Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis.

BACKGROUND: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients. METHODS: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients. RESULTS: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy. CONCLUSION: Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial.

PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Quality of life with adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant non-small-cell lung cancer: Results from the ADJUVANT (CTONG1104) study.

OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, p =  0.019; LCSS, 1.13, 1.04-1.22, p =  0.003; TOI, 88.39, 4.40-1775.05, p =  0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, p =  0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, p =  0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, p =  0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator for patients undergoing minimally invasive lung cancer surgery: Propensity score matching analysis using a prospective database.

OBJECTIVES: To evaluate prognostic significance of albumin-to-alkaline phosphatase ratio (AAPR) for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC) by a propensity score-matching (PSM) analysis. METHODS: This PSM study was conducted on the prospectively-maintained database in our institution between December 2013 and March 2015. Overall survival analyses and further subgroup analyses were both performed to distinguish the differences in postoperative survival between patients stratified by an optimal cutoff of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors. RESULTS: There were 390 patients with operable NSCLCs included. An AAPR of 0.57 was identified as the optimal cutoff regarding to postoperative survival. Both overall survival (OS) and disease-free survival (DFS) in patients with AAPR≤0.57 were significantly shortened compared to those in patient with AAPR>0.57 (Log-rank P < 0.001). Patients with AAPR≤0.57 had significantly lower rates of OS and DFS than those of patients with AAPR>0.57 (P < 0.001). These differences still remained significant after subgroup analyses and PSM analyses. Multivariate analyses on the entire cohort and the PSM cohort commonly indicated that low preoperative AAPR could be an independent prognostic factor for unfavorable OS and DFS of resected NSCLCs. CONCLUSIONS: AAPR can serve as a novel risk stratification tool to refine prognostic prediction for surgical NSCLC. It may help surgeons to screen high-surgical-risk patients and further formulate individualized treatment schemes.

Fat-free mass index is superior to body mass index as a novel risk factor for prolonged air leak complicating video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer.

BACKGROUND: To evaluate whether fat-free mass index (FFMI) could be predictive of prolonged air leak (PAL) complicating video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: A retrospective study was conducted on the prospectively-maintained database in our institution between January 2015 and July 2017. The gender-specific median values of FFMI for males and females were applied as their respective cutoffs to stratify patients into low-FFMI group and high-FFMI group in initial univariable analyses. An effective multivariable logistic-regression analysis was then performed to demonstrate the predictive value of dichotomized FFMI. RESULTS: There were 1,091 surgical patients with NSCLC included (616 males and 475 females), with a PAL incidence of 14.6%. The median FFMI values among males and females were 17.3 and 14.6 kg/m2, respectively. PAL cases in both male (16.9±1.5 vs. 17.4±1.5 kg/m2; P=0.002) and female (14.0±0.9 vs. 14.6±1.1 kg/m2; P<0.001) groups had a significantly lower mean FFMI than that of non-PAL cases. The incidence of PAL was significantly increased in male patients with FFMI <17.3 kg/m2 (23.7% vs. 14.3%; P=0.003) and female patients with FFMI <14.6 kg/m2 (12.7% vs. 5.0%; P=0.003). Lower dichotomized FFMI was also significantly associated with prolonged time to air leak cessation and length of stay (LOS). Finally, multivariable logistic-regression analysis indicated that lower dichotomized FFMI [odds ratio (OR) =1.98; 95% confidence interval (CI): 1.33-2.96; P=0.001] could independently predict the occurrence of PAL. CONCLUSIONS: FFMI acts as an excellent categorical risk factor for PAL complicating VATS lobectomy and shows a much superior significance than body mass index (BMI) in terms of the prediction of PAL.

Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study.

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

Lung Adenocarcinoma has a Higher Risk of Lymph Node Metastasis than Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Controversy still exists in which subtype of non-small-cell lung cancer [squamous cell carcinoma (SCC) or adenocarcinoma] is more likely to have lymph node (LN) metastasis. The aim of this study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma. METHODS: A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors. RESULTS: From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (P = 0.90) and rate of LN metastasis (P = 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7; P = 0.008) and a higher rate of LN metastasis (53% and 29%; P = 0.016) than those with SCC. CONCLUSIONS: Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.

The Unique Spatial-Temporal Treatment Failure Patterns of Adjuvant Gefitinib Therapy: A Post Hoc Analysis of the ADJUVANT Trial (CTONG 1104).

INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.

[The Development of Huaxi Intelligent Endoscopic Skill Training and Assessment System].

OBJECTIVE: To develop a novel objective standardized endoscopic skill training and assessment system based on artificial intelligence technology. METHODS: By designing five basic skill parts of endoscopic operation including vision location, clamping, delivering, shearing and suturing, we achieved objective standardized indexes which gained automatically with image recognition and refined perception. RESULTS: With Huaxi intelligent endoscopic skill training system, the accurate rates of vision location, clamping, delivering, shearing and suturing were 90%, 95%, 99%, 90%, and 89%, respectively. The response and performance time were 8-10 s, <1 s, <1 s, 1-3 s, and <1 s, respectively. CONCLUSION: Huaxi intelligent endoscopic skill training and assessment system has preliminarily possessed the capability to assess the endoscopic skills of surgeons objectively.

