Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy.
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Adult↗
Biomedical subjects
E L Korn
Publications and source records attributed to E L Korn.
Quality-of-life assessment in cancer treatment protocols: research issues in protocol development.
BACKGROUND: Interest in incorporating quality of life as an end point in clinical studies of cancer treatment has intensified in recent years. PURPOSE: We provide practical suggestions that will assist investigators considering including quality-of-life assessment in phase III therapeutic trials. METHODS: We discuss issues important in study planning, including quality-of-life definition, priority studies for quality-of-life assessment, eligibility requirements, and design. CONCLUSIONS: Many of the problems that quality-of-life studies have encountered, from protocol approval to data analysis, could be addressed and alleviated during protocol development. This discussion is intended to assist and stimulate investigators conducting research in this area.
Clinical Protocols↗
Phase II trial design considerations for small-cell lung cancer.
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Age Factors↗
Applications of crude incidence curves.
Crude incidence curves display the cumulative number of failures of interest as a function of time. With competing causes of failure, they are distinct from cause-specific incidence curves that treat secondary types of failures as censored observations. After briefly reviewing their definition and estimation, we present five applications of crude incidence curves to show their utility in a broad range of studies. In some of these applications it is helpful to model survival-time distributions with use of two different time metameters, for example, time from diagnosis and age of the patient. We describe how one can incorporate published vital statistics into the models when secondary types of failure correspond to common causes of death.
Antineoplastic Agents↗
Selecting dose-intense drug combinations: metastatic breast cancer.
A mathematical model previously described is applied to the problem of selecting drug combinations for metastatic breast cancer. The model accounts for the differing single-agent activities of the drugs as well as their differing profiles of toxicity. With no bone marrow protection, combinations with cisplatin offer a small improvement in total equivalent dose over therapy with the more active single-agents. Restricting consideration to the four most commonly used agents, single-agent doxorubicin has the greatest equivalent dose. With protection for leukopenia or willingness to accept a higher incidence of severe leukopenia, a combination with large doses of cyclophosphamide, doxorubicin, and fluorouracil, and a small dose of cisplatin has greatest equivalent dose. The doublets cyclophosphamide/fluorouracil or fluorouracil/cisplatin at higher doses are almost as good. With protection for leukopenia and thrombocytopenia, a cyclophosphamide/thiotepa combination at very high doses maximizes total equivalent dose. This approach can be used to identify regimens worthy of prospective evaluation.
Alkaloids↗
Mandibular remodeling measured on cephalograms. 1. Osseous changes relative to superimposition on metallic implants.
We report the results of a study aimed at quantifying remodeling of mandibular surfaces in a sample of growing children who represent those usually treated by orthodontists in the mixed and early adult dentition. The sample, 31 patients with metallic implants of the Björk-type, was monitored at annual intervals between 8 1/2 and 15 1/2 years of age. (Maxillary remodeling changes for the sample have been reported earlier.) The present article reports findings concerning changes at condyle, gonion, menton, pogonion, and point B as identified on lateral cephalograms. Data are reported in the Frankfort plane frame of reference with the cephalograms from different time points superimposed on the metallic implants. Mean displacement at condyle was larger than that at any other landmark and was similar in magnitude and direction to the observations of Björk when the difference in orientation of the vertical axis in the two studies is taken into account. The mean displacement of gonion was in an upward and backward direction at an angle of approximately 45 degrees to the Frankfort plane. Mean displacements at menton and pogonion were in a downward and backward direction but were very small. Mean displacement at point B was somewhat greater than that of menton and gonion, oriented in an upward and backward direction. Individual variation for most of the parameters measured was sufficiently large to warrant the inference that caution should be used when mean values are applied to the analysis of individual cases.
Adolescent↗
Mandibular remodeling measured on cephalograms: 2. A comparison of information from implant and anatomic best-fit superimpositions.
This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Björk type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between-superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerable, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem.
Adolescent↗
Postnatal width changes in the internal structures of the human mandible: a longitudinal three-dimensional cephalometric study using implants.
This paper presents case-specific quantitative evidence of the systematic lateral displacement of metallic implants in the mandibles of treated and untreated human subjects between the ages of 8.5 and 15.5 years. This evidence appears to be consistent with the inference of small, but systematic increases in distance between the internal structures of the two sides of the osseous mandible during growth. Such a conclusion, however, is inconsistent with traditional beliefs that the internal structures of the mandibular symphysis fuse at the midline during the first post-natal year and remain dimensionally constant thereafter. We recently published evidence of statistically significant transverse displacement of metallic implants in the mandibular body region for 12 of 28 subjects for whom longitudinal data were available. Of the twelve subjects for whom statistically significant changes were observed, widening occurred in eleven cases and narrowing in one. Matching data are now available on concurrent ramus changes for 22 of the same 28 subjects, including 11 of the 12 for whom statistically significant width changes had previously been noted in the body region. In eight of these 11 subjects, statistically significant widening in the ramus region was also observed. No subject had statistically significant widening in the ramus region without also having statistically significant widening in the body region. No subject had statistically significant trans-ramus narrowing.
Adolescent↗
Phase II trials of small-cell lung cancer.
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Carcinoma, Small Cell↗
Building quality of life assessment into cancer treatment studies.
Quality of life is increasingly recognized as an important outcome of cancer treatment. However, quality of life research poses considerable problems in design and implementation. This article provides guidelines for the preparation of phase III therapeutic protocols that include quality of life assessment. The guidelines emphasize the distinct requirements of quality of life research and provide specific recommendations for the questions that need to be addressed in protocol development.
Clinical Trials as Topic↗
Randomised clinical trials with clinician-preferred treatment.
The standard design for randomised clinical trials may be inappropriate when the clinician believes that one of the treatments being tested is superior for the patient, or when the clinician has a preference for one of the treatments. For such instances the suggestion is that the patient is randomly allocated to treatment only when there is clinical disagreement about treatment of choice for that patient, and then the patient is assigned to a clinician who had thought that the regimen allocated is the one most appropriate for that patient.
Clinical Trials as Topic↗
Selecting combinations of chemotherapeutic drugs to maximize dose intensity.
A mathematical model is described for selecting combinations of chemotherapeutic drugs in order to maximize antitumor dose intensity subject to constraints on toxicity to normal organ systems. Determination of which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibilities. The method described here offers one approach to identifying combinations worthy of evaluation in prospective comparative clinical trials.
Antineoplastic Combined Chemotherapy Protocols↗
Epidemiologic studies utilizing surveys: accounting for the sampling design.
BACKGROUND: Since large-scale health surveys usually have complicated sampling schemes, there is often a question as to whether the sampling design must be considered in the analysis of the data. A recent disagreement concerning the analysis of a body iron stores-cancer association found in the first National Health and Nutrition Examination Survey and its follow-up is used to highlight the issues. METHODS: We explain and illustrate the importance of two aspects of the sampling design: clustering and weighting of observations. The body iron stores-cancer data are reanalyzed by utilizing or ignoring various aspects of the sampling design. Simple formulas are given to describe how using the sampling design of a survey in the analysis will affect the conclusions of that analysis. RESULTS: The different analyses of the body iron stores-cancer data lead to very different conclusions. Application of the simple formulas suggests that utilization of the sample clustering in the analysis is appropriate, but that a standard utilization of the sample weights leads to an uninformative analysis. The recommended analysis incorporates the sampling weights in a nonstandard way and the sample clustering in the standard way. CONCLUSIONS: Which particular aspects of the sampling design to use in the analysis of complex survey data and how to use them depend on certain features of the design. We give some guidelines for when to use the sample clustering and sample weights in the analysis.
Epidemiologic Methods↗
Selecting drug combinations based on total equivalent dose (dose intensity)
We describe a mathematical model for selecting cytotoxic drugs and dosages for a combination regimen based on the antitumor activities of the drugs given as single agents and their organ-specific maximum tolerated doses. The regimen defined maximizes an approximate measure of antitumor effect subject to constraints on combined toxicity. This approach does not assume that the underlying dose-response curve is steep; nor does it assume that maximally dose-intense regimens are clinically appropriate in all situations. Whether the identified regimen is superior to standard treatments should be determined by prospective, randomized clinical trials. Determining which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibilities. The method described here offers one approach to identifying combinations worthy of evaluation in prospective trials.
Altretamine↗
Measures of explained variation for survival data.
The predictive power of a set of prognostic variables in a survival time model is a concept distinct from the statistical significance of the variables or the adequacy of the model fit. In this paper we discuss the importance of quantifying the predictive power of a prognostic model, and suggest measures of explained variation as a possible quantification. The important features of our approach are that (1) the measures are completely model-based; (2) a specification of the time range of interest is easily incorporated; and (3) the null models used for comparison are derived as mixtures of the predicted distributions.
Analysis of Variance↗
Projection from previous studies. A caution.
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Bayes Theorem↗
Transverse development of the human jaws between the ages of 8.5 and 15.5 years, studied longitudinally with use of implants.
We report longitudinal data on the transverse widening of the maxilla and mandible from a sample of normal subjects (11 males and 20 females) with metallic implants of the Bjork type. Data were from measurements on lateral and frontal (posterior-anterior) cephalograms generated at annual intervals between the ages of 8.5 and 15.5 years (although data were not available for all subjects at all time points). The maxillary data were, in general, similar to those reported by Bjork and Skieller (1974, 1977) for a smaller sample of slightly younger boys. During the age interval studied, transverse widening was greater in the more posterior part of the palate. [The mean annual rate of change in the posterior-most (zygomatic) region was 0.43 mm, sd = 0.18 mm; p less than 0.001.] Although the rate of palatal widening was not large in absolute terms, widening appeared to continue throughout the age interval under study, and there was no evidence to support the conventionally accepted idea that palatal growth in the transverse dimension tapers off substantially or even ceases during the age interval under observation. Evidence of statistically significant widening of the mandibular arch by means of transverse rotation of the osseous matrix was noted in nine of the 29 subjects for whom three-dimensional mandibular information was available. For these nine subjects, the estimated annual increase in mandibular arch angle ranged from 0.52 degrees to 1.40 degrees. As far as we are aware, this is the first report of mandibular matrix rotation in the transverse direction from a sample of subjects with metallic implants. The finding that spontaneous changes in this dimension are relatively common raises the possibility that classical attitudes concerning the immutability of osseous relationships in the symphyseal region during growth may be inappropriate.
Cephalometry↗
Use of the carbon dioxide laser for removal of lesions adjacent to the punctum.
Neoplasms, small or large, adjacent to the punctum can create a dilemma as to their removal and its repair. Punctal stenosis, total closure, and punctal ectropion are complications that can occur after surgery. Punctal complications can cause epiphora with secondary chronic blepharoconjunctivitis and skin excoriation due to chronic rubbing or wiping off of tears by the patient. This report will discuss carbon dioxide laser excision of neoplasms adjacent to the punctum. This laser approach provides a bloodless field, minimal postoperative pain, and good postoperative appearance without scar formation. Smaller adjacent lesions cause no punctal abnormality. Larger lesions adjacent to the punctum which have already caused ectropion did not worsen the ectropion postoperatively.
Adult↗