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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts’ discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.

Lung cancer has the highest morbidity and mortality among malignant tumors worldwidely. Targeted therapy related to non-small cell lung cancer (NSCLC) is the research hotspot in recent year. The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has brought a huge change in the treatment of patients with EGFR mutation. The patients with EGFR exon20 insertion are specific cohort in NSCLC. Reviewing the clinical researches to EGFR exon20 insertion mutation positive NSCLC, as well as summarizing character, testing methods and treatment, will provide a help for clinical application, bringing more benefits for patients at the same time.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients’ survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Background and objective Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has been widely applied in diagnosing mediastinal and hilar adenopathy. This study is further to evaluate value and safety of EBUS-TBNA in diagnosing intrathoracic metastasis from extrapulmonary malignancy. Methods Prospectively analysis of 41 patients suspected intrathoracic metastasis from previous diagnosed/concurrent extrapulmonary malignancies in Shanghai Chest Hospital, with radiologic findings showing mediastinal/hilar lymph node enlargement or intrapulmonary lesion requiring EBUS-TBNA examination for pathological diagnosis. Results 41 candidate patients enrolled, and 67 mediastinal/hilar lymph nodes and 5 intrapulmonary lesions were aspirated. 14 intrathoracic metastasis, 10 primary lung cancer, 9 reactive lymphadenitis, 4 sarcoid-like reactions, and 1 tuberculosis was diagnosed by EBUS-TBNA. Sensitivity and accuracy of EBUS-TBNA in diagnosing intrathoracic metastasis was 87.50% and 95.12%, respectively. Immunohistochemistry (IHC) was performed in 18 malignant tumors to obtain definite type or origin, twelve intrathoracic metastasis and 6 primary lung cancer were further confirmed. Conclusion EBUS-TBNA is a safe, effective method for the diagnosis of intrathoracic metastasis from extrapulmonary malignancy. IHC can provide additional evidence for distinguishing extrapulmonary malignancy from primary lung cancer.

Background and objective The aim of this study is to determine the best reference values of the optimal evaluation indexes that identify different disease types. Disease identification was conducted using the YUV quantitative analysis of autofluorescence bronchoscopy (AFB) images in the target areas. Furthermore, this study discusses the significance of AFB in the diagnosis of the central-type lung cancer. Methods A biopsy was conducted for cases that showed pathologic changes under either autofluorescence or white-light bronchoscopy. Moreover, MATLAB was used to carry out the quantitative analyses of lesion in multi-color spaces from AFB images. The cases were divided into different groups according to the pathological diagnosis of normal bronchial mucosa, inflammation, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer. SPSS 11.5 was used to process the data for statistical analysis. Results The Y values were different and statistically different between invasive cancer and LGD (P

Background and objective The aim of this study is to establish a HRM (high resolution melting curve) method for detection of deletion in human BIM gene and to detect this site deletion with the above method in 30 lung cancer samples and 30 normal samples. Methods The primers for detection of BIM deletion were designed and synthesized. The HRM method for geng deletion was established. And select the part of samples to detect BIM delection by normal PCR and sequencing assay. The Tm value of wild type PCR products was higher than that of the deletion PCR products. The difference of the corresponding Tm value is 2.5 oC. Results By detection with HRM methods, 1 samples were confirmed to be mutant, 7 samples were confirmed to be heterozygous and the other 22 samples were all wild type in the lung cancer samples. 2 samples were confirmed to be heterozygous and the other 28 samples were all wild type in the normal samples. Conclusion The HRM method for detection of BIM deletion established in this study is a sensitive, accurate, simple and high throughput method.

Background and objective Brain metastases are common in non-small cell lung cancer. Usual treatments include radiotherapy and chemotherapy. However, these methods result in poor patient prognosis. The aim of this study is to assess the effectiveness of surgical resection in the multimodality management of non-small cell lung cancer patients with synchronous solitary brain metastasis. Methods The clinical data of 46 non-small cell lung cancer patients with synchronous solitary brain metastasis were retrospectively reviewed. All patients underwent surgical resection of primary lung tumor, followed by whole brain radiotherapy and chemotherapy. In addition, 13 out of the 46 patients underwent resection of brain metastasis, whereas the remaining 33 patients received stereotactic radiosurgery. Results The median survival time of the enrolled patients was 16.8 months. The 1-, 2-, and 3-year survival rates were 76.1%, 20.9%, and 4.7%, respectively. The median survival times of the patients with brain metastasis resection or stereotactic radiosurgery were 18.3 and 15.8 months, respectively (P=0.091,2). Conclusion Surgical resection of primary lung tumor and brain metastasis may improve prognosis of non-small cell lung cancer patients with synchronous solitary brain metastasis. However, the survival benefit of surgical resection over brain metastasis resection or stereotactic radiosurgery is uncertain.

