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MoS2 thin film is deposited on ITO/CdS substrate by in-situ hydrothermal method, which is expected to be a potential absorber material for planar heterojunction solar cell due to its high absorber coefficient and carrier mobility. The CdS buffer layer provides a robust template for the quasi-epitaxial growth of MoS2 with (0 0 2) preferred orientation by enjoying the analogical hexagonal structures and the shared sulfur atoms, resulting in a benign interface of CdS/MoS2. Then a device with ITO/TiO2/CdS/MoS2/Carbon-Ag structure is assembled after coating carbon-Ag electrode. The effects of the growth characteristics, morphology changes and optical properties of MoS2 on the device performance are studied systematically. Finally, a primary efficiency of 0.12% is achieved using a P-type MoS2 absorber with a thickness of 305 nm, exhibiting an outstanding stability. The one-dimensional solar cell capacitance simulator (SCAPS) is further used to reveal the bottleneck of device performance. After optimizing the doping density (1 × 1015 cm−3) and defect density (

To elucidate the clinicopathological characteristics and oncological outcomes of clinical T1aN0M0 (c-T1N0M0) lung cancer based on the newest 8th TNM classification. A total of 257 patients with c-T1aN0M0 lung cancer were retrospectively included in this study. According to the solid component size manifesting on the high-resolution computed tomography (HRCT), all lesions were classified as the pure ground-glass nodule (pure-GGN) with a diameter > 3 cm (n = 19), part-solid (n = 174), and pure-solid (n = 64) groups. We evaluated the prognostic impact of clinicopathologic variables including radiological presentations by establishing Cox proportional hazards model. When we evaluated the prognostic impact based on the radiological subtypes, the 5-year recurrence-free survival (RFS) and overall survival (OS) were significantly different among pure-GGN, part-solid, and pure-solid groups (RFS: 100% versus 95.4% versus 76.6%, p < 0.0001; OS: 100% versus 98.9% versus 87.5%, p < 0.0001). Cox regression analysis revealed the preoperative carcinoembryonic antigen (CEA) level and consolidation tumor ratio (CTR) were independently significant prognosticators related to RFS and OS. Furthermore, a receiver operating characteristic (ROC) verified the CTR (area under ROC [AUC] 0.784, 95%CI 0.697–0.869) was equipped with good performance to predict the postoperative recurrence with a cutoff point at 0.5. Lung cancer with higher CTR tended to be associated with lower survival in the c-T1aN0M0 stage. For the c-T1aN0M0 lung cancer, pulmonary nodules manifested as the pure-GGN and part-solid subtypes had an excellent prognosis and may be considered as the “early-stage” cancer, whereas those with pure-solid appearance were associated with the high risk of recurrence despite the sub-centimeter size. • Radiological subtypes could further stratify the risk of lung cancer in cT1a. • Sub-solid nodule has a favorable survival in c-T1a lung cancer, whereas pure-solid nodule is not always “early-stage” lung cancer and is relatively prone to postoperative recurrence despite the sub-centimeter size. • The preoperative CEA level and CTR are valuable prognosticators to predict the recurrence in c-T1a lung cancer.

Background Chemotherapy remains the standard care for HER2 mutated advanced non-small cell lung cancer (NSCLC) even though several targeted drugs showed promising results in preliminary stages. This study aimed to investigate the association of mutation variants with clinical features and the efficacy of chemotherapy in patients with HER2 mutated advanced NSCLC. Methods ARMS-PCR was used to identify HER2 mutation in patients without common oncogenic alterations. Patients with detailed information were further enrolled for analysis of clinical features and efficacy of first line chemotherapy. Survival data was analyzed by Kaplan-Meier method and compared by log-rank test. Brain metastasis incidence was analyzed and compared by Gray's test. Results YVMA insertion accounted for the majority (68.4%, 67/98) of HER2 mutation, and associated with significantly higher incidence of baseline extrathoracic metastasis (P=0.009), notably brain metastasis (P=0.004). Among 82 patients those received first line chemotherapy, YVMA insertion remarkably associated with inferior treatment outcomes, namely, a significantly shorter median progression free survival (PFS) and lower objective response rate (ORR) both in total patients (PFS: 5.2 vs. 7.7 m, P=0.038; ORR: 30.9% vs. 51.9%, P=0.09) and pemetrexed subgroup (PFS: 5.2 vs. 6.5 m, P=0.022; ORR: 31.8% vs. 60.0%, P=0.054). Multivariate analysis further established YVMA insertion as prognostic factor of worse PFS both for total patients (HR =1.578, 95% CI, 0.956-2.606) and patients received pemetrexed-based chemotherapy (HR =1.789, 95% CI, 1.013-3.160). In addition, YVMA insertion associated with higher incidence of lifetime brain metastasis (P=0.002) compared by Gray's test, with estimated 12-month brain metastasis incidence as 40.2% compared with 3.6% in the non-YVMA group. Conclusions YVMA insertion is associated with a higher incidence of brain metastasis, and inferior outcomes to chemotherapy than non-YVMA variants in patients with advanced NSCLC and HER2 kinase domain mutations, which emphasized the unmet need of more potent anti-cancer therapies with high blood-brain barrier (BBB) penetration capacity for patients with YVMA insertion.

Objectives Immune checkpoint inhibitors (ICIs) have revolutionized the oncologic treatment landscape, but have been accompanied by immune-related adverse events (irAEs). ICI-related pneumonitis (ICI-pneumonitis) is a potentially fatal irAE. However, the risk factors associated with ICI-pneumonitis remain unclear. There is an urgent need to identify risk factors for ICI-pneumonitis using reliable and accessible parameters. Here, we aimed to identify baseline peripheral-blood biomarkers correlated with ICI-pneumonitis and clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICIs. Materials and Methods We conducted a retrospective analysis of eligible patients with advanced NSCLC who were treated with ICIs at our center. Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for analyzing risk of ICI-pneumonitis. Multivariate logistic analysis was performed to identify risk factors of ICI-pneumonitis. Clinical characteristics and treatment outcomes were collected and compared according to the optimal cutoff value. Results A total of 300 patients were included, in which 54 patients (18 %) experienced ICI-pneumonitis. Patients with ICI-pneumonitis had a high level of baseline peripheral-blood absolute eosinophil count (AEC) than those without ICI-pneumonitis (P = 0.013). The optimal threshold of baseline peripheral-blood AEC to predict ICI-pneumonitis was 0.125 × 109 cells/L. The incidence of ICI-pneumonitis was higher in the high-AEC group (AEC ≥ 0.125 × 109 cells/L; 27.7 %) than in the low-AEC group (AEC Conclusions Among patients treated with ICIs, a baseline feature of high AEC (≥0.125 × 109 cells/L) was associated with an increasing risk of ICI-pneumonitis, and with a better clinical outcome.

