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Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation.Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review.A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study.Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.

Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen., Cisplatin plus Lipusu (LP) regimen has comparable efficacy and more favorable toxicity profiles compared with cisplatin plus gemcitabine (GP) regimen for patients with advanced LSCC. The study also demonstrated that LP had a significant impact on the levels of plasma cytokines and a spectrum of cytokines were associated with clinical benefit in patients who received LP. Thus, our results provided a new option for patients with advanced LSCC.

In this golden age of rapid development of artificial intelligence (AI), researchers and surgeons realized that AI could contribute to healthcare in all aspects, especially in surgery. The popularity of low-dose computed tomography (LDCT) and the improvement of the video-assisted thoracoscopic surgery (VATS) not only bring opportunities for thoracic surgery but also bring challenges on the way forward. Preoperatively localizing lung nodules precisely, intraoperatively identifying anatomical structures accurately, and avoiding complications requires a visual display of individuals’ specific anatomy for surgical simulation and assistance. With the advance of AI-assisted display technologies, including 3D reconstruction/3D printing, virtual reality (VR), augmented reality (AR), and mixed reality (MR), computer tomography (CT) imaging in thoracic surgery has been fully utilized for transforming 2D images to 3D model, which facilitates surgical teaching, planning, and simulation. AI-assisted display based on surgical videos is a new surgical application, which is still in its infancy. Notably, it has potential applications in thoracic surgery education, surgical quality evaluation, intraoperative assistance, and postoperative analysis. In this review, we illustrated the current AI-assisted display applications based on CT in thoracic surgery; focused on the emerging AI applications in thoracic surgery based on surgical videos by reviewing its relevant researches in other surgical fields and anticipate its potential development in thoracic surgery.

Background High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. Methods In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. Results HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P Conclusion HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II–IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov), Lay abstract A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-0549

Background The relationship between insomnia and lung cancer is scanty. The Mendelian randomization approach provides the rationale for evaluating the potential causality between genetically-predicted insomnia and lung cancer risk. Methods We extracted 148 insomnia-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from published genome-wide association studies (GWASs). Summary data of individual-level genetic information of participants were obtained from the International Lung Cancer Consortium (ILCCO) (29,266 cases and 56,450 controls). MR analyses were performed using the inverse-variance-weighted approach, MR pleiotropy residual sum and outlier (MR-PRESSO) test, weighted median estimator, and MR-Egger regression. Sensitivity analyses were further performed using Egger intercept analysis, leave-one-out analysis, MR-PRESSO global test, and Cochran's Q test to verify the robustness of our findings. Results The results of the MR analysis indicated an increased risk of lung cancer in insomnia patients (OR = 1.1671; 95% CI 1.0754–1.2666, p = 0.0002). The subgroup analyses showed increased risks of lung adenocarcinoma (OR = 1.1878; 95% CI 1.0594–1.3317, p = 0.0032) and squamous cell lung cancer (OR = 1.1595; 95% CI 1.0248–1.3119, p = 0.0188). Conclusion Our study indicated that insomnia is a causal risk factor in the development of lung cancer. Due to the lack of evidence on both the epidemiology and the mechanism level, more studies are needed to better elucidate the results of the study.

BACKGROUND: Spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) exhibits dual intraoperative and postoperative advantages for patients with non-small cell lung cancer (NSCLC). However, there is a lack of data regarding its long-term survival superiority over the double-lumen intubated mechanical ventilation video-assisted thoracoscopic surgery (MV-VATS) or thoracotomy. METHODS: A retrospective study was conducted from 2011 to 2018 in the First Affiliated Hospital of Guangzhou Medical University among patients with NSCLC who underwent the SV-VATS or the MV-VATS. Patients receiving the SV-VATS were the study group, and patients receiving the MV-VATS were the control group. Propensity score matching (PSM) was performed to establish 1:1 SV-VATS versus MV-VATS group matching to balance potential baseline confounding factors. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints were perioperative outcomes. The baseline information of these patients was recorded. The perioperative data and survival data were collected using a combination of electronic data record system and telephone interview. A 1:1:1 SPM was also used to compare the OS in the SV-VATS, the MV-VATS and thoracotomy group by using another database, including patients undergoing thoracotomy and the MV-VATS. RESULTS: For the two-group comparison, after 1:1 PSM, a matched cohort with 400 (200:200) patients was generated. The median follow-up time in this cohort was 4.78 years (IQR, 3.78–6.62 years). The OS (HR =0.567, 95% CI, 0.330 to 0.974, P=0.0498) and the DFS (HR =0.546, 95% CI, 0.346 to 0.863, P=0.013) of the SV-VATS group were significantly better than the MV-VATS group. There were no statistically differences between the SV-VATS and the MV-VATS group on the operative time (158.56±40.09 vs. 172.06±61.75, P=0.200) anesthesia time (247.4±62.49 vs. 256.7±58.52, P=0.528), and intraoperative bleeding volume (78.88±80.25 vs. 109.932±180.86, P=0.092). For the three-group comparison, after 1:1:1 PSM, 582 (194:194:194) patients were included for the comparison of SV-VATS, MV-VATS and thoracotomy. The OS of the SV-VATS group was significantly better than the thoracotomy group (HR =0.379, 95% CI, 0.233 to 0.617, P

Background The presence of pleural effusion is an independent predictor for poor survival in patients with small‐cell lung cancer (SCLC). The aim of this study was to assess the efficacy and safety of anlotinib in patients with SCLC and pleural effusion. Methods This was a randomized, double‐blind, multicenter, phase II trial. Patients histologically diagnosed with SCLC and pleural effusion and had received at least two lines of chemotherapy were enrolled into the study. The patients received anlotinib 12 mg/day or a placebo. Results The overall response rate (ORR) was 3.7% for anlotinib (n = 27) and 0% in the placebo group (n = 15) (p = 1.000). The disease control rate (DCR) of the anlotinib group (63.0%) was higher than that of the placebo group (0%, p, Patients with pleural effusion in this study came from a double‐blind, randomized, multicenter, controlled, phase II study, which was designed to examine the efficacy and safety of anlotinib in limited‐ or extensive‐stage SCLC. The median PFS (mPFS) was higher in the anlotinib group (2.8, 95% CI: 1.4–4.1) months compared to the placebo group (0.7, 95% CI: 0.5–0.7) months. The HR of PFS for the anlotinib group vs. the placebo group was 0.10 (95% CI: 0.03–0.28, p

Summary Background Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. Methods In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797 . Findings Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p Interpretation Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Funding Betta Pharmaceuticals Translation For the Chinese translation of the abstract see Supplementary Materials section.

