M AUTHOR UEDE T AUTHOR ISHIGURO M AUTHOR TATEWAKI K AUTHOR KUROKAWA Y AUTHOR YOSHIDA Y TITLE A case of an intracerebral mass lesion consisting of traumatic granulation tissue. SOURCE NEUROLOGICAL SURGERY; 22 (10). 1994. 963-966. ABSTRACT BIOSIS COPYRIGHT: BIOL ABS. We reported a rare case of an intracerebral granulomatous lesion accompanying severe edema formation in the healing stage of traumatic brain contusions. A 44-year-old male patient came to our outpatient clinic due to progressing headache and nausea. Upon computed tomographic examination, a low density mass with strong surrounding edema was detected at the right frontal base. Magnetic resonance images revealed a high intensity mass on both T1- and T2-weighted images at the right frontal base. Upon intravenous injection of a contrast agent, this lesion exhibited multifocal marginal contrast enhancement. Two additional small enhanced mass lesions were detected at the tip of the right temporal lobe and the medial portion of the left temporal lobe. We tentatively diagnosed it as a right frontal brain tumor and attempted the total removal of the right frontal mass. Unexpectedly, pathological diagnosis was intracerebral granulation tissue associated with accumulation of hemosiderin-laden macrophages and capillary wall thickening. In addition, there was no reactive gliosis. We speculated on the pathogenesis of intracerebral granulation tissue as follows. Since the patient was a heavy drinker and often fell down when he was drunk, it is likely that he might be suffering from intracerebral hematomas due to traumatic contusions. This assumption may be supported by the fact that an old subdural hematoma was observed during the operation and the radiological examination revealed multiple lesions. The gathering and proliferation of mesenchymal cells possibly derived from blood circulation probably began at the site of the damaged brain tissue, thus forming intracerebral granulation tissue. To avoid an unnecessary operation, it is important to watch the development of an intracerebral mass lesion when we suspect it may be of traumatic origin. 40 AUTHOR KONDZIOLKA DS TITLE RADIOSURGICAL RADIOBIOLOGY OF NORMAL OR NEOPLASTIC BRAIN SOURCE Crisp Data Base National Institutes Of Health ABSTRACT RPROJ/CRISP The long-term objectives of the applicant involve the integration of clinical stereotactic neurosurgery and radiosurgery with pertinent clinical and laboratory research that examines the effects of single- session, precise, small-volume irradiation for brain tumors and vascular malformations. The applicant uses in vivo radiobiologic studies to investigate normal brain response and protection, and to study in vivo tumor responses. Prospective randomized clinical trials are used to investigate the medical and economic benefits of radiosurgery in comparison to conventional open neurosurgery or to conventional radiotherapy. The physiologic and histologic response of cranial nerves to high radiation doses must be determined because radiosurgery is used often for lesions at the skull base. A dose-response relationship for optic chiasm radiation sensitivity is determined after radiosurgery targeted to the rat optic chiasm (doses, 6-lOO Gy). Serial visual evoked potentials are performed followed by histologic analysis after one year. High-dose pentobarbital is studied as a radiation protector for single-fraction irradiation in the rat frontal lobe model. Rats are randomized to lOO Gy doses either under pentobarbital anesthesia for brain protection, or under ketamine anesthesia without protection. The brain response is determined at intervals from 60-365 days. An in vivo rat malignant glioma model is used to determine the effects of radiosurgery in combination with whole brain irradiation or sensitizing agents. Rats are randomized to a control group, radiosurgery (70 Gy, 14 days after implantation), radiosurgery plus whole brain fractionated radiotherapy (20 Gy), and radiosurgery plus a radiation sensitizer. Histologic effects, growth in cell culture, and changes in growth factor production are determined. An in vivo sub-renal capsule athymic mouse xenograft model is used to determine long-term histologic effects and effects on cell growth in culture. A prospective randomized trial evaluates stereotactic radiosurgery plus whole brain fractionated radiotherapy versus fractionated radiotherapy alone for the management of patients with multiple brain metastases. Patients with 2-4 metastatic tumors, each less than 25 mm in diameter, are randomized and studied in regard to local tumor control (tumor volume) and patient survival. Through these investigations, the applicant plans to clarify indications for radiosurgery and improve procedural results. Laboratory studies are designed to be of clinical importance and to stimulate concurrent work at other institutions so that long-term objectives within this proposal are sought on a national level. 