Background and objective In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Methods Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Results Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients’ disease-free survival and survival periods. Conclusion OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.

Background and objective At present the proportion of lung adenocarcinomas in NSCLC is higher than before. Thus, the study on prognosis of lung adenocarcinoma is extremely important. The predictive value of epidermal growth factor receptor (EGFR) mutations for prognosis in patients with resected lung adenocarcinomas has not be reported in China. The aim of this study is to analyze the association between the EGFR mutations and the outcomes of patients with resected lung adenocarcinomas. Methods Total of 301 patients with stage Ia-IIIa resected lung adenocarcinomas whose survival had been identified were retrospectively analyzed. Their EGFR mutations were detected by real-time quantitative PCR and DNA sequencing technology together. Results The proportion of EGFR mutation was 52.5% (158/301). The 2-year (disease-free survival, DFS) of EGFR-mutant group and wild-type EGFR group was 76.8%, 83.0%; 5-year overall survival (OS) of them was 67.7%, 65.7%. There was no significant difference for two groups (P=0.252, P=0.715). Further analysis for subgroups shows that the 2-year DFS, 5-year OS of mutant group and wild-type group in stage I-II was similar. For the patients with stage IIIa, the median DFS, 2-year DFS in mutant group was 12.2 months, 21.1%, lower than the 22.2 months, 42.1% in wild-type group. But there was no significant difference for both groups (P=0.584, P=0.295). The median OS, 5-year OS was 34.0 months, 30.8% in mutant group, while 38.7 months, 22.9% in wild-type group. There was no significant difference for both groups (P=0.907, P=0.444). Conclusion EGFR-mutant group with resected lung adenocarcinomas has a tendency of lower DFS than the wild-type EGFR group only in stage IIIa, but there was no significant difference for both groups. The EGFR mutation status was not associated with disease-free survival or overall survival in resected lung adenocarcinomas.

Background and objective The prognostic factors and salvage therapy after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy have brought concerns. This study aims to analyze retrospectively the clinical data of patients with advanced lung adenocarcinoma and explore their prognostic factors. Methods Patients with integral clinic dates and staged IV lung adenocarcinoma with performance status (PS) scores from 0 to 2 were enrolled between January 2009 and February 2012 and followed up until death. The primary endpoint was survival time after the failure of EGFR-TKI therapy. Results A total of 81 patients were enrolled into the study, and the median overall survival time was 9.6 months (QL-QU: 5.4-19.2). Univariate analysis showed that PS score, metastatic status, and the presence of plural effusion were significantly correlated with patient survival time (P

Background and objective The Expand Access Program (EAP) of Iressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QoL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program. Methods In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient. Meanwhile, the data of patients who had been on gefitinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively. Results A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors still enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in 15 different centers in China, and the remaining 875 patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5, respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive of EGFR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months. Conclusion A 250 mg dose of gefitinib offers good QoL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.

Background and objective Pemetrexed and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to determine their effects. This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs. Methods Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy. All patients received pemetrexed (500 mg/m2) as second (or higher)-line treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were used to evaluate the response to pemetrexed. Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria. Results There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However, these values were not statistically significant. The common toxicities of pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities, which were not observed in the no-EGFR-TKIs group. Both groups had one patient who reduced dosage because of myelosuppression (grade IV). There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed therapy not because of severe toxicities but due to subjective factors. Conclusion The DCRs, PFS periods, and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group, but the differences were not statistically significant. Therefore, sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs.