Antimony chalcogenide Sb2(S, Se)3 is attracting a lot of attention as photovoltaic absorber owing to its rewarding photoelectric properties, low toxicity, and earth abundance. However, its device efficiency is still limited by the absorber material quality and device interface recombination. In this work, a fluorine-doped tin oxide (FTO) substrate with ultra-thin SnO2 layer and a low-cost stabilized carbon paste are introduced as a front and back contact layer respectively in Sb2(S, Se)3 based planar solar cells. Over 5.2 % efficiency is demonstrated in the structure of FTO/SnO2/CdS/Sb2(S, Se)3/Carbon/Ag, where the Sb2(S, Se)3 is prepared by hydrothermal technique. The complementary device physics characterizations reveal that the interfacial recombination between TCO and CdS is significantly suppressed by the introduction of ultra-thin SnO2 layer, which is profited from the leakage protection and bandgap offset engineering by its high resistivity and suitable conduction band minimum. Meanwhile, the successful adoption of the low-cost stabilized carbon as a back contact here shows an enormous potential to replace the conventional organic hole transport materials and noble metal. We hope this work can provide positive guidance to optimize Sb2(S, Se)3 based planar solar cells in the future.

Introduction Immune checkpoint inhibitor (ICI) monotherapy has limited efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs). With the wide use of ICI-based combinations, the efficacy of different ICI combination strategies in patients with NSCLC and BMs needs to be further elucidated. Methods We retrospectively reviewed 526 patients with non-small cell lung cancer (NSCLC) treated with ICIs from January 2016 to December 2019 in the Shanghai Pulmonary Hospital. Patients with BMs treated with ICIs were further divided into two groups: those with BM prior to the ICI treatment (pBM group), and those with BM after the treatment (aBM group). We assessed intracranial progression-free survival (IPFS), systemic progression-free survival (SPFS), overall survival (OS), intracranial objective response rate (IORR), and intracranial disease control rate (IDCR). Results We found 77 patients out of 526 with BMs; 69 presented the BMs prior to the ICI treatments and 8 showed BMs after the ICI treatments. In the pBM group, the median IPFS and SPFS were 7.39 months and 5.39 months, respectively. Combination therapy significantly improved both the IPFS (p=0.007) and the SPFS (p=0.007) when compared with monotherapy. Further analysis demonstrated that ICIs combined with chemotherapy significantly improved both the IPFS (p=0.009) and the SPFS (p=0.006) when compared with monotherapy. While ICIs combined with anti-angiogenic therapy improved the SPFS (p=0.005) but not the IPFS (p=0.139). The median OS was 27.43 months for patients in the pBM group. Further analyses suggested that combination treatment also improved the OS when compared with monotherapy (p=0.003). Subgroup analysis results showed that ICIs combined with chemotherapy led to better OS than ICIs monotherapy (p=0.006). Radiotherapy had no significant impact on survival (IPFS p=0.272, OS p=0.142) in the patients of the pBM group. Conclusion ICIs combined with chemotherapy demonstrated survival benefits over ICI monotherapy in patients with NSCLCs and BMs.

Purpose of review To describe the current status of lung cancer in China, including incidence, prevention, molecular testing and treatment. Recent findings Lung cancer presents a major public health issue and an enormous burden on society in China, because of its increasing incidence and high mortality. Several distinct gene profiles were associated with lung cancer in China: high EGFR mutation rate, low KRAS mutation rate and more comorbidity of HBV infection. Thus, local Chinese Society of Clinical Oncology Guidelines with more consideration of drug accessibility, regional development differences were highly recommended for clinical practice. For treatment, targeted therapy has achieved fruitful progress. Immunotherapy in China was a little bit lag behind previously and now there is a surge of immunotherapeutic drugs under investigation. For future, more preventive strategies and more trials considering chrematistics of Chinese lung cancer are needed. Summary There are achievements and shortcomings for lung cancer prevention and treatment in China. More work considering distinct characteristic of lung caner in China are needed.

Since December, 2019, a 2019 novel coronavirus disease (COVID-19) infected by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, and the epidemic situation has continued to spread globally. The epidemic spread of COVID-19 has brought great challenges to the clinical practice of thoracic oncology. Outpatient clinics need to strengthen the differential diagnosis of initial symptoms, pulmonary ground-glass opacity (GGO), consolidation, interstitial and/or interlobular septal thickening, and crazy paving appearance. In the routine of oncology, the differential diagnosis of adverse events from COVID-19 is also significant, including radiation pneumonitis, checkpoint inhibitor pneumonitis (CIP), neutropenic fever, and so on. During the epidemic, indications of transbronchial biopsy (TBB) and CT-guided percutaneous thoracic biopsy are strictly controlled. For patients who are planning to undergo biopsy operation, screening to exclude the possibility of COVID-19 should be carried out. For confirmed or suspected patients, three-level protection should be performed during the operation. Disinfection and isolation measures should be strictly carried out during the operation. At last, more attention to the protection of cancer patients and give priority to the treatment of infected cancer patients.