44 AUTHOR NEUWELT EA TITLE OSMOTIC OPENING OF THE BLOOD-BRAIN-BARRIER SOURCE Crisp Data Base National Institutes Of Health ABSTRACT RPROJ/CRISP The presence of the blood-brain barrier (BBB) prevents most available antitumor agents from effectively penetrating brain tumors. A key factor may be the characteristic steep drug dose- response curve where reductions as small as 20% can result in dramatic loss of efficacy. Extensive animal studies have shown that BBB disruption markedly increases drug delivery to tumor & surrounding brain. Of agents evaluated, only methotrexate (MTX) & cyclophosphamide (CTX) are without significant neurotoxicity. This proposal continues the evaluation of antitumor agent delivery, toxicity & efficacy when administered with osmotic BBB disruption. BBB disruption prior to MTX, CTX & procarbazine treatment in patients with primary & metastatic brain tumors has resulted in significant efficacy particularly with primary CNS lymphoma. Two new antitumor agents will be investigated regarding delivery & efficacy in the nude rat model of intracerebral human tumor xenografts. Preclinical toxicity trials will be done in the dog. Monoclonal antibodies (MAb) specific for human tumor cell antigens will be intensively studied. BBB disruption significantly increases MAb (IgM, IgG & Fab) delivery to brain however, intact IgM tends to nonspecifically bind to brain. Thus, IgG & immunoglobulin fragments appear to have the greatest promise for diagnostic & therapeutic use. IgG, Fab & F(ab')2 fragments of specific & "nonsense" antibodies will be evaluated in tumor-bearing nude rats. Studies of immunohistology, quantitative auto- radiography & MAb concentration x time will evaluate binding & localization. MAb MG-21 (melanoma specific) & L6, which binds to human lung & breast cancer, have both shown systemic efficacy & thus will be evaluated for cytotoxicity in tumor-bearing rats. Delivery to intracerebral tumor after disruption of a panel of MAbs & efficacy of high specific activity radiolabeled MAb will also be assessed. Systemic drug inactivation with MAb will be investigated on the basis that brain tumors are much less permeable to higher molecular weight agents. Studies will examine the effects various anesthetics have on drug & protein delivery to brain after BBB disruption. The permeability effect of steroid treatment & BBB disruption in intracerebral tumor-bearing rats will also be examined. Our overall objective is to improve delivery to antitumor agents to the brain & brain tumors. This proposal is in response to the program announcement in Surgical Oncology & is a continuation of a surgical CREG. 48 AUTHOR Dropcho EJ AUTHOR Rosenfeld SS AUTHOR Morawetz RB AUTHOR Vitek J AUTHOR Brothers M AUTHOR Gorum T AUTHOR Bell S AUTHOR Gillespie GY AUTHOR Glantz M AUTHOR Mahaley MS Jr AUTHOR et al TITLE Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium. SOURCE J Clin Oncol; VOL 10, ISS 3, 1992, P452-8 ABSTRACT PURPOSE: This phase II study was performed to assess the response of patients with newly diagnosed, untreated malignant gliomas (anaplastic astrocytoma [AA] and glioblastoma multiforme [GBM]) to intracarotid (IC) cisplatin. PATIENTS AND METHODS: Eligibility criteria included surgical intervention limited to biopsy only, measurable contrast-enhancing tumor, and unilateral tumor location within the vascular territory of one internal carotid artery. Patients were scheduled to receive four infusions of IC cisplatin (75 mg/m2 every 4 weeks) before beginning standard radiotherapy. Twenty-six patients were treated, and 22 were assessable for response. RESULTS: Ten patients (45%) showed a greater than 25% decrease in the enhancing tumor