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Kaplan-Meier curves for progression-free survival in subgroups.

Purpose:Preclinical and retrospective studies suggested a role for metformin in sensitizing patients who have diabetes with non–small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs). We therefore examined its effects in combination with gefitinib in patients without diabetes harboring EGFR mutations (EGFRm).Patients and Methods:A total of 224 patients without diabetes with treatment-naïve stage IIIB–IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of IL6 were also examined in an exploratory analysis.Results:The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2% [95% confidence interval (CI), 30.0–52.2] with gefitinib plus metformin and 42.9% (95% CI, 32.6–52.7) with gefitinib plus placebo (P = 0.6268). Median PFS (10.3 months vs. 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group, while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of IL6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared with the control arm (78.38% vs. 43.24%).Conclusions:Our study showed that addition of metformin resulted in nonsignificantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in patients without diabetes with EGFRm NSCLC.

A newly designed copper loaded nitrogen-rich mesoporous carbon nitride for photocatalytic selective oxidative cleavage of C(sp3)–C(sp3) bonds at room temperature is presented.

Purpose To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients. Methods A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤ 3.17), high NLR group (NLR༞3.17), low PCT group (PCT ≤ 0.06; ng/ml), high PCT group (PCT༞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS. Results The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤ 3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; P = 0.675). Patients with low pretreatment PCT (PCT ≤ 0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT༞0.06; ng/ml) (6.9 months vs 5.7 months; P = 0.043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (P ≤ 0.001) and pretreatment PCT (HR = 0.516; 95%CI 0.326–0.817; P = 0.005) were identified as independent factors associated with PFS. Conclusion Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.

BACKGROUND Telehealth has emerged as an effective channel providing outpatient services in many countries. However, majority telehealth systems focus on operational functions offering sectional patient journey at the most. How to achieve comprehensive yet longitudinal real-world data by taking advantage of telehealth is yet to be studied. OBJECTIVE The primary purpose of this study is to understand the feasibility and benefits of building a live-fed longitudinal lung cancer real-world data platform supplemental to hospital electronic medical records systems. METHODS A telehealth platform was built and launched for physician and patient registration. Real-world data was collected and curated using a comprehensive data model. Patient stratification was performed directly from the database for statistical analysis. RESULTS Over a period of 15 months, 16035 unique users (13888 patients, 1539 friends and family members, 608 physicians) were registered. 232195 messages including EMRs and ePROs were curated and entered in the database, using medical records from 9907 patients as a basis. Comprehensive and longitudinal diagnosis and treatment data were established for 46% of the patients at the time of writing. Patient demographics from the database show the current treatment journey and practices of lung cancer in China. CONCLUSIONS This study indicates that a well-designed telehealth platform is feasible to acquire live- fed longitudinal real-world data, which further empowers physicians to effectively manage patients’ treatments and engagement.

Immunotherapy has been a revolutionary innovation in cancer therapy in recent years, but it is accompanied by various unique immune-related adverse events (irAEs). Among these irAEs, anaphylactic shock is very rare. Here, we report a case of a patient who developed anaphylactic shock after receiving one dose of atezolizumab. A 74-year-old male patient with small cell lung cancer experienced recurrence 10 years after surgery. After one cycle of treatment, the patient developed a grade 2 rash and recovered after receiving oral methylprednisolone tablets. In the second cycle, atezolizumab was discontinued. Then, the patient was scheduled to receive atezolizumab plus carboplatin and etoposide again after three weeks, but approximately three minutes after an intravenous infusion of atezolizumab, the patient developed signs and symptoms of anaphylactic shock, such as dyspnea, cold limbs, and loss of consciousness. At this point, the infusion was immediately stopped, and a normal saline infusion was administered. Meanwhile, ECG monitoring, supplemental humidified high-flow supplemental 100% oxygen, epinephrine, dopamine, hormone treatment with methylprednisolone, and other anti-shock treatments were carried out. For better recuperation, this patient was transferred to the intensive care unit for further treatment and was discharged two days later. Anaphylactic shock develops rapidly and is also a very severe complication. Prompt detection, diagnosis, and therapeutic intervention are the basics for survival.

