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Biomedical subjects

E C Halperin

Publications and source records attributed to E C Halperin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Randomized comparison of diaziquone and carmustine in the treatment of adults with anaplastic glioma.

PURPOSE: We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZQ with that of BCNU, the standard agent for brain tumor chemotherapy. PATIENTS AND METHODS: Randomization between the two regimens occurred 8 weeks after completion of radiotherapy. A total of 251 patients were randomized to receive either AZQ or BCNU, and there were no significant differences between the two treatment arms in any of the known prognostic variables, including age, histologic grade, and Karnofsky performance status (KPS). RESULTS: There was no significant difference in either time to tumor progression or survival between the two treatment arms. Age and histology were strong predictors of outcome, whereas KPS had relatively less effect. Three groups of patients with distinctly different outcomes could be identified: (1) older age (45+) and glioblastoma/gliosarcoma (GBM/GS) patients had a median survival of 37 weeks after randomization; (2) patients with either older age or GBM/GS had a median survival of 61 weeks; and (3) younger age (< 45) and non-GBM/GS (usually anaplastic astrocytoma) patients had a median survival of 147 weeks. Toxicity was primarily hematologic, although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU. Patients randomized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction (P = .011 and .016, respectively). CONCLUSION: There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study, although AZQ was somewhat better tolerated.

Adult↗
PubMed1993

Efficacy and toxicity of 9-beta-D-arabinofuranosylguanine (araG) as an agent to purge malignant T cells from murine bone marrow: application to an in vivo T-leukemia model.

9-beta-D-Arabinofuranosylguanine (araG), an analog of deoxyguanosine which is not degraded by purine nucleoside phosphorylase, has been previously shown in in vitro studies by our laboratory to be effective in purging malignant T cells from human bone marrow (1). We now describe studies in a murine model of T-cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow, contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T-cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100% mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. 100% of non-leukemia bearing lethally irradiated C3H/HeN mice transplanted with syngeneic bone marrow, treated ex vivo with 100 microM of araG for 18 hours, survived > 365 days post-transplant with full lymphohematopoietic reconstitution. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow derived hematopoietic progenitor cells was documented in experiments in which 75% of lethally irradiated mice transplanted with syngeneic bone marrow, contaminated with 6C3HED tumor cells and treated ex vivo with 100 microM araG for 18 hours, survived for > 250 to > 400 days. Death in 25% of mice was secondary to infection which developed before marrow reconstitution occurred. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T-cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T-cell depletion as a strategy to prevent graft-versus-host disease.

Animals↗
PubMed1992

Successful therapy for trilateral retinoblastoma.

Trilateral retinoblastoma, the intracranial malignancy associated with bilateral retinoblastoma, is an uncommon and clinically aggressive malignancy with a uniformly fatal outcome. Three children with newly diagnosed trilateral retinoblastoma were treated with systemic (cyclophosphamide and vincristine) and intrathecal (methotrexate, hydrocortisone, and cytarabine) chemotherapy, as well as craniospinal irradiation (one patient) in addition to therapy of the eye lesions. All three patients have had partial or complete response of the pineal tumors to chemotherapy, with no active disease eight or more years, 33 or more months, and 12 or more months, respectively, after diagnosis of the lesions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Syndrome of inappropriate secretion of antidiuretic hormone in a patient with carcinoma of the nasopharynx.

A patient with a primary undifferentiated carcinoma of the nasopharynx manifested the clinical syndrome of inappropriate antidiuretic hormone secretion (SIADH). Immunohistochemical techniques demonstrated the presence of vasopressin, neurophysin, and their precursor (propressophysin) in the cancer cells. In situ hybridization additionally confirmed the expression of propressophysin messenger RNA in these cells. To the knowledge of the authors, this represents not only the first case of SIADH caused by carcinoma of the nasopharynx, but also the first report of pathologic confirmation of the syndrome with the use of both molecular and immunologic probes.

Arginine Vasopressin↗
PubMed1992

Interspecies cytogenetic comparisons: studies with X-radiation and bleomycin sulfate.

