A predictive model based on liquid biopsy for non-small cell lung cancer to assess patient's prognosis: Development and application.

BACKGROUND AND OBJECTIVE: Improving ability to predict the prognosis of patients with progressive lung cancer is an important task in the era of precision medicine. Here, a predictive model based on liquid biopsy for non-small cell lung cancer (NSCLC) was established to improve prognosis prediction in patients with progressive NSCLC. METHODS: Clinical data and blood samples of 500 eligible patients were collected and screened from the electronic case database and blood sample center of Hwa Mei Hospital, University of Chinese Academy of Sciences and Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences. Patients were randomly assigned to training set (300 cases) and validation set (200 cases) in a ratio of 3:2 by random number method. Baseline levels of the two datasets were compared. Progression-free survival (PFS) analysis was performed on the training set using Kaplan-Meier method. The independent prognostic factors affecting patients' PFS were determined by multivariate Cox regression analysis. The prognosis predictive model of patients was constructed by using the nomogram. Calibration curve and C-index were used to evaluate the accuracy of the prognosis predictive model in both internal and external validations. RESULTS: In training set, the age distribution of patients was 59.00 (46.00, 71.00) years, including 137 (45.7 %) females and 163 (54.3 %) males, 198 cases (66.0 %) with Eastern Cooperative Oncology Group (ECOG) score 0-1, and 102 cases (34.0 %) with ECOG score 2. In verification set, the age distribution of patients was 60.00 (48.25, 73.00) years, including 92 females (46.0 %) and 108 males (54.0 %), 130 cases (65.0%) with ECOG score 0-1, and 70 cases (35.0 %) with ECOG score 2. Patients in training set showed PFS differences stratified by gene mutation type (p < 0.0001), differentiation degree (p < 0.0001), circulating tumor cell (CTC) content (p = 0.00026), and brain metastasis (p < 0.0001). Besides, multivariate Cox regression analysis indicated that gene mutation type, differentiation degree, CTC content (p = 0.002), and brain metastasis (p = 0.005) are independent prognostic factors for PFS. These factors were included in the nomogram parameters, and both internally validated calibration curve (C-index = 0.672) and externally validated calibration curve (C-index = 0.657), showing good predictive performance of the model. CONCLUSION: The predictive model has a good predictive ability for prognosis of patients with progressive NSCLC. Notably, the differentiation degree and CTC content are both impact factors for PFS of patients, and the performance of these indicators in predicting the survival of patients with progressive NSCLC needs to be clarified in the future.

Endocan, a Risk Factor for Developing Acute Respiratory Distress Syndrome among Severe Pneumonia Patients.

Background: Severe pneumonia (SP) has been widely accepted as a major cause for acute respiratory distress syndrome (ARDS), and the development of ARDS is significantly associated with increased mortality. This study aimed to identify potential predictors for ARDS development in patients with SP. Methods: Eligible SP patients at admission from January 2013 to June 2017 were prospectively enrolled, and ARDS development within hospital stay was identified. Risk factors for ARDS development in SP patients were analyzed by univariate and multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was performed for the predictive value of endocan for ARDS development. Results: A total of 145 SP patients were eventually enrolled into the final analysis, of which 37 developed ARDS during the hospital stay. Our final multivariate logistic regression analysis suggested plasma endocan expression as the only independent risk factor for ARDS development in SP patients (OR: 1.57, 95% CI: 1.14-2.25, P=0.021). ROC curve analysis of plasma endocan resulted in an AUC of 0.754, 95% CI of 0.642-0.866, a cutoff value of 11.6 ng/mL, a sensitivity of 78.7%, and a specificity of 70.3%, respectively (P < 0.01). Conclusions: Endocan expression at ICU admission is a reliable predictive factor in predicting ARDS in patients with SP.

Invasive-noninvasive Sequential Ventilation for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study aimed to evaluate the efficacy and safety of invasivenoninvasive sequential ventilation versus invasive ventilation in the treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, VIP database were searched by the index words to identify the qualified RCTs, and relevant literature sources were also searched. The latest research was conducted in June 2017. Relative Risks (RR), and Mean Difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: Twenty-nine RCTs were involved in this analysis of 1061 patients in the invasivenoninvasive sequential ventilation group (In-non group) and 1074 patients in the invasive ventilation group (In group). The results indicated that compared with the invasive ventilation, invasive-noninvasive sequential ventilation would significantly decrease the incidence of VAP (RR:0.20, 95%CI: 0.16-0.26), mortality (RR:0.38, 95%CI: 0.26-0.55), reintubation (RR:0.39, 95%CI: 0.27-0.55); and statistically reduced the duration of invasive ventilation (MD:-9.23, 95%CI: -10.65, -7.82), the total duration of mechanical ventilation (MD:-4.91, 95%CI: -5.99, -3.83), and the length of stay in the ICU (MD:-5.10, 95%CI: -5.43, -4.76). CONCLUSION: The results demonstrated that the application of noninvasive sequential ventilation after invasive ventilation at the pulmonary infection control window has a significant influence on VAP incidence, mortality, and the length of stay in the ICU, but further well-designed, adequately powered RCTs are required to validate the conclusion.