The influence of heparin on coagulation function of patients undergoing video-assisted major thoracic surgery.

BACKGROUND: Venous thromboembolism (VTE) remains a common complication after major thoracic surgery, especially resection of lung or esophagus cancer. This trial aims to explore the influence of preoperative usage of heparin on coagulation function of patients treated with video-assisted major thoracic surgery. METHODS: This prospective randomized control trial collected 91 patients who are diagnosed with lung or esophagus cancer intending to accept video-assisted neoplasm resection from June 2016 to May 2017 in West China Hospital, Sichuan University. After admission to hospital, the patients received heparin sodium (unfractionated heparin) 5,000 U twice a day before operation. The change of blood platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), international normalized ratio (INR) was collected and analyzed at the points of admission to hospital and post-operation. RESULTS: The mean value of all coagulation parameters (PLT, PT, APTT, TT, INR, FIB) were in normal range both before and after operation. Postoperative PLT and FIB were not significantly different from preoperative PLT and FIB respectively (P>0.05). Preoperative PT, APTT, and INR increased significantly compared to pre-operation respectively (P<0.05). Postoperative TT significantly decreased when compared to preoperative TT (P<0.05). Preoperative and postoperative abnormal rate of PT or APTT or TT or INR (number of abnormal cases/all cases) was not different significantly respectively (P>0.05). Postoperative mean drainage was 240 mL/d, mean time of hospital stay was 7.50 days, drainage tube was maintained for 4.22 days on average. CONCLUSIONS: All patients underwent video-assisted major thoracic surgery with preoperative use of heparin, there were significant differences in coagulation function after operation. However, mean values of all coagulation parameters stayed normal range clinically. In a word, the method showed no influence on coagulation function clinically.

Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing video-assisted thoracoscopic lung cancer lobectomy.

BACKGROUND: The purpose of our cohort study was to investigate the effects of pleural adhesions on perioperative outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: We performed a single-center retrospective analysis on the prospectively-maintained dataset at our unit from February 2014 to November 2015. Patients were divided into two groups (Group A: presence of pleural adhesions; Group B: absence of pleural adhesions) according to our grading system of pleural adhesions when entering the chest cavity. Demographic differences in perioperative outcomes between these two groups were initially estimated. A multivariate logistic-regression analysis was then performed to confirm the predictive value of the presence of pleural adhesions. RESULTS: A total of 593 NSCLC patients undergoing VATS lobectomy were enrolled. The conversion and postoperative morbidity rates were 3.2% and 29.2%, respectively. There were 154 patients with pleural adhesions (Group A) and 439 patients without pleural adhesions (Group B). Group A patients had significantly higher rates of conversion to thoracotomy (9.1% vs. 1.1%; P<0.001) and surgical complications (24.0% vs. 14.4%; P=0.006) than those of Group B patients. No significant difference was found in the overall morbidity and cardiopulmonary complication rates between these two groups. The presence of pleural adhesions was also significantly associated with the prolonged length of chest tube drainage (log-rank P<0.001) and length of stay (log-rank P=0.032). Finally, the presence of pleural adhesions was identified as an independent risk factor for conversion to thoracotomy [odds ratio (OR) =5.49; P=0.003] and surgical complications (OR =1.94; P=0.033) by multivariate logistic-regression analyses. CONCLUSIONS: Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing VATS lobectomy for NSCLC. Our study calls for an internationally accepted grading system for the presence of pleural adhesions to stratify the surgical risk.

Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

Oesophageal adenocarcinoma has a higher risk of lymph node metastasis than squamous cell carcinoma: a propensity score-matched study.

OBJECTIVES: The pattern of lymph node metastasis is a predominant element in tumour biology, which is closely related to optimal therapeutic modality. Controversy remains as to which histopathology type of oesophageal cancer-adenocarcinoma or squamous cell carcinoma (SCC)-is more likely to have lymph node metastasis. Therefore, this study aimed to apply propensity score-matched analysis to draw an objective conclusion for providing initial evidence of the potential need for different therapeutic strategies for these 2 cancer types. METHODS: A retrospective analysis of patients who underwent radical oesophagectomy with lymphadenectomy, but without preoperative treatment for pathologically and immunohistochemically diagnosed oesophageal adenocarcinoma or SCC, was conducted. Data for analysis included age, gender, body mass index, pathologic findings, procedures of oesophagectomy and rate of lymph node metastasis. Propensity score-matched analysis was conducted to eliminate the bias effects of confounding factors. RESULTS: A total of 1204 patients (including 118 with adenocarcinoma and 1086 with SCC) from January 2012 to June 2016 was included for analysis. In the analysis of unmatched patients, those with adenocarcinomas had significantly larger mean numbers of positive lymph nodes (3.8 and 1.5, respectively; P < 0.001) and higher rates of lymph node metastasis (71.2% and 49.0%, respectively; P < 0.001) than those with an SCC. However, other confounding factors such as surgical procedures, tumour location, pT stage and lymphovascular invasion also differed significantly between the adenocarcinoma and SCC cases. In the analysis of 96 matched patients, those confounding factors were well matched, and cases of adenocarcinoma still had a significantly larger mean number of positive lymph node (4.5 and 1.8, respectively; P = 0.003) and higher rate of lymph node metastasis (75.0% and 45.8%, respectively; P = 0.003) than did those with SCC. CONCLUSIONS: Cases of oesophageal adenocarcinoma had a higher risk of lymph node metastasis than did those with SCC in this series, which indicates that different therapeutic modalities should be applied for these 2 different malignant entities.

