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Improved prediction of recurrence after curative resection of colon carcinoma using tree-based risk stratification.

BACKGROUND: Patients who are at high risk of recurrence after undergoing curative (R0) resection for colon carcinoma may benefit most from adjuvant treatment and from intensive follow-up for early detection and treatment of recurrence. However, in light of new clinical evidence, there is a need for continuous improvement in the calculation of the risk of recurrence. METHODS: Six hundred forty-one patients with R0-resected colon carcinoma who underwent surgery between January 1, 1984 and December 31, 1996 were recruited from the Erlangen Registry of Colorectal Carcinoma. The study end point was time until first locoregional or distant recurrence. The factors analyzed were: age, gender, site in colon, International Union Against Cancer (UICC) pathologic tumor classification (pT), UICC pathologic lymph node classification, histologic tumor type, malignancy grade, lymphatic invasion, venous invasion, number of examined lymph nodes, number of lymph node metastases, emergency presentation, intraoperative tumor cell spillage, surgeon, and time period. The resulting prognostic tree was evaluated by means of an independent sample using a measure of predictive accuracy based on the Brier score for censored data. Predictive accuracy was compared with several proposed stage groupings. RESULTS: The prognostic tree contained the following variables: pT, the number of lymph node metastases, venous invasion, and emergency presentation. Predictive accuracy based on the validation sample was 0.230 (95% confidence interval [95% CI], 0.227-0.233) for the prognostic tree and 0.212 (95% CI, 0.209-0.215) for the UICC TNM sixth edition stage grouping. CONCLUSIONS: The prognostic tree showed superior predictive accuracy when it was validated using an independent sample. It is interpreted easily and may be applied under clinical circumstances. Provided that their classification system can be validated successfully in other centers, the authors propose using the prognostic tree as a starting point for studies of adjuvant treatment and follow-up strategies.

Adenocarcinoma↗

Prognostic stratification of patients with anaplastic gliomas according to genetic profile.

BACKGROUND: There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival. METHODS: The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression. RESULTS: The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas. CONCLUSIONS: The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.

Adult↗

Characterization of genotype-phenotype relationships and stratification by the CARD15 variant genotype for inflammatory bowel disease susceptibility loci using multiple short tandem repeat genetic markers.

The classification of ulcerative colitis (UC), Crohn disease (CD), and indeterminate colitis (IC) as forms of inflammatory bowel disease (IBD) is based on clinical, radiological, and histological criteria. The genetic basis of IBD is well founded, and susceptibility loci have been identified on several different chromosomes. We aimed to define genotype-phenotype relationships and interactions with the IBD susceptibility gene CARD15for various IBD susceptibility loci (IBD1, IBD2, IBD5, IBD6, IBD7, and chromosome 4) by characterizing previously described peak LOD score short tandem repeat (STR) markers. The study population consisted of 484 severely affected Caucasian patients with IBD, 144 healthy controls, and 348 nonaffected first-degree relatives of IBD patients. Associations were defined with the use of population- and family-based methodology. Correction for multiple testing was performed with a method based on an experimental false discovery rate. We provide novel evidence to show that IBD2 is involved in susceptibility to IC and terminal ileal CD in this population, with overrepresentation of IBD2 STR D12S83 (GenBank Z16592.1) allele 7 (g.49_60del[CA](6)) in IC (q = 0.038, P = 0.014) and underrepresentation of allele 8 (g.51_60del[CA](5)) in terminal ileal CD (q = 0.038, P = 0.016). The association of IBD2 with IC was confirmed by family-based testing. We also provide novel evidence to show that IBD5 is involved in susceptibility to IC and colonic/ileocolonic CD in this population, with overrepresentation of IBD5 STR D5S1984 (GenBank Z52623.1) allele 5 (g.183_186del[CA](2)) in both IC (q = 0.040, P = 0.005) and colonic/ileocolonic CD (q = 0.040, P = 0.004). Evidence is also given for potential interactions between CARD15and IBD2/IBD5. Other findings include an association of IBD2 with UC, and an association of IBD1 with terminal ileal and colonic/ileocolonic CD.

