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Background Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. Methods From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. Results ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. Conclusions For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

The presence of calcified or inflammatory lymph nodes between the target bronchus and pulmonary artery is a huge challenge when performing thoracoscopic lobectomy as it may frequently result in tearing of the vessel, and massive bleeding. Herein, we describe a simple strategy in which thoracoscopic lobectomy was safely completed in similar cases. After fissure dissection, the target pulmonary artery was exposed by more than two‐thirds of its circumference. A needle was passed across the nodes and the target vessel was closed with a proximal and distal suture. After dissection of lymphadenopathies, the target bronchus was exposed, and stapled. This strategy was applied with success to complete right lower lobectomies for cancer in three patients. No complications occurred during the operation. Only one patient had persistent air leaks that spontaneously ceased 11 days later. Final pathology showed pN0 disease in all cases., Calcified or inflammatory lymph nodes between the target bronchus and pulmonary artery is a huge challenge when performing thoracoscopic lobectomy. Here, we report a strategy to handle this clinical situation. A needle was passed across the nodes and the target vessel was closed with a proximal and distal suture, and then gradually transected with scissors. After dissection of adenopathies, the target bronchus was stapled.

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video‐assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers., Is video‐assisted thoracoscopic lobectomy associated with higher overall costs compared with open surgery? A review of the literature until May 2020 was performed, and 20 studies provided the most applicable evidence to evaluate this issue.Thoracoscopic lobectomy was associated with higher operative costs than open lobectomy, but lower indirect costs. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar in seven, and higher in three studies.The worry that thoracoscopic lobectomy might be associated with increased total cost is thus not warranted, and should not be used as an excuse against the use of thoracoscopy in surgery for early stage lung cancers.

BACKGROUND: We aim to establish neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms based on the clinical data and peripheral blood markers to predict the survivals of patients with limited-stage small-cell lung cancer (LS-SCLC). METHODS: A total of 299 LS-SCLC patients after surgery were enrolled in this study. Univariate and multivariate analyses were conducted to select independent prognostic factors to develop the nomograms and then subjected to bootstrap internal validation. The optimal cutoff value of NLR and PLR before surgery was calculated by X-tile (version 3.6.1) and the overall survival (OS) was analyzed by Kaplan-Meier method and compared by log-rank test. RESULTS: According to the X-tile calculation, the NLR value and PLR cutoff values are 2.6 and 156.7, respectively. The prognosis of patients with elevated NLR or PLR value was significantly worse than patients with lower NLR (HR =1.798, 95% CI: 1.284–2.518, P=0.001) or PLR (HR =1.781, 95% CI: 1.318–2.407, P

Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC., Graphical Abstract, Exosomes and microRNAs play important roles in tumorigenesis. In non-small lung cancer, the cancer-derived exosome miR-224-5p increased significantly. With exosomes transporting, miR-224-5p promoted the proliferation and metastasis ability of their receptor cells via targeting androgenic receptor. Consequently, exosomal miR-224-5p may have a promising prospect in lung cancer therapy.

Background Prognosis of patients with stage IIIA-N2 lung adenocarcinoma is still not optimistic. The aim of this study was to evaluate safety, feasibility, and outcomes of surgery after induction epidermal growth factor receptor–tyrosine kinase inhibitor therapy in a clinical trial setting. Methods Fourteen patients with IIIA-N2 lung adenocarcinoma and epidermal growth factor receptor mutation received erlotinib induction followed by surgery in a phase II clinical trial. Perioperative outcomes and survival results were compared with a control group of 15 patients receiving neoadjuvant chemotherapy during the same time period. Results Thirteen patients showed partial response to induction, whereas 16 patients remained stable. Serum carcinoembryonic antigen level in the erlotinib group was significantly higher than in the chemotherapy group before treatment but was reduced to similar levels after induction. Operation time, blood loss, resection extents, complete resection rates, postoperative drainage, complication rates, and length of hospital stay were all comparable between the 2 groups. Thoracoscopic resection was accomplished in 78.6% of patients in the erlotinib group and 80.0% of patients in the chemotherapy group (P = .924) but was higher in patients who responded to induction than those who did not (92.3% vs 68.8%, P = .119). A resection extent greater than lobectomy and incomplete resections were only seen in stable disease after induction. No significant difference was detected in 1-year and 3-year overall or disease-free survivals between the 2 groups. Conclusions Pulmonary resection is safe and feasible after induction treatment with erlotinib for stage IIIA-N2 lung adenocarcinomas. Better surgical and oncologic outcomes may be expected in patients who respond to effective induction therapies.

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad‐Cre, KrasG12D, and P53f/f). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual‐specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor‐promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target., ZNF251 promotes lung cancer by activating ERK signaling.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Objective To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT). Summary background data There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT. Methods The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified. Results A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27). Conclusions Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

Background Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. Methods All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. Results Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. Conclusions pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

BACKGROUND: Thoracoscopic segmentectomy is increasingly used in the surgical treatment of early-stage non-small cell lung cancer. However, it remains unclear whether pulmonary function loss after thoracoscopic lung resection is in direct proportion to the number of resected segments, and thus intentional thoracoscopic segmentectomy has the function-preserving advantage over thoracoscopic lobectomy. METHODS: In this prospective observational study, spirometry tests were performed preoperatively and 6 months postoperatively. The observed functional loss was compared with the expected loss estimated by the segment counting method. Resection extent index was introduced as the number of resected segments to total number of segments in the corresponding lobe. Spirometry changes after thoracoscopic lobectomy and intentional thoracoscopic segmentectomy were compared using propensity score matching. RESULTS: There were 338 thoracoscopic lobectomies and 321 thoracoscopic segmentectomies. Overall, the observed pulmonary function loss after segmentectomy was significantly less than after lobectomy. But the observed functional loss was significantly greater than the expected loss after segmentectomy. And pulmonary function loss per segment resected was almost doubled after segmentectomy comparing to lobectomy. For segmentectomies with a resection extent index less than 0.5, especially single segmentectomies, pulmonary function loss was significantly less than after corresponding lobectomies. Otherwise, no significant differences in spirometry changes between lobectomies and segmentectomies were detected. CONCLUSIONS: Pulmonary function loss after thoracoscopic lung resection cannot be accurately evaluated by the number of resected segments. According to the resection extent index, intentional thoracoscopic segmentectomy may help preserve more pulmonary function than thoracoscopic lobectomy only when less than half of the corresponding lobe are resected.