At present, there is no accurate biomarker for immune checkpoint inhibitors (ICIs). Since the efficacy of ICIs is associated with a variety of indicators, establishing a model to predict its efficacy is more clinically significant and in line with clinical needs.We collected and retrospectively analyzed the relationship between immunotherapy efficacy and clinicopathologic features in lung adenocarcinoma patients treated with ICIs. Progression-free survival (PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox proportional hazards regression analyses were conducted to identify prognostic factors associated with PFS. Besides, a clinical prediction model was established based on the results of the multivariate Cox regression analyses to predict PFS.A total of 201 lung adenocarcinoma patients treated with ICIs were assessed. Univariate analysis showed that male gender [hazard ratio (HR) =0.521, 95% confidence interval (CI): 0.356-0.761, P=0.001], smoking (HR =0.595, 95% CI: 0.420-0.843, P=0.003), epidermal growth factor receptor (EGFR) wild type (HR =2.766, 95% CI: 1.719-4.452, P0.001), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (HR =0.449, 95% CI: 0.271-0.743, P=0.001), positive programmed death ligand 1 (PD-L1) expression (HR =0.527, 95% CI: 0.336-0.825, P=0.004), early tumor node metastasis (TNM) stage (HR =0.581, 95% CI: 0.344-0.983, P=0.039), no liver metastasis (HR =1.801, 95% CI: 1.046-3.102, P=0.031), ICIs combined with chemotherapy (HR =0.560, 95% CI: 0.384-0.815, P=0.002), having immune-related adverse effects (HR =0.354, 95% CI: 0.228-0.511, P0.001) and first-line immunotherapy (HR =0.596, 95% CI: 0.420-0.845, P=0.003) were significantly associated with better PFS in patients with lung adenocarcinoma receiving immunotherapy. Multivariate analysis showed that smoking status, KRAS mutation, PD-L1 expression, line of immunotherapy and immune-related adverse effects were independent prognostic factors affecting PFS. A clinical prediction model was established to predict the PFS of lung adenocarcinoma patients treated with ICIs. The model showed good predictive ability via C-index, calibration curve and receiver operating characteristic (ROC) curve validation.The clinical prediction model developed in this study can be used to some extent to predict PFS after immunotherapy in lung adenocarcinoma patients. However, the model still needs to be validated in studies with large sample size.

Introduction Continuing tyrosine kinase inhibitor (TKI) therapy may be beneficial when patients with non–small-cell lung cancer and EGFR mutations experience gradual disease progression after initial EGFR-TKI treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients’ disease gradually progressed after first-line EGFR-TKI treatment. Patients and Methods Patients with gradual progression who were EGFR-T790M mutation negative were randomly divided into two groups. In the concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI. In the sequential group, patients continued with EGFR-TKI until the disease progressed again, according to RECIST, then switched to chemotherapy. We evaluated the patients’ progression-free survival (PFS) and overall survival times. Results Ninety-nine patients were enrolled: 49 in the concurrent group and 50 in the sequential group. The median PFS (mPFS) was 7.7 months (95% confidence interval [CI], 3.6-11.7) in the concurrent group and 5.7 months (95% CI, 3.5-7.9) in the sequential group (hazard ratio = 0.66; 95% CI, 0.44-1.00; P = .026), respectively. For the sequential group, the mPFS1 and mPFS2 were 1.8 months (95% CI, 1.4-2.3) and 3.8 months (95% CI, 3.1-4.5), respectively. The median overall survival of the concurrent group was longer than that of the sequential group (20.0 vs. 14.7 months; hazard ratio = 0.52; 95% CI, 0.32-0.85; P = .038). Conclusion For patients with advanced non–small-cell lung cancer and gradual progression who are EGFR-T790M mutation negative after initial EGFR-TKI therapy, EGFR-TKI combined with chemotherapy confers longer PFS and overall survival than sequential EGFR-TKI and chemotherapy does.

