Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion.

Malignant pleural effusion (MPE) is associated with a poor prognosis in lung cancer. Currently, no effective cure exists for MPE. Chloroquine (CQ) has been demonstrated to induce vascular normalization and inhibit tumor growth. The aim of this study was to assess whether CQ affects MPE. The xenografts mice were divided into normal saline (NS), CQ, or bevacizumab (BE) group. Tumor growth and microvascular density (MVD) were monitored. We explored the effect of CQ on the proliferation, survival, and proangiogenic signaling of tumor cells in vitro. We further evaluated the effects of CQ on the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). A chicken chorioallantoic membrane (CAM) model was used to elucidate the effects of CQ on angiogenesis. Finally, an MPE mouse model were treated by CQ, BE, or NS. The volume of pleural effusion, tumor foci, and MVD was evaluated. CQ therapy group exhibited decreased tumor volume, tumor weight, and MVD in the mouse xenografts. CQ inhibited the proliferation of the tumor cells. However, the expression of vascular endothelial growth factor was not affected. Additionally, CQ inhibited the proliferation, migration, and tube formation of HUVECs and also restrained angiogenesis in the CAM. Western blot showed that CQ might suppress angiogenesis by downregulating p-Akt, Jagged1, and Ang2 in HUVECs. In MPE mice, the volume of the pleural effusion, the number of pleural tumor foci, and the MVD were significantly reduced in the CQ group. Our work demonstrated that CQ played the role of an efficient treatment for MPE.

Predictive and prognostic significance of circulating endothelial cells in advanced non-small cell lung cancer patients.

The aim of this study was to evaluate the predictive and prognostic values of circulating endothelial cells (CECs) in patients with advanced non-small cell lung cancer (NSCLC). A total of 102 newly diagnosed advanced NSCLC patients were enrolled in this study. The amount of CECs was enumerated by flow cytometry (CD45- CD31+ CD146+) at baseline. CEC counts of 56 patients were detected before and after two cycles of chemotherapy. We correlated the baseline and reduction of CECs after therapy with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The CEC level was significantly higher in advanced NSCLC patients, ranging from 57 to 1300 cells/10(5) cells (mean ± SD = 299 ± 221 cells/10(5) cells), than in patients with benign lesions (205 ± 97 cells/10(5) cells) and healthy volunteers (117 ± 33 cells/10(5) cells). When the cutoff value of CEC counts was 210 cells/10(5) cells, there was no significant association between CEC counts and OR/PFS/OS of the enrolled patients. However, patients with CEC response after chemotherapy have more chances to achieve OR (P < 0.001), and such patients showed longer PFS (P = 0.048) and OS (P = 0.018) than those without CEC response. In the multivariate analysis, the independent prognostic roles of brain metastasis (HR 6.165, P = 0.001), and CEC response (HR 0.442, P = 0.044) were found. The CEC counts could be considered as diagnostic biomarker for advanced NSCLC patients. And the reduction of CECs after treatment might be more ideal than the baseline CEC counts as a predictive or prognostic factor in patients treated with chemotherapy or anti-angiogenic therapy.

Prognostic value of secreted phosphoprotein-1 in pleural effusion associated with non-small cell lung cancer.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of advanced lung cancer. Research has shown that secreted phosphoprotein-1 (SPP1) is essential in MPE associated with lung cancer. This retrospective study was performed to evaluate the prognostic significance of SPP1 in the MPE of patients with non-small cell lung cancer (NSCLC). METHODS: MPE specimens were obtained from 85 NSCLC patients (study group), and pleural effusion specimens were obtained from 24 patients with benign lung disease (control group). Specimens were tested for SPP1 using enzyme-linked immunosorbent assay (ELISA). Based on the cutoff value of receiver operating characteristic (ROC) curve analysis, the study patients were divided into a high-SPP1-expression subgroup and a low-expression subgroup. The primary and secondary endpoints of this study were progression-free survival (PFS) and overall survival (OS). RESULTS: The SPP1 levels of the study group were significantly higher compared to those of the controls (Mann-Whitney U test, P = 0.017). The number of extrapulmonary metastases was significantly higher in the high-SPP1-expressing patients than in the low-expressing patients (P = 0.03). Kaplan-Meier survival analysis showed that SPP1 levels were negatively associated with OS and PFS in both subgroups of study patients (P = 0.026; P = 0.039, respectively). Cox regression analysis showed that SPP1 was an independent prognostic factor in patients with NSCLC (HR = 1.832, 95% confidence interval: 1.003-3.345; P = 0.049). CONCLUSION: SPP1 in pleural effusion can be used for the auxiliary diagnosis of MPE and used to determine the prognosis of patients with NSCLC.