Background and objective Lung cancer is one of the most common cancers worldwide. Thus far, good tumor markers for diagnosing this disease have not been found. Therefore, the discovery of novel biomarkers through the application of new methods has become a hotspot in lung cancer research. The aim of this study is to analyze low-molecular-weight metabolites in the serum and urine samples of lung cancer patients and patients with other lung diseases through metabolomics and to explore potential tumor markers further. Methods Both serum and urine samples from 19 lung cancer patients and 15 patients with other lung diseases were subjected to metabolomic analysis using gas chromatography mass spectrometry. Orthogonal to partial least squares discriminant analysis was performed for modeling. Two sample t-test was used to identify differences in metabolite concentrations. Results A total of 57 metabolites were found in the serum, and 38 metabolites were found in the urine. Multivariate statistical analysis yielded a significant distinction in the metabolic profiles between lung cancer patients and patients with other lung diseases. The t-test results indicated a total of 13 metabolites in the serum and 7 metabolites in the urine with statistically significant differences. Conclusion Metabolomics is useful in discriminating between lung cancer and other lung diseases. As a novel approach, it has potential in the diagnosis of lung cancer at molecular level.

Background and objective The effectiveness of adjuvant chemotherapy in providing survival advantage for stage I non-small cell lung cancer (NSCLC) patients, especially those with stage Ib NSCLC, remains to be determined. The seventh edition of the Tumor Node Metastasis (TNM) Classification of Malignant Tumors is due to be published in 2009. The aim of the current study is to validate the value of this classification in Chinese early-stage NSCLC. The benefits of adjuvant chemotherapy to patients with early-stage NSCLC were also assessed. Methods The new staging project was validated in 433 patients who underwent complete surgical resection for early-stage NSCLC at the Single Institution of Shanghai Chest Hospital from June 1998 to June 2010. This new parameter was combined with other well-established prognostic factors, and multivariate survival analysis were performed. Variables in the analysis included age, gender, history of smoking, pathologic type, type of resection (pneumonectomy, lobectomy, bilobectomy, and sleeve resection), tumor size (largest tumor dimension), T-status, lymphovascular vessel invasion, and adjuvant chemotherapy. Results The three-year overall survival rates for females and males are 89.22% and 77.53%, respectively (P=0.001,8). Elder patients have worse prognoses: the survival rates for those aged ≥70 and

Background and objective At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy. Methods From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47) or pemetrexed combined with oxaliplatin (combination arm, n=36) as salvage therapy. All 83 patients had performance status (PS) scores of 0-2. Results Eighty-one patients were included in the final analysis. The median progression-free survival (PFS) in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268). The objective response rate (ORR) was 6.5% versus 20% (P=0.092), and the disease control rate (DCR) was 56.5% versus 65.7% (P=0.493), respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460) and 21.2% versus 25.0% (P=0.213), respectively. Conclusion For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.

Background and objective Erlotinib is a epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The standard dose is 150 mg/d. But some patients have to reduce the dose or stop treatment due to its side effects. The aim of this study is to evaluate the efficacy and safety of erlotinib 100 mg on patients with advanced adenocarcinoma lung cancer previously failed to chemotherapy. Methods Forty adenocacinoma patients with histologically confirmed diagnosis were enrolled to be given erlotinib 100 mg/d until disease progression or occurrence of intolerable toxicity. Relationships between therapeutic effects of erlotinib, progression-free survival, side effects and the clinical characters were analyzed. Results Among 40 patients, 11 got partial response, 14 had a stable disease and 15 had a progressive disease. The total response rate was 27.5%, and the disease control rate was 62.5%. The median progression-free survival was 5.5 months. Fifteen patients were positive for EGFR mutation according to the result of peripheral blood test. The response rate and disease control rate in 15 EGFR-mutation-positive patients were 33.3% and 73.3%, respectively, and the PFS was 8.4 months for 15 patients. The patients with ECOG 0-1 had a significant better PFS than those with ECOG 2 (6.1 vs 3.1 months) (P=0.043). The most frequent toxicities of erlotinib were rash and diarrhea which were easily controlled. Conclusion Erlotinib 100 mg is effective and safe in treatment of patients with advanced adenocarcinoma, especially for non-smoking patients, patients with good performance status and EGFR-mutation-positive patients.