Lung cancer with extrathoracic metastases is classified as M1c. However, extrathoracic metastases can be further classified into different patterns. The purpose of this study was to analyze the survival differences between different patterns of extrathoracic metastases in patients with stage M1c lung adenocarcinoma after receiving immunotherapy.This study included 160 stage M1c lung adenocarcinoma patients and treated with immunotherapy. The enrolled patients were divided into two groups: those with multiple extrathoracic metastases alone (EM group) and those with simultaneous multiple extrathoracic and intrathoracic metastases (EIM group). Progression-free survival (PFS) and overall survival (OS) were evaluated.The median PFS and OS in the whole group were 7.7 months and 25.4 months, respectively. The patients in the EM group show better PFS (13.0 months vs. 5.0 months; hazard ratio [HR] = 0.462, 95% confidence interval [CI] 0.317-0.673, P 0.0001) and OS (35.0 months vs. 18.9 months; HR 0.592, 95% CI 0.380-0.922, P = 0.019) compared with the EIM group. Furthermore, in patients with lung adenocarcinoma with simultaneous extrathoracic and intrathoracic metastases who received immunotherapy, immunotherapy combined with chemotherapy has better PFS and OS than immunotherapy alone. There was no difference between immunotherapy alone or combined with chemotherapy in patients with lung adenocarcinoma with extrathoracic metastasis alone.The different patterns of extrathoracic metastasis were related to the efficacy and prognosis of immunotherapy in M1c cohort. In addition, patients with simultaneous extrathoracic and intrathoracic metastases were more recommended to choose immunotherapy in combination with chemotherapy rather than immunotherapy alone.

BACKGROUND: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation. METHODS: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status. RESULTS: For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38–0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13–0.32, P

Comorbidity of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. Surgical operation is the initial treatment of lung cancer. But surgery operation will aggravate the symptoms of COPD, such as shortness of breath, chest tightness. On the other side, the COPD also increase the perioperative complications. Besides, the COPD may also influence the anti-cancer treatment and long-term survival of lung cancer patients. At present, there are guidelines for pulmonary rehabilitation (PR) of COPD or lung cancer respectively, but there is no reference expert consensus on the PR of patients with lung cancer who are comorbidity of COPD. Primary care has to satisfy the patient's complex needs holistically, and single-disease guidelines are unsuitable. In view of this, we organized experts from respiratory department, thoracic surgery department, oncology department, nursing department, etc., to write the expert consensus. We discussed the contents of the expert consensus through literature review, expert correspondence, expert meeting and discussion. This expert consensus contain five parts: introduction, respiratory assessment, timing of PR, PR strategies, perioperative PR management strategies in lung cancer patients with COPD. This expert consensus focuses on patients with COPD comorbid lung cancer and undergoing surgery operation, highlighting the concept of whole process management. For clinical medical staff, this expert consensus will promote the practice of PR in and out the hospital for this specific patient; for patients, this expert consensus is helpful to better understand PR and improve the enthusiasm of participating in PR in the whole process.

Feng Pan,1,* Ai-Ting Lu,1,2,* Xiaowei Mao,1,* Yefeng Chen,3 Yizhuo Zhao,1 Baohui Han1 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, 312000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohui Han; Yizhuo ZhaoDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaEmail 18930858216@163.com; zhyz920916@126.comBackground: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable tool for diagnosing pulmonary disease due to its efficiency and safety. We retrospectively analyzed patients with mediastinal masses who underwent diagnostic EBUS-TBNA at Shanghai Chest Hospital, and evaluated the clinical accuracy of EBUS-TBNA in the diagnosis mediastinal masses.Method: From 2009 and 2014, patients who received EBUS-TBNA to diagnose a isolated mediastinal mass were enrolled. Clinical follow-up was performed to ascertain the patient’s final diagnosis.Results: Forty-six patients were enrolled in this study. Thirty-seven were diagnosed with an oncologic disease, 3 were diagnosed with a mediastinal infection, and 2 were found to have a mediastinal goiter. The overall sensitivity, specificity, positive predictive value, negative predictive value, diagnostic yield was 63.6%, 100%, 100%, 42.9%, and 71.4%, respectively.Conclusion: EBUS-TBNA is a safe and effective means of diagnosing mediastinal masses.Keywords: EBUS-TBNA, mediastinum, diagnosis