Background Indication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas. Methods We retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections. Results Comparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893). Conclusions Solid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.

Background Histology is a traditional way to classify subtypes of thymoma, because of low cost and convenience. Yet, due to the diverse morphology of thymoma, this method increases the complexity of histopathologic classification, and requires experienced experts to perform correct diagnosis. Therefore, in this study, we developed an alternative method by identifying protein biomarkers in order to assist clinical practitioners to make right classification of thymoma subtypes. Methods In total, 204 differentially expressed proteins in three subtypes of thymoma, AB, B2, and B3, were identified using mass spectrometry. Pathway analysis showed that the differentially expressed proteins in the three subtypes were involved in activation-related, signaling transduction-related and complement system-related pathways. To predict the subtypes of thymoma using the identified protein signatures, a support vector machine algorithm was used. Leave-one-out cross validation methods and receiver operating characteristic analysis were used to evaluate the predictive performance. Results The mean accuracy rates were > 80% and areas under the curve were ≧0.93 across these three subtypes. Especially, subtype B3 had the highest accuracy rate (96%) and subtype AB had the greatest area under the curve (0.99). One of the differentially expressed proteins COL17A2 was further validated using immunohistochemistry. Conclusions In summary, we identified specific protein signatures for accurately classifying subtypes of thymoma, which could facilitate accurate diagnosis of thymoma patients.

Esophageal leiomyoma is the most common benign tumor of the esophagus, which usually arises from the muscularis propria or muscularis mucosae. Incidence of benign esophageal neoplasms was reported to be in the range of 0.005% to 7.9% in autopsy cases, while leiomyomas account for 70–80% of them (1). Options for management include surveillance for small-sized tumors and surgical or endoscopic resection for large or symptomatic ones. Leiomyoma is commonly located in the lower two-thirds of the esophagus. In open surgery, right-sided surgical approach is preferred for lesions in the middle and upper esophagus, and left-sided approach for those in the distal lower esophagus. Video-assisted thoracoscopic surgery (VATS) for esophageal leiomyoma was first described by Everitt in 1992 (2,3). As scattered researches reported, enucleation of benign esophageal tumors can be performed effectively and safely with low morbidity (4-6), mostly through right-sided approach. The major complication after the enucleation of esophageal leiomyomas is mucosal injury, which may lead to esophageal leakage or perforation. We hereby report a novel approach using combined thoracoscopy and endoscopy to facilitate tumor removal and prevent mucosal injury.

Background: The purpose of this study is to develop a predictive model to accurately predict the malignancy of solid solitary pulmonary nodule (SPN) by data mining methods. Methods: A training cohort of 388 consecutive patients with solid SPNs was used to develop a predictive model to evaluate the malignancy of solid SPNs. By using SPSS Modeler, we utilized logistic regression (LR), artificial neural network (ANN), k-nearest neighbor (KNN), random forest (RF), and support vector machines (SVM) classifiers to build predictive models. Another cohort of 200 consecutive patients with solid SPNs was used to verify the accuracy of the predictive model. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: There was no significant difference in patients’ characteristics between the training cohort and the validation cohort. The AUCs of LR, ANN, KNN, RF, and SVM models for the validation cohort were 0.874±0.0280 (P=0.605), 0.833±0.0351 (P=0.104), 0.792±0.0418 (P=0.014), 0.775±0.0400 (P=0.013), and 0.890±0.0323 (reference), respectively. The SVM algorithm had the highest AUC, and the best sensitivity (90.3%), specificity (80.4%), positive predictive value (93.9%), negative predictive value (71.2%) and accuracy (88.0%) for the validation cohort among the five models. Conclusions: Data mining by SVM might be a useful auxiliary algorithm in predicting malignancy of solid SPNs.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the treatment of lung cancers. But it is still unclear whether mediastinal lymph node dissection (LND) under VATS is safe and feasible. The aim of this study is to figure out whether LND by VATS is safe and feasible. METHODS: Consecutive patients with primary resectable lung cancers referred for lobectomy and LND or sampling by VATS between January 2012 and December 2016 were retrospectively reviewed. Clinicopathological characteristics and perioperative results were collected for statistical analysis. RESULTS: Seven-hundred and seventy-three VATS lobectomy patients were included in this study, 494 received LND and 279 received lymph node sampling (LNS). There were more male patients, higher pathological T and N stage in the LND group than in the LNS group. Multivariate analysis suggested that clinical N stage higher than cN0 category and LND were independent risk factors for finding pN2 diseases in all lung cancers, while higher than cN0 category, solid or micropapillary component, and LND were independently related to finding pN2 stage in adenocarcinomas. Propensity-score matching rendered 279 pairs of patients with no significant difference in age, gender, co-morbidity, tumor location, or T stage. Although the LND group had longer operation time (128 vs. 114 minutes, P

Esophageal cancer (EC) is a highly prevalent malignancy in China. According to the data released by National Cancer Registry Center of China in 2015, the prevalence of EC was 21.17/100,000 in China in 2012, ranking fifth among all malignancies; the mortality rate was 15.58/100,000, ranking fourth. It is expected that there will be 477,900 new EC cases nationwide in 2015, whereas 375,000 people will die from EC (1,2). Worldwide, EC is the 8 th most common malignancy, with 416,000 new cases in 2012 (3). At present, EC treatment is based on multidisciplinary treatment, but surgery remains the most effective therapy in optimizing long-term prognosis in patients without metastatic disease. The ideal surgical approach is a matter of debate.

Objective: In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). Results: In all patients, the median PFS was 3.02 months [95% confidence interval (CI): 2.63–3.65 months] and the OS was 6.11 months (95% CI: 4.40–7.79 months). The ORR was 7.34% (95% CI: 3.22%–13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR): 0.40, 95% CI: 0.24–0.68] and OS (HR: 0.37, 95% CI: 0.21–0.67). Conclusions: We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.

OBJECTIVES The aim of this study was to evaluate the efficacy of adjuvant chemotherapy (ACT) for thymic squamous cell carcinoma after completely resection. METHODS Patients with thymic squamous cell carcinoma treated with complete resection between January 2009 and December 2016 were retrospectively identified. Kaplan–Meier analysis was used to summarize the time-to-event variables. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS A total of 116 patients were analysed with 44 patients in the non-ACT group and 72 patients in the ACT group. No significant difference was found in the 5-year recurrence-free survival (RFS) rate (58.1% vs 51%, P = 0.33) or the 5-year overall survival (OS) rate (77.7% vs 67.1%, P = 0.26) between the ACT group and the non-ACT group. Masaoka stage was the only independent prognostic factor for both RFS and OS. Subgroup analysis showed significant improvement in 5-year RFS for Masaoka stage II patients (P = 0.035) and 5-year OS (P = 0.036) for Masaoka stage III patients when comparing ACT with non-ACT. No chemotherapy-related death occurred. The most frequent adverse effect higher than grade 3 was neutropenia. CONCLUSIONS For completely resected thymic squamous cell carcinoma, ACT significantly improved the 5-year RFS in Masaoka stage II patients and the 5-year OS in Masaoka stage III patients.

OBJECTIVES Neuroendocrine thymic tumours (NETTs) are a distinct subgroup of rare malignancies. An international, multicentre retrospective analysis was used to study the clinicopathological features, current pattern of diagnosis, treatment and outcomes of patients with NETT. METHODS One hundred and forty-six NETT treated from 1989 to 2016 at 21 centres in China, Europe and North America were retrospectively collected and reclassified according to the World Health Organization histological type and International Thymic Malignancy Interest Group (ITMIG)/International Association for Studies in Lung Cancer (IASLC)/Union for International Cancer Control (UICC) staging. Clinicopathological features, diagnostic and therapeutic approaches and outcomes were investigated. Results in the earlier and latter halves of the study period were also compared. RESULTS The pretreatment work-up relied exclusively on computed tomography in 85.6% (125/146) of cases. Most patients had advanced disease, with 32.2% (47/146) having lymph node involvement. Higher-grade histological type was associated with more advanced disease (P CONCLUSIONS Current management similar to that for thymomas is unsatisfactory in providing disease control or long-term survival for patients with NETT. Specific diagnostic tools and novel therapeutic agents are needed to improve management outcomes of this disease.

Objective To evaluate the outcome following the strategy of endoscopic R0 resection (ER) plus adjuvant treatment (AT) versus esophagectomy for esophageal squamous cell cancer in T1a invading muscularis mucosa (M3)-T1b stage. Methods We evaluated the outcomes of 46 esophageal squamous cell cancer (ESCC) patients with T1aM3-T1b stage who underwent ER + AT from the Esophageal Cancer Endoscopic Therapy Consortium (ECETC) and compared these outcomes to 92 patients who underwent esophagectomy. Propensity score matching (1:2) was used, with overall survival (OS) and relapse-free survival (RFS) being compared between the two groups. Results During a median follow-up of 32 months, there were no statistical differences (P = 0.226) in OS between the two groups. The 1-, 2-, and 3-year overall survival in the esophagectomy group was 95%, 91%, and 84%, respectively. There were no mortalities within three years in the ER + AT group. The RFS between the two groups was also not significantly different (P = 0.938). The 1-, 2-, and 3-year RFS of patients in the esophagectomy group was 90%, 90%, and 83%, respectively, while it was 97%, 94%, and 74% in the ER + AT group, respectively. The local recurrence rates between the two groups were not significantly different (P = 0.277). Conclusions This first multicenter analysis showed similar outcomes were found regarding OS and RFS between the two groups in T1aM3-T1b stage patients. ER + AT may be considered in high-risk patients or for those who refuse esophagectomy.

Background Surgery remains the mainstay of treatment for resectable stage III non-small cell lung cancer (NSCLC). The preliminary results from some pilot trials have shown that neoadjuvant immunotherapy in NSCLC is safe and tolerable.1 2Hypothesizing that neoadjuvant toripalimab (a humanized anti-PD-1 antibody) plus chemotherapy can improve the outcome in resectable NSCLC, we are conducting a randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of toripalimab plus platinum-based doublet chemotherapy as neoadjuvant/adjuvant therapy for patients with resectable stage III NSCLC. Methods This ongoing study enrolls patients aged 18–70 years with treatment-naive, histopathologically confirmed resectable stage III NSCLC without EGFR mutation or ALK translocation, ECOG PS 0–1, and adequate organ function. Eligible subjects are randomized (1:1) into experimental or control group, to receive perioperative toripalimab 240 mg or placebo combined with chemotherapy for 4 cycle in total (Docetaxel 60–75 mg/m2 or Paclitaxel 175 mg/m2 with platinum [squamous histology] or Pemetrexed 500 mg/m2 with platinum [non-squamous histology]) every 3 weeks for three cycles followed by surgery, and one more cycle after surgery, then monotherapy of toripalimab 240 mg or placebo every 3 weeks up to 13 cycles is delivered. Adjuvant radiotherapy is allowed. Randomization is stratified by tumor stage(IIIA vs IIIB), pathological type (squamous vs non-squamous), PD-L1 expression (PD-L1≥1% vs Results N/A Conclusions N/A Acknowledgements N/A Trial Registration The Clinical trials. gov no NCT04158440 Ethics Approval This study was approved by the Ethics Board of all the involved sites; Approval number of Shanghai Chest Hospital: LS1936 Consent N/A References Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer N Engl J Med 2018;378:1976–1986 Hellmann MD, Chaft JE, William WN Jr, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet oncol 2014;15:e42–50.