Purpose Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. Description Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. Evaluation The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. Conclusion Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.

Carinal reconstruction and omental flap harvesting are traditionally performed via open approaches. We reported a case in which carinal reconstruction with bronchial flap and omental flap reinforcement was performed using minimally invasive approaches. The omental flap was harvested laparoscopically, and wrapped around the anastomosis, which reduced the risk of airway anastomosis complications. Non-circumferential resection and reconstruction used bronchial flap, which made it easier to perform under video-assisted thoracoscopic surgery conditions. Minimally invasive carinal reconstruction with bronchial flap and omental reinforcement after neoadjuvant treatment, can be safely performed.

Background The electromagnetic navigation bronchoscopy (ENB) was increasingly used to mark small pulmonary nodules (PNs) for video-assisted thoracic surgery (VATS) resection due to high effectiveness and low risk. However, no study reports the learning curve of ENB-guided preoperative localization. In the study, we aimed to describe the learning curve of ENB-guided preoperative PNs localization initially. Methods Consecutive PNs cases that underwent ENB localizations between October 2018 and October 2019 by the same surgeon in our center were included in the study. The cumulative sum (CUSUM) method was used to analyze the learning curve of ENB localization. Results A total of 89 ENB localization from 64 patients were included in this study. The learning curve was divided into 3 phases: Phase I (the initial 11 cases), Phase II (the 12th to the 47th cases), and Phase III (the 47th to the 89th cases). The success rate of ENB localization has increased with the accumulation of operational experience in 3 phases (72.73%, 91.67%, and 97.62%, P=0.049). The distance from the ENB guide wire tip to the center of the lesion in Phase I was significantly longer than those in Phase II and Phase III (2.46±1.76 vs. 1.36±0.94 and 1.47±0.97 cm, P=0.014 and 0.027, respectively). Sex, bronchus sign, and learning curve phase were independent risk factors influencing operative time (OT) (OR =8.187, 18.847, and 13.920, respectively). Conclusions The technical competency, which is indicated by higher success rate, localization accuracy, and shorter OT, for ENB-guided preoperative PNs localization was achieved at the 47th operation.

Background There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression‐free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. Methods This was a post hoc analysis of a multicenter, double‐blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. Results The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5–11.0) versus 3.2 (95% CI: 1.2–5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2–0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0–11.0) vs. 4.8 (95% CI: 1.2–8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. Conclusions The occurrence of hypertension might be a clinical indicator predicting the efficacy of third‐line anlotinib treatment in patients with SCC., In SCC patients who received third‐line anlotinib treatment, the median PFS was longer in patients who developed hypertension than in those who did not. Our results suggest that the occurrence of hypertension during treatment might be a clinical indicator predicting the efficacy of third‐line anlotinib in patients with SCC.

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

Background Lung cancer patients with chronic obstructive pulmonary disease (COPD) are considered a high-risk population to receive radical surgical treatment due to the high incidence of cardiopulmonary complications. The aim of this study was to evaluate the clinical factors associated with postoperative complications in primary lung cancer patients with moderate to extremely severe grades of COPD. Methods From December 2015 to June 2020, 138 patients with moderate to extremely severe COPD who underwent video-assisted thoracoscopic surgery (VATS) lung cancer resection (lobectomy or sublobar resection) were retrospectively reviewed. Patients' postoperative complications were collected from clinical records. Clinical factors (such as COPD severity or surgical approaches, etc.) were evaluated to investigate the association with postoperative complications. Results Of the 138 patients included in the study, the mean age was 67 (63-74) years, the mean preoperative forced expiratory volume in one second (FEV1) was 1.33±0.39 L, the mean FEV1% was 51.23% (41.43-60.00%). 33% patients (46/138) had postoperative complications, and no mortality occurred. Univariate analysis revealed that incidence of overall complications (OCs) and respiratory complications (RCs) was markedly higher in extremely severe COPD patients compared to moderate (OCs, P=0.033; RCs, P=0.050) and severe (OCs, P=0.015; RCs, P=0.008) COPD patients, respectively. Multivariate analysis showed that COPD grade was an independent risk factor of RCs (P=0.024). Furthermore, the grades of COPD (moderate, P=0.029; severe, P=0.028; extremely severe, P=0.019) and the surgical procedure (lobectomy or sublobar resection, P=0.043) were independent risk factors for atelectasis, which was the most common postoperative complication. Conclusions The aggravation of COPD was accompanied by an increase in the incidence of respiratory system complications postoperatively, especially atelectasis. For patients with moderate to extremely severe grades of COPD, careful perioperative evaluation should be performed to identify the indicators that influence the surgical choice between lobectomy and sublobar resection.

BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC). METHODS: We conducted this Phase 2 trial at 11 institutions in China. Patients with pathologically confirmed SCLC who failed at least two lines of chemotherapy were enrolled. Subjects were randomly assigned in a 2:1 ratio to receive either anlotinib 12 mg orally once daily for 14 days every 3 weeks or placebo. The primary endpoint was progression-free survival (PFS). RESULTS: Between March 30, 2017 and June 8, 2018, a total of 82 and 38 patients were randomly assigned to receive anlotinib and placebo. The median PFS was significantly longer in the anlotinib group compared with the placebo group (4.1 months [95% confidence interval (CI), 2.8–4.2] vs 0.7 months [95% CI, 0.7–0.8]; hazard ratio (HR) 0.19 [95% CI, 0.12–0.32], p

BACKGROUND: As lymphatic vessel is a major route for solid tumor metastasis, they are considered an essential part of tumor drainage conduits. Apart from forming the walls of lymphatic vessels, lymphatic endothelial cells (LECs) have been found to play multiple other roles in the tumor microenvironment, calling for a more in-depth review. We hope that this review may help researchers gain a detailed understanding of this fast-developing field and shed some light upon future research. METHODS: To achieve an informative review of recent advance, we carefully searched the Medline database for English literature that are openly published from the January 1995 to December 2020 and covered the topic of LEC or lymphangiogenesis in tumor progression and therapies. Two different authors independently examined the literature abstracts to exclude possible unqualified ones, and 310 papers with full texts were finally retrieved. RESULTS: In this paper, we discussed the structural and molecular basis of tumor-associated LECs, together with their roles in tumor metastasis and drug therapy. We then focused on their impacts on tumor cells, tumor stroma, and anti-tumor immunity, and the molecular and cellular mechanisms involved. Special emphasis on lung cancer and possible therapeutic targets based on LECs were also discussed. CONCLUSIONS: LECs can play a much more complex role than simply forming conduits for tumor cell dissemination. Therapies targeting tumor-associated lymphatics for lung cancer and other tumors are promising, but more research is needed to clarify the mechanisms involved.