area before radiotherapy with stabilization or improvement of neurologic deficits, and three patients (14%) had a greater than 70% decrease in tumor area. The likelihood of response to IC cisplatin was not clearly linked to patient age, tumor histology, or pretreatment tumor size. Myelosuppression, nephrotoxicity, and ototoxicity were mild. Optic neuropathy occurred in one patient, seizures in two, and fatal postinfusion cerebral edema in one. CONCLUSION: This study design, which permits assessment of the drug sensitivity of the untreated glioma, has shown definite antitumor activity of IC cisplatin in newly diagnosed malignant glioma patients. 53 AUTHOR Epstein MA AUTHOR Packer RJ AUTHOR Rorke LB AUTHOR Zimmerman RA AUTHOR Goldwein JW AUTHOR Sutton LN AUTHOR Schut L TITLE Vascular malformation with radiation vasculopathy after treatment of chiasmatic/hypothalamic glioma. SOURCE Cancer; VOL 70, ISS 4, 1992, P887-93 ABSTRACT Chiasmatic/hypothalamic gliomas usually are histologically benign astrocytomas that may recur many years after diagnosis and treatment. Three children with chiasmatic/hypothalamic gliomas who were treated at the authors' institution returned 9.5, 11.5, and 2 years, respectively, after radiation therapy (RT) because visual and neurologic deterioration developed. Neuroradiographic studies, including arteriography in two of the patients, showed large mass lesions. These were presumed to be recurrence of tumor, and chemotherapy was administered. Pathologic examination of two children who died and of the third who had a biopsy revealed only a minimal amount of residual, histologically benign astrocytoma, whereas the bulk of the specimen consisted of numerous vessels of variable size. These probably represented incorporation of the rich vasculature in the chiasmal region into the tumor, which underwent degeneration secondary to RT. Radiographic methods did not distinguish progressive tumor growth from the vasculopathy and led to inappropriate clinical diagnoses and treatment. 54 AUTHOR Malkova EV AUTHOR Proskurin VV AUTHOR Bernadskaia MM TITLE [Somatogenic toxic-circulatory encephalopathies with pseudotumorous course] SOURCE Ross Med Zh, ISS 2, 1992, P21-3 ABSTRACT A progredient course of cerebral circulatory disorders in grave-condition somatic patients may present a clinical picture of toxic dyscirculatory encephalopathy with brain symptoms of mass lesions. Pseudotumorous run of a chronic vascular process requires a sound clinical analysis and adjuvant methods of examination to rule out primary tumor or brain metastases. 64 AUTHOR Kim JH AUTHOR Alfieri AA AUTHOR Rosenblum M AUTHOR Bravo S AUTHOR Kim SH TITLE Low dose rate radiotherapy for transplantable gliosarcoma in the rat brain. SOURCE J Neurooncol; VOL 9, ISS 1, 1990, P9-15 ABSTRACT Interstitial brachytherapy with low energy radionuclides is becoming widely used in conjunction with external beam radiotherapy in the treatment of primary malignant gliomas of the brain. Few radiobiological studies have been carried out with low dose rate brachytherapy for brain tumors. Since we have recently developed a non-invasive low dose rate radiotherapy model for the treatment of transplantable 9L gliosarcoma growing in the rat brain, we carried out a series of radiobiological studies to determine the dose rate effect on the tumor and normal brain tissue. Using TCD50 (the radiation dose to control 50% tumor control) as the endpoints, we obtained the results indicating that the tumor control rate was highly dependent on the dose rate and the total dose delivered to the tumor. The TCD50 of dose rates ranging from 100 cGy/min, 120 cGy/hr, and 40 cGy/hr were 25 Gy, 80 Gy, and 100 Gy, respectively. The normal tissue effects were most pronounced with high dose rate irradiation (100 cGy/min). The LD50 for high dose rate irradiation to the whole brain was 29 Gy. In contrast, the majority of animals treated with low dose rate radio-therapy behaved quite normal up to a year follow-up. The late histopathological changes of the irradiated brain usually consisted of vascular and white matter necrosis, although the extent of such changes showed a considerable individual variation within the long-term survivors. 