A series of in vitro experiments were conducted to determine if there are innate differences in the sensitivity of peripheral blood lymphocytes (PBLs) from different mammalian species to clastogens. Mouse, rat, and human whole blood samples were exposed to either 0, 0.38, 0.75, 1.5, or 3.0 Gy x-radiation or 0, 5, 10, 20, 40, or 80 micrograms/ml bleomycin for 4 hr. Bromodeoxyuridine-containing cultures were initiated and the PBLs stimulated to divide with phytohemagglutinin. All cultures were harvested following a 3-hr colcemid treatment. Slides were made and differentially stained, and first-division metaphases were scored for chromosome aberrations. In the x-radiation studies human PBLs were significantly more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs as measured by either the total percent aberrant cells or the number of dicentrics. Data from all three species could be fitted to a linear-quadratic model. Results with bleomycin suggest that the mouse and human PBLs are equally sensitive to the clastogenic effects of bleomycin. Both appeared to be more sensitive than the rat PBLs, but the variation between experiments was such that the results among species were not significantly different. These results indicate that there may be inherent differences in sensitivity among PBLs of mammalian species; however, more studies are needed to determine if the differences presented here hold for other agents.

Animals↗
PubMed1992

Endobronchial interstitial Au-198 implantation in the treatment of recurrent bronchogenic carcinoma.

Nineteen patients with non-small-cell bronchogenic carcinoma, recurrent following initial conventional external beam radiotherapy, were treated with endobronchial implantation of Au-198 seeds. Seventeen patients were symptomatic with primary symptoms of persistent hemoptysis (9), bronchial obstruction (2), or worsening dyspnea (6). Two patients were asymptomatic and implanted for bronchoscopic evidence of tumor recurrence. The dose delivered was described by three dosimetric parameters: 1) the total activity implanted (m Ci); 2) the midbronchial dose point; and 3) the volume of tissue that received greater than 20 Gy. Response was determined based on a system reflecting the primary indication for the implant. Seven of nine (78%) presenting with hemoptysis, four of six (67%) with increasing dyspnea, and one of two with bronchial obstruction responded. The overall median survival was 5.25 months (2.5-10 months 95% confidence interval). There was no clear correlation between any of the dosimetric parameters evaluated and a clinical response to therapy. Technical complications related to the inability to penetrate the scirrhous tumor surface adequately often led to less than optimal dose distribution. Endobronchial Au-198 implantation is associated with a poor calculated dose distribution but is, nonetheless, a relatively simple and comparatively inexpensive technique that often produces a clinical response and can be a useful option in the management of patients with recurrent bronchogenic carcinoma.

Adult↗
PubMed1992

Multiple-fraction-per-day external beam radiotherapy for adults with supratentorial malignant gliomas.

The prognosis following therapy for adults with supratentorial malignant gliomas is poor. Standard therapy of 60 Gy of external beam radiotherapy with chemotherapy achieves a median survival time of 35 to 51 weeks following surgery. A variety of innovative therapies have been considered for therapy of malignant gliomas. Multiple-fraction-per-day (MFD) external beam radiotherapy has been evaluated by many investigators. The rationale for MFD teletherapy is based upon exploiting differences in the recovery capacity for radiation damage between slowly and rapidly proliferating tissues and/or shortening the overall treatment time. A large number of clinical trials have, for the most part, failed to show any survival benefit from MFD radiotherapy. These trials have utilized b.i.d. and t.i.d. radiotherapy with fraction sizes of 0.89 to 2 Gy to total doses of 30-81.6 Gy. The linear quadratic model of the radiation cell survival curve suggests that a biological effective tumoricidal dose > or = 10% higher than standard daily radiotherapy, with approximately isoeffective normal tissue damage, could be achieved at 1.2 Gy b.i.d. to a total dose of approximately 72 Gy. Trials of low dose per fraction MFD radiotherapy, to total doses less than 72 Gy, would be predicted to be inadequate to the task.

Adult↗
PubMed1992

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Adenocarcinoma↗
PubMed1992

Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment.

Pre- and postoperative computerized tomography scans, simulator films, and computerized tomography scans documenting tumor recurrence were analyzed on 70 patients with supratentorial malignant glioma treated with whole brain plus boost radiation therapy to determine sites of recurrence in relation to the boost. The boost was planned using the postoperative computerized tomography scan. Tumor recurred in 53 patients--within the boost in 38 (72%), partly outside the boost in 12 (23%), outside the boost but within the brain in one (2%), in the boost and in the spinal cord in one (2%), and in the spinal cord only in one (2%). All recurrences confined to the brain were found within 4 cm of the enhancing tumor as defined by the preoperative computerized tomography scan. Recurrences outside the boost were more common with inadequate boost margins, small boost volumes, temporal lobe tumors, and homolateral wedge pair technique. Survival was not adversely affected by recurrence outside the boost. We recommend that patients with malignant glioma be treated by parallel opposed fields with a margin that is 4 cm beyond the edge of the preoperative enhancing tumor, as seen on computerized tomography scan.