BACKGROUND: Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy has boosted the prognosis in advanced lung cancer. Meanwhile, accumulating cases showed the correlation between tuberculosis (TB) reactivation and anti-PD-1/PD-L1 immunotherapy. However, the safety and efficacy of anti-PD-1/PD-L1 immunotherapy for lung cancer complicated with TB infection could only be learned from real-world data. METHODS: We retrospectively analyzed 562 patients with advanced lung cancer who received anti-PD-1/PD-L1 immunotherapy at Shanghai Pulmonary Hospital from 2015 to 2019, including 13 patients with TB infection. Besides, relevant literature reviews were performed online to analyze the safety and efficacy of immunotherapy and to explore the appropriate treatment strategies in this specific population. RESULTS: In our cohort, the initiation of anti-PD-1/PD-L1 immunotherapy was from June 2015 to December 2019. Among them, 13 patients had TB infection prior to immunotherapy including 11 latent TB and 2 active TB, and all of them were treated with anti-PD-1 immunotherapy. Patients with active TB infection were treated with concurrent anti-TB and anti-PD-1 treatments, and the remaining received either mono-immunotherapy or combined immunotherapy. Neither reactivation of latent TB nor progression of active TB was monitored in our cohort during immunotherapy. Severe immune-related adverse events (irAEs) were diagnosed in two patients. Treatment strategies such as discontinuation of immunotherapy and administration of corticosteroids were provided timely, and one with latent TB infection got gradually improved, but the other one with active TB died quickly. The median progression-free survival (PFS) was 5.5 months for tumor immunotherapy in our cohort. However, the PFS of immunotherapy was merely 2.1 and 2.2 months in lung cancer patients with active TB infection. CONCLUSIONS: Immunotherapy is relatively safe for lung cancer patients complicated with previously treated latent TB, and the efficacy of immunotherapy in this specified population is not inferior to that in lung cancer patients without TB infection. TB screening before anti-PD-1/PD-L1 immunotherapy is strongly recommended, and irAEs should be monitored more cautiously in lung cancer patients with active TB infection.

Background The impact of primary tumor size on the therapeutic outcomes of EGFR‐tyrosine kinase inhibitors (TKIs) in advanced non‐small cell lung cancer (NSCLC) with EGFR mutation remains unclear. Methods A total of 291 consecutive patients with advanced EGFR‐mutant NSCLC administered first‐line EGFR‐TKIs were enrolled. Computed tomography was used to assess primary tumor diameter. The amplification refractory mutation system plus was used to quantitatively evaluate the abundance of EGFR mutations. Associations between depth of response, abundance of EGFR mutations, and tumor size was investigated. Results Patients were divided into three groups according to T classification: ≤ 3 cm (n = 109), 3–5 cm (n = 121), and > 5 cm (n = 61). Median progression‐free survival (PFS) was significantly longer in the ≤ 3 cm and 3–5 cm groups compared to the > 5 cm group (10.8 vs. 10.5 vs. 7.1 months; P < 0.001). Subgroup analysis revealed a consistent result in patients with exon 19 deletion and 21 L858R mutation. Multivariate analysis revealed that tumor size was an independent predictive factor for PFS (hazard ratio 1.528, 95% confidence interval 1.104–2.115; P = 0.010). Larger tumors (> 5 cm) were marginally significantly less EGFR‐mutant abundant than smaller tumors (≤ 5 cm) (mean ± standard deviation 30.5 ± 29.5% vs. 45.8 ± 43.1%; P = 0.08). Conclusion Larger tumors (> 5 cm) were associated with inferior PFS of first‐line EGFR‐TKI therapy in advanced NSCLC patients with activating EGFR mutations. A potential explaination might be that EGFR mutations are less abundant in larger tumors.

BACKGROUND: Acute complications, such as venous thromboembolism (VTE), are common in patients with advanced severe lung cancers. However, current VTE risk scores cannot adequately identify high-risk patients with non-small cell lung cancer (NSCLC). The study proposed to elucidated the incidence of thromboembolism (TE) in patients with different oncogenic aberrations and the impact of these aberrations on the efficacy of targeted therapy in patients with NSCLC. METHODS: A systemic review was conducted in Web of Science, PubMed, Embase and the Cochrane Library to evaluate the incidence of TE in different molecular subtypes of NSCLC. Data from patients diagnosed of advanced NSCLC who harboring anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements since 2016 to 2019 were also retrospectively collected. A meta-analysis with random-effects model, sensitivity analysis and publication bias were performed. The principal summary measure was incidence of thrombotic events in NSCLC patients. And the efficacy of tyrosine kinase inhibitor (TKI) therapy was compared between the two subgroups. RESULTS: A total of 5,767 cases from 20 studies were included in the analysis of the incidence of thrombosis in patients with different oncogenic alterations. The pooled analysis showed a higher risk of thrombosis in ROS1-fusion types (41%, 95% CI: 35–47%) and ALK-fusion types (30%, 95% CI: 24–37%) than in EGFR-mutation (12%, 95% CI: 8–17%), KRAS-mutation (25%, 95% CI: 13–50%), and wild-type (14%, 95% CI: 10–20%) cases. A high prevalence of thrombosis (ALK: 24.4%; ROS1: 32.6%) was observed in the Shanghai Pulmonary Hospital (SPH) cohort of 224 patients with ALK or ROS1 fusion. Furthermore, patients with embolism had significantly shorter progression-free survival (PFS) after TKI therapy than those without embolism, both in the ALK+ cohort (5.6 vs. 12.9 months, P

BackgroundDespite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear.Patients and MethodsAdvanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case–control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment.ResultsFifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = −0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan–Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 vs 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 versus 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case–control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31–0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26–0.89, p = 0.05) and higher ORR (33.3 vs 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS.ConclusionPatients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.

Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients ( P = 0.0065 ). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

Background To investigate the impact of ALK variants on the features of brain metastases (BM), the outcome of chemotherapy and targeted therapy using crizotinib, as well as the progression pattern in patients with ALK fusion. Methods Patients with ALK fusion were retrospectively collected from January 2013 to July 2017 in Shanghai Pulmonary Hospital. ALK rearrangements were identified via ARMS-PCR. ALK variants were identified via Sanger Sequencing. Results A total of 135 patients and 41 with brain metastasis were identified. Radiological features showed that the patients with ALK variant 1 had a larger BM size compared with patients with ALK non-variant 1 (median tumor size: 16.89 vs. 11.01 mm, P=0.031). Similar time to treatment failure (TTF) was observed in patients with ALK variant 1 and non-variant 1 who received first-line crizotinib (median TTF: 15.7 vs. 13.8 months, HR =0.75, P=0.34). Patients with ALK variant 1 who had baseline BM had significantly shorter TTF than non-variant 1 with baseline BM when treated with first-line crizotinib (median TTF: 9.1 vs. 14.9 months, HR =2.68, P=0.037). In patients treated with chemotherapy, ALK variant 1 was associated with inferior TTF (median TTF: 5.6 vs. 8.1 months, HR =1.66, P=0.039). Progression pattern was similar between ALK variant 1 and non-variant 1. Conclusions Patients with ALK variant 1 and baseline BM had inferior TTF on first-line crizotinib treatment and presented with more aggressive radiological features. Patients with ALK non-variant 1 had better clinical outcome on first-line chemotherapy.

Single-agent osimertinib is the standard of care for the first-line treatment of advancedEGFR+ NSCLC and remained the only marketed third-generation EGFR tyrosine kinase inhibitor (TKI) until March 2020 when almonertinib (HS-10296) was approved in the People's Republic of China for the treatment of advanced EGFR T790M+ NSCLC based on a phase 2 expansion study of a phase 1/2 trial. In this review, we profiled many of the third-generation EGFR TKIs in late-stage clinical development (e.g., almonertinib, lazertinib, alflutinib11The name of ‘Alflutinib' was changed as per the requirements of the National Pharmacopoeia Committee of China and the "China drug generic naming principle", and the name of the drug has been changed from ‘Alflutinib' to ‘Furmonertinib'., rezivertinib, ASK120069, SH-1028, D-0316, and abivertinib) based on their interim results from phase 1 and phase 2 trials, and included the designs of the phase 3 trials and their chemical structures when publicly available. We also listed other third-generation EGFR TKIs in pipeline development based on the search of clinical trial registration websites. In addition, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, mavelertinib), including phase 3 results of rociletinib and naquotinib. We further profiled combination clinical trial design of the third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704), and ACROSS2 (NCT04500717) that if positive can potentially usher in the next standard of care for advanced EGFR+ NSCLC.

Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC. An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator. From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events. ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.

Summary Background Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China. Methods We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18–70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4–6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov , NCT03134872 (follow-up is ongoing). Findings Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0–14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6–15·4] vs 8·3 months [6·0–9·7]; hazard ratio 0·60 [0·45–0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. Interpretation The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1–positive population. Funding Jiangsu Hengrui Medicine.

Analyzing the seismic vulnerability of bridge structures is of great significance in assessing the sustainable capacity of bridges. However, previous seismic vulnerability analysis of bridge structures was based on theoretical simulation or experimental research, which couldn’t really reflect the actual seismic damage. Therefore, this paper used Bayesian updating method to obtain a corrected vulnerability curve of bridge structures considering the theoretical simulation and historical seismic data, which overcame the shortcomings that information couldn’t be updated. Specifically speaking, the seismic demand probability function of the bridge structure was obtained through numerical simulation, and a seismic vulnerability curve of a log-normal distribution with two parameters (median value c j and log-standard deviation ξ j ) was established, which was taken as the prior information. Then, combining the historical empirical damage data, the demand information is updated to obtain the posterior probability of the structural seismic demand. The possibility of exceeding the limit damage state of the bridge structure under different ground motion intensity can be obtained by using the corrected seismic vulnerability curve. The results show that the corrected seismic vulnerability curves are closer to theoretical simulation results, which provides a new idea for the reliability analysis of the bridge structure. Moreover, based on the corrected seismic vulnerability curve of Guxigou Middle Bridge, the post-earthquake traffic capacity of the bridge was evaluated by combining with traffic flow and traffic time. The research results show that the proposed method can quickly evaluate the sustainable traffic capacity of bridges after earthquakes, which has certain practicability and scientificity and provides the theoretical basis and practical guiding significance for the relief work after earthquakes.

Objectives Apatinib exhibits broad-spectrum antitumor activities by selectively inhibiting vascular endothelial growth factor receptor-2. This study evaluated the efficacy and safety of apatinib in patients with advanced non-squamous non–small-cell lung cancer who were heavily pretreated or not suitable to receive standard second-line chemotherapy. Patients and Methods This was an open-label, single-arm phase II clinical trial ( ClinicalTrials.gov NCT02515435 ). Patients received 500 or 750 mg apatinib daily until progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was the objective response rate. The secondary endpoints included disease control rate, progression-free survival, overall survival, and side effects. Apatinib administration was allowed beyond disease progression. Results Between March 2015 and August 2016, 40 patients were enrolled. Among them, 6 (15.0%), 16 (40.0%), and 18 (45.0%) received apatinib as the second-, third-, and fourth-line or beyond treatment, respectively. The mean dosage of apatinib was 477.0 ± 85.3 mg/day. Thirty-eight patients were available for response evaluation; the objective response rate and disease control rate were 13.2% and 63.2%, respectively. The median progression-free survival was 3.06 months (95% confidence interval [CI], 2.20-4.14 months). The median overall survival was 7.69 months (95% CI, 5.36 months to not estimable). The most common treatment-related adverse events were hand-foot-skin reaction (30.0%), proteinuria (27.5%), oral mucositis (22.5%), fatigue (20.0%), and hypertension (17.5%). Nine patients received apatinib after progression, and the median duration of apatinib therapy beyond progression was 5.13 months (95% CI, 4.27-7.82 months). Conclusion Apatinib shows promising efficacy and manageable toxicity in patients with advanced non-squamous non–small-cell lung cancer. Apatinib therapy beyond progression could provide further benefits in specific subpopulations.