Adult↗

Risk stratification and targeted antifungal prophylaxis for prevention of aspergillosis and other invasive mold infections after liver transplantation.

Antifungal prophylaxis has been proposed for liver transplant recipients at increased risk for invasive mold infection. Risk factors for invasive mold infection after liver transplantation were selected to divide recipients into 3 groups: (1) high risk-transplantation on hemodialysis or delay of hospital discharge beyond day 7 after transplantation because of allograft or renal insufficiency; (2) intermediate risk-retransplantation or transplantation for fulminant hepatic failure; (3) low risk-absence of conditions in groups 1 and 2. During an intervention period (February 1999-April 2001), prophylactic administration of a lipid complex of amphotericin (Abelcet) at 5 mg/kg intravenously every 24 to 48 hours was recommended for high-risk recipients. The frequency of mold infection was compared to that of a preintervention period (February 1998-January 1999) when antifungal prophylaxis was not provided. During the intervention period, invasive mold infection developed in 2 (6%) of 35 high-risk recipients, 0 of 28 intermediate-risk recipients, and 1 (0.5%) of 187 low-risk recipients. Overall, of 58 liver transplant recipients, 3 (5%) developed an invasive mold infection during the preintervention period, compared with 3 (1%) of 250 during the intervention period (P = 0.08). The only death from invasive mold infection occurred during the preintervention period. Rates of pulse corticosteroid treatment of rejection and cytomegalovirus infection were lower during the intervention period. In conclusion, readily identifiable patient characteristics can be used to stratify liver transplant recipients for risk of invasive mold infection. Antifungal prophylaxis given to high-risk recipients may provide cost-effective prevention of these infections.

Amphotericin B↗

Development of delta(15)N stratification of NO(3)(-) in soil profiles.

New evidence, obtained using a robust method for measuring the delta(15)N of NO(3)(-)-N in soil, is consistent with denitrification being the major determinant in the vertical distribution of NO(3)(-)-delta(15)N in soil profiles. These data also suggest that varying moisture regimes result in different effects of soil NO(3)(-)-N leaching on residual whole soil delta(15)N.

Air↗

The utility of prior information and stratification for parameter estimation with two screening tests but no gold standard.

When a gold standard screening or diagnostic test is not routinely available, it is common to apply two different imperfect tests to subjects from a study population. There is a considerable literature on estimating relevant parameters from the resultant data. In the situation that test sensitivities and specificities are unknown, several inferential strategies have been proposed. One suggestion is to use rough knowledge about the unknown test characteristics as prior information in a Bayesian analysis. Another suggestion is to obtain the statistical advantage of an identified model by splitting the population into two strata with differing disease prevalences. There is some division of opinion in the epidemiological literature on the relative merits of these two approaches. This article aims to shed light on the issue, by applying some recently developed theory on the performance of Bayesian inference in non-identified statistical models.

Bayes Theorem↗

Study duration for group sequential clinical trials with censored survival data adjusting for stratification.

The study duration in a clinical trial with censored survival data is the sum of the accrual duration, which determines the sample size in a traditional sense, and the follow-up duration, which more or less controls the number of events to be observed. We propose a design procedure for determining the study duration or for calculating the power in a group sequential clinical trial with censored survival data and possibly unequal patient allocation between treatments, adjusting for stratified randomization. The group sequential method is based on the use function approach. We describe a clinical trial recently activated by the Eastern Cooperative Oncology Group for an illustration of the proposed procedure.

Carcinoma, Non-Small-Cell Lung↗

Guidelines for the stratification of patients recruited to trials of therapy for low-risk gestational trophoblastic tumor.