[The Methods and Clinical Significance of Early Diagnosis of Lung Cancer].

Lung cancer is the leading contributor to morbidity and mortality from cancer worldwide, with its 5-year overall survival being only about 15.6%. Due to the lack of specific early screening methods for lung cancer, about 75% patients are diagnosed late. Therefore, it remains the big challenge for the early diagnosis of lung cancer. We need to pay more attention to the screening of lung cancer, and more precise assessment and management to the pulmonary nodules screened out. Further study on liquid biopsy, optimization of new fiberoptic bronchoscopy and the sampling methods to harvest small volume of lung tissue, could be helpful to improve the early diagnosis of lung cancer.

[Diagnosis and Surgical Treatment of Lung Ground-glass Opacities:a Review of 663 Cases].

OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

The safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery: a pilot randomized controlled study.

BACKGROUND: Patients undergoing major thoracic surgery especially for cancers are at a high risk of perioperative thromboembolism. Current guidelines recommended either heparin sodium (unfractionated heparin) or low-molecular-weight heparin (LMWH) for those patients at high risk of deep vein thrombosis (DVT). However, the rational timing of starting heparin has not yet been well established, because DVT can be caused by not only surgery but also comorbidities as well as prolonged hospital stay, and thoracic surgeons always concerned about heparin-related increased risk of intra- or post-operative bleeding. Therefore, this study aimed to establish the safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery. METHODS: From June to August 2016, patients intended for thoracoscopic lobectomy, esophagectomy, and thymectomy were randomly assigned into two groups: the case group (starting heparin sodium 5,000 U, bid preoperatively upon the admission into our department) and the control group (starting heparin sodium 5,000 U, bid postoperatively from postoperative day 1). The baseline data including demographic data and preoperative conditions were collected. The end points included operation time, intraoperative bleeding volume, postoperative chest tube drainage volume and duration as well as lab coagulation function data. RESULTS: A total of 58 qualified patients were randomized into case group (29 patients) and control group (29 patients), and after excluding 6 conversion patients, the case group and control group each had 26 patients for analysis. The baseline data of the two groups were comparable. Operation time (P=0.368), intraoperative bleeding volume (P=0.231), postoperative drainage days (P=0.466), and mean drainage volume per day (P=0.108) were not significantly increased in case group compared with those of control group. Moreover, there were no significant differences of perioperative coagulation function between these two groups. CONCLUSIONS: Preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery was safe and feasible. TRIAL REGISTRATION: NCT02940444 (https://register.clinicaltrials.gov/).

Efficacy of the fissureless technique on decreasing the incidence of prolonged air leak after pulmonary lobectomy: A systematic review and meta-analysis.

OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of fissureless technique in pulmonary lobectomy by applying a meta-analysis of the current evidence. METHODS: We searched the PubMed, EMBASE and the Web of Science databases to recognize the eligible articles. The relative risk (RR) and weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) served as the summarized estimates for dichotomous variables and continuous variables, respectively. Sensitivity analysis and publication bias tests were also performed to perceive potential bias risks. RESULTS: There were 6 studies with 843 surgical patients included into this meta-analysis. Finally, the meta-analysis demonstrated that fissureless technique could significantly reduce the incidence of prolonged air leak (PAL)[RR = 0.40; 95%CI=(0.24, 0.68); P = 0.001], the length of hospital stay [WMD = -0.52; 95%CI=(-0.87, -0.18); P = 0.003] and the duration of chest tube [WMD = -0.44; 95%CI=(-0.74, -0.14); P = 0.004]. Fissureless technique had also showed the benefit on decreasing the complication rate after lobectomy but without a statistical significance [RR = 0.77; 95%CI=(0.55, 1.07); P = 0.119]. In addition, no difference was observed in the operation time between the fissureless lobectomy and conventional lobectomy [WMD = 5.32; 95%CI=(-3.18, 13.83); P = 0.220]. CONCLUSIONS: Fissureless lobectomy is a superior alternative to conventional lobectomy in terms of preventing the PAL and shortening the length of hospital stay and chest tube duration. More multi-institution randomized controlled trials are required to confirm the validity of our findings in the future.