Biopsy, Fine-Needle ; methods ; Bronchi ; diagnostic imaging ; pathology ; China ; Endosonography ; methods ; Humans ; Lung Neoplasms ; diagnosis

OBJECTIVETo assess the value of thrombotic biomarkers in estimation of venous thromboembolism (VTE) risk in cancer patients.

METHODSA total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56 ± 17 years. The activities of von Willebrand factor antigen (vWF:Ag), factor VII (F VII:A), factor VIII (F VIII:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer. The level of D-dimer (D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic performance of the parameters. Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis.

RESULTSThe levels of vWF:Ag, D-D, and F VIII:A were significantly higher in all the specified tumor groups ( except the other tumor group ) than that of the control groups (P < 0.05). F VIII:A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group (P < 0.05). The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups (P < 0.05). The PS: A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05). The AT: A level was significantly lower in all tumor groups than in the control group (P<0.05). When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192% in the cancer group, the area under ROC curve = 0.828 (95% CI: 0.716 to 0.939). When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve = 0.915 (95% confidence interval: 0. 840 to 0.988). When the optimum cut-off point of PC: A for VTE diagnosis was 75.2% in the cancer group, the area under ROC curve = 0.764 (95% confidence interval: 0.630 to 0.898). The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients. The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value.

CONCLUSIONSThe plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability. It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.

Aged ; Antithrombins ; blood ; Biomarkers ; blood ; Factor VII ; analysis ; Factor VIII ; analysis ; Female ; Fibrin Fibrinogen Degradation Products ; Humans ; Male ; Middle Aged ; Neoplasms ; blood ; Prognosis ; Protein C ; analysis ; Protein S ; analysis ; ROC Curve ; Regression Analysis ; Risk Assessment ; Risk Factors ; Venous Thromboembolism ; etiology ; von Willebrand Factor ; analysis

Objective To study the prevalence of thrombocytosis in patients with non-small-cell lung cancer (NSCLC) and its correlation with clinicopathological features.Methods 156 patients with advanced NSCLC were retrospectively analyzed.The platelets degree between the groups with different sex,age,smoking,histological type of advanced NSCLC was compared and analyzed statistically.The relationship between the platelet count and chemotherapy effects was analyzed.Single analysis and Cox regression analysis were used for TTP and OS.Results Compared with the healthy persons,Plt significantly elevated in group with advanced NSCLC (36.5 ％,57/156 vs 5.0 ％,5/100) (P ＜ 0.01),and thrombocytosis group responded poorly to chemotherapy (22.8 ％,13/57 vs 39.4 ％,39/99) (P ＜ 0.05).The TTP (3.0 months vs 5.2 months) and OS (11.2 months vs 14.2 months) of Plt elevated group were significantly shorter than those of normal group.Conclusion Thrombocytosis is closely related to progress and metastasis of advanced NSCLC.Platelet count can be used as an assistant index in the prognosis judgment of patients with advanced NSCLC.

Objective To discuss the serum value of human epididymis protein 4(HE4) in the diagnosis of lung can-cer and to analyse the serum levels of HE4 in different pathological types and TNM staging of lung cancer patients. Meth-ods Forty-seven patients with lung cancer and thirty-one healthy controls were selected to join this study. According to various pathological types and TNM staging, the selected lung cancer patients were divided into different subgroups under the two categories. The serum HE4 levels were compared between subgroups. ROC curves of serum HE4 level and serum CEA level were drawn for the diagnosis of lung cancer with the pathological diagnosis as the golden standard. Results There was significantly higher level of serum HE4 in lung cancer group[(253.47±170.03) pmol/L] than that of healthy group [(84.09±51.03) pmol/L](t=5.365). There were no significant differences in serum levels of HE4 between different pathological subgroups of lung cancer patients [non-small cell carcinoma group (241.34±161.81) pmol/L vs small cell carcinoma group (293.5±198.76) pmol/L, t=0.847;squamous cell carcinoma group (304.29±287.61) pmol/L, adenocarcinoma group (224.39± 122.15) pmol/L and small cell carcinoma group F=0.969;and different TNM staging subgroups [ (stageⅠ~Ⅲgroup (255.27± 183.04) pmol/L vs stageⅣgroup (288.16±216.49) pmol/L, t=0.528]. Compared with ROC curves of serum HE4 and serum CEA,the area under the curve (AUC) of serum HE4 (0.902) was larger than that of serum CEA(0.765),( P>0.001). When the serum level of HE4 was 149.145 pmol/L, the sensitivity and specificity in the diagnosis of lung cancer were 72.3% and 90.3%. When the serum level of CEA was 4.685μg/L, the sensitivity and specificity in the diagnosis of lung cancer were 57.4%and 83.9%. Conclusion The serum level of HE4 is a sensitive and specific tumor marker in lung cancer. There are no significant differences in the serum levels of HE4 between different pathological types and different TNM staging in lung cancer patients. The detection of serum levels of HE4 are useful for the diagnosis of lung cancer.