The proteasome activator PA28γ, a negative regulator of p53, is transcriptionally up-regulated by p53.

PA28γ (also called REGγ, 11Sγ or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence -193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.

Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors or chemotherapy alone in advanced NSCLC: a meta-analysis of randomized controlled trials.

BACKGROUND: Most patients with advanced non-small-cell lung cancer (NSCLC) require systemic chemotherapy. Chemotherapy plus multitargeted antiangiogenic tyrosine kinase inhibitors (TKI; e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, axitinib) has recently been evaluated in patients with NSCLC. However, the advantage of this therapy over chemotherapy alone in patients with advanced NSCLC remains largely unknown. METHODS: A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and toxicity of chemotherapy plus multitargeted antiangiogenic TKI with chemotherapy alone in patients with advanced NSCLC. PubMed, the ASCO and ESMO databases, and the Cochrane Library were searched for references to published articles. Two reviewers independently assessed the quality of the trials. Data were extracted, and overall response rate (ORR), pooled progression-free survival (PFS), overall survival (OS) with 95 % confidence intervals (CI), and major toxicities/adverse effects were analyzed. RESULTS: Six RCTs involving 3,337 patients with advanced NSCLC were ultimately analyzed. Compared to chemotherapy alone, chemotherapy plus multitargeted antiangiogenic TKI significantly increased the ORR [relative risk (RR) 1.71, 95 % CI 1.43-2.05] and PFS [hazard ratio (HR) 0.83, 95 % CI 0.76-0.90], but not OS (HR 0.93, 95 % CI 0.83-1.03). Patients who received chemotherapy plus multitargeted antiangiogenic TKI exhibited more rash, diarrhea and hypertension (OR 2.78, 95 % CI 2.37-3.26; OR 1.92, 95 % CI 1.65-2.24; OR 2.90, 95 % CI 2.19-3.84, respectively) and less nausea and vomiting (OR 0.71, 95 % CI 0.60-0.83; OR 0.75, 95 % CI 0.61-0.92, respectively). The incidence of hemorrhage, fatigue, cough, constipation, anorexia, and alopecia were comparable between the two groups. CONCLUSIONS: Therapy consisting of chemotherapy plus multitargeted antiangiogenic TKI was found to have specific advantages over chemotherapy alone in terms of PFS and ORR. The toxicity was comparable between the two therapies. Therefore, chemotherapy plus multitargeted antiangiogenic TKI may be a safe and valid therapeutic option for patients with advanced NSCLC.

Competition and synergistic mechanisms of species in Phyllostachys edulis-Alsophila spinulosa association based on niche theory.

We examined the niche characteristics and interspecific covariant relationship of main species in Phyllostachys edulis-Alsophila spinulosa association in Chishui A. spinulosa National Nature Reserve under P. edulis disturbance condition, and analyzed the mechanism of competition and coexistence across different species. The results showed that there were 67 species from 53 genera and 40 families in the association. The importance values, Shannon niche breadth index (BS), and Levins niche breadth index (BL) of P. edulis were the largest, indicating its absolute dominant status in association. The importance value and BL of A. spinulosa ranked the second, while BS was the third. There were 190 pairs of 20 main species. The niche overlap between P. edulis and A. spinulosa was the largest, with niche overlap value of 0.64. 71.6% of species pairs had niche overlap of less than 0.2, indicating low niche overlap and high degree of niche differentiation among species. The overall association of main species in association was significantly positive, and the community was relatively stable. The correlation among the main species was not significant, the linkage was not strong, and the species were independent from each other. P. edulis showed significant positive correlation with A. spinulosa, Brassaiopsis glomerulata, Ficus virens, and Mallotus barbatus, while P. edulis showed significant negative correlation with Mallotus philippensis, Cinnamomum glanduliferum, and Machilus gamblei. Niche difference and fitness between P. edulis and natives affected the coexistence and competition among species. Controlling the expansion of P. edulis and limiting the size of species with negative correlation with A. spinulosa could create a favorable living environment for A. spinulosa.

[Screening of early lung cancer with low-dose computed tomography in high-risk populations: a meta-analysis].

OBJECTIVE: To explore the values of low-dose computed tomography (LDCT) in the screening of high-risk populations for early lung cancer through a meta-analysis of the relevant literature. METHODS: PubMed, EBSCO, Cochrane and other databases were searched with key words. And the studies were selected by the inclusion and exclusion criteria. The baseline data were collected and analyzed by statistical software. RESULTS: Ten random controlled trials (RCTs) were selected. Compared to the chest X ray (CXR) screening and no screening controls, LDCT screening had an odds ratio (OR) of 3.705, 95%CI 3.527 - 3.891. And in the subgroup analysis, a higher number of stage I lung cancer was detected (OR 4.464, 95%CI 2.860 - 6.969) by LDCT. Moreover, LDCT screening showed an increased detection of adenocarcinoma in lung cancer (OR 4.652, 95%CI 2.877 - 7.522). CONCLUSION: LDCT is superior to CXR in the early detection of lung cancer, especially stage I and adenocarcinoma.

Carcinoembryonic antigen in pleural effusion of patients with lung adenocarcinoma: a predictive marker for EGFR mutation.

BACKGROUND: Carcinoembryonic antigen (CEA) can reflect tumor growth, recurrence and metastasis, and also predict the clinical efficacy of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). In the present study, we investigated the association between CEA in serum and pleural effusion (PE) and EGFR mutations in patients with lung adenocarcinoma. METHODS: We retrospectively investigated 114 lung adenocarcinoma patients with malignant pleural effusion (MPE). CEA levels in serum and MPE were measured by immunoradiometric assay, we analysed the correlation between CEA and EGFR mutation status. RESULTS: Fifty-three cases had EGFR mutation (46.5%). EGFR mutations were more common in females, patients with high levels of PE (≥107.2 ng/mL) and serum CEA (≥87 ng/mL). There was no significant difference in EGFR mutation rate between in tumor tissue and PE samples (49.3% vs. 41.9%, P=0.440). The result of receiver operating characteristic (ROC) indicated that the cut off value of CEA in MPE was 107.2 ng/mL, which had the highest sensitivity (SEN) and specificity (SPE) for predicting EGFR mutation [SEN 66%, and SPE 62.3%, AUC =0.668, 95% confidence interval (CI): 0.569-0.767, P=0.025]. The combination of gender, smoking history, serum and MPE CEA level had a higher calculated AUC (0.718, 95% CI: 0.622-0.813, P=0.000). Moreover, multivariate analysis showed that CEA level in MPE but not in serum was confirmed as the only independent factor associated with EGFR gene mutation status (P=0.026) with an odds ratio of 2.885 (95% CI: 1.137-7.317). CONCLUSIONS: MPE CEA can probably serve as a predictive marker for EGFR mutation in advanced lung adenocarcinoma. Combining gender, smoking history, and CEA has a relatively better predictive value. However, detecting EGFR mutations in lung adenocarcinomas is necessary for determining EGFR-TKI treatment in clinic.

The pulmonary nodule "discovered" by pneumonia: a case report.

The number of patients diagnosed with pulmonary nodules increased as more patients with high risk of lung cancer choose low-dose computed tomography (CT) scans for the screening of cancer. Clinicians might get two questions from the patients: what is the definite diagnosis of the nodule? What should we do? We have already got many guidelines trying to solve these problems. There are also several prediction models for pulmonary nodules. However, guidelines are not suitable for all types of patients, and the reality of patients is more complicated. Here we reported a 58-year-old man with a lung nodule in the right upper lobe, which was occasionally found during a period of pneumonia. We suggested two periods of follow-up, and the patient was also admitted to a clinical trial about circulating tumor cells (CTCs). He finally accepted surgical excision with a pathologic diagnosis of adenocarcinoma. This case suggests that: we might suggest CT surveillance for patients with solid nodules about 8 mm maximum diameter; three-dimensional reconstruction of CT scans could provide more information about the details of nodules; CTCs counts of peripheral blood could be considered as a potential clue for malignancy.

Recurrent "pneumonia" in left lower lobe lasting for 8 years: a case report.

Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC.

Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. MATERIALS AND METHODS: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. RESULTS: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, <0.001), acute phase (85.1% vs 79.6%, <0.001), and delayed phase (71.4% vs 58.2%, <0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, <0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, <0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, <0.001; occurrence of vomiting: 22.6% vs 38.9%, <0.001; usage of rescue drugs: 23.5% vs 34.1%, <0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. CONCLUSIONS: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

Association of the metformin with the risk of lung cancer: a meta-analysis.