Background and objective At present non-small cell lung cancer (NSCLC) is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Logrank test respectively. The prognosis were analyzed by Cox multivariate regression. Results The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months). One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P < 0.001). Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months), bone for 9 months (8.3 months-9.6 months), brain for 8 months (6.8 months-9.1 months), liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months), and subcutaneous for 3 months (1.7 months-4.3 months). The median survival times of adenocarcinoma (n=1,086, 62%) and squamous cell carcinoma cases (n=305, 17.5%) were 12 months vs 8 months (P < 0.001). The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P < 0.001); the median survival times of with and without radiotherapy were 11 months vs 9 months (P=0.017). Conclusion Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

Background and objective The combination of pacilitaxel and carboplatin has become a widely used regimen in first-line therapy of advanced NSCLC. The aim of this study is to compare the efficacy and safety of paclitaxel plus carboplatin at two dose levels in the first-line treatment of advanced NSCLC patients. Methods From Dec 2006 to Jun 2008, 63 patients (ECOG 0-1) with advanced NSCLC were administered with paclitaxel 175 mg/m2 (42 patients) plus carboplatin (AUC 5) or paclitaxel 200 mg/m2 (21 patients) plus carboplatin (AUC 5), 3-4 weeks/cycle. Results The objective response rate of paclitaxel 175 mg/m2 group and paclitaxel 200 mg/m2 group was 28.57% vs 33.33% (P=0.698); median time to progression were 6.7 months vs 7.0 months (P=0.561); median overall survival time were 18.7 months vs 19.0 months (P=0.255); one and two-year survival rate were 61.9% vs 66.7% (P=0.711) and 31.0% vs 33.3% (P=0.852), respectively. Neutropenia 3/4 grade was 61.9% vs 33.3% in paclitaxel 200 mg/m2 group and paclitaxel 175 mg/m2 group (P=0.031). Conclusion 175 mg/m2 dose paclitaxel causes less neutropenia than higher dose paclitaxel. Response rate, survival rate, time to progression and survival time are not statistically significant in two groups.

Background and objective It has been proven that ribonucleotide reductase M1 (RRM1) expression level was closely related to gemcitabine drug-resistance to tumor cells. The aim of this study is to explore the relations between RRM1 protein expression levels and effects of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods The expressions of RRM1 in 75 advanced NSCLC tissues were qualitatively detected by immunohistochemical methods. Seventy-five patients had received gemcitabine and cisplatin (GP) chemotherapy regimen. General characteristics of patients, response to treatment, efficacy evaluation and survival time were retrospectively investigated. Differences between the groups were statistically analysed by chi-square test. Survival differences were analysed by temporal inspection and Kaplan-Meier survival curves. Results RRM1 protein expression rate was 38.7%. RRM1 protein expression had no obvious relationship with gender, age, smoking status, and the clinical stages and histopathological types (P > 0.05). Response rate in RRM1 protein high expression groups (31.3%) was remarkably lower than that in low expression groups (41.3%), the difference was statistically significant (P=0.005). 1-year survival rate in RRM1 protein high expression groups (27.6%) was remarkably lower than that in low expression group (58.7%), the difference was statistically significant (P=0.009). No significant different of median survival was observed between RMM1 protein high expression group and low expression group (P >0.245). Time to progression in RRM1 protein high expression groups (3.10 months) was remarkably lower than that in low expression group (5.11 months), the difference was statistically significant (P=0.042). Conclusion RRM1 protein expression levels are closely related to effects of gemcitabine and cisplatin chemotherapy and prognosis of advanced NSCLC patients.

Background and objective The incidence of lung adenocarcinoma increases rapidly, and IGF-IR is the key mediator of several growth factors signal transduction, therefore it plays an important role in the proliferation and differentiation of cancer cell. The aim of this study is to detect the expression of IGF-IR in lung adenocarcinoma and to evaluate its implication for the clinicopathological factors and prognosis of patients with this disease. Methods The IGF-IR expression was detected by immunohistochemical staining. Correlations between IGF-IR expression with clinicopathological factors were analyzed using the Chi-squared test. The Kaplan-Meier method was used to calculate the overall patient survival rate, and the difference in survival curves was evaluated using a Log-rank test. Univariate and multivariate analysis was carried out using the Cox proportional-hazard model. Results In 126 cases of tumor sections tested, IGF-IR were detected in 89 cases. Statistical analysis revealed that the IGF-IR expression was related to tumor size and T stage, while there were no relations between IGFIR expression and age, gender, smoking, pathological stages, and differentiation. Cox analysis indicated that metastasis and chemotherapy efficacy were the prognostic factors in these patients, while IGF-IR expression was not the independent prognostic factor. Conclusion The IGF-IR expression is related to tumor size and T stage, while there is no relation between IGF-IR expression and prognosis.

