Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer.

Background The prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing. Methods Tumors from patients (N = 1404) in the PETACC3 adjuvant chemotherapy trial were examined for BRAF and KRAS mutations, microsatellite instability (MSI), chromosome 18q loss of heterozygosity (18qLOH), and SMAD4 expression. Their importance in predicting relapse-free survival (RFS) and overall survival (OS) was assessed by Kaplan-Meier analyses, Cox regression models, and recursive partitioning trees. All statistical tests were two-sided. Results MSI-high status and SMAD4 focal loss of expression were identified as independent prognostic factors with better RFS (hazard ratio [HR] of recurrence = 0.54, 95% CI = 0.37 to 0.81, P = .003) and OS (HR of death = 0.43, 95% CI = 0.27 to 0.70, P = .001) for MSI-high status and worse RFS (HR = 1.47, 95% CI = 1.19 to 1.81, P < .001) and OS (HR = 1.58, 95% CI = 1.23 to 2.01, P < .001) for SMAD4 loss. 18qLOH did not have any prognostic value in RFS or OS. Recursive partitioning identified refinements of TNM into new clinically interesting prognostic subgroups. Notably, T3N1 tumors with MSI-high status and retained SMAD4 expression had outcomes similar to stage II disease. Conclusions Concomitant assessment of molecular and clinical markers in multivariable analysis is essential to confirm or refute their independent prognostic value. Including molecular markers with independent prognostic value might allow more accurate prediction of prognosis than TNM staging alone.

MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.

PURPOSE: O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). PATIENTS AND METHODS: In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. RESULTS: In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. CONCLUSION: In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.

Iowa Leading Indicators Index Report, July 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, August 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, September 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, October 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, November 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, December 2006

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, January 2007

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, February 2007

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, March 2007

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, April 2007

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.

Iowa Leading Indicators Index Report, May 2007

The Iowa Leading Indicators Index (ILII) is a tool for monitoring the future direction of the Iowa economy and State revenues. Its eight components include an agricultural futures price index, an Iowa stock market index, average weekly manufacturing hours in Iowa, initial unemployment claims in Iowa, an Iowa new orders index, diesel fuel consumption in Iowa, residential building permits in Iowa, and the national yield spread.