Multi-disciplinary approach to cranial base tumors.
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Brain Neoplasms↗
Biomedical subjects
J Horton
Publications and source records attributed to J Horton.
Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.
PURPOSE: The influence of tumor site, size, and extent of surgery on the survival of patients with glioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. METHODS AND MATERIALS: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.
Adult↗
Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.
BACKGROUND: Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma. PURPOSE: This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials. METHODS: We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. RESULTS: The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients. CONCLUSIONS: This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis. IMPLICATIONS: The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials.
Adult↗
The use of antiprotozoan and anthelmintic drugs during pregnancy and contraindications.
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Albendazole↗
Endotoxic shock has differential effects on renal and splanchnic eicosanoid synthesis.
This study examined the differential effects of endotoxin on renal and splanchnic vascular (SV + SI) eicosanoid synthesis. Dogs were anesthetized and subjected to a challenge of 1 mg/kg (i.v.) bolus of B-lipopolysaccharide endotoxin followed by a 3 h infusion of endotoxin at 0.5 mg/kg/h. The kidney and SV + SI were cannulated and perfused in vitro with Krebs buffer. The venous effluent from the kidney and SV + SI were assayed for 6-keto-PGF1a (PGI2), PGE2, Leukotriene B4 (LTB4), LTC4, and thromboxane B2 (TXB2) by enzyme immunoassay. Endotoxin treatment markedly increased splanchnic PGI2 release (splanchnic vasodilator) two fold and decreased release of all other measured eicosanoids. Endotoxin treatment markedly increased renal PGE2 (renal vasodilator) but did not significantly increase PGI2. These data showed that endotoxin treatment stimulated both the splanchnic vascular bed and kidney to increase synthesis and release of their major endogenous vasodilator eicosanoids.
Animals↗
Albendazole in human loiasis: results of a double-blind, placebo-controlled trial.
To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia.
Adolescent↗
Partnership programs in Poland.
Sponsored by the U.S. Agency for International Development (AID), Albany Medical College and the Marie Skłodowska-Curie Memorial Cancer Center and Institute of Oncology formed a Partnership in 1992 aimed at enhancing cancer control and care in Poland by providing technical assistance and education to foster existing programs and develop new oncologic programs. The initial focus of the partnership is on breast cancer. Three demonstration screening/early disease programs are being developed, as well as a clinical and clinical research program and a Polish Breast Cancer Trials Group. A program to foster accreditation of oncologic facilities and programs throughout Poland is being considered.
Breast Neoplasms↗
Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand.
The antimalarial efficacy of halofantrine was compared with mefloquine in an open-label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%).
Adolescent↗
Improvement in autonomic function following pancreas-kidney versus kidney-alone transplantation.
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Adult↗
Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells.
A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is approximately 4000-fold resistant to mitoxantrone was isolated by serial passage of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing concentrations of drug. MCF/MX cells were also approximately 10-fold cross-resistant to doxorubicin and etoposide but were not cross-resistant to vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This decrease in intracellular drug accumulation into MCF/MX cells was associated with enhanced drug efflux, which was reversed when cells were incubated in the presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent process. Incubation of MCF/MX cells with verapamil did not affect either the accumulation of mitoxantrone or the level of resistance in these cells. Furthermore, RNase protection and Western blot analyses failed to detect the expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be associated with the development of multidrug resistance in vitro. However, a polyclonal antibody directed against a synthetic peptide corresponding to the putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and 85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT. Functional assays and Western blot analysis for topoisomerase II revealed no differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus, resistance in this cell line is apparently associated with enhanced drug efflux involving a pathway distinct from the mdr1-encoded multidrug transporter P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
More luck than judgement.
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Cost-Benefit Analysis↗
Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials.
103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.
Adult↗
A comparison of scaphoid-trapezium-trapezoid fusion and four-bone tendon weave for scapholunate dissociation.
The contact characteristics of the radiocarpal joint (area, pressure, and ratios of scapholunate area, pressure and force transmitted) were determined with the use of pressure-sensitive film in seven normal wrists after ligament sectioning to create scapholunate instability, with reconstruction involving a scaphoid-trapezium-trapezoid fusion, and with reconstruction involving a four-bone tendon weave procedure. The results demonstrated that the scaphoid-trapezium-trapezoid fusion significantly altered the contact characteristics of the wrist, transferring load, pressure, and area to the radioscaphoid joint, thereby unloading the lunate. In contrast, the tendon weave reconstruction produced characteristics similar to those of the normal joint.
Arthrodesis↗
Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group.
A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
Altretamine↗
Racial differences in cardiovascular disease mortality and risk factors.
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Adult↗
Long-term survival in treated anaplastic astrocytomas. A report of combined RTOG/ECOG studies.
This report evaluates the long-term survival of patients with histologically confirmed anaplastic astrocytoma on several combined RTOG (Radiation Therapy Oncology Group) studies. Included in this analysis are the following studies: RTOG/ECOG (Eastern Cooperative Oncology Group) 74-01, RTOG 76-11, and RTOG 79-18, with the various treatment arms separated into radiation therapy (RT) only (47 patients) radiation therapy and chemotherapy (Chemo) (78 patients) and radiation therapy, chemotherapy, and misonidazole (Mizo) (24 patients). Pretreatment characteristics of age, prior surgery, performance status, and neurological function classification are identified. Median survival for patients treated with RT only is 3.0 years. Median survival for patients treated with RT + Chemo is 2.3 years, and for patients treated with RT + Chemo/Miso is 1.2 years. Five-year survival rates are 35% for patients treated with RT only, 29% for patients treated with RT + Chemo, and 24% for patients treated with RT + Chemo/Miso. Age and performance status have been identified in previous studies as important prognostic variables and are confirmed in this analysis. Patients treated with misonidazole had a significantly worse prognosis after adjustment for differences in prognostic factors. Addition of chemotherapy did not improve survival except in less favorable prognostic categories. In general, more aggressive treatment regimens are associated with decreased survival compared to conventional postoperative irradiation.
Adolescent↗
Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.
Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.
Ambulatory Care↗
Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma.
From November 1979 to July 1986, 52 patients (27 women and 25 men; median age 52 years) with advanced adrenocortical carcinoma entered a prospective, nonrandomized study evaluating moderate-dose mitotane and doxorubicin hydrochloride (Adriamycin). Thirty-two tumors (62%) were well differentiated and evidence of hormone production was present in 24 patients (46%). Patients with well-differentiated or functional tumors received mitotane, 6 gm daily; patients for whom mitotane failed or those with poorly differentiated, non-hormone-producing tumors received Adriamycin, 60 mg/m2 every 3 weeks. Initially, 36 patients were treated with mitotane and 16 patients with Adriamycin. Eight patients (22%) responded to mitotane and three (19%) responded to Adriamycin. No response was noted in the 15 patients for whom mitotane failed and who then received Adriamycin. Severe toxicity occurred in 36% of patients who received mitotane and in 26% who received Adriamycin. Overall median survival after onset of treatment was 14 months. We conclude that mitotane or Adriamycin used initially can induce tumor regression in about 22% and 19% of selected patients, respectively. However, Adriamycin is ineffective as second-line chemotherapy for patients with well-differentiated or functioning tumors for whom mitotane is ineffective.
Adrenal Cortex Neoplasms↗