Background and objective Bone metabolic markers are biomarkers derived from bone matrix or osteocyte reflecting bone metabolic situation. The aim of this study is to explore the diagnostic value of bone markers, cross-linked telopeptide of type I collage (ICTP) and bone-specific alkaline phosphatase (BAP) in lung cancer patients with bone metastases (B.M). Methods As a prospective control study, 110 cases were enrolled and divided into 3 groups. Totally 90 pre-treated, stage IV lung cancer cases were divided into two groups: 50 cases with bone metastases, 40 cases without bone metastases, as well as 20 healthy subjects were included as control. Serum ICTP was detected by enzyme-linked immunoassay (ELISA) and serum BAP was detected by electrochemiluminescence immunoassay. The relationships between factors of B.M and serum levels of ICTP, BAP were analyzed. Results The levels of serum ICTP and BAP in lung cancer patients with B.M were significantly higher than those in the healthy controls and those without B.M (P < 0.05). The level of serum BAP in patients with multiple B.M (lesions≥3) was significantly higher than that in patients with few B.M (lesions < 3) (P < 0.05). The level of serum BAP in patients with mixed pattern was significantly higher than that with lytic pattern. The sensibility of ICTP and BAP in the diagnosis of B.M in lung cancer patients was 18% and 40% respectively. The specificity of ICTP and BAP was 98.3% and 95% respectively. The accuracy rates of ICTP and BAP were 61.8% and 70.0% respectively. Joint detection of ICTP and BAP had improved sensibility and accuracy in the diagnosis of bone metastases in lung cancer patients (52% and 74.5% respectively). Conclusion Serum bone biochemical markers ICTP and BAP have diagnostic values for B.M in lung cancer patients with lower costs, noninvasiveness and convenience.

Background and objective Until now, there are still some questions that chemotherapy could block cancer immunologic escape or not. The aim of this study is to explore the mechanism of paclitaxel in the blocking of immunologic escape in 3LL bearing mice. Methods MHC class I components were detected by FACS antibodies TAP-1 and TAP-2 in 3LL group and 3LL pretreated with 5×10(-8) mmol/L paclitaxel. C57BL/6 mice were divided into 3 groups: tumor –bearing group, paclitaxel-treating group and tumor-free group. 3LL cells (0.3×10(6)) were injected via tail vein of mice. On day 8, paclitaxel (0.012 5 mg) was injected subcutaneously in the treatment group. On day 21, murine lung cells were suspended. With FACS triple staining, we analyzed expression of Treg in each group. Results The expression of TAP-1 (5.68%±0.65%), TAP-2 (89.54%±4.8%) was remarkably higher in paclitaxel-pretreating 3LL group than that in 3LL bearing mice group with TAP-1 (1.93%±0.25%), TAP-2 (67.78%±5.08%), P=0.006, P=0.036 respectively. The expression of regulatory T cells (Treg) in tumor bearing mice was significantly higher (25.46%±2.23%) than that of in normal mice (12.46%±1.21%) (P < 0.001). Expression of Treg in paclitaxel treated mice was remarkably inhibited (17.53%±1.24%) compared with that in 3LL bearing mice group (P=0.004). Conclusion Paclitaxel may block immunologic escape in the treatment of 3LL bearing mice partly through up-regulation TAP-1, TAP-2 and eliminatiing Treg cells.

Background and objective The aim of this study is to evaluate diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of bronchogenic carcinoma. Methods Between July, 2009 and February, 2010, 95 patients with mediastinal/hilar lymphadenopathy and/or intrathoracic peritracheal or peribronchial masses previously detected with CT scan underwent EBUS-TBNA. No rapid onsite cytology was performed. Results In all 95 patients, 60 cases were newly diagnosed lung cancer through the pathological examination and clinical follow-up certification. In 60 lung cancer cases, 112 samples were obtained from lymph nodes (LNs) and 11 samples were obtained from intrapulmonary lesions. Fifty-eight cases of patients were diagnosed, false negative in 2 cases. Sensitivity and specificity of EBUS-guided TBNA method in distinguishing benign from malignant LNs or thoracic masses were 96.67% and 100%, respectively. There was any major complication in this series, the procedure was uneventful. Conclusion EBUSTBNA seemed a safe and effective technique in making bronchogenic carcinoma diagnosis for mediastinal/hilar LNs and intrapulmonary masses.