OBJECTIVE: To assess the correlation between metformin and risk of developing lung cancer by meta-analysis. METHODS: Papers on the correlation between metformin and risk of lung cancer were searched from PubMed, MEDLINE, EMBASE, ISI Web of Science, and Cochrane Library. RESULTS: Six papers on case-control study were included in this study, involving 39,787 metformin users and 177,752 controls. Meta-analysis showed that the risk of developing lung cancer was lower in metformin users than in those without metformin (OR=0.55, 95% CI: 0.35-0.85, P<0.001). CONCLUSIONS: The risk of developing lung cancer is lower in metformin users than in those without metformin.

Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess the role of skin rash in predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the prognosis of patients with non-small cell lung cancer (NSCLC). METHOD: We systematically searched for eligible articles investigating the association between rash and the efficacy of EGFR-TKIs and the prognosis of patients with NSCLC. The summary risk ratio (RR) and hazard ratio (HR) were calculated using meta-analysis. RESULTS: We identified 33 eligible trials involving 6,798 patients. We used two different standards to group the patients [standard 1: rash vs. no rash, standard 2: rash (≥ stage 2) vs. rash (stage 0, 1)]. For standard 1, the objective response rate (ORR) and disease control rate (DCR) of the rash group were significantly higher than the no rash group [RR = 3.28; 95% CI: 2.41-4.47(corrected RR = 2.225, 95% CI: 1.658-2.986); RR = 1.96, 95% CI: 1.58-2.43]. The same results were observed for standard 2. For standards 1 and 2, the progression-free survival (PFS) (HR = 0.45, 95% CI: 0.37-0.53; HR = 0.57, 95% CI: 0.50-0.65) and overall survival (OS) (HR = 0.40, 95% CI: 0.28-0.52; HR = 0.53, 95% CI: 0.35-0.71) of the rash group were significantly longer than the control group, and the same results were observed in the subgroup analysis. CONCLUSIONS: skin rash after EGFR-TKI treatment may be an efficient clinical marker for predicting the response of patients with NSCLC to EGFR-TKIs. Furthermore, skin rash is also the prognostic factor of patients with NSCLC. Patients with skin rash have a longer PFS and OS.

Chemotherapy plus Vandetanib or chemotherapy alone in advanced non-small cell lung cancer: a meta-analysis of four randomised controlled trials.

AIMS: Most patients with advanced non-small cell lung cancer (NSCLC) require systemic chemotherapy. Vandetanib, targeting epidermal growth factor receptor and vascular endothelial growth factor receptor signalling in NSCLC, has recently been evaluated in combination chemotherapy in advanced NSCLC. However, the advantage of chemotherapy plus vandetanib over chemotherapy alone in advanced NSCLC remains largely unknown. A meta-analysis of randomised controlled trials was carried out to compare the efficacy and toxicity of chemotherapy plus vandetanib with chemotherapy alone in advanced NSCLC. MATERIALS AND METHODS: The PubMed database, American Society of Clinical Oncology, European Society for Medical Oncology and the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials. Data were extracted and the overall response rate, pooled progression-free survival, overall survival with 95% confidence intervals and main toxicity were analysed. RESULTS: Four randomised controlled trials involving 2160 patients with advanced NSCLC were ultimately analysed. Compared with chemotherapy alone, chemotherapy plus vandetanib significantly increased the overall response rate (relative risk = 1.96, 95% confidence interval = 1.53--2.52) and progression-free survival (hazard ratio = 0.79, 95% confidence interval = 0.71-0.87), but there was no significant difference in overall survival (hazard ratio = 0.91, 95% confidence interval = 0.79-1.03). Patients who received chemotherapy plus vandetanib had more rash, diarrhoea, hypertension and QTc prolongation (odds ratio = 2.32, 95% confidence interval = 1.93-2.79; odds ratio = 1.64, 95% confidence interval = 1.37-1.97; odds ratio = 4.08, 95% confidence interval = 2.51-6.01, odds ratio = 17.77, 95% confidence interval = 3.54-61.66, respectively), and less nausea and vomiting (odds ratio = 0.70, 95% confidence interval = 0.58-0.85; odds ratio = 0.69, 95% confidence interval = 0.55-0.86, respectively). The incidences of haemorrhage, fatigue and cough were comparable between the two groups. CONCLUSIONS: Although similar in overall survival, chemotherapy plus vandetanib showed particular advantages over chemotherapy alone in terms of progression-free survival and overall response rate. The toxicity was comparable between the two groups. Therefore, chemotherapy plus vandetanib might be a safe and valid therapeutic option for advanced NSCLC patients.