Non-small cell lung cancer (NSCLC) is the most common and fatal tumor worldwide, with 2.1 million new cases and 1.77 million deaths per year (1). With the wider application of examination approaches and the improvement of health awareness, higher proportions of surgically resectable early and mid-stage lung cancers have been detected. In overall, only 50% of patients have been cured after radical resection. In other cases, however, NSCLC is highly active and recurrence and/or metastasis can easily occur after surgery. In these patients, systemic therapy as a postoperative adjuvant therapy is required to eliminate or reduce residual micro-lesions to lower the risk of recurrence; meanwhile, the patients should be closely monitored to detect early recurrence. EGFR mutation is a major mutation type in lung cancer, and is seen in about 40% of lung cancer cases in Asia (2). Compared with wild types and other mutation types, EGFR-mutant NSCLC has its unique biological properties and drug susceptibilities, and thus requires specific diagnosis and treatment strategies. This expert consensus aims to review the current evidence and provide recommendations on key issues. A consensus and guideline development panel, with its members including top thoracic surgeons and oncologists all around the world, was established to decide the methodologies, processes, levels of evidence, and related recommendations. The panel members proposed the core clinical issues in the consensus document and wrote and submitted the outlines to the panel for approval. The panel carried out a problem-oriented literature search for articles published since 1997 in Chinese and foreign databases. The level of evidence was defined using the following criteria: Categories of Evidence and Consensus, Category 1: based upon high-level evidence, there is uniform consensus that the intervention is appropriate; Category 2A: based upon lower-level evidence, there is uniform consensus that the intervention is appropriate; Category 2B: based upon lower-level evidence, there is consensus that the intervention is appropriate; Category 3: based upon any level of evidence, there is major disagreement that the intervention is appropriate. The strength of recommendations was classified as strong or weak according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system (3), and the recommendation statement was composed based on the real-world evidence. A “strong” recommendation generally refers to recommendations based on high-level evidence with consistency between clinical behavior and outcome expectancy; in contrast, a “weak” recommendation is typically based on low-level evidence with uncertainty between clinical behavior and outcome expectancy. After the first draft had been completed, all the panel members were involved in revising and finalizing this document.

Objectives The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee-Thymic Domain conducted a web-based cross-sectional survey to assess the acceptance of the TNM thymic staging system in the thoracic community. Methods A 50-item, web-based questionnaire was circulated among the members of the major thymic organizations worldwide from September to December 2018. The survey consisted of six sections (general information; overall perception of the TNM system; pretreatment staging; T category; N category; and perioperative treatments). Results In total, 217 responses were collected from 37 countries in four continents. The TNM classification was considered useful by 78% of the responders (N = 169); the Masaoka-Koga staging system was being used by 87% of the responders (N = 189). With regard to the T category, most responders (mostly surgeons) felt that the capsular and mediastinal pleural involvements should be considered separate T categories. As for the N category, 48% of the responders (N = 105) used the International Thymic Malignancies Interest Group/International Association for the Study of Lung Cancer thymic nodal map, and lymph node dissection (N1/N2) was performed for 50%/21% thymomas and 66%/41% thymic carcinomas. While analyzing the results by the three continents (Europe, Asia, and Americas), responders in Asia were found to report the largest use of the TNM system, the greatest attention to the N category, and the best participation in international thymic databases. Conclusions The survey indicates that the Union for International Cancer Control/American Joint Committee on Cancer TNM stage classification of thymic tumors is gaining acceptance among the scientific community. The present results will guide the work of the Staging and Prognostic Factors Committee-Thymic Domain for the revision of the ninth edition of the TNM stage classification of thymic tumors.

Benign tracheal stenosis is a life-threatening condition that needs a prompt treatment when the tracheal lumen is less than 5 mm. In patients unfit for surgery, endoscopic dilation with stent insertion (if indicated) remains the main alternative to restore airway patency and assure ventilation. Endoscopic management of tracheal stenosis may be a cumbersome procedure, that sometimes takes a long time, and may be complicated by stent dislocation especially in cases of complex stenosis, near to vocal folds. In recent years, the 3D printing industry has undergone rapid development, and 3D printing model has been increasingly applied to different medical fields where therapeutic interventions rely on defining complex anatomic structural relationships. Thus, in this review we aimed to evaluate whether the use of 3D printing model as tool for preoperative planning could facilitate the endoscopic treatment of tracheal stenosis and improve outcome. Three papers evaluated this issue: one paper reported a consecutive series of patients while the remaining single case report. All authors concluded that the 3D model aided the understanding of patient's anatomy and the stenosis's characteristic. The possibility of recreating the endoscopic procedure in the 3D model facilitated and shorted the procedural time in live patient. Furthermore, the 3D model was additionally useful to choose the length, diameter and shape of stent and to define the exact distance of the proximal end of stent from the vocal folds after its insertion. Finally, it represented an educational tool for patients and his/her family to understand the procedure, and for residents and fellows to improve endoscopic skills.

Our aim was to investigate appropriate postoperative management based on the risk of disease recurrence in thymic epithelial tumors after complete resection.The Chinese Alliance for Research in Thymomas retrospective database was reviewed. Patients having stage I to IIIa tumors without pretreatment and with complete resection were included. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram for building a recurrence predictive model.A total of 907 cases, including 802 thymomas, 88 thymic carcinomas, and 17 neuroendocrine tumors, were retrieved between 1994 and 2012. With a median follow-up of 52 months, the 10-year overall survival rate was 89.5%. Distant and/or locoregional recurrences were noted in 53 patients (5.8%). The nomogram model revealed histologic type and T stage as independent predictive factors for recurrence, with a bootstrap-corrected C-index of 0.86. On the basis of this model, patients with T1 thymomas or T2 or T3 type A, AB, or B1 thymomas had a significantly lower incidence of recurrence (low-risk group) than those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine tumors (high-risk group) (2.7% versus 20.1% [p0.001]). In the high-risk group, more than half of the recurrences (55.2% [16 of 29]) were seen within the first 3 postoperative years, whereas all recurrences but one were recorded within 6 years after surgery. Recurrence occurred quite evenly over 10 postoperative years in the low-risk group.A 6-year active surveillance should be considered in high-risk patients regardless of adjuvant therapy. For low-risk patients, annual follow-up may be sufficient. Studies examining postoperative adjuvant therapies would be plausible in high-risk patients.

In 1883, Leyden successfully performed percutaneous transthoracic needle biopsy (PTNB) of the lung in three patients with pneumonia according the records (1); three years later, Menetrier was the first recorded to employ this technique for the diagnosis of lung cancer (2).

