Postoperative survival of lung cancer patients: are there predictors beyond TNM?

BACKGROUND/AIM: We report on survival data of 595 patients with stage I-III lung cancer with respect to TNM classification. MATERIALS AND METHODS: We constructed a basic model consisting of stage and grade, and assessed the improvement of survival prediction after adding comorbidity data, spirometric data, clinical and laboratory parameters. RESULTS: Body mass index (BMI) and presence of a cardiac disease reached statistical significance for prediction of overall survival in a Cox regression model. In addition to BMI (<25 kg/m(2)) and the presence of cardiovascular disease, the spirometric variable (FEV1) predicted early death (less than five months postoperatively). When the survival random forest method was employed to predict disease outcome, creatinine levels and VO2 max became additional variables of interest for predicting survival. CONCLUSION: We propose that our lung cancer database may help to identify variables (aside from histomorphological variables) that are suitable for identifying patients at risk of death after surgical treatment of lung cancer.

Seizure 6-like (SEZ6L) gene and risk for lung cancer.

DNA pooling in combination with high-throughput sequencing was done as a part of the Sequenom-Genefinder project. In the pilot study, we tested 83,715 single nucleotide polymorphisms (SNP), located primarily in gene-based regions, to identify polymorphic susceptibility variants for lung cancer. For this pilot study, 369 male cases and 287 controls of both sexes (white Europeans of Southern German origin) were analyzed. The study identified a candidate region in 22q12.2 that contained numerous SNPs showing significant case-control differences and that coincides with a region that was shown previously to be frequently deleted in lung cancer cell lines. The candidate region overlies the seizure 6-like (SEZ6L) gene. The pilot study identified a polymorphic Met430Ile substitution in the SEZ6L gene (SNP rs663048) as the top candidate for a variant modulating risk of lung cancer. Two replication studies were conducted to assess the association of SNP rs663048 with lung cancer risk. The M. D. Anderson Cancer Center study included 289 cases and 291 controls matched for gender, age, and smoking status. The Liverpool Lung Project (a United Kingdom study) included 248 cases and 233 controls. Both replication studies showed an association of the rs663048 with lung cancer risk. The homozygotes for the variant allele had more than a 3-fold risk compared with the wild-type homozygotes [combined odds ratio (OR), 3.32; 95% confidence interval (95% CI), 1.81-7.21]. Heterozygotes also had a significantly elevated risk of lung cancer from the combined replication studies with an OR of 1.15 (95% CI, 1.04-1.59). The effect remained significant after adjusting for age, gender, and pack-years of tobacco smoke. We also compared expression of SEZ6L in normal human bronchial epithelial cells (n = 7), non-small cell lung cancer (NSCLC; n = 52), and small cell lung cancer (SCLC; n = 22) cell lines by using Affymetrix HG-U133A and HG-U133B GeneChips. We found that the average expression level of SEZ6L in NSCLC cell lines was almost two times higher and in SCLC cell lines more than six times higher when compared with normal lung epithelial cell lines. Using the National Center for Biotechnology Information Gene Expression Omnibus database, we found a approximately 2-fold elevated and statistically significant (P = 0.004) level of SEZ6L expression in tumor samples compared with normal lung tissues. In conclusion, the results of these studies representing 906 cases compared with 811 controls indicate a role of the SEZ6L Met430Ile polymorphic variant in increasing lung cancer risk.

[National Disease Management Guideline for Asthma: recommendations and evidence for "asthma prevention" issues]. / Nationale VersorgungsLeitlinie Asthma: Empfehlungen und Evidenz zum Thema "Asthma-Prävention".

The National Disease Management Program (NDM Program) represents the basic content of structured, cross-sectoral healthcare. In particular, the NDM Program is directed towards coordinating different disciplines and areas of healthcare. The recommendations are developed through interdisciplinary consensus of the scientific medical societies on the basis of the best available evidence. Within this scope the scientific medical societies concerned with the prevention, diagnosis, therapy and rehabilitation of asthma consented upon a National Disease Management Guideline for Asthma in 2005. Among other things, the following cornerstones of asthma prevention were agreed upon: Breastfeeding and non-smoking were suggested as primary prevention measures for (expectant) parents. With respect to secondary prevention, recommendations have been made for allergen avoidance, active/passive smoking and immunotherapy. Regarding tertiary prevention, position statements on vaccination and specific immunotherapy are developed. The present paper presents both the original texts of the recommendations and the evidence underlying them.

Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.

PURPOSE: Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample. PATIENTS AND METHODS: A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancer patients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls. RESULTS: Patients with genotypes GG or CG for the rs1862214 single nucleotide polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared with those with the common genotype CC showed an increased risk of lung cancer (odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship (HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. CONCLUSION: These results suggest that the rs1862214 polymorphism in PDCD5 is predictive for lung cancer risk and prognosis, and that PDCD5 may represent a novel tumor suppressor gene influencing lung cancer.

Solitary pulmonary nodules: dynamic contrast-enhanced MR imaging--perfusion differences in malignant and benign lesions.

PURPOSE: To determine whether dynamic contrast material-enhanced magnetic resonance (MR) imaging with use of kinetic and morphologic parameters reveals statistically significant differences between malignant and benign solitary pulmonary nodules. MATERIALS AND METHODS: Fifty-eight patients met the inclusion criteria of a solitary 5-40-mm pulmonary nodule without calcification or fat at computed tomography. Fifty-one patients were examined successfully; 46 received a histologic diagnosis, and five received a diagnosis by means of observation over 2 years. Dynamic MR images were acquired every 10 seconds for a total of 4 minutes. Diagnostic characteristics for differentiation were examined by using threshold values for maximum peak enhancement, slope of enhancement, and washout. Receiver operating characteristic curves were calculated to test the usefulness of these parameters. The diagnostic performance of a combination of curve profiles and morphologic contrast material distribution were tested by using a decision tree. RESULTS: Frequency of malignancy was 53% (27 of 51 nodules). Malignant nodules showed stronger enhancement with a higher maximum peak and a faster slope (P <.001). Significant washout (>0.1% increase in signal intensity per second) was found only in malignant lesions (14 of 27 lesions). Sensitivity, specificity, and accuracy were 96%, 88%, and 92%, respectively, for maximum peak; 96%, 75%, and 86% for slope; and 52%, 100%, and 75% for washout. When curve profiles and morphologic enhancement patterns were combined, sensitivity increased to 100%. CONCLUSION: Dynamic MR imaging delineates significant kinetic and morphologic differences in vascularity and perfusion between malignant and benign solitary pulmonary nodules. Washout seems to be highly specific for malignancy.