Prognostic value of the ratio of ground glass opacity on computed tomography in small lung adenocarcinoma: A meta-analysis.

INTRODUCTION: Lung cancer is the leading cause of cancer-associated death. In many countries, adenocarcinoma is the most common histologic type in lung cancer. Previously, few factors are identified to be prognostic indicators for the patients with small lung adenocarcinoma. Recently, the ground glass opacity (GGO) area found on high-resolution computed tomography (HRCT) scanning was identified as a prognostic indicator in some studies. But no clear consensus has been defined. METHODS: The PubMed/MEDLINE, EMBASE, Cochrane library and SpringerLink electronic databases were searched for articles related to ground glass opacity on computed tomography in patients with small lung adenocarcinoma. Data was extracted and analyzed independently by two investigators. An estimate of the hazard ratio (HR) for comparing high GGO ratio with low GGO ratio was extracted. The respective HRs was combined into a pooled HR, and 95% confidence interval (CI) was calculated for each study. The publication heterogeneity was assessed graphically using performing Beggs' funnel plot. All the statistical tests used in our meta-analysis were performed with STATA version 11. RESULTS: Thirteen studies, encompassing 2,027 patients, were included in our meta-analysis. Ten of these studies revealed that the GGO ratio in small lung adenocarcinoma is a good prognostic indicator. Seven studies were combined in a meta-analysis using overall survival (OS) as the end point of interest. The weighted HR of 7 studies was 0.85, with relative 95% CI ranging from 0.78 to 0.93 (P=0.009). For the surgical patient population, the primary endpoint of relapse-free survival (RFS) was superior with high GGO area on computed tomography (The combined HR 0.82, 95% CI 0.74-0.90; P=0.007). CONCLUSIONS: The result of our meta-analysis suggested that the GGO area measured on HRCT had a prognostic value of overall survival and relapse-free survival in small lung adenocarcinoma. The GGO ratio may be an independent prognostic factor for small lung adenocarcinoma.

Baseline and decline of serum ADAM28 during chemotherapy of advanced non-small cell lung cancer: a probable predictive and prognostic factor.

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small cell lung cancer (NSCLC) with correlation to cancer proliferation, tumor size and lymph node metastasis. In the present study, we investigated the predictive and prognostic value of ADAM28 during chemotherapy in patients with advanced NSCLC. 122 advanced NSCLC cases, 37 patients with benign lung disease and 40 healthy controls were enrolled in the study. The serum levels of ADAM28 were measured by enzymelinked immunosorbent assays. Data were correlated with diagnosis, radiologic objective response and survival. Serum levels of ADAM28 in advanced NSCLC group were significantly elevated compared to benign lung disease group (P<0.001) and healthy controls (P<0.001). And the expression of ADAM28 had relationship to the tumor size and lymph metastasis in NSCLC patients. When the cut-off value of ADAM28 was 225.54 pg/ml, the area under the ROC curve was 0.843 (95% confidence interval [CI]: 0.784-0.902); the sensitivity (SEN) and specificity (SPE) were both the best, with a SEN of 76% and a SPE of 83%. The patients who had ADAM28-response and no ADAM28-response had significantly difference in objective response to treatment (P<0.001). The median Progression-free survival from response assessment was 5 months. In the multivariate analysis, performance status (hazard ratio [HR], 1.68; 95% CI: 1.06-2.67), the level of serum ADAM28 (HR, 1.01; 95% CI: 1.01-1.02), and ADAM28-responses (HR, 047; 95% CI, 0.26-0.83), were significant correlated with prognosis. The levels of ADAM28 and ADAM28-responses appeared to be reliable surrogate markers to predict tumor response and survival in patients with advanced NSCLC.

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study.