Objectives To establish a circulating tumor cell (CTC) enrichment system for non-small cell lung cancer (NSCLC) patients who received first-line treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKI), using EGFR magnetic liposomes (EGFR-ML). Materials and methods An inverted evaporation method was used to develop antibody modified EGFR-ML. Peripheral blood was collected from NSCLC patients who underwent first-line EGFR-TKI treatment for CTC enumeration. Results Protein electrophoresis, magnetic saturation curve, and ultraviolet absorption spectrum showed successful incorporation of the EGFR antibody on the surface of the magnetic microspheres, and the development of EGFR-ML was ascertained based on cell morphology and particle size. Using EGFR-ML, CTC were successfully enriched from blood samples and were identified in 77.3% (99/128) of the cohort. When compared to the 21L858R variant, EGFR-19del showed lower CTC counts by EGFR-ML (CTCEGFR). At one month after EGFR-TKI, a lower CTCEGFR was associated with partial response (PR) during treatment (CTCEGFR Conclusion We showed that establishing a CTC enrichment system by antibody modified EGFR-ML in NSCLC is feasible. CTC enumeration by EGFR-ML may have the potential to supplement RECIST in dynamically monitoring the response of NSCLC patients’ to first-line EGFR-TKI.

Immunotherapy has been a revolutionary innovation in cancer therapy in recent years, but it is accompanied by various unique immune-related adverse events (irAEs). Among these irAEs, anaphylactic shock is very rare. Here, we report a case of a patient who developed anaphylactic shock after receiving one dose of atezolizumab. A 74-year-old male patient with small cell lung cancer experienced recurrence 10 years after surgery. After one cycle of treatment, the patient developed a grade 2 rash and recovered after receiving oral methylprednisolone tablets. In the second cycle, atezolizumab was discontinued. Then, the patient was scheduled to receive atezolizumab plus carboplatin and etoposide again after three weeks, but approximately three minutes after an intravenous infusion of atezolizumab, the patient developed signs and symptoms of anaphylactic shock, such as dyspnea, cold limbs, and loss of consciousness. At this point, the infusion was immediately stopped, and a normal saline infusion was administered. Meanwhile, ECG monitoring, supplemental humidified high-flow supplemental 100% oxygen, epinephrine, dopamine, hormone treatment with methylprednisolone, and other anti-shock treatments were carried out. For better recuperation, this patient was transferred to the intensive care unit for further treatment and was discharged two days later. Anaphylactic shock develops rapidly and is also a very severe complication. Prompt detection, diagnosis, and therapeutic intervention are the basics for survival.

Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P = 0.004 ), mutant TP53 (PFS = 5.0 months, P = 0.011 ), and mutant BRCA2 (PFS = 6.7 months, P = 0.046 ) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038–6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096–3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721–12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181–0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.

Objective: Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and c-MET; therefore, it exhibits both antitumor and anti-angiogenetic activities. A phase III trial has shown that anlotinib improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC), who presented with progressive disease or intolerance after standard chemotherapy. This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods: Data were collected from March 2015 to January 2017 from a randomized, double-blind, placebo-controlled, multicenter, phase III trial of anlotinib (ALTER0303). A total of 437 patients were enrolled and randomly allocated (2:1) to the anlotinib and placebo groups. Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS. Cox proportional hazards model was adopted for multivariate prognostic analysis. Results: Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS. Meanwhile, elevated thyroid-stimulating hormone, blood glucose, and triglyceride levels; hypertension; and hand–foot syndrome were independent protective factors of PFS. High post-therapeutic peripheral blood granulocyte/lymphocyte ratio, an Eastern Cooperative Oncology Group (ECOG) score ≥ 2, and the sum of the maximal target lesion length at baseline were independent risk factors of OS, and hypertriglyceridemia was an independent protective factor of OS. Conclusions: This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC, and the baseline characteristics of the therapeutically dominant populations were then identified.

The application of iron nitrides in lithium-ion batteries is greatly hindered by the fast capacity decay. Fabricating iron nitride/porous carbon composite will bring about a superior electrochemical performance, but facile and green synthesis of this composite is a great challenge. In this work, a facile and green method is developed to prepare a novel Fe24N10/porous carbon composite. The obtained Fe24N10 particles are grown in porous carbon, which can significantly alleviate volume change during the cyclic process and elevate electrical conductivity and Li+ ion transfer. As a result, a high discharge capacity of 370 mA h g−1 is retained at 2000 mA g−1 after 300 cycles.

Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and tumor cell proliferation. The efficacy of anlotinib as a third-line or beyond therapy for SCLC was confirmed in the ALTER1202 trial. For lung cancer patients treated with antiangiogenesis agents, the phenomenon of cavitation is commonly seen in the lung target lesions. The impact of tumor cavitation on survival in lung cancer patients treated with vascular-targeted therapy remains controversial. Our retrospective study was to investigate the prognostic value of tumor cavitation in extensive-stage SCLC patients treated with anlotinib. A total of 73 extensive-stage SCLC patients confirmed by histopathology from January 2018 to January 2019 were retrospectively analyzed. All patients received anlotinib therapy at Shanghai Chest Hospital. We defined tumor cavitation of the lung target lesions as that part of solid component was changed to air-filled area according to chest CT. Progression-free survival (PFS) was calculated from the beginning of anlotinib therapy to the disease progression or the last follow-up visit. Eleven (15.0%) patients had tumor cavitation during anlotinib therapy. The ORR of the 73 patients was 15.1%. Multivariate logistic regression analysis showed that tumor cavitation during anlotinib therapy was not associated with gender (P = 0.630), age (P = 0.190), smoking status (P = 0.165), anatomy type (P = 0.641), and the line of anlotinib therapy (P = 0.302). The median PFS of all patients was 2.6 months (95%CI 2.1–3.2). According to the univariate analysis, the median PFS in patients with and without tumor cavitation was 5.0 months and 2.2 months, respectively, and the difference was statistically significant (P = 0.041). According to the multivariate analysis, tumor cavitation was an independent factor for PFS after adjusting gender, age, smoking status, anatomy type, the line of anlotinib therapy, tumor cavitation, and response to anlotinib (adjusted HR 0.316, 95%CI 0.142–0.702; P = 0.005). In 73 extensive-stage SCLC patients treated with anlotinib, no demographic/clinical characteristic was related to tumor cavitation, and tumor cavitation was an independent factor in predicting better PFS.

Purpose: Preclinical and retrospective studies suggested a role for metformin in sensitizing patients who have diabetes with non–small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs). We therefore examined its effects in combination with gefitinib in patients without diabetes harboring EGFR mutations (EGFRm). Patients and Methods: A total of 224 patients without diabetes with treatment-naïve stage IIIB–IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of IL6 were also examined in an exploratory analysis. Results: The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2% [95% confidence interval (CI), 30.0–52.2] with gefitinib plus metformin and 42.9% (95% CI, 32.6–52.7) with gefitinib plus placebo (P = 0.6268). Median PFS (10.3 months vs. 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group, while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of IL6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared with the control arm (78.38% vs. 43.24%). Conclusions: Our study showed that addition of metformin resulted in nonsignificantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in patients without diabetes with EGFRm NSCLC.

// Shaohua Cui 1, * , Wei Zhang 1, * , Liwen Xiong 1 , Feng Pan 1 , Yanjie Niu 1 , Tianqing Chu 1 , Huimin Wang 1 , Yizhuo Zhao 1 , Liyan Jiang 1 1 Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China * These authors contributed equally to this work Correspondence to: Liyan Jiang, email: Jiang_liyan2000@126.com Yizhuo Zhao, email: zhyz920916@126.com Keywords: liquid biopsy, anaplastic lymphoma kinase (ALK), capture-based next-generation sequencing, cell-free DNA (cfDNA), non-small-cell lung cancer (NSCLC) Received: September 23, 2016 Accepted: November 23, 2016 Published: December 01, 2016 ABSTRACT Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK -positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK -positive samples were identified by capture-based NGS among the 24 samples with tissue ALK -positivity. In addition to EML4-ALK , 2 rare fusion types ( FAM179A-ALK and COL25A1-ALK ) were also identified. The overall sensitivity, specificity and accuracy for all cases were 54.2%, 100% and 71.8%, respectively. For patients without distant metastasis (M0-M1a) and patients with distant metastasis (M1b), the sensitivities were 28.6% and 64.7%, respectively. In the 15 patients who received crizotinib, the estimated median PFS was 9.93 months. Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis. This non-invasive method is clinically feasible for detecting ALK fusion in patients with advanced-stage NSCLC who cannot undergo traumatic examinations or have insufficient tissue samples for molecular tests.