OBJECTIVES Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the management of thymic epithelial tumours. However, its oncological efficacy remains to be proved. The purpose of this study is to compare the oncological outcomes following thoracoscopic versus open surgery in the case-matched groups of patients with early-stage thymic tumours from the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS Between 1994 and 2012, a total of 1087 patients who underwent surgery for UICC (Union for International Cancer Control) pathological Stage I tumours from the ChART retrospective database were recruited for this study. A propensity score-matched analysis was used to compare the long-term outcomes in patients who received VATS or open surgery. RESULTS VATS resection was performed in 271 patients (24.9%) and open surgery in 816 patients (75.1%). Before propensity score matching, the VATS group had a smaller tumour size (P = 0.002), lower grade histology (P = 0.034), lower T stage (P < 0.001) and less adjuvant therapy (P < 0.001). Propensity score matching by gender, myasthenia gravis, tumour size, histological classification, pathological T stage, extent of thymectomy, adjuvant radiotherapy and adjuvant chemotherapy identified 110 patients in each group. After matching, there was no significant difference in patient demographics, tumour characteristics or adjuvant therapy. All matched patients had R0 resection. Overall survival, disease-free survival and cumulative incidence of recurrence were only predicted by WHO histology, but not by surgical approach, in both univariable and multivariable analyses. There was no significant difference in the overall survival (85.7% vs 93.1%, P = 0.539), disease-free survival (92.5% vs 91.9%, P = 0.773), cumulative incidence of recurrence (7.1% vs 5.8%, P = 0.522) and improvement rate of myasthenia gravis (83.3% vs 88.2%, P = 0.589) between the 2 groups. CONCLUSIONS This propensity score-matched study suggests that VATS and open surgeries are associated with similar oncological outcomes for Stage I thymic epithelial tumours. Minimally invasive surgery might be an acceptable surgical approach for early-stage thymic malignancies.

Cancer is an independent major risk factor for venous thromboembolism (VTE), which is the second leading cause of death in medically and surgically treated patients with cancer (1-5). The association between VTE and lung cancer has been reported more than 20 years ago (6,7).

Limited resections for early stage lung cancer have been of increasing interests recently. However, it is still unclear to what extent a limited resection could preserve pulmonary function comparing to standard lobectomy, especially in the context of minimally invasive surgery. The purpose of this study was to evaluate postoperative changes of spirometry in patients undergoing video-assisted thoracic surgery (VATS) lobectomy or limited resections.Spirometry tests were obtained prospectively before and 6 months after 75 VATS lobectomy, 34 VATS segmentectomy, 15 VATS wedge resection. Eleven VATS mediastinal procedures without lung resection were taken as a control group. Results were compared between groups of different resection extent.Demographic characteristics and preoperative pulmonary function showed no differences among the four groups. Forced vital capacity (FVC) loss after lobectomy was significantly greater than after segmentectomy (P=0.048), and much significantly greater than after wedge resection (P0.001). Forced expiratory volume in 1 second (FEV1) loss after lobectomy was similar to segmentectomy (P=0.273), both significantly greater than after wedge resection (P0.01). Diffusing capacity of the lungs for carbon monoxide (DLCO) loss was similar among these three groups (P=0.293). There was no significant difference in any spirometry index between wedge resection and mediastinal procedures (FVC: P=0.856; FEV1: P=0.671; DLCO: P=0.057). When compared by average value per segment resected, pulmonary function loss was significantly less after lobectomy than after segmentectomy in all spirometry indexes (P0.001). On average, pulmonary function loss was around 5% per segment for VATS lobectomy and 10% per segment for VATS segmentectomy.In minimal invasive surgery, wedge resection best preserves pulmonary function with similar spirometry change with VATS mediastinal procedures without lung resection. Compared with VATS lobectomy, VATS segmentectomy may help minimize loss of FVC but not FEV1 or DLCO. Pulmonary function loss per segment resected is doubled after VATS segmentectomy than after lobectomy. These results should be taken into account when deciding the extent of resection for patients with early stage lung cancer.

Background: Segmentectomy for small-sized stage Ia non-small cell lung cancer (NSCLC) may be comparable to lobectomy regarding prognosis and local recurrence. However, the clinical results of wedge resection for such patients are still under debate. In this international multicenter study, we retrospectively studied surgical outcomes of sublobar resections for patients with small-sized stage Ia adenocarcinoma to elucidate whether wedge resection is inferior to segmentectomy for such patients. Methods: Between March 2000 and August 2011, 173 patients underwent segmentectomy (group I), and 181 patients underwent wedge resection (group II) at three institutions in Japan and China. The tumor was defined as Ground glass opacity (GGO) type when the proportion of GGO was equal or more than 50% in HRCT, while solid type was defined as the proportion of GGO less than 50%. Clinicopathologic factors, local recurrence rate, and survival were compared. Results: The two groups were similar in sex, comorbidity rate, and composition of Noguchi type. There was no in-hospital death. Postoperative morbidity rate of group I was significantly higher than that of group II (11.0% vs . 2.2%, P=0.016). Local recurrence rates were similar between group I (4.0%) and group II (4.4%), while no patient with GGO type tumors had local recurrence. Overall and lung cancer-specific survivals were of no significant difference between the two groups. Lung cancer-specific survival rates at 10 years were significantly better in patients with GGO type tumors than in those with solid type tumors (100% vs . 76.9%, P Conclusions: Our data suggests that sublobar resection is an acceptable procedure for small lung adenocarcinomas without nodal involvement, and wedge resection may not be inferior to segmentectomy for small GGO type tumors. Our study also demonstrates that GGO type is an independent prognostic factor of disease-free survival for small-sized (diameter ≤2.0 cm) stage Ia lung adenocarcinomas.