Patients with sensitive epidermal growth factor receptor (EGFR) mutations often respond to tyrosine kinase inhibitors (TKIs), but acquired resistance will eventually develop. The most common mechanisms of acquired resistance include secondary EGFR mutation, MET amplification, and histologic transformation. Besides, gene fusions could also mediate the process of acquired resistance. Various gene fusions including rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and anaplastic lymphoma kinase (ALK) could take place after TKIs resistance, the incidence of which is around 1%. The clinical cases and experiments both in vitro and in vivo have proved the role of gene fusions in EGFR-TKI resistance. The combination of EGFR inhibitors and gene fusion inhibitors might be an effective therapeutic method. The understanding of gene fusions at EGFR-TKI resistance may contribute to the subsequent diagnosis and treatment strategy.

BRAF gene mutation is found in about 2%-4% of the patients with non-small cell lung cancer (NSCLC). This type of NSCLC is characterized by high malignancy, low efficacy of chemotherapy and poor prognosis. Although the combination treatment of BRAF inhibitor and MEK inhibitor has achieved remarkable results in advanced NSCLC patients with BRAF V600E mutation, which has been written into the National Comprehensive Cancer Network (NCCN) guidelines, severe side effects of the combination therapy are frequently observed. There isn't effective treatment strategy after drug resistance, and targeted therapy for non-V600E mutation patients is still lacking. In this paper, we summarized the researches on expression of immune markers in NSCLC patients with mutant BRAF and analyzed the studies on efficacy of immune checkpoint inhibitor (ICI), so as to provide more options for prolonging survival of the patients.
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Targeted therapy and immunotherapy are important treatments for non-small cell lung cancer (NSCLC). At present, the clinical and basic research of epidermal growth factor receptor (EGFR) mutation NSCLC is still in the exploratory stage, needing to optimize the efficacy, combination, sequence and dosage of immunotherapy and other treatments, to clarify the relationship between EGFR mutation, immune microenvironment and the efficacy of immunotherapy. In this review, we summarized the newly updated data about immunotherapy in EGFR mutant NSCLC in term of pre-clinical study, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutation burden and treatment.
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With the development of sequencing technology, the detection rate of de novo T790M mutation is increasing. The emergence of the third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide treatment opportunities. Secondary T790M mutation is often emphasized in clinic, but de novo T790M mutation is neglected. This review found that the incidence of de novo T790M mutation fluctuated greatly, which was mainly affected by sequencing techniques. The de novo T790M mutation is mainly low in mutation abundance, easy to combine with other gene changes, a poor predictor and prognostic factor and the efficacy of the first and second generation EGFR-TKIs is limited. The therapeutic value of osimertinib needs to be studied.
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Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; enzymology ; genetics ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; enzymology ; genetics ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use

Small cell lung cancer (SCLC), which accounts for about 15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Despite sensitive to chemotherapy and radiotherapy, SCLC is vulnerable to get resistant and has high recurrence rates. In recent years, immunotherapy has shown good antitumor activity, especially programmed death receptor-1/ligand-L1 (PD-1/L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) Checkpoint inhibitors have changed the pattern of tumor treatment, and SCLC has high immunogenicity, high mutation load and other favorable immune factors, so immuno-checkpoint inhibitors may become an important breakthrough in SCLC treatment. This article will briefly review the clinical research of immunotherapy for small cell lung cancer.
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Humans ; Immunologic Factors ; genetics ; immunology ; Immunotherapy ; methods ; trends ; Lung Neoplasms ; genetics ; immunology ; therapy ; Programmed Cell Death 1 Receptor ; genetics ; immunology ; Small Cell Lung Carcinoma ; genetics ; immunology ; therapy

Molecular target therapy is one of the most popular field of non-small cell lung cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearragement are the most important two oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK rearrangements are mutually exclusive, but isolated cases or small sample research with concomitant EGFR and ALK alterations have been constantly reported. The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co-alterations was about 1%, however, little has been known about clinicopathologic feature and treatment. This review summarized published case report, EGFR and ALK alterations are common in female, Asian origin, never smoker, IV stage, and denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase inhibitors (TKIs). However, studies about the origin and resistance mechanism in EGFR/ALK co-alterations are little, require more experimental and clinical research.
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Anaplastic Lymphoma Kinase ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; enzymology ; genetics ; ErbB Receptors ; genetics ; Humans ; Lung Neoplasms ; diagnosis ; enzymology ; genetics ; Mutation ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics