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Abstract Objective This study aims to examine the impact of nurses’ nursing information competence on their creative self-efficacy and innovation behavior, and to investigate its role as a mediating factor between these two elements. Methods A survey was conducted from July to September 2023 involving 1,200 nurses from two tertiary-level oncology specialty hospitals in Beijing, selected through convenience sampling. Instruments used included the Creative Self-Efficacy Scale, Nursing Information Competence Assessment Scale, and Nurses’ Innovative Behavior Scale. Data analysis was conducted using SPSS 25.0 and R 4.1.2; AMOS26 was used to construct structural equation models and Bootstrap method was used to test the mediating hypotheses. Results Out of the distributed questionnaires, 1,166 were valid, yielding an effective response rate of 97.16%. Pearson correlation analysis revealed significant correlations between innovation self-efficacy, nursing information competence, and nurses’ innovative behaviors (P

Abstract Background Several studies have proposed grading systems for risk stratification of early‐stage lung adenocarcinoma based on histological patterns. However, the reproducibility of these systems is poor in clinical practice, indicating the need to develop a new grading system which is easy to apply and has high accuracy in prognostic stratification of patients. Methods Patients with stage I invasive nonmucinous lung adenocarcinoma were retrospectively collected from pathology archives between 2009 and 2016. The patients were divided into a training and validation set at a 6:4 ratio. Histological features associated with patient outcomes (overall survival [OS] and progression‐free survival [PFS]) identified in the training set were used to construct a new grading system. The newly proposed system was validated using the validation set. Survival differences between subgroups were assessed using the log‐rank test. The prognostic performance of the novel grading system was compared with two previously proposed systems using the concordance index. Results A total of 539 patients were included in this study. Using a multioutcome decision tree model, four pathological factors, including the presence of tumor spread through air space (STAS) and the percentage of lepidic, micropapillary and solid subtype components, were selected for the proposed grading system. Patients were accordingly classified into three groups: low, medium, and high risk. The high‐risk group showed a 5‐year OS of 52.4% compared to 89.9% and 97.5% in the medium and low‐risk groups, respectively. The 5‐year PFS of patients in the high‐risk group was 38.1% compared to 61.7% and 90.9% in the medium and low‐risk groups, respectively. Similar results were observed in the subgroup analysis. Additionally, our proposed grading system provided superior prognostic stratification compared to the other two systems with a higher concordance index. Conclusion The newly proposed grading system based on four pathological factors (presence of STAS, and percentage of lepidic, micropapillary, and solid subtypes) exhibits high accuracy and good reproducibility in the prognostic stratification of stage I lung adenocarcinoma patients.

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

Abstract Objective This study aims to investigate the determinants and the dose–response relationship of fear of cancer recurrence among patients with early‐stage non‐small cell lung cancer (NSCLC), aiming to inform prevention and intervention strategies. Methods Employing a cross‐sectional design, we analyzed data from 677 postoperative NSCLC patients who received treatment at National Cancer Center between January 2022 and August 2023. Data collection involved a general demographic survey, the Fear of Progression Questionnaire‐Short Form, Hope Herth Index, and Social Support Rating Scale. We employed logistic regression and restricted cubic spline models to identify factors influencing fear of recurrence (FCR). Results Univariate regression analysis identified female gender and having minor children as significant risk factors, while being older than 60, a higher income, and elevated levels of hope and social support emerged as protective factors. Multivariate logistic regression revealed age (OR = 0.392, 95% CI 0.205–0.750), monthly income (OR = 0.016, 95% CI 0.315–0.886), hope level (OR = 0.305, 95% CI 0.187–0.496), and social support (OR = 0.584, 95% CI 0.375–0.908) as independent influencers of recurrence fear. The restricted cubic spline model indicated a nonlinear impact of hope and social support on this fear. Conclusion Analysis using the restricted cubic spline model underscores the influence of age, income, hope, and social support on FCR, with a nonlinear dose–response relationship evident between hope, social support, and fear. Prioritizing the enhancement of social support before increasing hope levels can rapidly and effectively alleviate FCR.

Abstract Background Accurate prediction of lymph node metastasis (LNM) is critical for selecting optimal surgical procedures in early‐stage lung adenocarcinoma (LUAD). This study aimed to develop nomograms for intraoperative prediction of LNM in clinical stage IA LUAD. Methods A total of 1227 patients with clinical stage IA LUADs on computed tomography (CT) were enrolled to construct and validate nomograms for predicting LNM (LNM nomogram) and mediastinal LNM (LNM‐N2 nomogram). Recurrence‐free survival (RFS) and overall survival (OS) were compared between limited mediastinal lymphadenectomy (LML) and systematic mediastinal lymphadenectomy (SML) in the high‐ and low‐risk groups for LNM‐N2, respectively. Results Three variables were incorporated into the LNM nomogram and the LNM‐N2 nomogram, including preoperative serum carcinoembryonic antigen (CEA) level, CT appearance, and tumor size. The LNM nomogram showed good discriminatory performance, with C‐indexes of 0.879 (95% CI, 0.847–0.911) and 0.880 (95% CI, 0.834–0.926) in the development and validation cohorts, respectively. The C‐indexes of the LNM‐N2 nomogram were 0.812 (95% CI, 0.766–0.858) and 0.822 (95% CI, 0.762–0.882) in the development and validation cohorts, respectively. LML and SML had similar survival outcomes among patients with low risk of LNM‐N2 (5‐year RFS, 88.1% vs. 89.5%, Pp = 0.790; 5‐year OS, 96.0% vs. 93.0%, p = 0.370). However, for patients with high risk of LNM‐N2, LML was associated with worse survival (5‐year RFS, 64.0% vs. 77.4%, p = 0.036; 5‐year OS, 66.0% vs. 85.9%, p = 0.038). Conclusions We developed and validated nomograms to predict LNM and LNM‐N2 intraoperatively in patients with clinical stage IA LUAD on CT. These nomograms may help surgeons to select optimal surgical procedures.

Background: Whether minimally invasive esophagectomy (MIE) is superior to open esophagectomy (OE) in the treatment of esophageal squamous cell carcinoma (ESCC) is still uncertain. Therefore, this multicenter prospective study aimed to compare MIE with OE in postoperative parameters and long-term survival. Methods: All hospitalized patients with cT1b-3N0–1M0 thoracic ESCC treated by MIE or OE were enrolled from 19 selected centers from April 1, 2015 to December 31, 2018. The propensity score matching (PSM) was performed to minimize the selection bias. The basic clinicopathological characteristics and 3-year overall survival (OS) as well as disease-free survival (DFS) of two groups were compared by R version 3.6.2. Results: MIE were performed in 1,387 patients and OE in 335 patients. 335 cases in each group were finally matched by PSM, and no significant differences in the essential demographic characteristics were observed between the MIE and OE groups after PSM. Compared with OE, MIE had significantly less intraoperative bleeding, less total drainage volume, shorter postoperative hospital stay, and harvested significantly more lymph nodes (LNs) (all P < 0.001). There were no significant differences in the major postoperative complications and death rates between MIE and OE. The 3-year OS and DFS were 77.0% and 68.1% in the MIE group versus 69.3% and 60.9% in the OE group (OS: P = 0.03; DFS: P = 0.09), and the rates were 75.1% and 66.5% in the MIE group versus 66.9% and 58.6% in the OE group for stage cII patients (OS: P = 0.04, DFS: P = 0.09), respectively. Conclusions: Compared with OE, MIE is a safe and effective treatment approach with similar mortality and morbidity. It has the advantages in harvesting more LNs, improving postoperative recovery and survival of stage cII ESCC patients.

AbstractObjective To screen and identify microRNAs (miRNAs) associated with the prognosis of lung adenocarcinoma (LUAD) using clinical samples and construct a prediction model for the prognosis of LUAD.Methods 160 patient samples were used to screen and identify miRNAs associated with the prognosis of LUAD. Differentially expressed miRNAs were analyzed using gene chip technology. The selected miRNAs were validated using samples from the validation sample group. Cox proportional hazards regression was used to construct the model and Kaplan-Meier was used to plot survival curves. Model power was assessed by testing the prognosis of the constructed model using real-time polymerase chain reaction (RT-PCR) data.Results The data showed that miR-1260b, miR-21-3p and miR-92a-3p were highly expressed in the early recurrence and metastasis group, while miR-2467-3p, miR-4659a-3p, miR-4514, miR-1471 and miR-3621 were lowly expressed. It was further confirmed that miR-21-3p was significantly highly expressed in the early recurrence and metastasis group (p = 0.02). Receiver operating characteristic (ROC) curve results showed cut-off point value of 0.0172, sensitivity of 88.2% and specificity of 100%. The predictive results of the constructed model were in good agreement with the actual prognosis of patients by using the validation sample test (Kappa = 0.426, p

Abstract Background Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. Methods CCK8, Transwell and wound‐healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. Results Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F‐actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. Conclusion MARCKSL1 promotes cell migration and invasion by interacting with F‐actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.

Abstract Alternative RNA splicing is one of the most important mechanisms of posttranscriptional gene regulation, which contributes to protein diversity in eukaryotes. It is well known that RNA splicing dysregulation is a critical mechanism in tumor pathogenesis and the rationale for the promising splice-switching therapeutics for cancer treatment. Although we have a comprehensive understanding of DNA mutations, abnormal gene expression profiles, epigenomics, and proteomics in lung adenocarcinoma (LUAD), little is known about its aberrant alternative splicing profiles. Here, based on the multi-omics data generated from over 1000 samples, we systematically studied the RNA splicing alterations in LUAD and revealed their biological and clinical implications. We identified 3688 aberrant alternative splicing events (AASEs) in LUAD, most of which were alternative promoter and exon skip. The specific regulatory roles of RNA binding proteins, somatic mutations, and DNA methylations on AASEs were comprehensively interrogated. We dissected the functional implications of AASEs and concluded that AASEs mainly affected biological processes related to tumor proliferation and metastasis. We also found that one subtype of LUAD with a particular AASEs pattern was immunogenic and had a better prognosis and response rate to immunotherapy. These findings revealed novel events related to tumorigenesis and tumor immune microenvironment and laid the foundation for the development of splice-switching therapies for LUAD.

BackgroundSolid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.MethodsWe conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.ResultsAlong with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.ConclusionsCompared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.

Abstract Background Immunotherapy using immune checkpoint inhibitors (ICIs), such as antibody of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has showed as a promising treatment for esophageal squamous cell carcinoma (ESCC), but resistance is unavoidable. This study aimed to find more immune-related genes to promote the efficiency of immunotherapy. Materials and methods Three datasets were downloaded from Gene Expression Omnibus (GEO) database. Gene differential analysis was performed to identify differentially expressed genes (DEGs), then ceRNA network was constructed based on differentially expressed lncRNAs and mRNAs. Next, Functional enrichment analysis and protein–protein interaction (PPI) network were built to reveal the potential function of mRNAs in ceRNA network. Survival analysis and immune cell infiltration level analysis were utilized to identify prognostic immune-related genes. Finally, pan-cancer analysis was performed to show the role of immune-related genes in other cancers. Results The data of 215 samples in total were obtained from GEO database (98 normal tissues and 117 tumor tissues), and 1685 differentially expressed mRNAs (176 downregulated and 1509 upregulated) and 3 upregulated lncRNAs (MCM3AP-AS1, HCP5 and GUSBP11, all upregulated) were found. ceRNA network was constructed to reveal some special correlation. Function enrichment showed some potential functions of mRNAs in ceRNA network such as mitotic cell cycle process, negative regulation of DNA-binding transcription factor activity, ossification, VEGFA-VEGFR2 signaling pathway, epithelial to mesenchymal transition, embryonic morphogenesis and so on. PPI network showed the physical interactions between each mRNA in ceRNA network. Through survival analysis and immune cell infiltration level analysis, GINS4 was confirmed as an immune-related prognostic gene in ESCC. GSEA showed some potential functions such as negative regulation of monocyte chemotaxis, antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, positive regulation of antigen processing and presentation, dendritic cell antigen processing and presentation and so on. Finally, pan-cancer analysis revealed that GINS4 might be a novel immune-related prognostic gene in ESCC and other cancers. Conclusion Our study suggested that GINS4 was correlated with prognosis and immune cell infiltration level of ESCC and other cancers. It may deserve further investigation as a potential immune-related prognostic biomarker of ESCC and other cancers.

BackgroundIt is still uncertain whether the newly released eighth American Joint Committee on Cancer (AJCC) post-neoadjuvant pathologic (yp) tumor-node-metastasis (TNM) stage for esophageal carcinoma can perform well regarding patient stratification. The current study aimed to assess the prognostication ability of the eighth AJCC ypTNM staging system and attempted to explore how to facilitate the staging system for more effective evaluation of prognosis.Materials and methodsA total of 486 patients treated with neoadjuvant radiotherapy/chemoradiotherapy (nRT/CRT) were enrolled. ypN stage was reclassified by recursive partitioning. Prognostic performance, monotonicity, homogeneity, and discriminatory of yp and modified yp (myp) staging systems were assessed by time-dependent receiver operating characteristic (ROC), linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and Akaike information criterion (AIC).ResultsThe ypT stage, ypN stage, and pathologic response were significant prognostic factors of overall survival. Survival was not discriminated well using the eighth AJCC ypN stage and ypTNM stage. Recursive partitioning reclassified mypN0-N2 as metastasis in 0, 1–2, and ≥3 regional lymph nodes. Applying the ypT stage, mypN stage, and pathologic response to construct the myp staging system, the myp stage performed better in time-dependent ROC, linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and AIC.ConclusionsThe eighth AJCC ypTNM staging system performed well in differentiating prognosis to some extent. By reclassifying the ypN stage and enrolling pathologic response as a staging element, the myp staging system holds significant potential for prognostic discrimination.

BackgroundLittle is known about the effect of histology on the efficacy of immune checkpoint inhibitors (ICI) in non-small-cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to assess the potential differences in the efficacy of ICIs between squamous NSCLC (SQ-NSCLC) and non-squamous NSCLC (non-SQ-NSCLC).MethodsSystematic searches of PubMed, Embase, Scopus, and Cochrane Library databases were conducted. All randomized clinical trials of ICIs with available hazard ratios (HR) for progression-free survival (PFS) or overall survival (OS) according to histology were included. The primary endpoint was to assess the difference in the efficacy of ICIs between SQ-NSCLC and non-SQ-NSCLC, measured by the ratio of the HR in SQ-NSCLC to the HR in non-SQ-NSCLC (RHR).ResultsA total of 40 trials were included in the meta-analysis. ICI monotherapy could improve OS in both SQ-NSCLC (OS-HR 0.71, 95% CI 0.65-0.77) and non-SQ-NSCLC (OS-HR 0.80, 95% CI 0.73-0.87) while OS benefit was larger in SQ-NSCLC (OS-RHR 0.89, 95% CI 0.80-0.99). In terms of PFS, ICI monotherapy could reduce the risk of progression by 35% (PFS-HR 0.65, 95% CI 0.56-0.77) in SQ-NSCLC while the PFS benefit was smaller (10%) and not statistically significant in non-SQ-NSCLC (PFS-HR 0.90, 95% CI 0.76-1.07). Similarly, ICI-based combination treatments could reduce the risk of both progression and death in SQ-NSCLC (OS-HR 0.70, 95% CI 0.61-0.80; PFS-HR 0.56, 95% CI 0.48-0.65) and non-SQ-NSCLC (OS-HR 0.78, 95% CI 0.74-0.83; PFS-HR 0.63, 95% CI 0.57-0.69) while the survival benefits were larger in SQ-NSCLC (OS-RHR 0.83, 95% CI 0.70-0.99; PFS-RHR 0.82, 95% CI 0.70-0.96).ConclusionsICIs could deliver survival benefits in both SQ-NSCLC and non-SQ-NSCLC while the magnitude of survival benefits was histology-dependent. Future researches should consider the effect of histology on the efficacy of ICIs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42022299603].

Background Uniportal video‐assisted thoracoscopic surgery (VATS) is being more widely used in lung cancer, yet reports on its application in pneumonectomies are limited. This study aimed to evaluate the safety and feasibility of uniportal video‐assisted thoracoscopic left pneumonectomy for lung cancer. Methods A series of 18 lung cancer patients who had received uniportal video‐assisted thoracoscopic left pneumonectomies were included in the study. Their clinical, pathological, and surgical features, as well as postoperative recovery, were analyzed. Results The majority of the patients were male and smokers and their average age was 62.0 ± 8.9 years. All had primary lung cancer, while three (16.7%) had received neoadjuvant therapy. A total of 16 (88.9%) patients had stage II–III disease, with an average tumor size of 3.6 ± 1.5 cm. The average surgery time was 137.4 ± 47.0 minutes, with a 16.7% (3/18) conversion rate. The mean blood loss was 37.5 ± 59.4 mL and no patients needed blood transfusion during, or after, surgery. There was no perioperative death and the overall complication rate was 22.2% (4/18). Two (11.1%) patients needed to stay in the intensive care unit after surgery, and the average length of hospital stay after surgery was 6.3 ± 1.1 days (range 4–7 days). Conclusions Uniportal video‐assisted thoracoscopic left pneumonectomy is a safe and feasible procedure for selected lung cancer patients. The use of uniportal VATS in right pneumonectomies and the effect of uniportal video‐assisted thoracoscopic pneumonectomy on the survival of patients merits further study. Patients receiving uniportal VATS pneumonectomies had standard surgical results and recovery. Uniportal VATS pneumonectomy is safe for properly selected lung cancer patients. Key points Significant findings of the study: • Patients receiving uniportal VATS left pneumonectomies had standard surgical results and recovery. What this study adds: • Uniportal VATS left pneumonectomy is safe for properly selected lung cancer patients.

Abstract Background Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety. Methods Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established. Discussion This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. Trial registration Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.

Resectable non-small cell lung cancer (NSCLC) is currently considered as a potentially curable disease. Surgery is still the main treatment mode for resectable NSCLC, but quite a few patients will have local recurrence and distant metastasis after surgery. Therefore, preoperative and postoperative adjuvant therapy may be necessary in order to improve the long term outcome. Immunocheckpoint inhibitor has been demonstrated clinically to be effective andapproved as first- or second-line treatment agent in metastatic NSCLC or partially locally advanced NSCLC. The remarkable efficacy of immunotherapy for advanced lung cancer has attracted more and more attention from the researchers to the role of immunotherapy as neoadjuvent therapy in resectable non-small cell lung cancer. This article systematically reviewed the clinical trials of neoadjuvant immunotherapy for resectable NSCLC before surgery.

Abstract Background Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0–28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. Method This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135–150 mg/m2) plus cisplatin or nedaplatin (50–75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. Discussion This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. Trial registration clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

Background. Gangliosides act as important roles in tumor progression. B4GALNT1 is a key enzyme in ganglioside biosynthesis. B4GALNT1 expression is linked to tumorigenesis and the prognosis of tumor patients. Nevertheless, the role of B4GALNT1 in pan-cancer remains unclear. Methods. Several databases, including TCGA, GEO, GTEx, NCI-60, and TIMER, were searched. Methods including correlation analysis, Cox regression analysis, and Kaplan-Meier analysis were used to explore the expression pattern, prognosis, tumor infiltration pattern, genetics and epigenetics, and drug sensitivity of B4GALNT1 in pan-cancer patients from the above datasets. Results. B4GALNT1 was found to be aberrantly expressed in multiple types of tumors. The survival status of tumor patients was significantly related to B4GALNT1 expression, but the correlations were tumor-specific. Moreover, the expression of B4GALNT1 was associated with ImmuneScore and StromalScore in 21 and 27 tumor types, respectively. Also, B4GALNT1 was significantly associated with TMB, MSI, MMR, and DNA methylation. Additionally, the sensitivity of 9 drugs was correlated with the expression of B4GALNT1. Conclusion. A correlation of B4GALNT1 expression with prognosis exists in multiple types of cancers. In addition, B4GALNT1 expression may play a role in TME and tumor immunity regulation. Further investigation of the biological mechanisms of its different roles in tumorigenesis and clinical application as a biomarker is still required.

Background: The spatial distributions of different types of cells could reveal a cancer cell's growth pattern, its relationships with the tumor microenvironment and the immune response of the body, all of which represent key “hallmarks of cancer”. However, the process by which pathologists manually recognize and localize all the cells in pathology slides is extremely labor intensive and error prone. Methods: In this study, we developed an automated cell type classification pipeline, ConvPath, which includes nuclei segmentation, convolutional neural network-based tumor cell, stromal cell, and lymphocyte classification, and extraction of tumor microenvironment-related features for lung cancer pathology images. To facilitate users in leveraging this pipeline for their research, all source scripts for ConvPath software are available at https://qbrc.swmed.edu/projects/cnn/. Findings: The overall classification accuracy was 92.9% and 90.1% in training and independent testing datasets, respectively. By identifying cells and classifying cell types, this pipeline can convert a pathology image into a “spatial map” of tumor, stromal and lymphocyte cells. From this spatial map, we can extract features that characterize the tumor micro-environment. Based on these features, we developed an image feature-based prognostic model and validated the model in two independent cohorts. The predicted risk group serves as an independent prognostic factor, after adjusting for clinical variables that include age, gender, smoking status, and stage. Interpretation: The analysis pipeline developed in this study could convert the pathology image into a “spatial map” of tumor cells, stromal cells and lymphocytes. This could greatly facilitate and empower comprehensive analysis of the spatial organization of cells, as well as their roles in tumor progression and metastasis. Keywords: Deep learning, Convolutional neural network, Lung adenocarcinoma, Pathology image, Cell distribution and interaction, Prognosis