Introduction Programmed death-ligand 1 (PD-L1) expression using immunohistochemistry is approved by the US Food and Drug Administration to guide treatment with anti-programmed death-1/PD-L1 monoantibodies. However, intratumoral heterogeneity of PD-L1 expression and the accordance between primary and metastatic lesions remains unresolved. Materials and Methods PD-L1 expression was evaluated in tumor cells and tumor-infiltrating lymphocytes (TILs) of surgically resected lung adenosquamous carcinoma. Discrepancy of PD-L1 expression and cluster of differentiation 8-positive TILs of different histologic components was investigated. PD-L1 expression was also compared between primary tumor and nodal metastases. Results The study included a total of 72 lung adenosquamous carcinomas. Fifteen patients (20.8%) and 25 patients (34.7%) were positive for PD-L1 expression in adenomatous and squamous components respectively, with a cutoff value of 5%. We found that 57.8% of cases showed consistent PD-L1 expression in tumor cells in the different histological components at a cutoff of 1%, and 48.1% of cases were likewise consistent at a cutoff of 5%. In paired squamous components of metastatic nodes and primary lesions, 90% and 80% of cases of PD-L1 expression were consistent, at cutoffs of 1% and 5%, respectively. For the adenomatous component of tumor/metastasis pairs, 77.8% of cases at the 1% cutoff and 74.1% of cases at the 5% cutoff were consistent, partially attributed to the difference of predominant histologic patterns. Conclusion PD-L1 expression showed discrepancy in different histological components within a tumor and consistency in paired histological type between tumor and metastases. Different pathological features might contribute to the heterogeneous PD-L1 expression in patients with non–small-cell lung cancer.

Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described.We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups.The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34).We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered.

Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC. Moreover, addition of anti-angiogenic agents to chemotherapy showed robust efficacy in advanced NSCLC, regardless of tumor histology. Here, we present the case of a heavily pretreated lung adenocarcinoma patient who was treated with apatinib and apatinib continuation plus docetaxel re-challenge. He was negative for several driver genes, including EGFR, ALK, KRAS, ROS1, HER2, RET and BRAF. The previous treatment included platinum-based doublets, pemetrexed monotherapy, docetaxel plus bevacizumab, gefitinib monotherapy, nab-paclitaxel monotherapy, irinotecan plus oxaliplatin and radiotherapy. He obtained a partial response after both apatinib monotherapy and apatinib plus docetaxel treatment, with progression-free survival durations of 5 months and 6 months, respectively. This case indicated that apatinib monotherapy or apatinib plus docetaxel might be regarded as a therapeutic option for heavily pretreated patients with advanced non-squamous NSCLC.

Objectives Small-cell lung cancer (SCLC) has been viewed as a smoking-related disease, with only 2% to 5% patients being never-smokers. This study aimed to investigate the clinical characteristics of never-smoking and its association with treatment outcomes in Chinese SCLC patients in real world. Methods We performed a retrospective study of 303 patients with SCLC and grouped into smokers and never-smokers. The clinical characteristics and treatment outcomes of two groups were collected and compared. Results In total, 113 patients with limited-stage (LS) SCLC and 190 patients with extensive-stage (ES) SCLC were enrolled. Sixty-nine (22.8%) patients were never-smokers. Both the median progression-free survival (PFS) and overall survival (OS) were significantly longer in never-smokers than in smokers (PFS, 8.37 vs. 7.10 months, P = 0.036; OS, 19.73 vs. 14.40 months, P = 0.044) in all populations. Multivariate analysis suggested that never-smoking was a significant favorable prognostic factor for PFS (HR = 0.753; P = 0.047) instead of OS (HR = 0.780; P = 0.236) in patients with SCLC. The objective response rate (ORR) to first-line therapy were similar between two group (52.6% vs. 59.4%, P = 0.315). Moreover, prophylactic cranial irradiation (PCI) resulted in marginally significantly longer PFS than observation in patients with ES-SCLC who obtained objective response after first-line therapy (10.57 vs. 7.73 months, P = 0.075). Conclusion The current study indicated that never-smokers are increasingly prevalent in Chinese patients with SCLC. Never-smokers with SCLC had significantly longer PFS and OS compared with smokers, and smoking was an independent poor prognostic factor for PFS in patients with SCLC.

Rationale To investigate whether the mutational landscape of circulating cell-free DNA (cfDNA) could predict and dynamically monitor the response to first-line platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods Eligible patients were included and blood samples were collected from a phase III trial. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment in a 1.15M size panel covering exon regions of 1,086 genes. Molecular mutational burden (MMB) was calculated to investigate the relationship between molecular features of cfDNA and response to chemotherapy. Results In total, 52 eligible cases were enrolled and their blood samples were prospectively collected at baseline, every cycle of chemotherapy and time of disease progression. At baseline, alterations of 17 genes were found. Patients with partial response (PR) had significantly lower baseline MMB of these genes than those patients with either stable disease (SD) (P = 0.0006) or progression disease (PD) (P = 0.0074). Further analysis revealed that the mutational landscape of cfDNA from pretreatment blood samples were distinctly different among patients with PR vs. SD/PD. For patients with baseline TP53 mutation, those with PR experienced a significant reduction in MMB whereas patients with SD or PD experienced an increase after two, three or four cycles of chemotherapy. Furthermore, patients with low MMB had superior response rate and significantly longer progression-free survival than those with high MMB. Conclusion This study indicated that the mutational landscape of cfDNA has potential clinical value to predict the therapeutic response to first-line platinum-based doublet chemotherapy in NSCLC patients. At the single gene level, dynamic change of molecular mutational burden of TP53 is valuable to monitor efficacy (and, therefore, might aid in early recognition of resistance and relapse) in patients harboring this mutation at baseline.

