Jack M. Rozental

Defining the role of radiosurgery in the management of brain metastases

The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.

Stereotactic radiosurgery for glioblastoma multiforme: Report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage

PURPOSE Prospective evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma. METHODS AND MATERIALS From 5/89 to 12/92, 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery, in addition to 54 Gy in 1.8 Gy/fraction following biopsy (n = 12) or resection (n = 19). Eligibility required supratentorial glioblastoma, tumor not > 4 cm in > 1 axis, age > 18 years, and location > 1 cm from optic chiasm. Patient characteristics were: age 20-78 years (median = 57); 22 male, 9 female; Karnofsky score 20-90 (m = 70), and volume of 2.3-59.7 c.c. (m = 17.4). Eighteen patients were treated with 1 collimator, 5 with 2, 7 with 3, and 1 with 4; peripheral isodoses were 40-90% (m = 72.5) and minimum and maximum tumor dose ranges were 10-20 (m = 12) and 15-35 Gy (m = 18.75). Patients were followed clinically and radiographically every 8-12 weeks to analyze survival, quality of life, and toxicity. RESULTS With a follow-up of 12-171 weeks, 8 out of 31 (26%) patients are alive. Median survival is 42 weeks. Twelve and 24-month actuarial survival are 38 and 28%. Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7% (p < 0.05). Extent of resection and performance status were associated with improved survival in a multivariate analysis. No significant acute toxicity was encountered. Four patients (13%) developed clinically significant necrosis verified by biopsy or positron emission tomography scan at 9-59 weeks after radiosurgery. CONCLUSION The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine, but the 2-year survival may be superior. Future randomized trials of radiosurgery are recommended, and ad hoc use of this modality should be discouraged.

Early changes in tumor metabolism after treatment : the effects of stereotactic radiotherapy

Four patients with intracranial neoplasms, two with malignant gliomas and two with brain metastases, were treated with stereotactic radiotherapy. Patients received between 15 and 27.5 Gray of photon irradiation to the central tumor target point; the 80% isodose line covered the periphery of the tumor as determined by contrast enhanced computed tomography. Patients underwent a sequence of three Positron Emission Tomographic scans using [18F]-fluorodeoxyglucose (PET-FDG)--a baseline scan the day before treatment, and follow-up scans 1 and 7 days after treatment. Ratios between the maximal tumor regional cerebral metabolic rate for glucose (rCMRGlu) (T*) and the contralateral remote white matter rCMRGlu (RW), that is, the glucose uptake ratio (T*/RW), were calculated. The percent change in ratios relative to each patients baseline scan were calculated. Ratios increased 25% to 42% 1 day post-radiotherapy, then decreased to between 10% above and 12% below the baseline value 7 days post-radiotherapy. The T*/RW increased acutely after stereotactic radiotherapy in a fashion similar to that previously described following chemotherapy with a complex multi-drug regimen. A common metabolic pathway may underlie the increase in T*/RW after these different treatments.

Energy transduction in quinone inhibition of insect feeding

Abstract Variously substituted 1,4-naphthoquinones inhibited (deterred) feeding by Periplaneta americana. Certain sensilla on the antennae were important receptors for the deterrent stimulus. Dendritic branches of sensory neurons in the sensilla are exposed to the exogenous inhibitory chemicals via pores which penetrate the cuticle. The order of relative degree of complexing of a given naphthoquinone to density-gradient fractions of antennal homogenates rich in nerve membrane fragments matched the order of relative deterrency of that chemical to feeding. Sulphhydryl groups of protein in the antennae were important sites of reaction. Energy transduction at the receptor site involved complexing of the quinone with the receptor chemical and the ultimate reduction of the quinone to its quinol. Energy transfer between sulphhydryl groups and quinones provided a mechanism which could bring about a change in conformation of the receptor macromolecule which could allow inorganic ion flows to generate the action potential of the neuron.

Tumors of the spine and spinal cord.

OBJECTIVES To provide an overview of spinal cord neoplasms with a focus on location, histology, pathophysiology, diagnosis, treatment and nursing assessment and management. DATA SOURCES Published books and peer-reviewed articles. CONCLUSIONS Tumors of the spine and spinal cord are rare, and they can have grave implications for the patient. The key in the management of spinal cord tumors is their timely diagnosis and treatment to preserve function. IMPLICATIONS FOR NURSING PRACTICE A thorough nursing assessment and timely intervention can have a positive impact on the outcome of patients with tumors of the spine and spinal cord.

Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells

The purpose of this study was to characterize the effects of sodium 4-phenylbutyrate (phenylbutyrate) on the proliferation, morphology, migration and invasiveness of malignant glioma cells in vitro. Phenylbutyrate is a novel differentiating and cytotoxic compound used clinically with low toxicity in the treatment of β-thalassemia, sickle cell anemia and urea cycle disorders. Preliminary clinical trials testing phenylbutyrate as an anti-cancer agent have included patients with malignant glioma. However, little information is available regarding the effects of phenylbutyrate on glioma cells, particularly with respect to the expression of genes important in the pathogenesis of glial malignancy. In experiments reported here, glioma cell lines and explant cells from a tumor patient were exposed to 2, 4 and 8 mM phenylbutyrate and compared to untreated control cells. The effect on cellular proliferation was assessed using cell counts and DNA flow cytometry. Changes in morphology were evaluated using vimentin staining. Scratch and Matrigel assays were performed to assess changes in cellular migration and invasiveness. Finally, Northern blot analysis was used to study c-myc and urokinase expression. Phenylbutyrate was found to have dose-dependent inhibitory effects on glioma cell proliferation, morphology, migration, invasiveness and c-myc and urokinase expression. Mean growth-inhibitory (IC50) phenylbutyrate concentrations ranged from 0.5 mM for T98G cells to 5.0 mM for explant cells. Phenylbutyrate treatment reduced % S phase cells, increased % G0/G1 cells, and produced morphologic changes consistent with induction of differentiation. 24 hours of treatment with 4 mM phenylbutyrate resulted in a 50% reduction in migration and invasiveness. Northern blots showed a decrease in urokinase and c-myc expression at non-cytotoxic doses. We conclude that phenylbutyrate is a promising candidate compound for treating patients with malignant glioma.

Changes in glucose uptake by malignant gliomas: preliminary study of prognostic significance

SummarySequential positron emission tomographic scans with [18F]-2-fluorodeoxyglucose (PET-FDG) were performed on 14 patients with malignant gliomas. All patients had prior brain irradiation. Five patients received adjuvant eight-drugs-in-one-day chemotherapy (experimental subjects) and 9 did not (control subjects). Ratios between the maximal tumor regional cerebral metabolic rate for glucose (rCMRGlu) and the contralateral white matter rCMRGlu, the glucose uptake ratio, were determined. Percent changes in the ratio 1 day after chemotherapy in experimental subjects, and 30 days after the baseline scan in controls, were of prognostic significance. In both groups, patients with the largest percent changes in rCMRGlu had the shortest survival. In contrast, the baseline glucose uptake ratio did not predict length of survival.

Energy Transduction: Inhibition of Cockroach Feeding by Naphthoquinone

1,4-Naphthoquinones inhibit feeding of Periplaneta americana by complexing with sulfhydryl groups of receptor protein in sensory neurons, by oxidizing the sulfhydryl groups, and by being reduced.

Acute changes in glucose uptake after treatment: the effects of carmustine (BCNU) on human glioblastoma multiforme

SummarySequential positron emission tomographic scans with [18F]-2-fluorodeoxyglucose (PET-FDG) were performed on 6 patients with glioblastoma multiforme who were treated with adjuvant BCNU. Scans were acquired before and 24 hours after BCNU. All patients had prior brain irradiation. Ratios between the maximal tumor FDG uptake and the contralateral white matter FDG uptake, the glucose uptake ratio, were determined. Percent changes in the glucose uptake ratio between the baseline scan and the 24 hour post-treatment scan were of prognostic significance. Patients with the largest percent changes in FDG uptake had the shortest survival. In contrast, neither the baseline glucose uptake ratio nor the visual tumor grade accurately predicted length of survival.

'Eight - Drugs -in -One- Day ' ' Chemotherapy Administered Before and After Radiotherapy to Adult Patients With Malignant Gliomas

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 < 1000/mm3 in 9% of cycles and 1000–2500/mm3 in 25%; thrombocytopenia was < 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.