Background: A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC). Methods: The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort ( n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort ( n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group. Results: Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively ( p

BackgroundLung adenocarcinoma (LUAD) is the most common type of lung cancer and is a severe threat to human health. Although many therapies have been applied to LUAD, the long-term survival rate of patients remains unsatisfactory. We aim to find reliable immune microenvironment-related lncRNA biomarkers to improve LUAD prognosis.MethodsESTIMATE analysis was performed to evaluate the degree of immune infiltration of each patient in TAGA LUAD cohort. Correlation analysis was used to identify the immune microenvironment-related lncRNAs. Univariate cox regression analysis, LASSO analysis, and Kaplan Meier analysis were used to construct and validate the prognostic model based on microenvironment-related lncRNAs.ResultsWe obtained 1,178 immune microenvironment-related lncRNAs after correlation analysis. One hundred and eighty of them are independent prognostic lncRNAs. Sixteen key lncRNAs were selected by LASSO method. This lncRNA-based model successfully predicted patients’ prognosis in validation cohort, and the risk score was related to pathological stage. Besides, we also found that TP53 had the highest frequency mutation in LUAD, and the mutation of TP53 in the high-risk group, which was identified by our survival model, has a poor prognosis. lncRNA-mRNA co-expression network further suggested that these lncRNAs play a vital role in the prognosis of LUAD.ConclusionHere, we filtered 16 key lncRNAs, which could predict the survival of LUAD and may be potential biomarkers and therapeutic targets.

Background Whether postoperative radiotherapy is beneficial in the treatment of esophageal squamous cell carcinoma with one or two regional lymph node (LN) metastases (pN1) after esophagectomy is uncertain. This study aimed to explore the effect of postoperative radiotherapy (PORT) on survival. Methods Propensity score‐matching (PSM) analysis was conducted to balance the two arms (surgery only [S] or surgery plus postoperative radiotherapy [PORT]). The survival rate was calculated by the Kaplan‐Meier method and analyzed using the log‐rank test. Results A total of 992 cases confirmed positive for one or two regional LN metastases were eligible. After PSM, 622 patients were reviewed. Each group consisted of 311 cases. The median follow‐up was 80.7 months. For the overall cohort, the one‐, three‐ and five‐year overall survival (OS) were 90.6%, 51.9% and 38.2%, respectively. Disease‐free survival (DFS) was 76.0%, 41.4% and 32.1%, respectively. The five‐year OS and DFS were 45.0% and 39.8% for PORT, which was significantly higher than the S group (31.3% and 24.2%, both P

T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCRβ repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCRβ repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% ± 0.002% vs. 0.016% ± 0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 ± 305.96 vs. 166.20 ± 101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 ± 295.3 vs. 291.8 ± 233.6, P = 0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients. Keywords: Adaptive immune response, T cell receptor repertoire, Lung cancer, High-throughput sequencing, TCR diversity

Lung squamous cell carcinoma (LUSC) is one of the leading causes of tumor-driven deaths in the world. To date, studies on the tumor heterogeneity of LUSC at genomic level have only revealed limited therapeutic benefits. Therefore, system-wide research of LUSC at proteomic level may further improve precision medicine strategies on individual demands. To this end, we performed proteomic and phosphoproteomic study for LUSC samples of 25 Chinese patients. From our results, two subgroups (Cluster I and II) based on proteomic data were identified, which were associated with distinct molecular characteristics and clinicopathologic features. Combined with phosphoproteomic data, our result showed that spliceosome pathway was enriched in Cluster I, while focal adhesion pathway, immune-related pathways and Ras signaling pathway were enriched in Cluster II. In addition, we found that lymph node metastasis (LNM) was associated with our proteomic subgroups and cell cycle pathway was enriched in patients with LNM. Further analysis showed that MCM2, a DNA replication licensing factor involved in cell cycle pathway, was highly expressed in patients with poor prognosis, which was further proved by immunohistochemistry (IHC) analysis. In summary, our study provided a resource of the proteomic and phosphoproteomic features of LUSC in Chinese patients.