Adolescent↗
PubMed1992

The radiation dose-response relationship in a human glioma xenograft and an evaluation of the influence of glutathione depletion by buthionine sulfoximine.

We have used an extensively characterized human glioma cell line in an athymic mouse model to evaluate new therapeutic approaches for human supratentorial high grade gliomas. The tumor, D-54MG, is a subline of a human anaplastic glioma. Eight days after homozygous nu/nu BALB/c athymic mice received intracranial (IC) injections of a tumor homogenate, the whole brain was irradiated with either single fractions of 4, 8, 9, and 12 Gy or twice daily fractions, separated by least 6 hr, of 2.28 Gy x 2 or 7.53 Gy x 2. To evaluate whether or not glutathione depletion influenced animal survival, animals at each dose level received either intraperitoneal (IP) buthionine sulfoximine (BSO) alone or I.P. BSO plus BSO in the drinking water. There was a stepwise prolongation of animal survival with increasing doses of external beam radiation. Mean survival in 9 of the 10 control groups (8-12 animals per group) ranged from 14.1 to 18.8 days. Mean survival ranged from 15.3 to 22.5 days at 4 Gy, 25 to 30 days at 8 Gy, 22.3 to 29.7 days at 9 Gy, and 32.9 to 33.6 days at 12 Gy single dose irradiation. At 2.28 Gy x 2 split dose irradiation mean survival was 29.3 days, for 7.53 Gy x 2 mean survival was over 47 days. The data for single fraction irradiation fit a linear regression line (r = 0.908) of mean animal survival = (1.22 [dose in Gy] + 16.7) days. Tumor GSH levels were decreased with all BSO dosing regimens tested. The most aggressive regimen (I.P. BSO+oral BSO for 5 days), reduced tumor GSH to 6.2% of control. Increased survival in irradiated glutathione depleted mice versus mice receiving radiation alone was not seen.

Animals↗
PubMed1992

Influence of coralline hydroxyapatite used as an ocular implant on the dose distribution of external beam photon radiation therapy.

Coralline hydroxyapatite spheres are used as buried integrated ocular implants after enucleation or evisceration surgery. Because such implants are used after surgery for intraocular malignancy and because some patients may require postoperative radiation therapy for orbital tumor recurrence, the radiation attenuation characteristics of the implant are of interest. The authors evaluated the attenuation and scattering properties of coralline hydroxyapatite implants using a 4 MV photon beam and film dosimetry. Optical density analyses indicate that coralline hydroxyapatite implants have no significant influence on the attenuation or scattering properties of the photon beam. As such, there is no basis for concern that such implants might adversely affect external beam photon irradiation.

Absorptiometry, Photon↗
PubMed1992

Medical oaths.

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Ceremonial Behavior↗
PubMed1992

Multiple authorship in two English-language journals in radiation oncology.

Multiple authorship is the listing of more than one person as author of an article in the scholarly literature. Editors, researchers, and others in science publishing have raised concerns about the increasing number of authors being listed per article, the practice of "honorary authorship" (listing as an author someone who made little or no contribution to the work being reported), and the danger of the dilution of responsibility when many authors are involved. The authors studied multiauthorship in the two most popular English-language journals on radiation oncology, examining 1,908 papers and letters published in the International Journal of Radiation Oncology, Biology, and Physics (IJROBP) and Radiotherapy and Oncology (RO) from 1983 through 1987. There was no increase in the number of authors per article during this period, when the median number for IJROBP was four and that for RO was three. The number of authors varied by type of article, by country (France had the largest median number, six for IJROBP and five for RO), and by the authors' institution. The first author's gender was unrelated to the number of subsequent authors for an article. The proportion of men first authors varied widely between countries and institutions. Possible explanations for these variations include the multidisciplinary nature and complexity of some forms of research, institutional policies concerning the use of authorship as a commodity of exchange, and social-cultural factors.

Authorship↗
PubMed1991

Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495.

Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.

Adolescent↗
PubMed1991

Reversible neurotoxicity following hyperfractionated radiation therapy of brain stem glioma.

Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. 18FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation-related neurotoxicity.

Adolescent↗