Superior pulmonary sulcus tumor is a cancer arising in the apex of the lung that with potential invasion of the brachial plexus, upper ribs, vertebrae, subclavian vessels, and stellate ganglion. Induction concurrent chemoradiotherapy followed by radical surgical resection with lobectomy combined with any structures in the thoracic inlet invaded by tumor and thorough mediastinal lymph node dissection is the preferred treatment. Both anterior and posterior approaches are applied for resection. Here, we report a 61-year-old man with an 8.6 cm × 5.1 cm mass arising from the right upper lobe invading the apex of the chest wall. Brachial plexus magnetic resonance imaging suggested tumor invasion of the inferior trunk of the brachial plexus, anterior portion of the first 2 ribs, and suspicious involvement of the subclavian artery. Biopsy of the mass showed stage cT4N2M0, IIIB, poorly differentiated adenocarcinoma. The patient was treated by induction concurrent chemoradiotherapy, which was followed by surgical resection of the right upper lobe and the affected chest wall via the transmanubrial approach. The patient suffered prolonged postoperative air leak and empyema. After continuous chest tube drainage and intrapleural fibrinolytic therapy, he recovered well and was discharged safely. Final pathology showed no viable residue tumor, pathologic complete response of the tumor to induction treatment, a tumor size of 4.1 cm, and no lymph nodes; therefore, the final stage was ypT0N0M0. The transmanubrial approach is feasible for resection of tumor invading the branches of the subclavian artery; however, postoperative empyema which might have resulted from prolonged air leak should be carefully treated by meticulous air leak management.

9051 Background: Lung adenocarcinoma (LUAD) is further classified into several histological subtypes with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) as the three major subtypes according to the extent of invasion. AIS has been considered as a precursor of IAC. Considering the significantly higher mutation burden among IAC tumors than AIS tumors, it seems likely that AIS tumors undergo a process of accumulating various somatic mutations to gain invasive ability. To understand the gene mutations involved in this transformation, we compared the mutational features of AIS and IAC tumors. Methods: This retrospective study included 2,769 Chinese patients diagnosed with stage 0-IIIA LUAD. Targeted sequencing was performed on tissue DNA isolated from 246 AIS tumors and 2,523 IAC tumors using 68 lung cancer-related genes (Lung Core, Burning Rock Biotech). Results: Analysis of mutation profiles revealed that mutation count was significantly lower for AIS ( P< 0.01) as compared to IAC tumors. Moreover, AIS tumors had significantly higher mutation detection rates for ERBB2 exon 20 insertion (20ins) ( P≤0.05), EGFR 20ins ( P≤0.05), non-V600E BRAF mutations ( P≤0.05), and MAP2K1 small insertion-deletion variants ( P≤0.05). These 4 gene mutations were grouped and referred to as AIS-like mutations for further analysis. Detection rates of AIS-like mutations were 54.9% for AIS tumors and 7.8% for IAC tumors. Patients with AIS-like mutation-positive AIS tumors were significantly younger than those with AIS tumors without AIS-like mutations ( P =0.018), while age were similar for IAC tumors with or without AIS-like mutations. Mutation count was similar between AIS tumors with or without AIS-like mutations. Interestingly, IAC tumors harboring AIS-like mutations had a significantly higher mutation count than those harboring known oncogenic drivers ( P= 0.045). Further investigation of the molecular profiles of IAC tumors harboring AIS-like mutations (n = 198) revealed the presence of various concurrent mutations in 8 genes including TP53 (39.4%), EGFR (non-20ins) (16.7%), RB1 (7.1%), PIK3CA (6.6%), MET (5.1%), ROS1 (4.0%), FLT3 (4.0%), and PTEN (3.5%), which were absent among AIS tumors, particularly those that harbor AIS-like mutations. In addition to TP53 (35.8%), PIK3CA (4.5%), and RB1 (4.0%), IAC tumors without AIS-like mutations (n = 2,324) had additional concurrent mutations in 2 other genes CDK4 (5.7%) and STK11 (3.9%) as compared to AIS tumors. Conclusions: Our data suggest that AIS-like mutations could be involved in the early stages of tumorigenesis by initiating the accumulation of other gene mutations that are required for the transformation of AIS tumors into IAC tumors. Our study contributes to a deeper understanding of the distinct gene mutations between AIS and IAC tumors among Chinese LUAD patients.

8524 Background: Neoadjuvant treatment has demonstrated efficacy in several types of cancer and is increasingly used for the treatment of early-stage cancers with the potential of cancer downstaging to enhance complete surgical resection and to improve clinical outcomes. Recent evidences have demonstrated that the neoadjuvant use of first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may provide clinically meaningful improvement in EGFRm non-small cell lung cancer (NSCLC) patients, however, limited data were reported on osimertinib, the third-generation EGFR-TKI, in the neoadjuvant setting. Here we present an interim analysis of osimertinib as neoadjuvant treatment for resectable EGFRm NSCLC. Methods: NEOS is a prospective, multi-center, single-arm study to evaluate the efficacy and safety of osimertinib as neoadjuvant treatment in resectable EGFRm (19del/L858R) lung adenocarcinoma. Eligible patients were treated with osimertinib 80 mg orally per day for six weeks followed by surgery. Assessment of response to neoadjuvant therapy was performed according to RECIST 1.1. The primary endpoint was response rate. Secondary endpoints included safety, R0 surgical resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate. Results: As of Dec. 17, 2020, 18 eligible patients (median age 61 [range 46-73], 27.8% male, 22.2% ECOG PS 1) have been enrolled. Patients with clinical stages IIa, IIb, and IIIa (8th AJCC) accounted for 16.7%, 22.2% and 61.1%, respectively. Half (9/18) of the patients had EGFR exon 21 L858R mutations and the other half (9/18) had EGFR exon 19del mutations. Amongst all 15 patients who completed efficacy assessment after neoadjuvant osimertinib, the response rate (RR) was 73.3% (11/15) and the disease control rate (DCR) was 100% (15/15). R0 surgical resection was performed in 93.3% (14/15) patients. Pathological downstaging occurred in 53.3% (8/15) patients. 42.9% (3/7) of the patients with confirmed N2 lymph nodes experienced downstaging to N0 disease after receiving neoadjuvant osimertinib. One patient was identified with a pCR. Adverse events (AEs) were reported in 66.7% (12/18) of patients, with the most common AE being rash (8/18, 44.4%), oral ulceration (8/18, 44.4%), and diarrhea (5/18, 27.8%). No grade 3-5 AEs or serious AEs were reported. Conclusions: Interim analysis from this study indicated neoadjuvant osimertinib as an effective and feasible treatment in patients with resectable stage II-IIIB EGFRm NSCLC. The trial is ongoing and the final results will be provided in the future. Clinical trial information: ChiCTR1800016948.