Background and objective Erlotinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the efficacy and safety of erlotinib for the treatment of advanced NSCLC. Methods Ninety-two patients with advanced NSCLC who had failed or not tolerated or refused chemotherapy received 150 mg oral doses of erlotinib once daily until the disease progression or intolerable toxicity. Results Among the 92 NSCLC patients, 2 patient got complete response (2.2%), 22 partial response (23.9%), 48 stable disease (52.2%) and 20 progressive disease (21.7%). The overall response rate and the disease controlled rate of erlotinib was 26.1% (24/92) and 78.3% (72/92), respectively. The response rate of erlotinib were significantly higher in rash and ECOG 0-1 than no rash and ECOG ≥ 2. The disease controlled rate of erlotinib was significantly higher in female and non-smokers than male and smokers (P < 0.05). The response rate of erlotinib did not show significant differences within pathological type or previous treatment. The most common side effects were rash and diarrhea with 84.8% and 31.5%, respectively, but usually were mild. Conclusion Erlotinib is effective and safe in the treatment of advanced NSCLC patients.

Background and objective Brain metastases are common in non-small-cell lung cancer (NSCLC) and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI), which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. Methods The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. Results In terms of intracranial lesions, partial response (PR) was observed in 2 patients (6.7%), with stable disease (SD) in 17 patients (56.7%), for overall disease control rate (DCR) of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%), with SD in 5 patients (16.7%), for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP) and median survival time (MST) was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients’ PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. Conclusion The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases in NSCLC patients and appears to be a possible new treatment option.

Background and objective Second-line chemotherapy with taxanes for the patients with non-small cell lung cancer (NSCLC), who had disease recurrence or failure in previously treated with platinum-based chemotherapy, has been shown to be effective. Besides docetaxel, paclitaxel, the other available taxane, has also demonstrated potential activity in the same indication in a few studies. The aim of this study is to compare the treatment efficacy and safety between paclitaxel and paclitaxel plus oxaliplatin as the second-line treatment of advanced NSCLC. Methods Sixty-six patients from Sep 2000 to Sep 2007 whose disease progressed after first-line chemotherapy were enrolled and randomized into 2 groups: one group was administered with only paclitaxel (44 patients), the other was given paclitaxel plus oxaliplatin (22 patients), ECOG 0-2. The regiments were: single agent paclitaxel (175 mg/m2, d1) or paclitaxel (175 mg/m2, d1) plus oxaliplatin(130 mg/m2, d1), 3-4 weeks/cycle. Results The overall response rate of single paclitaxel and paclitaxel plus oxaliplatin were 13.6% and 18.2%, respectively. The median time to progression were 3.2 months vs 4.5 months. Median survival time were 6.9 months vs 8.2 months. There were no statistical differences. The haematological toxicities of paclitaxel plus oxaliplatin group were more severe than single agent group: grade 3/4 leukopenia (P=0.039). The rate of nausea, vomiting and acroaesthesia in paclitaxel plus oxaliplatin group was higher than that of single-paclitaxel group, but there were no statistical differences. Other adverse effects were mild. Conclusion Singlepaclitaxel administration as the second-lined treatment of advanced NSCLC is tolerable and has the response effect no worse than the combined chemotherapy.

Background and objective Lung lymphoepithelioma-like carcinoma is a rare subtype of large cell carcinomas of the lung. The aim of this study is to retrospectively analyze the clinical characteristics, surgical methods, laboratory inspection, chemotherapy, radiotherapy and prognosis of LELC. Methods From 2004 to 2008, clinical data were collected from 21 patients who were treated in Shanghai Chest Hospital. The correlation between clinicopathological characteristics and prognosis was evaluated. Results Of the 21 patients, 15 patients had lobectomy; 4 patients had wedge resection; 1 patient had pneumonectomy and 1 patient had sleeve resection. 12 patients received chemotherapy and 3 patients received radiotherapy after operation. Until 2009-4-31, 4 patients died, and the median survival time (MST) was 49 months. Conclusion Lymphoepitheliomalike carcinoma of the lung is a very rare and unique subtype of large cell carcinomas of the lung, which has a better prognosis with surgical, chemotherapy and radiotherapy.