69 AUTHOR Kleinschmidt-DeMasters BK AUTHOR Geier JM TITLE Pathology of high-dose intraarterial BCNU. SOURCE Surg Neurol; VOL 31, ISS 6, 1989, P435-43 ABSTRACT Current radiotherapy and chemotherapy for high-grade and/or recurrent astrocytomas result in only moderate increases in survival time. In an attempt to improve this, high-dose intraarterial 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) was utilized on 41 patients with these neoplasms over a 4-year period at our institution. Eight of the 41 patients came to biopsy or autopsy at times sufficiently following intraarterial BCNU infusion and with adequate tissue samples to evaluate the histological changes induced by the drug. Two of the eight patients received no additional radiotherapy or chemotherapy. The other five received conventional whole brain irradiation, and one additionally received 50 mg of intravenous 2-deoxy-5-fluorouridine (FUdR). The eight patients showed mild to severe amounts of bland coagulative necrosis, vascular hyalinization, perithelial fibroblastic proliferation, and endothelial atypia. One of these patients had a recognized severe clinical leukoencephalopathy, and the pathological changes were maximal in this individual. Six patients had radiological evidence of increased necrosis and clinical deterioration prebiopsy or preautopsy, but, within this group, there were no distinguishing clinical features. Microscopic changes were severe in two of these patients. A final patient died of unrelated septic shock 5 days after a single infusion of intraarterial BCNU, and the microscopic changes were least extensive in her. This study suggests that high-dose intraarterial BCNU can cause a leukoencephalopathy, sometimes severe, either alone or in synergistic fashion with cranial irradiation. Occurrence of such leukoencephalopathy is not always predictable based on BCNU dosage and cannot always be reliably distinguished from tumor regrowth or tumor necrosis by radiological and clinical evaluation. Hence, caution most be exercised in continuation of high-dose intraarterial BCNU protocols. 70 AUTHOR Rosenblum ML AUTHOR Berens ME AUTHOR Rutka JT TITLE Recent perspectives in brain tumor biology and treatment. SOURCE Clin Neurosurg; VOL 35, 1989, P314-35 (REF: 106) ABSTRACT Tumors are composed of tumor cells, normal host cells, and an ECM. Tumor growth depends on the balance between tumor cell proliferation and tumor cell loss and is significantly influenced by normal vascular, immune, and glial cells of the host. Furthermore, tumor size and growth regulation are probably influenced by components of the ECM and by edema within and surrounding the tumor. To increase the therapeutic value of treatment regimens, investigators must study normal tissues and attempt to identify tumor-specific vulnerabilities and ways to inhibit toxicity to the host. We are entering an era of increased awareness of the complexities of tumor biology. Although our knowledge of tumor cell biology has had only a limited impact on the treatment for brain tumors, rationally developed approaches based upon new knowledge are bound to result in more effective treatment and improved prognosis for patients with brain tumors. 72 AUTHOR Rozental JM AUTHOR Robins HI AUTHOR Finlay J AUTHOR Healey B AUTHOR Levin AB AUTHOR Steeves RA AUTHOR Kohler PC AUTHOR Schutta HS AUTHOR Trump DL TITLE "Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas. SOURCE Cancer; VOL 63, ISS 12, 1989, P2475-81 ABSTRACT Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas. 74 AUTHOR Greenberg HS AUTHOR Chandler WF AUTHOR Diaz RF AUTHOR Ensminger WD AUTHOR Junck L AUTHOR Page MA AUTHOR Gebarski SS AUTHOR McKeever P AUTHOR Hood TW AUTHOR Stetson PL AUTHOR et al TITLE Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas. SOURCE J Neurosurg; VOL 69, ISS 4, 1988, P500-5 ABSTRACT Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas. 77 AUTHOR Peiffer J TITLE Encephalomyelopathies associated with extracerebral malignant tumors. SOURCE Pathol Res Pract; VOL 182, ISS 5, 1987, P585-608 (REF: 145) ABSTRACT It was the aim of this study to examine the probability of pathogenetical relations between extracerebral malignant tumors and lesions of CNS. The term paraneoplastic should be questioned. Among a running series of 2,000 brain autopsies, 456 patients (22.8%) showed such tumors, 362 of these combined with lesions in brain or spinal cord. Out of these cases, 100 had metastases, meningoses blastomatosae or leukotic hemorrhages, 218 other, non-tumoral lesions, and 44 both tumoral and non-tumoral lesions. The last-mentioned 262 cases were the target of the examination. We distinguished 6 groups: a) various well-definable impacts, diseases or genetical defects (n = 18), b) unspecific terminal resp. agonal changes (n = 49), c) vascular or circulatory disorders incl. embolizations (20 non-leukotic hemorrhages, 148 anemic infarctions or selective neuronal necroses), thromboses, angiitis or calcifications, d) infections and other inflammatory alterations (n = 37), e) metabolic and toxic lesions (9 Wernicke's disease, 12 central pontine myelinolyses, f) anomalies difficult to classify (51 cases with subacute cerebellar atrophy, diffuse leukoencephalopathy, focal spongious axonopathic lesions, myelomalacia and other). After analysing the various lesions and discussing the probable pathogenesis we grouped according to the following scheme: I) tumor-unrelated (casual coincidence) (43.2%), II) therapy-dependent (3.7%), III) agony-related (10.7%), IV) homoiogenic disorders (e.g. larynx carcinoma and Wernicke's disease) (2.0%), V) nosocomial disorders (12.9%), VI) tumor-dependent (local neighbourhood effects, primary or secondary remote effects). As the central group there remain the primary remote effects (17.3%), separable into specific functional anomalies by tumorous organ destruction, remote effects of tumor cell-born (ectopic) release of hormones or hormone-like substances (n = 2), tumor antigen-dependent immune reactions (n = 20), and pathogenetically still uncleared mechanisms (n = 51). One should apply the term paraneoplastic only for the three last-mentioned conditions. 78 AUTHOR Lichtner RB AUTHOR Nicolson GL TITLE Effects of the pyrimido-pyrimidine derivative RX-RA 85 on metastatic tumor cell-vascular endothelial cell interactions. SOURCE Clin Exp Metastasis; VOL 5, ISS 3, 1987, P219-31 ABSTRACT An important step in the metastatic process is the interaction of blood-borne malignant cells with the vascular endothelium. Among the agents that may interfere with this process are pyrimido-pyrimidines, such as RX-RA 85, developed originally as an antiplatelet agent. Using an endothelial cell momolayer attachment assay we have investigated the effects of RX-RA 85 on tumor cell and endothelial cell properties. Exposure of bovine aortic endothelial cells for 3 h to greater than 4 micrograms/ml RX-RA 85 produced toxic effects, resulting in vacuole formation, retraction and finally rounding up of the cells. Endothelial cells derived from different sources behaved dissimilarly; human brain, human meninges, mouse brain, mouse lung and rat lung endothelial cells were less sensitive to drug treatment than bovine aortic endothelial cells. RX-RA 85 treatment of bovine aortic endothelial cells increased B16-F1 melanoma cell adhesion. When B16-F1 cells were exposed to 4-8 micrograms/ml RX-RA 85, increased adhesion to the subendothelial matrix occurred, whereas exposure to higher drug concentrations (8-16 micrograms/ml RX-RA 85) decreased adhesion. Indirect immunofluorescence staining of cytoskeletal structures in B16-F1 cells adhering to and spreading on matrix revealed that the differential effects of RX-RA 85 on the organization of microtubules and microfilaments might explain the dose-dependent differences in adhesion kinetics. 79 AUTHOR Johnson DW AUTHOR Parkinson D AUTHOR Wolpert SM AUTHOR Kasdon DL AUTHOR Kwan ES AUTHOR Laucella M AUTHOR Anderson ML TITLE Intracarotid chemotherapy with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in 5% dextrose in water in the treatment of malignant glioma [published erratum appears in Neurosurgery 1987 Aug;21(2):270] SOURCE Neurosurgery; VOL 20, ISS 4, 1987, P577-83 ABSTRACT After radiotherapy, 20 patients, 18 with documented progression of malignant glioma and 2 with Grade II astrocytoma, received a total of 52 courses of intracarotid 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) at a dose of 150 mg/m2 dissolved in 5% dextrose in water. The patients were treated at 6-week intervals for a maximum of five courses of chemotherapy per patient. Response to treatment was analyzed on computed tomographic scans by measuring the volume of the enhancing tumor and any central low