Background: Discuss an appropriate strategy for treatment of invasive thymoma invading adjacent great vessels. Methods: A retrospective study on 25 patients with invasive thymoma invading neighboring great vessels was performed. The corresponding data including clinical presentation, operation procedure, adjuvant radio-chemotherapy and follow-up were reviewed. Results: Twenty of 25 (80%) patients with invasive thymoma underwent complete resection of the tumor along with vessel reconstruction. Intraoperatively, different types of operation were conducted, namely, brachiocephalic vein (BCV)-right atrial appendage (RAA) reconstruction in 11 cases, complex vessel reconstruction (more than one graft) in 1 case and superior vena cava (SVC)-SVC reconstruction in the remaining cases. Ringed polytetrafluoroethylene (PTFE) grafts were used for vessel reconstruction. Postoperatively, three cases suffered from pulmonary infection, and three cases had haemothorax, chylothorax and atelectasis, respectively. Two patients died due to acute respiratory distress syndrome within 90 days after the surgery. Within the remaining patients, 11 cases (44%) experienced a relapse and finally 8 (32%) patients died. Compared to R1 resection group, R0 resection group had a better prognosis (Log-rank P=0.0196). The 3- and 5-year survival rates were 79.6% and 59.1%, with median survival time of 84 months. Conclusions: Reconstruction of mediastinal vessels for invasive thymoma is a feasible technology method. Radical resection of the tumor with involved neighboring structures is the key to prolong overall survival for patients suffered from invasive thymoma.

OBJECTIVES Surgeons at different institutions worldwide choose different types of operations for thymic tumours. It is not known whether these differences affect the outcomes of the patients. METHODS A total of 1430 patients with Masaoka-Koga pathological Stage I-II thymic tumours without myasthenia gravis or pre-treatment were identified from the International Thymic Malignancy Interest Group retrospective database. Outcomes of patients from 3 major continents (Europe, North America and Asia) were compared. RESULTS Patients from the 3 continents were comparable in gender and performance status. More European patients had more paraneoplastic syndromes; North American patients had the smallest tumour sizes and less adjuvant therapy; and Asian patients were younger and had more Stage I disease but higher grade tumours. Partial thymectomy was performed more often in Asian patients (31.7%) than in European (2.4%) and North American (5.4%; P

Accurate assessment of the invasion of intrathoracic structures by stage III thymic tumors assists their appropriate management. The present study aimed to evaluate the efficacy of computed tomography (CT) features for the prediction of stage III thymoma invasion. The pre-operative CT images of 66 patients with confirmed stage III thymic tumors were reviewed retrospectively. The CT features of invasion into the mediastinal pleura, lungs, pericardium and great vessels were analyzed, and their sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy were calculated. For mediastinal pleural and pericardial invasion, an absence of space between the tumor and the mediastinal pleura/pericardium with mediastinal pleural/pericardial thickening and pleural/pericardial effusion exhibited a specificity and PPV of 100%, respectively. For lung invasion, a multi-lobular tumor convex to the lung with adjacent lung abnormalities exhibited a specificity and PPV of 91.2 and 81.3%, respectively. For vessel invasion, the specificity and PPV were each 100% for tumors abutting ≥50% of the vessel circumference, and for tumor oppression, deformation and occlusion of the vessel. In conclusion, recognition of the appropriate CT features can serve as a guide to invasion by stage III thymic tumors, and can facilitate the selection of appropriate pre-operative treatment.

Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer. Long non-coding RNAs (lncRNAs) have been reported to serve prominent roles in cancer progression. However, the expression patterns and potential roles of lncRNAs in NSCLC remain to be elucidated. In the present study, four public datasets were analyzed to identify differentially expressed lncRNAs (DElncs) in NSCLC. A further dataset, GSE19188, was analyzed to validate the findings. A total of 38 upregulated and 31 downregulated lncRNAs were identified in NSCLC, compared with samples from healthy controls. Among these, 12 lncRNAs were associated with the progression of NSCLC, and dysregulated between high grade (stage III and IV) and low grade (stage II) NSCLC samples. Moreover, dysregulation of lncRNA-SIGLEC17P, GGTA1P, A2M-AS1, LINC00938, GVINP1, LINC00667 and TMPO-AS1 was associated with overall survival time in patients with NSCLC. Co-expression analyses, combined with the construction of protein-protein interaction networks, were performed to reveal the potential roles of key lncRNAs in NSCLC. The present study revealed a series of lncRNAs involved in the progression of NSCLS, which may serve as novel biomarkers for the disease.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.

2018 was a banner year for all thoracic oncology, but especially for early-stage NSCLC. Three seminal events occurred in the approximately 18 months from mid-2017 to the end of 2018: in June 2017 at the American Society of Clinical Oncology Annual Meeting a small, relatively unheralded study from Max Diehn's group at Stanford University reported on the use of a novel "cancer personalized profiling by deep sequencing" circulating tumor-DNA technology to identify minimal residual disease in patients after curative-intent radiation or surgery for NSCLC; in April 2018 at the American Association for Cancer Research Annual Meeting, Drew Pardoll presented a small pilot study of 21 patients who had received two doses of preoperative nivolumab; in September 2018, at the 19th World Conference on Lung Cancer, Harry J. De Koning presented the long-awaited results of the Dutch-Belgian Lung Cancer Screening Trial (NELSON). These three seminal studies, along with others which are reviewed in this paper, promise to accelerate our progress towards a world in which lung cancer is identified early, more patients undergo curative-intent treatment that achieves the promised cure, and those at risk for failure after treatment are identified early, when the cancer remains most vulnerable. The day is around the corner when lung cancer is defanged and no longer the worldwide terror it currently is. We herein present an overview of the most recent body of work that moves us inexorably towards that day.

Background: Currently, there are no randomized trials on the effect of antiangiogenic therapy in patients with esophageal squamous cell carcinoma (ESCC). The following study investigated the efficacy and safety of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced ESCC who are refractory to chemotherapy. Methods: This randomized, placebo-controlled, double-blind phase 2 trial was conducted across 13 hospitals in China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC who were previously treated with chemotherapy, and were randomly assigned (2:1) to receive either oral anlotinib 12 mg or placebo on days 1-14 (the treatment was repeated every 21 days). The primary endpoint was PFS. This study is registered with ClinicalTrials.gov (NCT02649361). Findings: One hundred and sixty-five patients were randomly assigned to the anlotinib (n=110) or the placebo (n=55) arm. The median treatment duration was 2·6 months (range 0·5-20·9) in the anlotinib group and 1·2 months (range 0·5-10·8) in the placebo group. Median PFS was 3·02 months (95% CI 2·63-3·65) in the anlotinib group and 1·41 months (95% CI 1·38-1·41) in the placebo group (hazard ratio 0·46 [95% CI 0·32-0·66]; p

Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.