Background Treatments for superior sulcus tumor (SST) have evolved, with induction chemoradiotherapy providing an improved R0 resection rate. We reviewed the treatment and outcomes of SSTs in a single institution to identify prognostic factors and optimal treatment strategy. Methods Details of patients who underwent any type of treatment for SST from 1997 through 2014 were retrospectively collected. Survival was calculated by the Kaplan-Meier method. Proportional hazards regression was used to test the prognostic significance of factors in univariate and multivariate models. Results Eighty-nine patients were identified, 8 of whom had M1 disease and were excluded from the analysis. Of the 48 surgical patients, 44 received preoperative induction treatments, with 12 (25%) achieving a pathologic complete response (pCR), 23 with minimal residual disease, and 9 with gross residual disease. Complete resection was achieved in 40 surgical cases. As expected, nonsurgical patients had worse survival than did surgical patients (median survival, 2.1 versus 5.8 years; nonsurgical versus surgical hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2–3.7; p = 0.01). By multivariable Cox analysis, smoking status (HR, 4.4; 95% CI, 1.5–13.0; p = 0.01) and previous or concurrent malignancy (HR, 4.73; 95% CI, 1.6–13.9; p = 0.0.005) were prognostic factors for surgical patients. There were no statistically significant prognostic factors for nonsurgical patients. Conclusions Chemoradiotherapy followed by surgical treatment is our favored treatment for operable candidates. Preoperative induction treatments were associated with a 25% pCR rate for surgical patients. Candidates for surgical therapy are expected to have longer survival than those who are not candidates for resection.

// Ye Gu 1,* , Hong Shi 2,* , Chunxia Su 3 , Xiaoxia Chen 3 , Shijia Zhang 3 , Wei Li 3 , Fengying Wu 3 , Guanghui Gao 3 , Hao Wang 1 , Haiqing Chu 4 , Caicun Zhou 3 , Fei Zhou 3 and Shengxiang Ren 3 1 Department of Endoscopy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 2 Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 3 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine & Tongji University School of Medicine Thoracic Cancer Institute, Shanghai, China 4 Department of Respirology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Shengxiang Ren, email: // Fei Zhou, email: // Keywords : elastography, EBUS-TBNA, diagnosis, lung cancer, lymph nodes Received : October 19, 2016 Accepted : March 15, 2017 Published : July 06, 2017 Abstract Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used for diagnosis and mediastinal lymph nodes staging in patients with suspicious lung cancer. Ultrasound elastography is a novel sonographical technique that can evaluate tissue compressibility. The aim of the present study was to investigate the diagnostic yield of elastography for differentiating malignant and benign mediastinal lymph nodes. Conventional EBUS B-mode features, including size, shape, border distinction, echogenicity, central hilar structure with central blood vessel and coagulation necrosis were also evaluated. The ultrasonic features were compared with the pathological results from EBUS-TBNA. 133 lymph nodes in 60 patients were assessed. Elastography displayed the highest area under the curve (AUC) (type 3 versus type 1: AUC, 0.825; 95% confidence interval [CI], 0.707-0.910) with an impressive sensitivity (100%) and an acceptable specificity (65%). The combined model covering the four positive criteria (elastography, heterogeneity, size, and shape) showed that the odds ratio for malignance is 9.44 with a 95% CI of 3.99 to 22.32 ( p

Advanced non-small cell lung cancer (NSCLC) patients harboring non-resistant uncommon epidermal growth factor receptor (EGFR) mutations have stepped into the era of targeted therapy. This study aimed to investigate the incidence of acquired T790M mutation and their outcome to subsequent osimertinib in patients of advanced NSCLC harboring uncommon EGFR mutations.Patients with EGFR mutation and performed re-biopsy after progression on prior EGFR-tyrosine kinase inhibitors (TKIs) were reviewed and analyzed. Those with T790M mutation and received subsequent osimertinib treatment were further collected for survival analysis.Finally, 754 patients, including 48 with uncommon mutation, 362 with 19del and 344 with L858R were enrolled. T790M mutation was identified in 341 patients (341/754, 45.2 %). The incidence of T790M mutation was 27.1 % in patients harboring uncommon mutations, significantly lower than 55.2 % and 37.2 % of 19del and L858R (p 0.001). Logistic regression analysis further found uncommon mutation associated with significantly lower probability of developing T790M (odds ratio [OR] = 0.32, 95 % confidence interval [CI] 0.16-0.64). Among 236 patients received subsequent osimertinib treatment (including 12 uncommon mutation, 145 19del and 79 L858R), patients harboring uncommon mutations showed significantly shorter progression free survival (PFS) (median: 4.6 vs. 11.6 vs. 12.1 months, p 0.001) and overall survival (OS) (median: 8.1 vs. 35.4 vs. 24.9 months, p = 0.001) compared with 19del and L858R, also associated with numerically lower objective response rate (ORR) (p = 0.085) and lower disease control rate (DCR) (p = 0.074). Multivariate analysis further found that uncommon mutation was the only one significantly associated with both PFS (hazard ratio [HR] = 3.44, 95 %CI 1.79-6.58) and OS (HR = 3.64, 95 %CI 1.66-7.99).Uncommon EGFR mutation showed a significantly lower incidence of acquired T790M mutation and benefited significantly less from subsequent osimertinib treatment than common EGFR mutations in patients with advanced NSCLC.

In this paper, the three-dimensional magnetic field analysis of a dual-stator permanent magnet spherical motor is carried out by the finite element simulation software ANSYS. This method uses ANSYS Parametric Programming Language (APDL) to simulate the motor and then analyze the data through MATLAB. Parametric modeling involves building geometric models, assigning material properties and meshing, and then applying loads and boundary conditions to solve them. Compared with traditional Graphical User Interface (GUI) modeling methods, parametric analysis can modify parameters, analyze multiple sizes, adjust to achieve harmonic analysis, and successfully implement the function of 3D magnetic field analysis. The results verify that the method has high precision and high efficiency.

Introduction: Programmed death-ligand 1 (PD-L1) staining is used in clinical practice to guide the proper use of immune checkpoint inhibitors. This study aimed to investigate the accuracy of PD-L1 staining of non-small cell lung cancer (NSCLC) cytological cell block samples. Methods: Paired cytological cell block and surgical resection samples were consecutively collected from January 2016 to February 2017 in Shanghai Pulmonary Hospital, Tongji University. Two trial-validated PD-L1 assays (28-8 and SP142) were used to quantify PD-L1 expression. Results: A total of 112 pairs of specimens were collected, including 68(60.7%) adenocarcinomas and 28(25.0%) squamous cell carcinomas. Based on a tumor proportion score (TPS) cutoff of 1% for the 28-8 and SP142 assays, PD-L1 expression was positive in 78.6% and 58.9% of surgical samples respectively, while PD-L1 expression was positive in 67.9% and 25.0% of cytological cell block samples. Based on staining by each antibody, fair to substantial concordance of PD-L1 expression was observed for cytological cell block specimens as compared to surgical resection (𝛋 ranges from 0.377 to 0.686). However, as the tumor cells in the cell block specimen increased, the consistency of PD-L1 expression increased. The concordance of PD-L1 expression in cell blocks with abundant cellularity was nearly perfect with various cutoffs (28-8: tumor cells over 400; SP142: tumor cells over 500). Conclusion: Cytological cell block specimens may serve as a surrogate for PD-L1 staining in patients of NSCLC when more than 400-500 cancer cells were contained (over 400 cancer cells for 28-8, over 500 cancer cells for SP142).