density. From these data, tumor doubling times ranging from 110 to 968 days were obtained. An 11 to 60% reduction in enhancing tumor volume was noted in 8 patients, 2 of whom had a greater than 50% decrease in tumor volume. One patient had no change in tumor volume 110 weeks after the initiation of BCNU chemotherapy. Four patients had tumor in more than one vascular territory; tumor growth was arrested in the perfused territory, but continued in the nonperfused area. In 1 of the 4 patients, tumor also grew along a shunt catheter tract and spread over the surface of the ipsilateral hemisphere. One patient developed clinically asymptomatic leukoencephalopathy after five courses of BCNU. Two patients had postradiation leukoencephalopathy before BCNU treatment. Seventeen patients had peritumoral low density with mass effect after BCNU; thus, the true incidence of BCNU-related leukoencephalopathy could not be determined. All patients experienced transient unilateral orbital pain during the infusion and scleral erythema that lasted for several hours afterward. Loss of vision was noted in 2 patients, although it seemed to be related to the therapy in only 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS) 80 AUTHOR Vance RB AUTHOR Kapp JP TITLE Supraophthalmic carotid infusion with low dose cisplatin and BCNU for malignant glioma. SOURCE J Neurooncol; VOL 3, ISS 4, 1986, P287-90 ABSTRACT Arterial infusion of select chemotherapeutic agents has been shown to deliver increased drug concentration to brain tumors with reduced systemic toxicity. In this study, nine patients with histologically confirmed malignant glioma received cisplatin 110 mg and BCNU 300 mg fixed dose. All patients had received standard doses of cranial radiation after their initial surgical procedures. In three patients, intraoperative modification of the cerebral circulation was accomplished prior to the actual infusion because the vascular supply of the tumor arose from major arteries other than a single internal carotid artery. Supraophthalmic catheterization technique was employed. No neurological deficits occurred post infusion. The radiographic response rate was 25%. No responses were seen in patients who received less than 69 mg/M2 cisplatin this combination. The longest survival is 11+ months in a patient with anaplastic astrocytoma. Our first thirteen patients received cisplatin 150-200 mg and BCNU 300 mg for each infusion with a response rate of 83% in evaluable patients. Since modest reduction in cisplatin dose dramatically reduced the response rate, future studies should be directed at fine tuning the dose of this drug, or at neutralizing recirculating drug after its high dose first pass through the arterial circulation. 81 AUTHOR Kleinschmidt-DeMasters BK TITLE Intracarotid BCNU leukoencephalopathy. SOURCE Cancer; VOL 57, ISS 7, 1986, P1276-80 ABSTRACT Intracarotid 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) is now a frequently used chemotherapeutic agent for high-grade glial neoplasms. The toxicity from such therapy has not been well-documented. A 50-year-old man with a left frontoparietal grade 4 astrocytoma received three injections of intracarotid BCNU, 400 mg each, over a 2-month period. No radiation or other chemotherapy was ever given. He tolerated the BCNU injections well, with some reduction of tumor bulk, until the third dose. After his last injection, his condition gradually deteriorated; he became obtunded, and died 5 weeks later. At autopsy, the brain showed extensive cavitation and coagulative necrosis, fibrinoid vascular necrosis, edema, swollen axons, and bizarre cellular morphologic features confined to the BCNU perfusion territory. Grade 4 astrocytoma remained in the right hemisphere and in the left occipital lobe, sites outside the area of BCNU perfusion. Intracarotid BCNU can result in a severe leukoencephalopathy similar to that seen with methotrexate or delayed radionecrosis. 