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  • 1
    ISSN: 1573-7373
    Keywords: edema ; enhancement ; glioblastoma multiforme ; MRI scan ; necrosis ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor necrosis, enhancement, and associated edema in patients with glioblastoma multiforme (GBM) represent biological variables that can be quantitated on preoperative MRI scans. We reviewed 48 highly selected patients, all of whom had supratentorial lesions, had undergone gross total tumor resection, and had received adjuvant treatments (radio- and chemotherapies). None of these patients had had surgery for recurrent tumor resection and none had harbored multifocal tumors. The median age was 50 years. The median Karnofsky performance score was 80. Multivariate analysis using the Cox regression model revealed that the strongest prognostic variable was the amount of tumor necrosis on preoperative scan (P 〈 0.001), with median survivals of 42, 24, 15, and 12 months for tumor necrosis grades of 0 (7 ‘pts’), I (11 ‘pts’),11 (9 ‘pts’), and III (21 ‘pts’), respectively. The intensity of enhancement of the tumor nodule was another prognostic factor (P = 0.003), with median survivals of 35, 18, and 13.5 months for enhancement grades of 0 (2 ‘pts’), I (22 ‘pts’), and II (24 ‘pts’), respectively. The extent of peritumoral edema had a quadratic effect (P = 0.001), with grades I (19 ‘pts’), II (22 ‘pts’), and III (7 ‘pts’) surviving for 24,12, and 20 months respectively. Location and volume of tumors were not statistically significant predictors of survival (P 〈 0.05). In conclusion, in this highly selected group, GBM patients with little or no necrosis and with less tumor nodule enhancement on preoperative MRI survive longer than patients with greater amounts of necrosis and greater degrees of tumor enhancement. In addition, a moderate degree of peritumoral edema is associated with worse prognosis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 17 (1999), S. 155-167 
    ISSN: 1573-0646
    Keywords: clinical trial ; dose-finding study ; phase I trial ; phase II trial ; Bayesian inference ; safety monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Most statistical methods for dose-finding in phase I clinical trials determine a maximum tolerable dose based on toxicity while ignoring efficacy. Most phase II designs assume that an acceptable dose has been determined and aim to estimate treatment efficacy, possibly with early stopping rules for safety monitoring. The purpose of this paper is to describe a new statistical strategy for dose-finding in single-arm clinical trials where patient outcome is characterized in terms of both response and toxicity. The strategy, which may be considered a phase I/II hybrid, was first proposed by Thall and Russell [1] and subsequently modified by Thall [2]. The underlying mathematical model expresses the probabilities of response and toxicity as interdependent functions of dose. The method is based on fixed standards for the minimum probability of response and the maximum probability of toxicity appropriate for the particular trial. The best acceptable dose is chosen for each successive patient cohort adaptively, based on the fixed standards and the dose-outcome data from patients treated previously in the trial. The scientific goals are to select one best acceptable dose for future patients and to estimate the response and toxicity probabilities at that dose, or to stop the trial early if it becomes sufficiently unlikely that any dose is both safe and efficacious. An application of the method to a trial of donor lymphocyte infusion as salvage therapy for chemo-refractory AML/MDS patients is described. To illustrate the method's flexibility and potential breadth of application, two additional examples are provided, including a hypothetical trial in which a 5% response rate is of interest.
    Type of Medium: Electronic Resource
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