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Biomedical subjects

E Alexander

Publications and source records attributed to E Alexander.

At least 109 records · Page 6Linked to original sources
PubMed1993

Tolerance of cranial nerves of the cavernous sinus to radiosurgery.

PURPOSE: Stereotactic radiosurgery is becoming a more accepted treatment option for benign, deep seated intracranial lesions. However, little is known about the effects of large single fractions of radiation on cranial nerves. This study was undertaken to assess the effect of radiosurgery on the cranial nerves of the cavernous sinus. METHODS AND MATERIALS: We examined the tolerance of cranial nerves (II-VI) following radiosurgery for 62 patients (42/62 with meningiomas) treated for lesions within or near the cavernous sinus. Twenty-nine patients were treated with a modified 6 MV linear accelerator (Joint Center for Radiation Therapy) and 33 were treated with the Gamma Knife (University of Pittsburgh). Three-dimensional treatment plans were retrospectively reviewed and maximum doses were calculated for the cavernous sinus and the optic nerve and chiasm. RESULTS: Median follow-up was 19 months (range 3-49). New cranial neuropathies developed in 12 patients from 3-41 months following radiosurgery. Four of these complications involved injury to the optic system and 8 (3/8 transient) were the result of injury to the sensory or motor nerves of the cavernous sinus. There was no clear relationship between the maximum dose to the cavernous sinus and the development of complications for cranial nerves III-VI over the dose range used (1000-4000 cGy). For the optic apparatus, there was a significantly increased incidence of complications with dose. Four of 17 patients (24%) receiving greater than 800 cGy to any part of the optic apparatus developed visual complications compared with 0/35 who received less than 800 cGy (p = 0.009). CONCLUSION: Radiosurgery using tumor-controlling doses of up to 4000 cGy appears to be a relatively safe technique in treating lesions within or near the sensory and motor nerves (III-VI) of the cavernous sinus. The dose to the optic apparatus should be limited to under 800 cGy.

Abducens Nerve↗
PubMed1993

Dynamic field shaping for stereotactic radiosurgery: a modeling study.

PURPOSE: This work assesses the relative field shaping advantages of dynamic field shaping devices for stereotactic radiosurgery using a linear accelerator. METHODS AND MATERIALS: We selected 43 intracranial tumors (2.0-4.2 cm maximum dimension, 1.5-25.5 cc tumor volume) out of the first 64 intracranial tumors treated with radiosurgery at the Joint Center for Radiation Therapy. We modeled five field shaping devices, each including a fixed auxiliary circular collimator: (a) fixed circular collimator alone; (b) two independent parallel jaws; (c) four independent rectangular jaws; (d) four independent rotatable jaws; and (e) "ideal" multileaf collimator. We adjusted the model parameters until the minimum target isodose was 80% of the dose delivered to isocenter. We defined the treatment volume ratio as the target volume divided by the treatment volume (volume receiving at least the minimum target dose). We used the treatment volume ratio to compare the five models and the actual patient treatments. RESULTS: For 34 tumors originally treated with one isocenter, the median Treatment Volume Ratio was higher for all of the device models except the fixed circular collimator compared to the actual patient treatments. For the nine tumors originally treated with multiple isocenters, the median Treatment Volume Ratio for the actual multiple isocenter treatments was similar to that for two parallel jaws, four rectangular jaws and four rotatable jaws. Only the median "ideal" collimator treatment volume ratio was higher for these nine tumors. CONCLUSION: Simple field shaping devices have approximately 50% of the conformal advantage of an "ideal" multileaf collimator. Approximately 50% of typical radiosurgical tumors between 2 and 4 cm have field shaping advantages which exceed the geometrical uncertainties inherent in linear accelerator radiosurgery treatments. The three models, two parallel, four rectangular, or four rotatable independent jaws would improve current linear accelerator technology by providing homogeneous doses with equivalent field shaping for most tumors originally treated with inhomogeneous multiple isocenter plans (6/9 tumors in the current series).

Brain Neoplasms↗
PubMed1993

Stereotactic techniques in managing pediatric brain tumors.

Stereotactic techniques available for managing pediatric brain tumors include not only stereotactic biopsy but also stereotactic craniotomy, brachytherapy, and stereotactic radiosurgery. This paper illustrates the use of these techniques in brain tumors in children over a 2-year period at Children's Hospital, Boston. Stereotactic biopsy was used in six cases of deep-seated tumor, with successful tissue diagnosis in all six. Stereotactic craniotomy, in which excision of a mass was done in the stereotactic frame with computed tomography-guided localization and control, was employed in three children. Interstitial radiation using implanted 125I seeds was carried out in two children with malignant astrocytomas: in both it provided good local control but there was later distant recurrence. Stereotactic radiosurgery with a modified linear accelerator was used in eight children as adjunctive therapy for local control. These cases illustrate the versatility of stereotactic techniques involved in a comprehensive approach to pediatric brain tumors.

Adolescent↗
PubMed1993

Thallium-201 technetium-99m HMPAO single-photon emission computed tomography (SPECT) imaging for guiding stereotactic craniotomies in heavily irradiated malignant glioma patients.

SPECT scanning with Tl-201 and Tc-99m offers a unique, inexpensive functional imaging modality to combine with CT stereotactic craniotomy for guiding resection of necrosis and/or tumour in patients treated with escalated doses of radiation (> 6000 cGy) by either brachytherapy or radiosurgery. Thirty-two cases were analyzed, with a detailed description of the imaging and operative techniques.

Astrocytoma↗
PubMed1992

Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies.

OBJECTIVE: To determine whether anti-Ro/SS-A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization. METHODS: An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed. RESULTS: Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti-La/SS-B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti-native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produced alterations in membrane repolarization. CONCLUSION: Anti-Ro/SS-A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus.

Action Potentials↗
PubMed1992

Distribution of etanidazole into human brain tumors: implications for treating high grade gliomas.

Etanidazole was developed as an oxygen-mimetic radiosensitizer less lipophilic than misonidazole. Sensitization depends on an adequate concentration of drug in the tumor at the time of irradiation. Therefore, due to the presence of the blood-brain barrier, brain tumors may theoretically be difficult to radiosensitize due to the hydrophilic characteristics of etanidazole. Based on previous reports of loss of BBB integrity in brain tumors, we investigated the ability of etanidazole to penetrate into malignant gliomas of patients receiving etanidazole as part of a Phase I continuous infusion protocol. The patients had completed previous external beam irradiation. Twenty-two patients were studied and their etanidazole plasma and biopsy data were compared to the 2-compartment model derived from a second group of 19 patients with bolus etanidazole. Etanidazole concentration in brain tumor biopsies varied widely and appeared to be clustered into a higher and a lower pharmacokinetic group having mean tumor to well-perfused second compartment ratios of 1 and 0.25, respectively. Both high and low etanidazole concentrations were evident in different biopsies obtained from the same patient. Correlations between histology and tissue concentrations suggested that the higher level correspond to malignant tissue. These data indicate that the blood brain barrier is disrupted to varying degrees by the brain tumor and/or prior irradiation and that etanidazole penetrates into brain tumors.

Brain Neoplasms↗
PubMed1992

Final report of the phase I trial of continuous infusion etanidazole (SR 2508): a Radiation Therapy Oncology Group study.

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Brachytherapy↗
PubMed1992

Radiosurgery as part of the initial management of patients with malignant gliomas.

PURPOSE: Between May 1988 and May 1991, 41 patients with malignant gliomas were enrolled onto a prospective study designed to evaluate the role of radiosurgery as a component of initial management. PATIENTS AND METHODS: Thirty-seven patients underwent radiosurgery according to the protocol and were assessable for survival and complications of treatment. Diagnoses included glioblastoma multiforme (GBM) in 23 (62%) cases and anaplastic astrocytoma in 14 (38%) cases. In 20 (54%) cases, surgical resection was attempted initially, whereas 17 (46%) patients underwent biopsy only. Patients in the study group received external-beam radiotherapy that consisted of 5,940 cGy given in 33 fractions to partial brain fields that encompassed the primary tumor with a 3 to 4 cm margin. Radiosurgery, used as a technique for boosting the dose to any residual contrast-enhancing mass lesion, was given 2 to 4 weeks after the completion of conventional radiotherapy. Minimum radiosurgical doses ranged from 1,000 to 2,000 cGy (median, 1,200 cGy), whereas maximum doses ranged from 1,250 to 2,500 cGy (median, 1,500 cGy). The median tumor volume at the time of radiosurgery was 4.8 cm3 (range, 1.2 to 72 cm3). Adjuvant chemotherapy was not given. RESULTS: After a median follow-up of 19 months, only nine of 37 (24%) patients have died. Six patients (all glioblastoma multiforme) died of recurrent tumor, whereas death was attributable to complications of treatment in two cases and intercurrent disease in one case. Four patients with recurrent tumor failed at the margins of the radiosurgical treatment volume, whereas two patients progressed locally. One patient is alive with local and marginal failure. Seven (19%) patients underwent reoperation at a median time of 5 months (range, 1 to 14 months) after radiosurgery. CONCLUSION: We conclude that radiosurgery is a useful adjunct to other modalities in the initial management of patients with small, radiographically well-defined malignant gliomas.

Actuarial Analysis↗