Ehud Arbit

Lumbar stenosis : A clinical review

A brief history, classification, clinical presentation, and pertinent anatomy of spinal stenosis is presented. A thorough understanding of the etiology, pathologic features, and the correlation between symptoms and precisely where the thecal sac and nerve root impingement occurs is essential to interpret imaging studies and plan appropriate treatment.

Acoustic Neuroma: Potential Benefits of Fractionated Stereotactic Radiosurgery

BACKGROUNDnSingle-fraction radiosurgery of acoustic neuromas less than 3 cm in diameter is remarkable for high control but not infrequent incidence of facial and trigeminal neuropathy. Larger tumors treated surgically often result in deafness and facial neuropathy. Fractionated stereotactic radiosurgery was used in an effort to maintain effective therapy while minimizing toxicity of treatment.nnnMETHODSnThe authors described 38 patients with acoustic neuromas, with age range 35-89 years (mean, 60 years). 2,000 cGy in divided weekly doses of 400 or 500 cGy was most commonly prescribed. Tumors > or = 3 cm (n = 16) received the 5 fraction schema. Mean tumor volume was 6.9 cm3, with range from 0.1 to 32.0 cm3.nnnRESULTSnMedian clinical follow-up was 27.1 months, while neuroimaging follow-up had a median of 16.3 months. All tumors were controlled. Of 23 tumors smaller than 3 cm, 14 (61%) decreased in size, and 9 showed cessation of growth. Thirteen of 16 (81%) large acoustic neuromas (3-5 cm) diminished in size. The remaining 3 showed cessation of growth. Median radiographic follow-up was 20 months, with a median clinical follow-up of 28 months. No patient developed fifth nerve symptoms after treatment nor did any patient require surgery for treatment failure. Only one had temporary seventh nerve palsy.nnnCONCLUSIONnFractionated stereotactic radiosurgery offers a therapeutic approach producing high control rates while avoiding morbidity frequently seen after single-fraction radiosurgery or microsurgery.

Adoptive cellular immunotherapy for the treatment of malignant gliomas.

UNLABELLEDnThe median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reoperation can extend the median survival an additional 26-32 weeks. We have developed an aggressive treatment program that utilizes low doses of interleukin-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via an indwelling catheter placed into the surgical resection cavity. Autologous leukocytes were collected during a standard 3-4 h, outpatient leukapheresis procedure, then activated ex vivo for 4-5 days with high doses of IL-2. The treatment protocol consisted of two 2-week cycles of therapy over a 6-week period. Patients with stable disease or objective response on follow-up MRI scans were retreated at 3-month intervals. Acute and cumulative IL-2-related toxicities were observed, but limited, and included fever, headache and transient neurologic irritation. Corticosteroid levels and usage were strictly controlled during immunotherapy, although higher doses were used intermittently to mitigate toxicity. Biologic changes included lymphocytic infiltration, regional eosinophilia, tumor necrosis, and the localized production of IL-2, IFN-gamma and IL-12, demonstrated by in situ hybridization and immunohistochemistry.nnnSUMMARYnIL-2 plus autogeneic LAK cells can be safely administered intracavitary to treat high grade primary brain tumors with limited toxicity within the central nervous system. Six out of 28 patients had long-term survival of greater than 2 years post-reoperation plus immunotherapy with 2 patients alive over 8 years. The presence of a marked regional eosinophilia appeared to correlate with increased survival and may be predictive of a biologic and therapeutic response. Regional adoptive immune therapy was well tolerated and should be considered an option for patients with high-grade tumors refractive to standard therapeutic approaches.

Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report.

PURPOSEnSurgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer.nnnMETHODS AND MATERIALSnThe treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2.nnnRESULTSnThe median survival was 14.2 months, 1-year survival was 50%.nnnCONCLUSIONSnSurvival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.

Recurrent Glioblastoma multiforme: Potential Benefits Using Fractionated Stereotactic Radiotherapy and Concurrent Taxol

UNLABELLEDnA pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous Taxol as a radiation sensitizer.nnnMETHODSnThe treatment outcome was analyzed in two groups of patients with recurrent glioblastoma. Group 1 was analyzed retrospectively, and consisted of 9 patients with a median tumor volume of 9.2 cm3 treated with single-fraction stereotactic radiosurgery alone (mean radiation dose of 19.2 Gy). In group 2, prospectively analyzed, were 14 patients treated with fractionated stereotactic radiotherapy and concurrent Taxol.nnnRESULTSnThe median survival in group 2 was 14.2 months versus 6.3 months in group 1 (p < 0.04). One-year survival for patients who received fractionated radiotherapy with Taxol was 50% compared to 11% for those treated with single-fraction radiotherapy only (p = 0.05).nnnCONCLUSIONSnSurvival for group 2 patients was significantly better compared to those treated with single-fraction radiotherapy alone. These data should stimulate the investigation of both fractionated stereotactic radiotherapy and the development of radiation sensitizers to further enhance treatment.

Treatment of refractory recurrent malignant glioma with adoptive cellular immunotherapy: a case report

We report the successful treatment of a patient with recurrent malignant glioma with adoptive cellular immunotherapy. The patient is a young adult with recurrent progressive disease refractory to aggressive multi-modality therapy including repetitive surgical resection, radiation, radiosurgery and chemotherapy. He received multiple courses of local administration of autologous lymphokine-activated killer (LAK) cells in combination with a low dose of interleukin-2 (IL-2) through an Ommaya reservoir-catheter system. The side-effects of this treatment were limited and manageable. The patient achieved a complete remission, as demonstrated by MRI and confirmed by glucose-positron emission tomography (PET) imaging 11 months after initiation of immune therapy. Twenty-six months later, the patient is still in remission with improving performance status. Adoptive cellular immunotherapy utilizing autologous LAK cells with low dose IL-2 appears to be a safe and effective therapy for a subset of patients with primary, recurrent or progressive malignant glioma following conventional therapy.

Brain tumors do not affect thiopental dosing requirements.

We used the biphasic electroencephalographic (EEG) response to increasing concentrations of thiopental to measure regional brain responses to thiopental. Eight patients with cortical parietal brain tumors, 3.3 (SD 1.3) cm in diameter, and eight control patients with lung cancer and normal brain computed tomography scans received thiopental by infusion (50-75 mg/min) until burst suppression (50% isoelectric activity) on the EEG occurred. Infusion lasted 10.7 (SD 2.4) min, and the average dose of thiopental administered was 810 (SD 170) mg [11.2 (SD 1.9) mg/kg]. During infusion the EEG was continuously recorded from the F3, F4, P3, and P4 electrodes. On-line power spectral analysis was performed, and data were saved for later analysis. Four EEG parameters [log beta (15-30 Hz) power, percent beta power, spectral edge 95% and spectral edge 70%] were plotted against calculated brain concentration of thiopental [using an assumed plasma-effect site rate constant (ke0) of 0.58] for each individual. Three points were measured on each curve (50% upslope, peak, and zero intercept) to quantitate the EEG response. Statistical comparisons were performed between the following sets of data: EEG response at electrode closest to brain tumor versus electrode farthest from tumor (in the same patient); and electrodes closest to brain tumors (parietal P3 and P4) versus same electrode pair in control patients (patients with thoracic tumors) using analysis. No differences were found in any comparison. Thus, the presence of a brain tumor does not affect the response of the brain in this region to thiopental as measured using EEG.