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy.

BACKGROUND: This study aimed to identify potential predictive factors for the survival of advanced non small-cell lung cancer (NSCLC) patients undergoing first-line platinum-based chemotherapy. METHODS: A total of 270 advanced NSCLC patients who underwent first-line platinum-based chemotherapy from June, 2011 to June, 2015 were enrolled. A receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the albumin-to-fibrinogen ratio (AFR) for overall survival (OS). The predictive factors for survival were evaluated by univariate and multivariate analyses via the Cox proportional hazards regression model. The OS and progression free survival (PFS) results were determined via the Kaplan-Meier method using the log-rank analysis. RESULTS: Based on the results of the ROC curve analysis, 8.02 was accepted as the cut-off AFR value for OS. The metastasis stage (M0 vs M1a/b, HR: 1.73, 95% CI: 1.15-2.59, P = 0.020) and AFR (≤8.02 vs > 8.02, HR: 1.80, 95% CI: 1.09-2.78, P = 0.025) were two independent risk factors for PFS by multivariate Cox regression analysis. The AFR (≤8.02 vs > 8.02, HR: 1.79, 95% CI: 1.11-2.59, P = 0.029) was a significant predictive factor for OS in advanced NSCLC patients. The PFS (P = 0.008) and OS (P = 0.003) in the high AFR group were significantly improved compared with those in the low AFR group via the Kaplan-Meier method using the log-rank analysis. CONCLUSIONS: The AFR could be a potential effective predictive factor for the survival in advanced NSCLC patients undergoing first-line platinum-based chemotherapy.

A meta-analysis survey of appropriate bone turnover markers in the detection of bone metastasis in lung cancer.

BACKGROUND: A number of studies have investigated the clinical significance of bone turnover markers (BTMs) for the diagnosis of bone metastasis (BM) in lung cancer; however, they led to contradictory results. The aim of this meta-analysis was to investigate whether BTMs differ between lung cancer patients with and without BM. METHODS: Articles were identified by searching Medline, Embase, Web of Science and Scopus. The studies that were identified were pooled and the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) were calculated. Subgroup analyses and publication bias detection were also conducted. RESULTS: A final analysis of 1720 subjects (707 patients with BM and 1013 patients without BM) was performed from 16 cohort studies. From the pooled data in the meta-analysis, the total alkaline phosphatase (TALP) (104.35 U/l [95% CI 33.36-175.34]), bone-specific ALP (BALP) (13.24 µg/l [95% CI 8.50-17.98] or 6.84 U/l [95% CI 2.98-10.70]), C-terminal cross-linked telopeptide of type I collagen (ICTP) (5.07 µg/l [95% CI 3.58-6.56]) and N-terminal cross-linked telopeptide of type I collagen (NTX) (5.08 nM bone collagen equivalent/l [95% CI 2.82-7.33]) were significantly lower among BM patients than non-BM patients. Subgroup analyses detected that the serum level of tartrate-resistant acid phosphatase isoform 5b was significantly reduced in Caucasian patients with BM (-0.64 U/l [95% CI -1.02 to -0.25]), while increased in Asian patients with BM (2.69 U/l [95% CI 0.08-5.31]), compared to patients without BM. CONCLUSIONS: The present meta-analysis suggested that serum measurement of TALP, BALP, ICTP and NTX might be helpful in detecting BM in lung cancer.

Circulating 25-hydroxyvitamin D level and prognosis of lung cancer patients: A systematic review and meta-analysis.

BACKGROUND: Previous studies suggested a possible influence of circulating 25-hydroxyvitamin D [25(OH)D] level on the prognosis of lung cancer patients, but conflicting findings were reported. A systematic review and meta-analysis was thus conducted to comprehensively assess the influence of circulating 25(OH)D level on the prognosis of lung cancer patients. METHODS: Prospective or retrospective cohort studies assessing the influence of circulating 25(OH)D level on the prognosis of lung cancer patients were considered eligible. Hazard Ratios (HR) were pooled using meta-analysis. RESULTS: Eight studies with 2166 lung cancer patients were included. Meta-analysis of unadjusted HRs from four studies showed low circulating 25(OH)D level was significantly correlated with poor overall survival in lung cancer (HR=1.30, 95%CI 1.08-1.55, P=0.004). Meta-analysis of adjusted HRs from eight studies suggested that low circulating 25(OH)D level was not significantly correlated with poor overall survival (HR=1.25; P=0.13). However, sensitivity analysis suggested an obvious change in the pooled HRs when excluding single study by turns. When the study by Liu et al. was omitted, low circulating 25(OH)D level was significantly correlated with poor overall survival (HR=1.34; P=0.04). CONCLUSION: The present systematic review and meta-analysis suggested a correlation between low circulating 25(OH)D level and poor overall survival in lung cancer. More studies are needed to further validate the finding above.