BACKGROUND: Prior cancer history is a common exclusion in thymoma trials. However, whether prior cancer impacts the survival of thymoma patients and the outcomes of clinical trials remains uncertain. The aim of this study is to identify the impact of prior cancer on outcomes in thymoma. METHODS: Patients with thymoma diagnosed between 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age, histologic types, and thymoma size were stratified to analyze. Propensity score matching (PSM), Kaplan-Meier methods and Cox proportional hazard models were used to analyze the prognostic effect of prior cancer on overall survival (OS). RESULTS: A total of 3,827 thymoma patients were enrolled, of whom 13.22% had a prior cancer history. The Kaplan-Meier curves showed statistically significantly different survival before (P

Background Localization of small pulmonary nodules (SPNs) is challenging in minimally invasive pulmonary resection, and it is unknown whether computer tomography (CT) guided by indocyanine green (ICG) can provide accurate localization with minimal complications. Methods We performed a retrospective study of patients who underwent thoracoscopic resection of pulmonary nodules after CT-guided preoperative localization with ICG from May 2019 to May 2020. Demographics, procedural data, postoperative complications, and pathologic information, were collected, and an analysis of the accuracy and complications after surgery was conducted. Results In 471 patients, there was a total of 512 peripheral pulmonary nodules that were ≤2 cm in size. The average time for CT-guided percutaneous ICG injection for localization was 18 minutes, and 98.4% (504/512) of the nodules were successfully localized. The average size of the nodules was 9.1 mm, and the average depth from the pleural surface was 8.9 mm. Overall, 5.9% (28/471) of the patients had asymptomatic pneumothorax after localization, but none needed a tube thoracostomy. All the nodules were resected using video-assisted thoracoscopy technique. Conclusions Preoperative CT-guided transthoracic ICG injection is safe and feasible for localization of small lung nodules for minimally invasive pulmonary resection. This technique should be considered for preoperative CT-guided localization of small lung nodules.

Common lung diseases are first diagnosed using chest X-rays. Here, we show that a fully automated deep-learning pipeline for the standardization of chest X-ray images, for the visualization of lesions and for disease diagnosis can identify viral pneumonia caused by coronavirus disease 2019 (COVID-19) and assess its severity, and can also discriminate between viral pneumonia caused by COVID-19 and other types of pneumonia. The deep-learning system was developed using a heterogeneous multicentre dataset of 145,202 images, and tested retrospectively and prospectively with thousands of additional images across four patient cohorts and multiple countries. The system generalized across settings, discriminating between viral pneumonia, other types of pneumonia and the absence of disease with areas under the receiver operating characteristic curve (AUCs) of 0.94-0.98; between severe and non-severe COVID-19 with an AUC of 0.87; and between COVID-19 pneumonia and other viral or non-viral pneumonia with AUCs of 0.87-0.97. In an independent set of 440 chest X-rays, the system performed comparably to senior radiologists and improved the performance of junior radiologists. Automated deep-learning systems for the assessment of pneumonia could facilitate early intervention and provide support for clinical decision-making.

BACKGROUND: Growing evidence suggests that female reproductive factors, like age at first birth (AFB), may play a potential role in the progression of lung cancer (LC). However, previous studies are susceptible to confounding factors, inadequate attention to variation by histology or reverse causality. Few studies have comprehensively evaluated their association and the causal effect remains unclear. METHODS: We aimed to determine whether AFB is causally correlated with the risk of LC, by means of utilizing aggregated data from the large genome-wide association studies conducted on AFB (251,151 individuals) and data of LC from International Lung and Cancer Consortium (ILCCO, 11,348 cases and 15,861 controls). We used 10 AFB-related single nucleotide polymorphisms as instrument variables and applied several two-sample Mendelian randomization (MR) methods. Secondary results according to different histological subtypes of lung cancer were also implemented. RESULTS: Conventional inverse-variance weighted method indicated that genetic predisposition towards number unit (1 year) increase of AFB was associated with a 18% lower risk of LC [odds ratio (OR) =0.82, 95% confidence interval (CI): 0.69–0.97; P=0.029]. When results were examined by histotypes, an inverse association was observed between genetically predisposed number unit (1 year) increase of AFB and lung adenocarcinoma (OR =0.75, 95% CI: 0.59–0.97, P=0.017) but not with squamous cell lung cancer (OR =0.77, 95% CI: 0.57–1.05, P=0.103). The results demonstrated no association between number unit decrease of AFB and LC. Pleiotropy was not presented through sensitivity analyses including MR pleiotropy residual sum and outlier test (P=0.412). Genetic predisposition towards older AFB was additionally associated with longer years of schooling (OR =1.12, 95% CI: 1.08–1.16, P

Background It remains uncertain whether there is a protective effect of inhaled corticosteroids (ICs) against lung cancer in chronic obstructive pulmonary disease (COPD) patients. Methods Databases including PubMed, Web of Science, EMBASE, and Medline were comprehensively searched. Random-effects model meta-analysis was conducted to calculate the hazard ratios (HRs) for lung cancer incidence among ICs users versus non-ICs users in patients with COPD. Stratified analysis was performed based on region and age of each study. This review was registered on PROSPERO (registration number CRD42020159082). Results Based on data from 181,859 COPD patients with a total follow-up duration of 1,109,339.9 person-years, we identified that the use of ICs in COPD patients was associated with a decreased risk of lung cancer [HR: 0.73, 95% confidence interval (CI): 0.62-0.86; P

