Diagnostic utility of LUNX mRNA and VEGF mRNA in pleural fluid for differentiating benign from malignant origin.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of lung-specific X protein (LUNX) mRNA and vascular endothelial growth factor mRNA in differentiating pleural effusion of different origin. METHODS: A total of 136 patients with pleural effusion (46 cases of malignant pleural effusion caused by lung cancer, 30 cases of malignant pleural effusion caused by other cancers and 60 cases of benign pleural effusion) were enrolled in this study. Levels of LUNX mRNA and vascular endothelial growth factor mRNA in pleural fluid were detected by real-time quantitative polymerase chain reaction. Pleural fluid carcinoembryonic antigen and Cyfra21-1 were also measured simultaneously. RESULTS: The LUNX mRNA level was significantly higher in malignant pleural effusion caused by lung cancer than in malignant pleural effusion caused by other cancers and in benign pleural effusion. In malignant pleural effusion caused by cancers of different origin, the vascular endothelial growth factor mRNA level was significantly higher than in benign pleural effusion. For the diagnosis of malignant pleural effusion caused by lung cancer, LUNX mRNA exhibited higher sensitivity (80%), when compared with vascular endothelial growth factor mRNA (65%), carcinoembryonic antigen (67%) and Cyfra21-1 (61%), with the same specificity (95%). The combination of LUNX mRNA and cytology achieved a sensitivity of 85%. The combined use of LUNX mRNA and vascular endothelial growth factor mRNA and cytology raised the sensitivity to 89%, with 95% specificity. In initial cytology-negative pleural effusion from lung cancer, LUNX mRNA achieved the highest positive result (65%) among the four markers. CONCLUSIONS: The detection of LUNX mRNA and vascular endothelial growth factor mRNA in pleural fluid may be a complementary tool for the diagnosis of malignant pleural effusion. In particular, pleural fluid LUNX mRNA provided a valuable adjunct in distinguishing malignant pleural effusion caused by lung cancer from benign pleural effusion.

Prognostic factors in elderly patients with advanced non-small cell lung cancer treated with chemotherapy.

OBJECTIVE: The prognosis of advanced non-small cell lung cancer (NSCLC) is poor. The aim of this study was to assess the outcome of chemotherapy for elderly patients with advanced NSCLC, focusing on the prognostic factors influencing survival. METHODS: We reviewed retrospectively the medical records of 109 elderly patients with advanced NSCLC treated with chemotherapy from January 1999 to December 2006. Collected data included demographic information, clinical assessment before therapy, and information on treatment and outcome. Survival was estimated using the Kaplan-Meier method, and prognostic factors were analyzed by the log-rank test and Cox regression model. RESULTS: The median survival time for the entire group was 10.5 (95% confidence interval: 9.15-11.88) months, with 1- and 2-year survival rates of 31.2 and 9.2%, respectively. Univariate analysis showed that performance status (PS; p = 0.013), comorbidity (p = 0.006), chemotherapy cycle (p = 0.006) and second-line therapy (p = 0.002) significantly influenced overall survival. In multivariate analysis, comorbidity, chemotherapy cycles and second-line therapy were identified as independent prognostic factors. CONCLUSIONS: Survival of elderly patients with advanced NSCLC treated with chemotherapy is significantly influenced by the patient's PS, comorbidity, chemotherapy cycle and second-line therapy. These results may help to choose the appropriate treatment in clinical practice.

Survivin mRNA expression in blood as a predictor of the response to EGFR-tyrosine kinase inhibitors and prognosis in patients with non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) mutations have been proven to be a reliable predictive marker for the response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the responses to EGFR-TKIs vary even among patients with EGFR mutation. Recent study showed that survivin overexpression attenuated EGFR-TKI-induced apoptosis and inhibited the antitumor effect of EGFR-TKIs on EGFR mutation NSCLC cells. We investigated the role of survivin mRNA expression in peripheral blood on predicting response and prognosis in NSCLC patients treated with EGFR-TKIs. Survivin mRNA expression levels in blood was detected using quantitative real-time-PCR assay in 62 patients with advanced NSCLC before (D0) and 4 weeks after treatment of EGFR-TKIs (D4w). The associations between survivin mRNA expression in blood and tumor response to treatment, time to progression (TTP), and overall survival (OS) were analyzed. Blood survivin mRNA levels at D0 and D4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. The detections of blood survivin mRNA positivity at D0 and D4w were associated with unfavorable response to EGFR-TKIs treatment and shorter TTP and OS. Multivariate Cox analysis showed that blood survivin mRNA positivity before and 4 weeks after EGFR-TKIs treatment were independent predictor for worse TTP and OS. In conclusion, Blood survivin mRNA positivity was strongly related to a poor treatment outcome of EGFR-TKIs and may be a potential non-invasive biomarker for NSCLC treatment.

Survival and prognostic factors in small cell lung cancer.

The purposes of this study were to evaluate the treatment outcome of patients with small cell lung cancer (SCLC), focusing on the prognostic factors for response to therapy and overall survival. A retrospective analysis was performed on 116 consecutive patients with SCLC diagnosed from January 1997 to December 2005. Collected data included demographic information, pretreatment clinical assessment, treatment regimen, and outcome information. Prognostic factors were analyzed by log-rank test and Cox regression model. Results showed that performance status (PS) 0-1, limited disease, normal serum carcinoembryonic antigen (CEA), and vascular endothelial growth factor (VEGF) level were associated with improved response rate. The univariate analysis showed that sex, disease extent, PS, serum CEA, and VEGF level significantly influenced overall survival. In multivariate analysis, disease extent, PS, serum CEA, and VEGF level were identified as independent prognostic factors. In addition, prophylactic cranial irradiation (PCI) and number of metastatic sites were independent prognostic factors in limited disease and extensive disease, respectively. We concluded that disease extent, PS, serum CEA, and VEGF level are strong predictors of both response and survival. Female sex was a favorable prognostic factor for survival. Moreover, the prognostic factors for limited disease were good PS, normal serum CEA and VEGF level, and PCI, the prognostic factors for extensive disease were good PS, one metastatic site, normal serum CEA, and VEGF level. The identification of prognostic factors may be useful for the better evaluation of treatment outcome in clinical trials and the use of a targeted and specific treatment.