Since the discovery of anaplastic lymphoma kinase (ALK)-rearrangement in non-small lung cancer (NSCLC) in 2007, there are now four approved ALK tyrosine kinase inhibitors (TKIs) (crizotinib, ceritinib, alectinib, brigatinib) in the US with the most recent one (brigatinib) approved in the US on April 28, 2017 (1).

9620 Background: Lung cancer is the leading cause of cancer death worldwide. Kinase fusion represents an important type of somatic alterations which promote oncogenesis and serve as a diagnostic marker in lung cancer. This study aims to identify the landscape of kinase fusions in lung cancer and expand our understanding of druggable fusions, together providing valuable information for therapeutics decision making. Methods: We performed genomic profiling of tumor/plasma biopsies of a total of 18,839 Chinese lung cancer patients using next generation sequencing (NGS) by targeting 425 cancer-relevant genes. Patients’ clinical characteristics and treatment history were retrospectively studied. Results: A total of 1,048 patients (5.56%, 1,048/18,839) were identified with kinase fusions, including 815 adenocarcinomas (ADCs) and 34 squamous cell carcinomas (SCCs). Briefly, a total of 198 unique gene fusion events have been observed, including 37 recurrent fusions and 114 novel fusions which have previously not been documented. ADC patients with kinase fusions were relatively younger than SCC patients (median: 53 vs 61 years old, p< 0.01). The most frequently observed fusion was EML4-ALK for both ADCs (50.0%) and SCCs (32.4%), followed by FGFR3-TACC3 (29.4%) in SCCs and KIF5B-RET (11.8%), CD74-ROS1 (9.2%), CCDC6-RET (3.9%) and SLC34A2-ROS1 (2.3%) in ADCs, retrospectively. A total of 14 recurrent fusions including FN1-ALK, MEMO1-ALK, CUX1-ALK, KIF13A-RET and PHF20-NTRK1 were also identified at low frequencies. Of note, EML4- or STRN- ALK fusion events mainly rearranged in the intron 19 of ALK, but the breakpoints of VCL-ALK were mostly located upstream of ALK exon 18. Meanwhile, CD74-, SLC34A2- and TPM3- ROS1 rearrangement mainly occurred in the ROS1 introns 31, 33 and 34. In addition, among patients with novel fusions, RORB- ALK and AFF2-RET may potentially function as oncogenic drivers in lung cancer and have demonstrated clinical benefit from crizotinib treatment. Conclusions: Our data have depicted a comprehensive overview of the landscape of kinase fusions in lung cancer, which helps recognize potentially druggable fusions and translate into therapeutic applications.

To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p

Background HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas. Methods Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS). The efficacy of first line pemetrexed-based chemotherapy was investigated in patients with HER2-mutant and those with EGFR-mutant, ALK/ROS1-rearranged and KRAS-mutant advanced adenocarcinomas. Results HER2 mutations were detected in 29 of 572(5.1%) specimens from a selected population of EGFR/KRAS/BRAF/ALK/ROS1 negative patients. All of them are adenocarcinomas. Among patients with HER2-mutant lung cancers, 25 received pemetrexed-based first line chemotherapy. The objective response rate(ORR) was 36.0%. Their median progression free survival(PFS) was 5.1 months, which was similar with that of KRAS-mutant group (n = 40,5.0 months, p = 0.971), numerically shorter than that of EGFR-mutant group(n = 74, 6.5 months, p = 0.247) and statistically significantly shorter than that of ALK/ROS1-rearranged group (n = 39,9.2 months, p = 0.004). Furthermore, HER2 variants subgroup analysis showed that PFS was inferior in A775_G776insYVMA group compared with other variants (4.2 vs 7.2 months, p = 0.085). Conclusions Patients with advanced HER2-mutant lung adenocarcinomas showed an inferior outcome of first line pemetrexed-based chemotherapy compared to those with ALK/ROS1 rearrangements, which strengthen the need for effective HER2-targeted drugs in clinical practice. Electronic supplementary material The online version of this article (10.1186/s12885-018-4277-x) contains supplementary material, which is available to authorized users.

Background Non–small-cell lung cancer (NSCLC) patients with both epidermal growth factor receptor (EGFR) positive mutation and B-cell chronic lymphocytic leukemia/lymphoma-like 11 (BIM) deletion polymorphism had a poor clinical response to EGFR-tyrosine kinase inhibitors (TKIs). The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus chemotherapy versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletion polymorphism. Methods A retrospective, non-randomized analysis was conducted. BIM deletion polymorphism was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from peripheral blood cells. Clinical characteristics, overall survival (OS), progress-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared between EGFR-TKIs alone versus EGFR-TKIs plus chemotherapy group. Results 65 patients were enrolled. 36 of them received EGFR-TKIs and 29 received EGFR-TKIs plus chemotherapy. EGFR-TKIs plus chemotherapy had significantly higher ORR than TKIs alone (65.5% vs. 38.9%, P = 0.046). Median PFS was significantly longer in EGFR-TKIs plus chemotherapy group than in TKIs group (7.2 vs 4.7 m; P = 0.008). Median OS was numerically longer in EGFR-TKIs plus chemotherapy group than in TKIs alone (18.5 vs 14.2 m; P = 0.107). EGFR-TKIs plus chemotherapy was associated with more grade 3 or 4 hematological toxic effects than EGFR-TKIs alone. Conclusion EGFR-TKIs plus chemotherapy conferred a significantly higher ORR, prolonged PFS and numerically longer OS in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism. Further prospective studies are needed to validate these findings.