Purpose: Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8+ T cells and reducing recruitment of tumor-associated macrophages. We hereby conducted a clinical trial to evaluate this combination in pretreated patients with advanced non–small cell lung cancer (NSCLC). Patients and Methods: The study included phase Ib apatinib dose-escalation and phase II expansion cohorts. Patients received apatinib at doses of 250–500 mg orally once daily, in combination with camrelizumab 200 mg intravenously every 2 weeks. Results: From March 2017 to October 2018, 105 chemotherapy-pretreated patients with nonsquamous NSCLC were enrolled and received apatinib 250 mg (recommended phase II dose) and camrelizumab. Among them, one (1.0%) complete response, 28 (26.7%) partial responses, and 48 (45.7%) stable diseases were observed. In the efficacy-evaluable population (n = 94), objective response rate (ORR) was 30.9% [95% confidence interval (CI), 21.7–41.2]. The median progression-free survival was 5.7 months (95% CI, 4.5–8.8) and overall survival was 15.5 months (95% CI, 10.9–24.5). Efficacy of combination therapy was evident across all PD-L1 and tumor mutation burden subgroups, and appeared to be improved in patients with STK11/KEAP1 mutation (mutant vs. wild-type, ORR: 42.9% vs. 28.1%; 1-year survival rate: 85.1% vs. 53.1%). No unexpected adverse events were observed. Conclusions: Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485).

There are increasing numbers of synchronous multiple primary lung cancer (SMPLC) patients in clinical practice, with most lesions presenting as ground-glass opacity (GGO). For SMPLC patients, surgical resection should be a prior option for all lesions suspected of being malignant, if medically and technically feasible. However, it is frequently a dilemma for the management of residual GGO lesions that were unresected simultaneously with the main tumor in SMPLC patients. We report a case of SMPLC, in which the patient underwent surgical resection of the major lesion with EGFR mutation and then received compelling EGFR-TKI treatment for one enlarging residual GGO lesion after 12 months since operation. Furthermore, a comprehensive literature review about the risk for the progress of GGOs unresected simultaneously with the main lesion and the management of these residual GGOs was also summarized. With the treatment of EGFR-TKI gefitinib for 3 months, the biggest residual GGO lesion (more than 10mm) achieved a complete response (CR), three lesions reduced in size, and the other three lesions remained stable in this case. Surgical resection for major lesion and EGFR-TKI treatment on unresected GGOs might bring favorable outcome for patients with EGFR-mutated multifocal lung cancer. This strategy is safe and effective, which could be a promising therapeutic approach for unresectable GGO lesions in EGFR-mutated SMPLC patients after primary surgery. Notably, folate receptor-positive circulating tumor cell (FR+-CTC) for therapeutic monitoring was more sensitive for GGO-featured lung adenocarcinoma than serum markers.

BACKGROUND: The appropriate approach for video-assisted thoracoscopic surgery for early stage thymoma remains unclear. The present study aimed to explore the safety and feasibility of subxiphoid and subcostal arch thoracoscopic thymectomy in comparison with unilateral thoracoscopic thymectomy for treatment of early stage thymoma. METHODS: The outcomes of 237 patients without myasthenia gravis who had undergone thoracoscopic thymectomy for Masaoka stage I and II thymoma from January 2015 to May 2019 at our center were retrospectively evaluated (subxiphoid and subcostal arch approach, 39; unilateral video-assisted thoracoscopic surgery approach, 198). A propensity score matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner. RESULTS: There was no surgery-related mortality in included patients. Matching of patients according to propensity score resulted in a cohort that consisted of 39 patients in both groups. Patients had similar clinical characteristics in both groups. Compared with patients in the unilateral group, patients in the subxiphoid group yielded lower pain scores at 24 and 72 hours after operation, respectively (P < .01). In addition, the operation time was longer in the subxiphoid group (147.5 ± 43.6 vs 93.2 ± 33.8 minutes, P < .01). There were no significant differences in blood loss, total volume and time of drainage, complications, or postoperative hospital stays between the two groups. CONCLUSIONS: Subxiphoid and subcostal arch thoracoscopic thymectomy for early stage thymoma appears to be a safe and feasible procedure. It is considered to be less invasive as it may cause minimal postoperative pain compared with the unilateral video-assisted thoracoscopic surgery approach. ispartof: ANNALS OF THORACIC SURGERY vol:113 issue:5 pages:1656-1662 ispartof: location:Netherlands status: published

Vascular anastomosis is an essential step for many surgery procedures, especially for cardiovascular surgeries and lung transplantation (LTx). Although hand-sewn anastomosis is known as the standard method for vascular anastomosis,there are many limitations for hand-sewn anastomoses, such as the requirement of technical expertise, time-consuming, and a limit for developing minimally invasive surgery. In this study, we introduce a new idea to conduct the great vascular mechanical anastomosis through the arterial flap using an endo-stapler.

Background Sleeve lobectomy has been reported to be a safe procedure after neoadjuvant chemotherapy. We aim to evaluate the oncological and surgical outcomes of neoadjuvant chemoimmunotherapy (IO+C) for local advanced non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy. Methods NSCLC patients that underwent sleeve lobectomy between December 2016 and December 2019 were retrospectively included. Patients were divided into two groups: neoadjuvant IO+C and chemotherapy. Oncological, intraoperative and postoperative variables were compared. Results In total, 20 patients underwent sleeve lobectomy after neoadjuvant IO+C (n=10) or chemotherapy (n=10). In the neoadjuvant IO+C group, 8/10 (80%) patients achieved a partial response (PR), 1/10 (10%) patients had a complete pathological response (CPR), and 5/10 (50%) patients achieved a major pathological response (MPR). In the neoadjuvant chemotherapy group, only 3/10 (30%) patients had PR, and 3/10 (30%) patients achieved MPR. No complications were found in the neoadjuvant IO+C group, 1 chylothorax occurred in the neoadjuvant chemotherapy group. Other peri- and postoperative outcomes were similar: bleeding volume (365.00 vs. 347.50 mL; P=0.267), operation time (291.88 vs. 287.50 min; P=0.886), chest tube duration (5.40 vs. 5.00 day; P=0.829), total drainage volume (815.50 vs. 842.50 mL; P=0.931) and the length of hospital-stay (7.00 vs. 6.56 day; P=0.915). In addition, less N1 (average number 4.70 vs. 7.40) and N2 (average number 9.80 vs. 20.10) lymph nodes were acquired in the neoadjuvant IO+C group than the neoadjuvant chemotherapy group. The number of lymph nodes positive for tumor cells was also less in the neoadjuvant IO+C group than the neoadjuvant chemotherapy group, both in N1 (0.40 vs. 1.60) and N2 (0.10 vs. 1.30). The positive lymph node ratio (LNR) was lower in the neoadjuvant IO+C group, both in N1 (0.05 vs. 0.15) and N2 (0.01 vs. 0.09). A greater destruction on elastic fiber of the blood vessels, vascular wall degeneration, fibrinoid necrosis and fibrosis, and greater pulmonary interstitial exudation were found in neoadjuvant IO+C patients compared to the neoadjuvant chemotherapy patients. Conclusions Sleeve lobectomy for advanced NSCLC following IO+C is feasible, although the operations become more complex, neoadjuvant IO+C did not delay postoperative recovery.