Superior sulcus tumor of the lung is a bronchogenic tumor occurred in the apex of the upper lobe of the lung and is a unique clinical subtype of non-small cell lung cancer (NSCLC), which account for less than 5% of all bronchogenic carcinomas. It often involves the first rib, brachial plexus, subclavian vessels, sympathetic chain, stellate ganglion or vertebra. A lot of progress has been achieved in the treatment of superior sulcus tumor over the past decades. Several clinical trials reported in recent years have confirmed that concurrent chemoradiotherapy followed by surgical resection can improve the rate of complete resection, local control and pathological remission of the tumor, and prolong the total-survival time. It has become the most effective treatment mode for the superior sulcus tumor, and recommended as a standard treatment mode for superior sulcus tumor by National Comprehensive Cancer Network (NCCN) and American College of Chest Physicians (ACCP) guidelines. This article reviews relevant literatures at home and abroad, and briefly introduces the advances in surgical treatment and comprehensive treatment of superior sulcus tumor.

Background and objective Surgeons are the direct decision-makers and performers in the surgical treatment of patients with lung cancer. Whether the differences among doctors affect the survival of patients is unclear. This study analyzed the five-year survival rates of different thoracic surgeries in patients undergoing surgery to assess the physician's impact and impact. Methods A retrospective analysis of five years between 2002-2007 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, for surgical treatment of lung cancer patients. According to different surgeons grouping doctors to compare the basic information of patients, surgical methods, short-term results and long-term survival differences. Results A total of 712 patients treated by 11 experienced thoracic surgeons were included in this study. The patients have nosignificant difference with gender, age, smoking, pathological type between groups. There were significant differences in clinical staging, surgery type, operation time, blood transfusion rate, number of lymph node dissection, palliative resection rate, postoperative complications and perioperative mortality. There was a significant difference in five-year survival rates among patients treated by different doctors. This difference can be seen in all clinical stage analyzes with consistency. In the multivariate analysis, it was suggested that surgeon was an independent factor influencing the prognosis of patients. Conclusion Thoracic surgeon has a significant effect on the therapeutic effect of lung cancer patients.

Zebrafish have become a popular animal model for studying various biological processes and human diseases. The metabolic pathways and players conserved among zebrafish and mammals facilitate the use of zebrafish to understand the pathological mechanisms underlying various metabolic disorders in humans. Adipocytes play an important role in metabolic homeostasis, and zebrafish adipocytes have been characterized. However, a versatile and reliable zebrafish model for long-term monitoring of adipose tissues has not been reported. In this study, we generated stable transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) in adipocytes. The transgenic zebrafish harbored adipose tissues that could be detected using GFP fluorescence and the morphology of single adipocyte could be investigated in vivo. In addition, we demonstrated the applicability of this model to the long-term in vivo imaging of adipose tissue development and regulation based on nutrition. The transgenic zebrafish established in this study may serve as an excellent tool to advance the characterization of white adipose tissue in zebrafish, thereby aiding the development of therapeutic interventions to treat metabolic diseases in humans.

Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. The site of primary lung carcinoma may affect the route and status of lymph node metastasis. Up to now, anatomical lobectomy and mediastinal lymph node dissection is deemed to be the standard surgical treatment for NSCLC. However, it is still controversial in the extent of lymph node dissection for T1 NSCLC. More and more surgeons intend to perform selective mediastinal lymph node dissection instead of complete mediastinal lymph node dissection for T1 NSCLC in recent years.

Currently in China, the incidence and death rate of lung cancer with low five-year survival rates has ranked the first position among all cancers. Early detection of lung cancer and early treatment are of great importance. However, patients with early satge lung cancer always do not present with any synptoms or signs, only to demonstrate solitary pulmonary nodules (SPNs) in radiology findings. So it is very critical to improve the ability to identify the SPNs, and with the development of sorts of diagnostic modalities, the accuracy in the evaluation of the SPNs has imporved greatly.