Background There is a lack of well-established biomarkers to predict the efficacy of pemetrexed-based therapy. In this prospective phase II study, we investigated the correlation of folate receptor (FR)-positive circulating tumor cell (CTC) level with pemetrexed efficacy in patients with advanced non-squamous non-small cell lung cancer (nsNSCLC). Methods A total of 98 nsNSCLC patients were enrolled. Peripheral blood was collected from each patient prior to initiation of treatment. FR-positive CTCs were enriched by immunomagnetic leukocyte depletion and quantified using LT-PCR method. Results Patients with relatively low CTC level (11-16 FU/3 mL, n = 32) showed a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to the ‘high CTC level group’ (≥16 FU/3 mL, n = 28; median PFS: 133 versus 320 days, hazard ratio[HR]=4.78, P = 0.0008; median OS: 632 days versus ‘not reached’, HR = 10.89, P = 0.0013). The ‘high CTC level group’ also achieved superior objective response rate (ORR) and disease control rate (DCR) over the ‘low CTC level group’ (ORR: 40.9% versus 9.5%, P = 0.0339; DCR: 100% versus 81.0%, P = 0.0485). The efficacy of pemetrexed in the ‘negative-CTC group’ ( Conclusions Our results implied that FR-positive CTC is an efficacious biomarker to predict the outcome of first-line pemetrexed-based therapy in nsNSCLC patients. Clinical trial identification ChiCTR-ONC-13003475. Legal entity responsible for the study Shanghai Pulmonary Hospital. Funding This study was partially supported by Shanghai Committee of Science and technology (No. 14411970800). The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Disclosure All authors have declared no conflicts of interest.

ALK-positive patients with non-small-cell lung cancer (NSCLC) exhibit more aggressive clinical progression, a poorer response to chemotherapy, and less favorable survival outcomes in comparison with ALK-negative patients. Although crizotinib has proved effective in treating ALK-positive NSCLC, this agent penetrates the blood–brain barrier poorly and CNS progression is common. As pemetrexed, a multitargeted antifolate chemotherapeutic agent, has demonstrated benefit in the control of brain metastases in patients with NSCLC, treatment with pemetrexed was added to crizotinib in a young male patient with ALK-positive NSCLC who had developed brain metastases during crizotinib therapy. After four cycles of pemetrexed chemotherapy, the patient’s brain lesions were significantly reduced in size and a chest CT scan showed that the lung lesions had stabilized.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival.A total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC. EGFR/BRAF/Kras mutations and ALK/ROS1 translocations were detected. Overall survival (OS) was evaluated by the Kaplan-Meier plots.The majority of LCNEC proved to be of the peripheral type (64.3%, 81/126). Central tumors were associated with smoking habit (p = 0.047), higher TNM-stage (p = 0.014) and larger tumor size (p 0.001). Expression of neuroendocrine markers (CD56, CGA, and SYN) was not significantly different by tumor location but central tumors had higher serum levels of NSE (p = 0.004). Peripheral tumors had a higher incidence of EGFR mutations (18.8% vs. 0%, p = 0.023). ROS1 translocation was detected in 1 patient with peripheral LCNEC. RB1 protein was more frequently expressed in peripheral tumor than central tumor. The median OS was 3.71 years in the entire cohort. Peripheral tumors had better survival compared with central tumors (median OS: 4.04 vs. 1.51 years, p 0.001). Multivariate analyses demonstrated tumor location (hazard ratio [HR], 6.07, 95% confidence interval [CI], 1.57-23.44, p = 0.009), resection status (HR, 6.58, 95% CI, 1.92-22.51, p = 0.003) and EGFR mutational status (HR, 0.18, 95% CI, 0.04-0.75, p = 0.018) were independent prognostic factors for OS.Primary tumor location of LCNEC, divided into central and peripheral type, has distinct clinicopathologic features, genomic characteristics and survival. These differences are likely due to differences in the origin cells and pathogenesis of these tumors.

Background CD73 is one of the critical component in the formation of immunosuppressive microenvironment in cancers. We aimed to provide an overview of the current status of CD73 expression and its relationship with clinicopathlogical features and prognosis in different cancers. Methods PubMed, Web of Science, EMBASE and Cochrane library were searched to identify the relevant studies. CD73 expression level in distinct cancers and its relationship with clinicopathlogical characteristics and prognosis were investigated using online database. Meta-analyses were conducted using RevMan v5.0 and STATA v12.0. Results Fourteen publications with 2951 cases were included. The incidence of high CD73 expression was 0.50 (95% CI: 0.36–0.63). Data from Oncomine validated that median CD73 expression level in tumor tissues was markedly higher than that in normal tissues in most kinds of cancers except cecum adenocarcinoma and ovarian cancer (P

74 Background: In China, lung cancer pts see different hospitals in various places, but medical info is not shared among different medical centers. It is difficult to obtain complete medical info to evaluate the quality of drug treatment & prognosis of lung cancer pts. Methods: We created a pt’s self-submitted data interactive platform to record and store pt’s info such as locations, gender, diagnosis, treatment etc., & to follow up on pt’s real-world medical info in real time. Based these records, a scientific method was used to establish a real medical treatment data set for lung cancer pts to reflect actual medical treatment process. Results: Between 9/13/2018 - 5/30/2019, 5 rare mutation projects (ROS1, RET, EGFR exon20, HER2, EGFR resistance) were initiated. Data cutoff is 6/15/2019. In all 5 projects, we collected by far the largest number of real-world pt’s self-submitted data reported in China. All cases were confirmed by commercial NGS or PCR. In all 5 projects, there were significant differences in regional distributions of patients. The median age for all 5 projects are: 50, 55, 57, 56 and 55, respectively. A total of 95.6% of pts submitted their 1st-line treatment info & 93.8% received 1st-line treatment. Conclusions: Pts self-submitted interactive platform provides valuable insights for trial design to reconsider site selection, & pts’ criteria selection for the success of the trial in rare mutations lung cancer. [Table: see text]