BACKGROUND: Abraxane is a novel Cremophor-free nanoparticle paclitaxel that has been demonstrated to improve efficacy in the treatment of solid tumors. We undertook this retrospective study to evaluate the efficacy and safety of Abraxane in the progressive or recurrent non-small cell lung cancer (NSCLC) patients. METHODS: From August 2009 to April 2011, 33 patients who were diagnosed with progressive or recurrent NSCLC and treated with one or more prior platinum-based chemotherapies, were enrolled. The patients were injected with Abraxane, 260 mg/m2 , d1, and were evaluated for efficacy and safety. The treatment was repeated every three weeks unless progressive lesions or unacceptable toxicities were found. RESULTS: There were no complete response and 11 partial responses (33.3%). Patients with squamous cell carcinoma showed better responses than those with adenocarcinoma (41.7% and 21.1%, respectively). Fourteen patients had stable disease, and the disease control rate was 75.8%. The median progression-free survival was five months (95% confidence interval [CI]: 3.5-6.5). Four patients (12.1%) experienced grade 3-4 hematologic toxicities; one anemia (3.0%), two leucopenia (6.1%) and one thrombocytopenia (3.0%). Six patients (18.2%) experienced grade 3-4 non-hematologic toxicities; two abnormal hepatic functions (6.1%), one fatigue (3.0%), one peripheral neuropathy (3.0%), and two alopecia (6.1%). CONCLUSION: Recurrent and progressive NSCLC patients pretreated with platinum-based chemotherapy might benefit from Abraxane with tolerable adverse events.

Single-agent maintenance therapy in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to elucidate this issue. METHODS: The electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated. RESULTS: Eleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95%CI: 2.15 - 3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95%CI: 0.62 - 0.71) and overall survival (OS) (HR: 0.84, 95%CI: 0.78 - 0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95%CI: 4.61 - 9.01). CONCLUSION: In patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.

Diagnostic performance of integrated positron emission tomography/computed tomography for mediastinal lymph node staging in non-small cell lung cancer: a bivariate systematic review and meta-analysis.

INTRODUCTION: Accurate clinical staging of mediastinal lymph nodes (MLNs) of patients with non-small cell lung cancer (NSCLC) is important in determining therapeutic options and prognoses. Integrated positron emission tomography and computed tomography (PET/CT) scanning is becoming widely used for MLN staging in patients with NSCLC. We performed a bivariate meta-analysis to determine the pooled sensitivity (SEN) and specificity (SPE) of this imaging modality. METHODS: The PubMed/MEDLINE, Embase, and SpringerLink databases were searched for articles related to PET/CT for MLN staging in patients with NSCLC. SEN and SPE were calculated for every study. Hierarchical summary receiver operating characteristic curves were used to summarize overall test performance and assess study quality. Potential between-study heterogeneity was explored by subgroup analyses. RESULTS: Fourteen of 330 initially identified reports were included in the meta-analysis. When we did not consider the unit of analysis, the pooled weighted SEN and SPE were 0.73 (95% confidence interval [CI]: 0.65-0.79) and 0.92 (95% CI: 0.88-0.94), respectively. In the patient-based data analysis, the pooled weighted SEN was 0.76 (95% CI: 0.65-0.84) and the pooled weighted SPE was 0.88 (95% CI: 0.82-0.92). In the MLN-based data analysis, the pooled SEN was 0.68 (95% CI: 0.56-0.78) and the pooled SPE was 0.95 (95% CI: 0.91-0.97). CONCLUSIONS: Integrated PET/CT is a relatively accurate noninvasive imaging technique, with excellent specificity for MLN staging in patients with NSCLC. Nevertheless, current evidence suggests that we should not depend on the results of PET/CT completely for MLN staging in patients with NSCLC.

Diagnostic efficiency and complication rate of CT-guided lung biopsy: a single center experience of the procedures conducted over a 10-year period.

BACKGROUND: Computed tomography (CT)-guided transthoracic lung biopsy is a well-established technique for the diagnosis of pulmonary lesions. The objective of this study was to evaluate the diagnostic efficiency and complication rate of CT-guided lung biopsy in a Chinese population. METHODS: CT-guided cutting needle lung biopsies were performed in our institution on 1014 patients between January 2000 and October 2010. A chest radiograph was taken after the biopsy. Data about basic patient information, final diagnosis, and complications secondary to biopsy procedure (pneumothorax and bleeding) were extracted. RESULTS: The diagnostic efficiency of CT-guided lung biopsy was 94.8%; only 53 patients did not get a final diagnosis from lung biopsy. Final diagnoses found 639 malignant lesions (63.0%) and 322 benign lesions (31.8%). Pneumothorax occurred in 131 patients and 15 required insertion of an intercostal drain. Small hemoptysis occurred in 41 patients and mild parenchymal hemorrhage occurred in 16 patients. The overall complication rate was 18.5%. CONCLUSIONS: CT-guided cutting needle biopsy of pulmonary lesions is a relatively safe technique with a high diagnostic accuracy. It can be safely performed in clinical trials.