Background and objective The sixth edition of TNM system is hard to illuminate the survival of different tumor load precisely. This retrospective study attempted to evaluate the prognostic clinicopathologic features of non-small cell lung cancer (NSCLC). Especially we subclassified tumor sizes to validate the new T classification of international union against cancer (UICC). Methods We reviewed the clinical data of 327 stageⅠNSCLC with complete resection. Survival was analysed by Kaplan-Meier method and Log-rank test. The multivariate analysis was performed with Cox’s proportion risk model. Results The 5-year survival rate of poorly differentiated histologic grade and moderate-well differentiated histologic grade were 60.49% and 73.98% respectively (P=0.02574); The 5-year survival rate of preoperative anemia or not were 64.44% and 73.00% (P=0.0182); Tumor size was divided into ≤2 cm, 2.1 cm-3 cm, 3.1 cm-5 cm and 5.1 cm-7 cm with 5-year survival rate of 86.30%, 72.73%, 62.50% and 58.33% respectively (P < 0.0001). Conclusion Histologic grade, preoperative anemia and tumor size are the independent prognostic factors in complete resection of stageⅠNSCLC. The patients with moderate-well differentiated histologic grade, non-preoperative anemia and smaller tumor size have longer survival time. Changes in tumor size classification are to subclassify into≤2 cm, 2.1 cm-3 cm, and 3.1 cm-5 cm, which is consistent with new T-staging system protocol of UICC.

Background and objective Cisplatin is an important drug in lung cancer chemotherapy. It has been proven that ERCC1, RRM1, p53 expressions were related to resistance to platinum and prognosis of the patcents with lung cancer. The aim of this study is to analyze the association of the expression of ERCC1, RRM1, p53 withpostoperative survival in patients with stage Ⅰ-Ⅱ non-small-cell lung cancer (NSCLC), and to explore the relationship between the expression of ERCC1, RRM1, p53 and resistance to cisplatin. Methods A total of 75 patients with stage Ⅰ-Ⅱ NSCLC receiving radical resection from Feb. 1992 to Jan. 1994 were followed up. Postoperative patients with stage Ⅰ were randomized two groups (chemo and non-chemo groups). All patients with stage Ⅱ received adjuvant cisplatinbased chemotherapy. Immunohistochemical staining was used to detect the expression of ERCC1, RRM1, p53 in paraffinembedded specimens. Results In stageⅠ NSCLC, the prognosis of the patients with high expression of ERCC1 (High-ERCC1) was better than those with low expression of ERCC1 (Low-ERCC1). 1, 3, 5-year survival rate in the patients with high expression of ERCC1 was 100.00%, 91.30%, 86.74% and in those with Low-ERCC1 was 96.43%, 60.71%, 57.14%, respectively (P =0.0058). The patients with High- ERCC1 had a better survival rate than those with Low-ERCC1 in stageⅠ NSCLC without chemotherapy. MST in high and low expression of ERCC1 was 72.00+ months and 64.67 months, respectively (P =0.0327). In contrary to stage Ⅰ NSCLC, the patients with had a better survival rate than those with in stage Ⅱ. MST was 60.00+ months in stage Ⅱ patients with low expression of ERCC1, but MST was only 25.50 months with (P =0.0442). The postoperative survival of NSCLC patients was not any statistical different between with high expression and low expression of RRM1 and p53. Conclusion High expression of ERCC1 is a better independent prognostic factor in stage Ⅰ NSCLC patients. Cisplatin-base chemotherapy prolongs survival in stage Ⅱ NSCLC patients with. Adjuvant chemotherapy regimen is determined according to ERCC1 expression levels in resected NSCLC.

Background and objective Non-small cell lung cancer (NSCLC) are more common in elderly people. The elderly patients are usually intolerable to platinum-based chemotherapy for other accompanying diseases. But many recent researches show the age factor is not the absolute contraindication. The aim of this study is to compare thetoxic effects, disease progression time and overall survival time between advanced NSCLC patients 60 or older than 60 and younger than 60 who are administrated with palitaxel plus platinum-based agents. Methods One hundred and ninety two patients were retrospectively divided into two groups according to the age of 60. The regimen is palitaxel (175 mg per square meter on day 1) combined with cisplatin (75 mg per square meter on day1)/carboplatin (ar an area under the curve of 5 mg per millimeter per minute on day 1), 3-4 weeks per cycle. Results The respond rate in groups ≥60 and