Rationale: Platinum-based chemotherapy is one of treatment mainstay for patients with advanced lung squamous cell carcinoma (LUSC) but it is still a "one-size fits all" approach. Here, we aimed to investigate the predictive and monitoring role of circulating cell-free DNA (cfDNA) profiling for the outcome of first-line chemotherapy in patients with advanced LUSC. Methods: Peripheral blood samples of 155 patients from a phase IV trial and 42 cases from an external real-world cohort were prospectively collected. We generated a copy number variations-based classifier via machine learning algorithm to integrate molecular profiling of cfDNA, named RESPONSE SCORE (RS) to predict the treatment outcome. To monitor the treatment efficacy, cfDNA samples collected at different time points were subjected to an ultra-deep sequencing platform. Results: The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set (P < 0.001), validation set (P < 0.001) and real-world cohort (P = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, P < 0.001; validation set: P < 0.001; real-world cohort: P = 0.019) and overall survival (training set, P < 0.001; validation set: P = 0.037) between high and low RS group. Notably, variant allele frequency (VAF) calculated from an ultra-deep sequencing platform significantly reduced in patients experienced a complete or partial response after 2 cycles of chemotherapy (P < 0.001), while it significantly increased in these of non-responder (P < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate (P < 0.001) and progression-free survival (P < 0.001) than those with detectable VAF. Conclusions: These findings indicated that the RS, a circulating cfDNA sequencing-based stratification index, could help to guide first-line chemotherapy in advanced LUSC. The change of VAF is valuable to monitor the treatment response.

Embryonal rhabdomyosarcoma (ERMS) is associated with a low prevalence, poor prognosis, and limited treatment efficacy. Here, we report a case of a 21-year-old male whose disease relapsed in the thoracic cavity following traditional chemotherapy. The patient received eight sequential cycles of traditional chemotherapy using a combination of the cyclophosphamide + vincristine + doxorubicin hydrochloride liposome (CAV) and etoposide + ifosfamide (IE) regimens. The therapeutic effect of the combination regimen had been worked in short times. After a month, ERMS had relapsed in the whole lung after traditional chemotherapy. The treatment method was changed immediately and the patient received targeted therapy with a combination of pazopanib and olaratumab. The therapeutic effect of the combination regimen was evaluated for a complete response (CR). After two months, CT imaging revealed that most of the metastatic lesions in the lung had disappeared. This is the first case to report the use of pazopanib and olaratumab in relapsed ERMS with a curative effect resulting in a CR. Pazopanib is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Thus, combining pazopanib with targeted therapy may play an important role and provide a reference for the treatment of relapsed ERMS.

Lung cancer is the leading cause of cancer-related death worldwide and in China (1). According to the statistics of the National Cancer Center of China, there were 733,300 new cases of non-small cell lung cancer (NSCLC) and approximately 610,200 related deaths in 2015 (2). For patients with early staged disease, surgery is the mainstay of treatment, and it is commonly followed by adjuvant chemotherapy for patients with locally advanced resectable NSCLC. Although complete surgical resection may be curative for NSCLC, 25–70% of patients (with different proportion according to stage) eventually relapse despite complete resection (3). Platinum-based adjuvant chemotherapy has been shown to marginally increase the 5-year survival rate of patients by 4–8% (4-6). Even after treatment with surgery and indicated adjuvant therapies in eligible cases, approximately 20–30% of stage I, 50% of stage II, and 60% of stage IIIA patients still die within 5 years (7). In the past decade, experts have conducted a number of investigations on the perioperative management of resectable NSCLC; however, progress remains slow, and patients still have a high risk of recurrence and death. Neoadjuvant therapy is defined as any therapy delivered prior to definitive local therapy intended to increase the cure rate. It provides several theoretical benefits in managing such patients with NSCLC. In the setting of, neoadjuvant therapy given prior to radical surgery this approach can also have the goals of downstaging, improving the resection rate, and more promptly treating subclinical micro-metastases than adjuvant approaches, delivered after the definitive local therapy. In addition, the compliance with neoadjuvant therapy has been shown to be better than in the adjuvant setting, and the biological effect of the neoadjuvant therapy can be analyzed directly in the resected tumor specimens (8). A meta-analysis on patients with stage IB‒IIIA NSCLC that compared chemotherapy plus subsequent surgery vs. surgery alone showed that the 5-year survival rate was 5% higher after receiving neoadjuvant chemotherapy (NCT) (9). Therefore, the comprehensive NSCLC data suggest that, for resectable NSCLC, NCT improves survival compared with surgery alone but appear to show no significant survival benefit compared with adjuvant chemotherapy (10). In the last 5 years, immune checkpoint inhibitors (ICIs) have profoundly changed the treatment paradigm for patients with advanced NSCLC (11-15). Immunotherapy has provided hope for long-term survival benefits to a minority of patients with metastatic lung cancer. For treatment-naive patients with driver mutation-negative NSCLC, the 5-year survival rate of single agent pembrolizumab was 23.2%; for the previously treated patients with driver mutation-negative NSCLC, the 5-year survival rates of single agent pembrolizumab and nivolumab were 15.5% and 16%, respectively (16,17). Given the profound impact made by immunotherapy drugs for patients with advanced disease, significant attention has been directed in recent years toward investigating the potential role for early-stage NSCLC patients, and whether they, too, can achieve long-term benefits from the inclusion of immunotherapy into their treatment algorithms. Many phase Ib/II clinical trials have reported promising results, and a series of large-scale phase III clinical trials are underway. However, these various investigations have employed different strategies of neoadjuvant immunotherapy, in terms of the specific regimens as well as number of treatment cycles (18). To better guide Chinese thoracic surgeons in the neoadjuvant immunotherapy of NSCLC, well-known thoracic surgeons in China participated in an in-depth discussion on the hot topics and controversial issues of neoadjuvant immunotherapy and formed the Expert consensus on neoadjuvant immunotherapy for non-small-cell lung cancer by incorporating the latest evidence on neoadjuvant immunotherapy.