OBJECTIVE: The aim of the study was to initiate a search for factors which might independently predict the need for salvage therapy in patients with low-risk gestational trophoblastic tumor. METHODS: The independent effect of six factors on the need for salvage chemotherapy was assessed in patients with low-risk gestational trophoblastic tumor who were treated with low-dose methotrexate and folinic acid. The accuracies of World Health Organization and Charing Cross Hospital scores were also compared. RESULTS: Age, pretreatment beta hCG, antecedent pregnancy-treatment interval, and the presence of chest metastases detected on chest X ray were not significantly predictive. The size of tumor (P = 0.001) and the presence of chest metastases on chest computerized tomography (P = 0. 00028) had independent, statistically significant predictive power, and a simple prognostic index was derived from these variables. The World Health Organization score was found to be significantly better than the Charing Cross Hospital score. The accuracy of the simple prognostic index was slightly greater than that of the World Health Organization score, although this was not statistically significant. CONCLUSIONS: These results confirm that patients entered into studies of different therapies for low-risk gestational trophoblastic tumor should be stratified and that a simple score, derived from the results of tumor size and chest computerized tomography, is potentially as good as the World Health Organization score for predicting the need for salvage therapy.

Adolescent↗

Risk stratification of coronary heart disease in Greece: final results from the CARDIO2000 Epidemiological Study.

BACKGROUND: In past years several risk factors have been associated with the incidence of coronary heart disease. The aim of this study was to investigate the associations between the risk of developing acute coronary syndromes and several risk factors in Greece. METHODS: During 2000-2002, 700 male (59 +/- 10 years old) and 148 female (65 +/- 9 years old) patients with the first event of an acute coronary syndrome were randomly selected from cardiological clinics of all Greek regions. Afterward, 1,078 population-based controls were randomly selected from the same hospitals and matched to the patients by sex and age. Detailed information regarding their medical and psychosocial status and various lifestyle habits related to coronary risk was recorded. RESULTS: The frequency ratio between males and females in the case series of patients was 4:1. The statistical analysis showed that smoking (odds ratio = 1.61, P < 0.001), hypertension (odds ratio = 1.99, P < 0.001), hypercholesterolemia (odds ratio = 3.53, P < 0.001), diabetes mellitus (odds ratio = 2.44, P < 0.01), family history of CHD (odds ratio = 3.19, P < 0.001), exposure to passive cigarette smoking (odds ratio = 1.54, P < 0.01), and depressive episodes (odds ratio = 1.35, P < 0.01) were associated with an increased coronary risk, while physical activity (odds ratio = 0.81, P = 0.01), adoption of Mediterranean diet (odds ratio = 0.80, P < 0.05), and high education (odds ratio = 0.81, P < 0.001) were associated with a significant reduction of the coronary risk. Also, a J-shape association was found between alcohol intake and coronary risk. CONCLUSION: Several emerging lifestyle risk factors (education, depression, diet, passive smoking), in addition to the conventional ones, may contribute to the risk of coronary events in this population.

Aged↗

Polymerase chain reaction-assisted papillomavirus detection in cervicovaginal smears: stratification by clinical risk and cytology reports.

Seven hundred and twelve patients from cancer screening, pregnancy care, outpatient clinics for patients at risk for cervical dysplasia and human immunodeficiency virus (HIV) infection were tested simultaneously for cytological aberrations and human papillomavirus (HPV). Classification of these cases, and of all cytology records throughout 1991 and 1992 was performed according to the "Münchner Nomenklatur" and the Bethesda classification. HPV-directed polymerase chain reaction analysis was carried out with general primers, patients at risk for cervical dysplasia were tested by subsequent hybridization with HPV 16 and 18 probes. Patients from cancer screening and pregnancy care showed similar HPV prevalences ranging between 19.4%-24.6%. In contrast, patients from dysplasia and HIV units were infected in 56.2%-62.3% and 75.0%-76.9% respectively in centre of disease control stage III-IV, HPV detection rates in patients from dysplasia and HIV units increased gradually from 40.1%-52.9% in non-suspicious smears to 80.8%-100% in atypical smears. High risk HPV 16 and 18 infections were detected in 64% of smears with cytological evidence of HPV infection (koilocytosis) to 84.2% in severe dysplasia. Following the Bethesda guidelines, 2.9%-14.7% of all smears initially reported as Pap 2 K (suggestive of HPV infection) would be qualified as risk lesions (low grade squamous intraepithelial lesions), although they tested HPV negative in more than a third of cases. Thus, when using the Bethesda system, HPV analysis is needed to prevent overclassification and overtreatment. The "Münchner Nomenklatur" avoids this dilemma by not mixing morphological statements on infection, atypia and cancer risk.

Adult↗