Background and objective VEGF plays an important role in the development of cancer. The aim of this study is to observe the structural alterations in multiple organs of high VEGF expression mice, and insight into the role of tumor-derived VEGF in the development of CASS. Methods Murine fibrosarcoma of T241-VEGF and T241- Vector tumor cells were transplanted subcutaneously in mice to construct the xenograft tumor model. The mice gross examinations were observed and the percentage of survival animals in each group is presented. The level of hemoglobin, the numbers of erythrocytes and serum concentration of VEGF in peripheral blood were analyzed. Histological analysis of liver, spleen, adrenal gland and bone-marrow were applied. Vascular networks in tumors were analyzed under a confocal microscope. Results The VEGF-expressing tumor bearing mice manifested CASS by severe anemia, hepatosplenomegaly and loss of body weight. The survival rate of mice was decreased. The level of hemoglobin and erythrocytes in circulating blood were significantly reduced (P

Background and Objective The role of Preoperative chemotherapy in patients with resected non-small-cell lung cancer (NSCLC) remains unclear, this study is aimed at evaluating the effectiveness of Preoperative chemotherapy in patients with resected non-small-cell lung cancer (NSCLC), by performing a meta-analysis of relevant trials. Methods Searching the literature from MEDLINE, pubmed, OVID, The Cochrane library, Cancerlit, Clinicaltrials.gov, ASCO, ESMO and CBM database, a meta-analysis was carried out to compare patients with NSCLC receiving chemotherapy before surgery with those undergoing surgery alone. The odds ratio (OR) was estimated to assess the survival advantage of Preoperative chemotherapy. Results Thirteen eligible randomized controlled trials (RCT) were identified, including 2561 patients, the meta-analysis showed preoperative chemotherapy improved survival with a OR of 0.80 (95% confidence interval, 0.68-0.94; P=0.008) in a subset analysis patients with IIIa stage also benefit from the preoperative chemotherapy. There was no evidence of statistical heterogeneity. Conclusion This analysis shows a significant benefit of preoperative chemotherapy and is currently the best estimate of the effectiveness of this therapy.

Background and Objective Lung cancer has become one of the most common malignant tumors in China. The prognosis of lung cancer is poor mainly because of relapse and distant metastases and brain metastasis occurs frequently. This study attempts to evaluate the prognostic factors in lung cancer patients with brain metastases. The information in the study may be useful for the clinicians to make some decisions. Methods The clinical data of 352 lung cancer patients with brain metastases in our hospital from the year of 1997 to 2005 were retrospectively reviewed. The multivariate analysis was performed with Cox's proportion risk model. Survival analysis was compared with Kaplan-Meier method and log-rank test was used respectively. Statistical significance was defined as P

RNA-based next-generation sequencing (NGS) has been recommended as a method for detecting fusion genes in non-small cell lung cancer (NSCLC) according to clinical practice guidelines and expert consensus. The primary targetable alterations in NSCLC consist of gene mutations and fusions, making the detection of gene mutations and fusions indispensable for assessing the feasibility of targeted therapies. Currently, the integration of DNA-based NGS and RNA-based NGS allows for simultaneous detection of gene mutations and fusions and has been partially implemented in clinical practice. However, standardized guidelines and criteria for the significance, application scenarios, and quality control of RNA-based NGS in fusion gene detection are still lacking in China. This consensus aims to provide further clarity on the practical significance, application scenarios, and quality control measures of RNA-based NGS in fusion gene detection. Additionally, it offers guiding recommendations to facilitate the clinical implementation of RNA-based NGS in the diagnosis and treatment of NSCLC, ultimately maximizing the benefits for patients from fusion gene detection. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. Immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD-1) antibody, programmed cell death ligand 1 (PD-L1) antibody, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody. It has brought significant survival benefits to some patients with advanced lung cancer and changed the treatment pattern of advanced lung cancer. Previous studies have shown that the objective response rate of PD-1/PD-L1 antibody in advanced non-small cell lung cancer (NSCLC) is only about 20%. So reliable biomarkers are urgently needed to screen out the potential benefit population of ICIs and improve the clinical response rate. Tumor mutational burden (TMB) is an emerging biomarker of immunotherapy in addition to PD-L1 expression. There is little correlation between PD-L1 expression and TMB in lung cancer. It is estimated that TMB can expand the benefit population of immunotherapy. However, in clinical practice, the detection of TMB, the determination of cut-off value and the clinical guidance strategy are still not standardized. This consensus will give guiding suggestions on the detection and application scenarios of TMB, so as to promote the standardization of TMB application for immunotherapy in lung cancer. [ABSTRACT FROM AUTHOR]