The association between polycystic ovary syndrome (PCOS) and breast cancer remains inconclusive. Conventional observational studies are susceptible to inverse causality and potential confounders. With a Mendelian randomization (MR) approach, we aimed to investigate the causal relationship between genetically predicted PCOS and breast cancer risk. Our study included 11 PCOS-associated single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association study. Individual-level genetic summary data of participants were obtained from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. The inverse-variance weighted method was applied to estimate the causality between genetically predicted PCOS and breast cancer risk. To further evaluate the pleiotropy, the weighted median and MR-Egger regression methods were implemented as well. Our study demonstrated that genetically predicted PCOS was causally associated with an increased risk of overall breast cancer (odds ratio (OR) = 1.07; 95% confidence interval (CI) 1.02–1.12, p = 0.005). The subgroup analyses according to immunohistochemical type further illustrated that genetically predicted PCOS was associated with an increased risk of estrogen receptor (ER)-positive breast cancer (OR = 1.09; 95% CI 1.03–1.15, p = 0.002), while no causality was observed for ER-negative breast cancer (OR = 1.02; 95% CI 0.96–1.09, p = 0.463). In addition, no pleiotropy was found in our study. Our findings indicated that PCOS was likely to be a causal factor in the development of ER-positive breast cancer, providing a better understanding for the etiology of breast cancer and the prevention of breast cancer.

Background The addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-L1) inhibitor is a more effective option as a first-line treatment for advanced non-small cell lung cancer (NSCLC). It might also inhibit an overactive immune response and thereby reduce immune-related adverse events (irAEs). This meta-analysis assessed the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) versus a PD-(L)1 inhibitor alone (I) and evaluated the indirect relative risk (RR) of I+C versus I. Methods The protocol of this study was registered with PROSPERO (CRD42020139923). The pooled rates of irAEs at different grades were calculated by a single-arm meta-analysis weighted by sample size, and RRs were determined by direct meta-analysis and indirect treatment comparison. Results Overall, I+C had a lower rate of grade 3 or higher irAEs than I (7.1% vs 10.6%; indirect RR, 0.516; 95% confidence interval [CI], 0.291-0.916), although irAEs of any grade were similar. The rate of pneumonitis with I+C was lower than the rate with I for any grade (5.9% vs 7.1%; indirect RR, 0.217; 95% CI, 0.080-0.588) and for grade 3 or higher. In the endocrine system, I+C was associated with a lower overall ratein comparison with I (16.1% vs 20.1%; indirect RR, 0.260; 95% CI, 0.120-0.564), whereas irAEs of the digestive system were similar with I+C and I. In other systems, I+C decreased the rate of skin reactions, including rash, in comparison with I (10.4% vs 12.9%; indirect RR, 0.474; 95% CI, 0.299-0.751). The rate of grade 3 or higher skin reactions (excluding rash) also decreased with I+C versus I (1.1% vs 2.0%) with an indirect RR of 0.158 (95% CI, 0.032-0.765), whereas other included irAEs were similar. Conclusions In comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreased the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate. Lay summary In the first-line treatment of advanced non-small cell lung cancer (NSCLC), the addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor is a more effective option. Adding chemotherapy might reduce immune-related adverse events (irAEs). Thus, this article assesses the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) in comparison with a PD-(L)1 inhibitor alone (I) and evaluates the indirect relative risk (RR) with I+C versus I. The key finding is that in comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreases the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.

Background Epidemiological evidence suggested that systemic lupus erythematosus (SLE) might be correlated with an increased risk of lung cancer. Nevertheless, few studies have comprehensively investigated their correlation and the causal effect remains unclear. With a meta-analysis and Mendelian randomization (MR) approach, we were able to systematically investigate the relationship between SLE and lung cancer risk. Methods A systematic search of cohort studies was conducted using network databases from the inception dates to February 1, 2020. Meta-analysis was performed to calculate standardized incidence rate (SIR) and their 95% CI. Furthermore, utilizing 33 SLE-related single nucleotide polymorphisms as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predisposed SLE and lung cancer risk using summary statistics from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). The Inverse variance-weighted method was applied to estimate the causality and we further evaluated the pleiotropy by means of the weighted median and the MR-Egger regression method. Subgroup analysis according to different histotypes of lung cancer was also conducted. Results Through meta-analysis of 15 cohort studies involving 110,519 patients, we observed an increased risk of lung cancer among SLE patients (SIR =1.63, 95% CI, 1.39-1.90). Subgroup analysis suggested that female patients (SIR =1.28, 95% CI, 1.13-1.44) have a relatively higher lung cancer risk compared with male patients (SIR =1.15, 95% CI, 1.02-1.30). MR analysis indicated that genetically predisposed SLE was causally associated with an increased lung cancer risk (OR =1.045, 95% CI, 1.005-1.086, P=0.0276). When results were examined by histotypes, a causal relationship was observed between genetically predisposed SLE and squamous cell lung cancer (OR =1.065, 95% CI, 1.002-1.132, P=0.0429). Additionally, the results demonstrated the absence of the horizontal pleiotropy. Conclusions Both meta-analysis and MR analysis results suggested that SLE was associated with an increased lung cancer risk. Further investigations are warranted to investigate the etiology underlying the attribution of SLE to lung cancer.

Immune checkpoint blockade therapies that target CTLA-4 and PD-1/PD-L1 have ushered in a new era of cancer treatment. Nevertheless, a significant proportion of patients demonstrated primary or acquired resistance. Harnessing gut microbiota has been an emerging novel therapeutic strategy to overcome resistance. Here we summarized the current research status of gut microbiota in immune checkpoint blockade therapies, clinical trials, underlying mechanisms and challenges of microbiome research in checkpoint immunotherapy. Findings from preclinical models, standardized microbiome analysis and progress of multi-omic approaches may better disclose the interaction between gut microbiota and immune checkpoint inhibitors (ICIs) and traditional Chinese medicine can be a potential microbiome modulator to sensitize the response to ICIs.