A tumor can be viewed as a special "organ" that undergoes aberrant and poorly regulated organogenesis. Progress in cancer prognosis and therapy might be facilitated by re-examining distinctive processes that operate during normal development, to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity. The global gene expression signatures of 44 human lung tissues at four development stages from Asian descent and 69 lung adenocarcinoma (ADC) tissue samples from ethnic Chinese patients were profiled using microarrays. All of the genes were classified into 27 distinct groups based on their expression patterns (named as PTN1 to PTN27) during the developmental process. In lung ADC, genes whose expression levels decreased steadily during lung development (genes in PTN1) generally had their expression reactivated, while those with uniformly increasing expression levels (genes in PTN27) had their expression suppressed. The genes in PTN1 contain many n-gene signatures that are of prognostic value for lung ADC. The prognostic relevance of a 12-gene demonstrator for patient survival was characterized in five cohorts of healthy and ADC patients [ADC_CICAMS (n = 69, p = 0.007), ADC_PNAS (n = 125, p = 0.0063), ADC_GSE13213 (n = 117, p = 0.0027), ADC_GSE8894 (n = 2, p = 0.01), and ADC_NCI (n = 282, p = 0.045)] and in four groups of stage I patients [ADC_CICAMS (n = 22, p = 0.017), ADC_PNAS (n = 76, p = 0.018), ADC_GSE13213 (n = 79, p = 0.02), and ADC_qPCR (n = 62, p = 0.006)]. In conclusion, by comparison of gene expression profiles during human lung developmental process and lung ADC progression, we revealed that the genes with a uniformly decreasing expression pattern during lung development are of enormous prognostic value for lung ADC.

Aims: To explore the current situation, influencing factors and pathways of safety behaviour of nurses in tumour specialized hospitals, in order to provide a theoretical basis for managers to manage and train nurses, improve their safety behaviour level and ensure medical safety. Design: An anonymous cross-sectional survey. Method: A total of 2147 nurses from Grade A cancer hospitals in 15 provinces of China were selected by a convenient sampling method. Questionnaires were collected through the Questionnaire Star platform. Nurses' safety behaviour was measured using the nurse Safety Behaviour Scale, Self-efficacy by the General Self-efficacy Scale, and nurses' occupational burnout was measured by the occupational Burnout Scale, and work engagement through the the Work Engagement Scale. Structural equation modelling was used to test the relationship among nurses' safety behaviour, general self-efficacy, occupational burnout and work engagement. SPSS25.0 software was used to test the relationship among the safety behaviour of nurses, general self-efficacy, occupational burnout and work engagement. Results: The total score of safety behaviour of nurses was 55.45 ± 6.879, the total score of general self-efficacy was 31.39 ± 5.729, the total score of occupational burnout was 44.99 ± 26.587, and the total score of work engagement was 38.48 ± 13.433; the scores of the Nurse Safety Behaviour Scale, Self-Efficacy Scale, and Work Engagement Scale were positively correlated (all p< .001); the occupational burnout scale was negatively correlated with the scores of self-efficacy scale, work engagement scale and nurse safety behaviour scale (all p< .001); Structural equation model analysis shows that self-efficacy and work engagement have a direct positive impact on nurse safety behaviour(β= .103, β= .096, all p< .001); Occupational burnout has a direct negative impact on self-efficacy, work engagement and nurse safety behaviour(β= −.371, β= −.413, β= −.328 all p< .001). Bootstrap analysis showed that occupational burnout and job involvement had a significant chain mediating effect between self-efficacy and the safety behaviour of nurses (95% CI: 0.148–0.21). The total effect of self-efficacy on the safety behaviour of nurses was 0.283 (p< .001, 95% CI: 0.225–0.301), the direct effect was 0.096 (p< .001, 95% CI: 0.042–0.15), and the indirect effect was 0.179 (p< .001, 95% CI: 0.085–0.215), The mediating effect accounted for 63.3% of the total effect size. Conclusion: Occupational burnout and work engagement play a partial mediating role between self-efficacy and nurse safety behaviour. It is necessary to strengthen training on nurse safety culture awareness, improve the nurse self-efficacy and work engagement, reduce nurse occupational burnout, and thereby improve the level of nurses' safety behaviour. [ABSTRACT FROM AUTHOR]