84 AUTHOR Waxweiler RJ AUTHOR Alexander V AUTHOR Leffingwell SS AUTHOR Haring M AUTHOR Lloyd JW TITLE Mortality From Brain Tumor And Other Causes In A Cohort Of Petrochemical Workers SOURCE Journal of the National Cancer Institute, Vol. 70, No. 1, pages 75-81, 24 references, 19831983 ABSTRACT The incidence of brain tumors was investigated in petrochemical workers. Vital status was determined through company records, social security records, and the state bureau of vital statistics for 7595 male workers who had worked in a petrochemical facility between 1941 and 1977. Observed and expected deaths from brain tumors were tabulated through 1979. Death certificates were obtained and classified. Through 1977, 96.7 percent of the cohort members were successfully traced. Deaths among white male hourly workers were 80 percent of expected, and non white hourly and white salaried workers had death rates 56 and 61 percent of expected, respectively. Mortality due to vascular lesions of the central nervous system and respiratory disease that was not malignant was much lower than expected. Mortality due to neoplasia showed a marked excess risk for brain tumors among all hourly workers. A slightly elevated risk was found for leukemia and very low risks for cancers of the buccal cavity and pharynx, stomach, rectum, and gential organs. Salaried workers had no deaths from brain tumors, with 1.5 expected. The standardized mortality ratio for brain tumors increased with increasing duration of employment. A total of 22 deaths from brain tumors occurred in hourly workers from 1941 to 1979, with 10.7 expected. The authors conclude that there may be an occupational cause for brain tumor deaths in petrochemical workers. 87 AUTHOR Campbell AN AUTHOR Chan HS AUTHOR Becker LE AUTHOR Daneman A AUTHOR Park TS AUTHOR Hoffman HJ TITLE Extracranial metastases in childhood primary intracranial tumors. A report of 21 cases and review of the literature. SOURCE Cancer; VOL 53, ISS 4, 1984, P974-81 ABSTRACT A clinical and pathologic review of primary intracranial tumors (917 cases in a 62-year period) at The Hospital for Sick Children, Toronto, identified 21 cases with systemic metastases (2.3%). This included 15 cases of medulloblastoma and 1 case each of astrocytoma, meningeal sarcoma, malignant melanoma, ependymoblastoma, teratoma, and endodermal sinus tumor, adding to the pediatric literature of 94 previously reported cases (72 medulloblastoma and 22 cases of other brain tumors). Like adults, children with medulloblastoma tend to develop bone and bone marrow metastases, while those with other brain tumors frequently invade adjacent tissues, and then spread to regional lymph nodes and the lungs. The prognosis is almost uniformly fatal, although prolonged palliation could be achieved with radiation and/or chemotherapy. The pathogenesis of systemic metastases is related to breakage of the blood-brain barrier, whether at surgery, or with tumor invasion into vascular channels, and especially with preoperative systemic-cerebrospinal fluid shunting. Thirteen of 16 patients who developed systemic metastases, including 5 with peritoneal involvement, had ineffective or no millipore filters within their shunts, suggesting their possible prophylactic role against tumor dissemination. A greater understanding of the pathogenesis of systemic metastases may aid the design of future effective preventive measures. 88 AUTHOR Vespignani H AUTHOR Legras B AUTHOR Weber M AUTHOR Micheletti G AUTHOR Micheletti M AUTHOR Remy C AUTHOR Rohmer F AUTHOR Kurtz D AUTHOR Feuerstein J TITLE [Frequency and semeiological evolution of epileptic seizures occurring between 40 and 65 years of age (author's transl)] SOURCE Rev Electroencephalogr Neurophysiol Clin; VOL 11, ISS 3-4, 1981, P524-30 ABSTRACT 458 patients who had their first epileptic fit between the ages of 40 and 65 are classified into 5 groups according to the seizure symptomatology: when the symptomatology remains unchanged, the frequency of fits is less than 1 per month in 84% of generalized fits and more than 1 per month in 52% of focal fits. When the symptomatology changes, the frequency of fits is less than 1 per month when the inaugural fit is generalized (23 out of 27) and more than 1 per month when the inaugural fit is focal (15 out of 21). Modifications of the symptomatology correlate positively with a prevalence of tumor aetiology. Primary generalized epilepsies are rare (4.4%). Non-specific secondary generalized epilepsies (including vascular, metabolic or toxic encephalopathies) account for 24.4% of the cases. Focal epilepsies are the most common form (40.7%), elementary fits being four times more frequent than complex fits.