We performed a meta‐analysis to determine cancer risks at multiple sites and their associations with tumor mutation burden (TMB), an index for immunogenicity, in heart or lung transplant recipients. A comprehensive search of PubMed, Web of Science, EMBASE, and Medline was conducted. Random effects models were used to calculate standardized incidence ratios (SIRs) versus the general population and to determine the risks of different cancers. Weighted linear regression (WLR) was used to analyze the associations between the SIRs and TMBs. (PROSPERO CRD42020159599). Data from 21 studies including 116,438 transplant recipients (51,173 heart transplant recipients and 65,265 lung transplant recipients) with a total follow‐up of 601,330.7 person‐years were analyzed. Compared with the general population, heart transplant recipients displayed a 3.13‐fold higher cancer risk [SIR: 3.13; 95% confidence interval (CI): 2.38–4.13; p, Our study demonstrated that both heart and lung transplant recipients displayed a higher risk of certain site‐specific cancers. These findings can provide individualized guidance for clinicians for detection of cancer among heart or lung transplantation recipients. In addition, we provided evidence that increased risks of post‐transplant cancers can be attributed to immunosuppression.

Background Combined small cell lung cancer (CSCLC) is a subtype of small cell lung cancer (SCLC) which contains both components of SCLC and non-small cell lung cancer (NSCLC). The prognostic outcomes and treatment strategy of it are still unclear. A large-scale retrospective study was performed to investigate proper treatments for CSCLC. Methods All cases of CSCLC were identified from the SEER database during the period of 2004-2016. Clinical characteristics, first-line treatments, surgical procedures and survival data including overall survival (OS) and cancer-specific survival (CSS) were analyzed. Results A total of 37,639 SCLC patients were identified. CSCLC accounted for 2.1% (784/37,639). The mean age of CSCLC cohort is 67.3±9.9 years old. Male and white ethnicity patients were accounted for larger proportions (55.7% and 80.4%). The oncological characteristics of CSCLC were consistent with SCLC that most of patients were diagnosed as higher grade and advanced stages. The prognosis of CSCLC was better than SCLC but worse than NSCLC in IA-IIIA stages. No difference was observed in IIIB-IV. Surgery was beneficial in IA-IB stage CSCLC. Adjuvant chemotherapy seemed to have few effects on early stage patients. Trimodality treatment could significantly improve OS in IIA-IIIA CSCLC patients. Chemotherapy-based treatment is predominant choice in advanced stage patients. Conclusions CSCLC is a rare and special subtype of SCLC. It has better survival outcome than non-CSCLC in early stage. Surgical treatment is crucial in early stage of CSCLC. Prognostic improvement might be achieved from trimodality treatment in stage IIA-IIIA. Chemotherapy-based treatments should be considered in advanced stage. The effect of surgical treatments in advanced stage patients should be further investigated.

We aimed to elucidate the associations between aspirin use with risk of lung cancer, by conducting a meta-analysis and Mendelian randomization (MR) analyses from published Genome-Wide Association Studies (GWAS). Cohort studies, nested case–control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer incidence were included. Relative risk (RR) and its 95% confidence interval (CI) were evaluated in eligible studies. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using summary statistics obtained from two large consortia [Neale Lab and International Lung Cancer Consortium (ILCCO)] to assess the possible causal relationship of aspirin on lung cancer incidence. Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for the incidence of lung cancer was 0.95 (95% confidence interval (CI) 0.91–0.98). In subgroup meta-analyses, a significant protective effect was observed in squamous cell lung cancer (RR = 0.80; 95% CI 0.65–0.98). In terms of gender, the chemopreventive value was only observed among men (RR = 0.87; 95% CI 0.77–0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer incidence, with evidence of a decreased risk for overall lung cancer (OR = 0.042; 95% CI 0.003–0.564) and squamous cell lung cancer (OR = 0.002; 95% CI 1.21 × 10–5–0.301). Our study provided evidence for a causal protective effect of aspirin on the risk of lung cancer incidence among men, particularly on the squamous cell lung cancer risk.

Objective Differences in efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been observed between non-small cell lung cancer (NSCLC) patients with 19 exon deletion (19Del) and L858R mutation. We explored whether the total number or pattern of concomitant mutations of 19Del and L858R may explain their different sensitivities. Patients and methods This study contained the mutational profiles of EGFR-mutated NSCLC patients from two cohorts: Guangzhou (G1) and database (G2). Concomitant mutation status and EGFR-TKI response information were retrieved. Results A total of 403 patients covered 283 genes in the G1 and 803 patients with a different gene set in the G2 were included. Similar prevalence of total concomitant mutation number was observed in both G1 (19Del 32.48% vs L858R 30.45%; P=0.68) and G2 (19Del 74.9% vs L858R 73.2%; P=0.65) cohorts. Only HGF/c-Met pathway same more related to L858R mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. 19Del showed a higher objective response (OR) rate compared with L858R, regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in 19Del (53.8% vs 83.3%; P=0.021) and L858R (51.4% vs 77.8%; P=0.029). In particular, total concomitant mutations (OR=0.27; P=0.03), sensitive EGFR mutations (OR=2.21; P=0.04), and T790M (OR=0.244; P=0.02) significantly affected the TKI response. Conclusion Concomitant mutations were widespread in 19Del and L858R and were associated with poorer OR to EGFR-TKIs. However, 19Del and L858R had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.

BACKGROUND: The 8(th) edition staging system for malignant pleural mesothelioma (MPM) has been proposed. The size of tumor is not taken into consideration. We intend to elucidate the prognostic value of the size of MPM and evaluate the current staging system via the data of SEER database. METHODS: All cases of primary MPM were identified and extracted from the SEER database during the period of 2004–2016. The endpoints were overall survival (OS) and cancer-specific survival (CSS) which were analyzed using Kaplan-Meier method. Log-rank test and Cox regression were utilized to identify the prognostic factors. RESULTS: A total of 2,138 patients were included in the primary cohort. The 1-, 3- and 5-year survival rates of MPM were 39.4%, 11.8% and 3.8%. Older, male and advanced stage patients accounted for larger proportion of the cohort. Besides tumor extension, lymph node involvement and metastatic status, tumor size, pathological type and differentiation grade were significant prognostic factors. In the stratified analysis of tumor extension, size is a significant prognostic factor in T2 patients and indicates inferior survival outcomes. Surgery, chemotherapy and radiation can increase both OS and CSS in MPM patients. Triple combination treatments showed a superiority to other treatments. CONCLUSIONS: Tumor size matters in the prognosis of MPM especially in the early stage of MPM patients. The adjusted TNM staging system incorporating tumor size has better accuracy than the 8(th) edition IMIG system. However, some stages had not been fully identified. More cases of early stages are warranted for essential revision.