The biological functions of N6-methyladenosine (m6A) RNA methylation are mainly dependent on the reader; however, its role in lung tumorigenesis remains unclear. Here, we have demonstrated that the m6A reader YT521-B homology domain containing 2 (YTHDC2) is frequently suppressed in lung adenocarcinoma (LUAD). Downregulation of YTHDC2 was associated with poor clinical outcome of LUAD. YTHDC2 decreased tumorigenesis in a spontaneous LUAD mouse model. Moreover, YTHDC2 exhibited antitumor activity in human LUAD cells. Mechanistically, YTHDC2, via its m6A-recognizing YTH domain, suppressed cystine uptake and blocked the downstream antioxidant program. Administration of cystine downstream antioxidants to pulmonary YTHDC2-overexpressing mice rescued lung tumorigenesis. Furthermore, solute carrier 7A11 (SLC7A11), the catalytic subunit of system XC−, was identified to be the direct target of YTHDC2. YTHDC2 destabilized SLC7A11 mRNA in an m6A-dependent manner because YTHDC2 preferentially bound to m6A-modified SLC7A11 mRNA and thereafter promoted its decay. Clinically, a large proportion of acinar LUAD subtype cases exhibited simultaneous YTHDC2 downregulation and SLC7A11 elevation. Patient-derived xenograft (PDX) mouse models generated from acinar LUAD showed sensitivity to system XC− inhibitors. Collectively, the promotion of cystine uptake via the suppression of YTHDC2 is critical for LUAD tumorigenesis, and blocking this process may benefit future treatment., Graphical abstract Image 1, Highlights • The m6A reader YTHDC2 is frequently suppressed in LUAD and indicates poor prognosis. • YTHDC2 suppresses the antioxidant function of system XC− via its m6A reading domain. • The mRNA encoding SLC7A11 is a direct target of YTHDC2. • YTHDC2 preferentially accelerates the decay of m6A-methylated SLC7A11 mRNA. • LUAD with YTHDC2 suppression is sensitive to system XC− inhibitors.

Thymoma is an epithelial neoplasm of the thymus. It commonly lies in the anterior mediastinum and represents 20–30% of mediastinal tumours in adults. In this report we present a case of giant thymoma locating in the anterior-inferior mediastinum. A 46-year-old male came to our institute with slight pectoralgia and dyspnea. Chest CT shows a giant tumor measuring 19 cm × 16 cm × 15 cm in the left thoracic cavity. After careful examination, we performed surgery. At surgery, we found the tumor was adherent to left upper lobe of the lung, mediastinal pleura, and parietal pleural. The tumor was completely resected with combined resection of part left upper lobe of lung. The weight of the tumor was 2,135 g. Pathological diagnosis indicated a type AB thymoma according to the World Health Organization classification and a diagnosis of Masaoka stage IIB was made.

Background: Surgical resection remains the mainstay of treatment for patients with early-staged thymic tumors, while chemotherapy is most commonly used in stage IV cases. As for locally advanced thymic tumors, especially those unsuitable for surgery, the optimal therapy is still controversial. Thus, we conducted this retrospective study by comparing three nonsurgical treatment modalities to find some clues. Methods: Three treatment modalities were used in 42 patients from October 2000 to December 2010, including radiotherapy (RT) alone, sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT). Objective response rate (ORR), overall survival (OS) and toxicity of the three regimens were compared accordingly. Results: The ORR in all 42 patients was 61.9%, and 5-year OS was 46%. The ORR of RT, SCRT and CCRT were 43.8%, 50% and 87.5%, respectively (RT vs. SCRT, P=0.692; RT vs. CCRT, P=0.009; SCRT vs. CCRT, P=0.051). The 5-year OS of RT, SCRT and CCRT were 30%, 50% and 61.9%, respectively. (RT vs. SCRT, P=0.230; RT vs. CCRT, P=0.011; SCRT vs. CCRT, P=0.282). Eleven patients developed neutropenia of grade 3–4, with 7 in CCRT group and 4 in SCRT, respectively. Nine patients experienced esophagitis of grade 3 with 2 in RT, 3 in SCRT and 4 in CCRT. There were also two cases of grade 3 radiation induced pneumonitis in CCRT group. No life-threatening side effects were noted. Conclusions: When used to treat locally advanced thymic tumors unsuitable for surgery, CCRT performed more favorably than RT alone or SCRT in both tumor response and long time survival, but probably with the increasing risk of pulmonary damage. CCRT may offer the best chance of disease control in the management of locally advanced disease.

The correlations between histological, clinical features and prognosis of stage I invasive mucinous adenocarcinoma (IMA) have not been thoroughly studied for its rare incidence. This study aimed to compare the prognosis among IMA with different percentage of mucinous component and the effect of adjuvant chemotherapy on IMA patients. A total of 145 stage I IMA and 3536 invasive nonmucinous adenocarcinoma patients with R0 resection were included. Based on the percentage of mucinous pattern presented in tumor, IMA were classified into two subgroups: pure mucinous (>90 % invasive mucinous pattern) and mixed mucinous/nonmucinous (≥10 % of each histologic component). Invasive nonmucinous adenocarcinomas were classified into three subgroups: lepidic (LEP), acinar/papillary (ACN/PAP) and solid/micropapillary (SOL/MIP). Disease-free survival (DFS) and overall survival (OS) were assessed and compared among IMA and invasive nonmucinous patients. For IMA patients, DFS (p = 0.003) was worse for mixed mucinous/nonmucinous compared with pure mucinous subgroup, OS (p = 0.514) was not prognostically different between two groups. There were no significant difference for DFS (p = 0.428) and OS (p = 0.232) between IMA and invasive nonmucinous adenocarcinoma. However, statistical significance were seen for DFS (p