As the computer processing technique and display technology evolved dramatically, the surgical approach to early-stage non-small cell lung cancer (NSCLC) has made a rapid progress within the past few years. Currently, the gold standard for NSCLC is lobectomy. After the introduction of video-assisted thoracoscopic surgery (VATS), lung resection can now be conducted mini-invasively, enabling better prognosis for patients and better operation condition for surgeons. At the very beginning, the conventional two-dimensional (2D) system enabled operators to have a closer, magnified and illuminated view inside the body cavity than open thoracotomy. With the introduction of the glasses-assisted three-dimensional (3D) and glasses-free 3D display system, multiple viewing angles were further enhanced, thus a more stable, easier to master and less invasive video-assisted thoracoscopic surgery (VATS) appeared. However, given that the standard VATS is associated with limited maneuverability and stereoscopy, it restricts the availability in more advanced cases. Hopefully, most of the limitations of standard VATS can be overcome with the robotic-assisted thoracic surgery (RATS). The RATS system consists of a remote console and a robotic unit with 3 or 4 arms that can duplicate surgeons’ movements. Also, it provides a magnified, 3D and high definition (HD) operation field to surgeons, allowing them to perform more complicated procedures. Apart from these, some new technologies are also invented in combination with the existing surgery system to solve difficult problems. It is hoped that the higher costs of innovative surgical technique can be offset by the better patient outcomes and improved benefits in cost-effectiveness.

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Background Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. Methods We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. Results Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. Conclusions While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19.

Corona Virus Disease 2019(COVID-19)-affected patients with severe immune abnormalities have a risk of cytokine release syndrome. The definition, prevention, and treatment of symptoms of cytokine release syndrome in critically ill patients with COVID-19 are important problems. This was a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The termination date of follow-up was February 19, 2020. In this single-center analysis of 11 critically ill patients with COVID-19, 8 patients were determined to have characteristics of cytokine release syndrome (CRS), including pulmonary inflammation, fever, and dysfunction of non-pulmonary organs; an increase of- Interleukin-6 (IL-6) in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

Few studies have investigated the relationship between vitiligo and risks of various types of cancers, especially those other than skin cancer. Conventional observational studies are susceptible to potential confounders and inverse causation. With a Mendelian randomization approach, we were able to evaluate the causality between vitiligo and different cancer risks. 37 vitiligo-related single-nucleotide polymorphisms identified by the published genome-wide association studies were used as instrumental variables in our study. Summary data of individual-level genetic information were obtained from corresponding studies and cancer consortia. A total of 246,706 cases and 1,021,154 controls were included. The inverse variance-weighted method was applied to estimate the causation between vitiligo and different cancers. The results revealed that vitiligo patients were at lower risks of lung cancer [odds ratio (OR) 0.9513; 95% confidence interval (CI) 0.9174–0.9864; p = 0.0070], breast cancer (OR 0.9827; 95% CI 0.9659–0.9997; p = 0.0468), ovarian cancer (OR 0.9474; 95% CI 0.9271–0.9682; p

Background Anlotinib showed significant survival benefits in advanced non‐small cell lung cancer (NSCLC) patients as a third‐ or further‐line treatment in the ALTER0303 trial. We aimed to evaluate the efficacy of anlotinib in patients with different histologies. Methods The ALTER0303 trial was a randomized, open‐label, phase 3 study of anlotinib in NSCLC patients previously treated with at least two lines of chemotherapy or a tyrosine kinase inhibitor (TKI) in 31 centers in China. Patients were randomly assigned at a 2:1 ratio to receive anlotinib (12 mg QD from days 1 to 14 of a 21‐day cycle) or placebo until progression or intolerable toxicity. The primary endpoint was overall survival (OS). We assessed the efficacy of anlotinib in histological subgroups in the full analysis set. Results In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. In the ACC subgroup, the median OS time was significantly improved with anlotinib compared with placebo (9.6 months vs 6.9 months, P = .0051), as was the median progression‐free survival (PFS) time (5.5 months vs 1.4 months, P, In this study, we evaluated the efficacy of anlotinib as third‐ or further‐line treatment for patient with different histological types of NSCLC. In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. Our findings suggest that anlotinib significantly improves PFS and OS in ACC patients and has a tendency to prolong survival in SCC patients.

Background This Bayesian network meta-analysis (NMA) was conducted to compare efficacy and safety of programmed death 1/ligand 1 (PD-1/L1) inhibitors in previous untreated advanced non-small cell lung cancer (NSCLC) patients. Methods Eligible studies evaluating first-line anti-PD-1/L1 based regimens in advanced NSCLC patients were included. Overall survival (OS), progression free survival (PFS), objective response rate (ORR), as well as treatment-related severe adverse events (tr-SAE) were synthesized within the Bayesian framework. Subgroup analysis was conducted according to PD-L1 expression. Results Twelve studies including 7,490 patients and 9 treatment strategies were enrolled in this study. For the PD-L1 expression non-selective patients, all chemo-immunotherapies were significantly better than chemotherapy for prolonging OS and PFS, except for caremlizumab plus chemotherapy (HR =0.72) failed to show advantages for OS. In addition, pembrolizumab plus chemotherapy showed better PFS than nivolumab plus ipilimumab (HR =0.66). In PD-L1 ≥50% patients, all immunotherapy was better than chemotherapy for OS, except for nivolumab (HR =0.83) and nivolumab plus ipilimumab (HR =0.70). For PFS, pembrolizumab plus chemotherapy (HR =0.39), atezolizumab plus chemotherapy (HR =0.47) and pembrolizumab (HR =0.67) were significantly better than chemotherapy. In PD-L1 1-49% patients, pembrolizumab plus chemotherapy (HR =0.52) and atezolizumab plus chemotherapy (HR =0.70) were better than chemotherapy for PFS. In the PD-L1 positive or negative group, all included corresponding regimens were equivalence according to OS and PFS. Conclusions We conducted a systematic comparison of first line immunotherapy for advanced NSCLC. Chemo-immunotherapies were better than chemotherapy and mono-immunotherapies in most patients. Pembrolizumab might have better efficacy than other PD-1/L1 inhibitors.