Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

The clinical outcome of resectable non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy is good but varies greatly. In addition, the pathological response after neoadjuvant chemoimmunotherapy is significantly associated with survival outcomes. The aim of this retrospective study was to identify which population of patients with locally advanced and oligometastatic NSCLC has a favorable pathological response after neoadjuvant chemoimmunotherapy. NSCLC patients treated with neoadjuvant chemoimmunotherapy were enrolled between February 2018 and April 2022. Data on clinicopathological features were collected and evaluated. Multiplex immunofluorescence was performed on pre-treatment puncture specimens and surgically resected specimens. In total, 29 patients with stages III and IV locally advanced or oligometastatic NSCLC who received neoadjuvant chemoimmunotherapy and R0 resection were enrolled. The results showed that 55% (16/29) of patients had a major pathological response (MPR) and 41% (12/29) of patients had a complete pathological response (pCR). In the stroma area of the pre-treatment specimen, the higher infiltration of CD3+ PD-L1+ tumor-infiltrating lymphocytes (TILs) and the lower infiltration of CD4+ and CD4+ FOXP3+ TILs were more likely to appear in patients with pCR. However, in the tumor area, the higher infiltration of CD8+ TILs was more likely to appear in patients with non-MPR. In the post-treatment specimen, we found increased infiltration of CD3+ CD8+ , CD8+ GZMB+ , and CD8+ CD69+ TILs and decreased infiltration of PD-1+ TILs both in the stroma and tumor areas. Neoadjuvant chemoimmunotherapy achieved an MPR rate of 55% and induced greater immune infiltration. In addition, we observed that the baseline TILs and their spatial distribution correlate to the pathological response.

Complete response to first-line osimertinib monotherapy in a complex epidermal growth factor receptor mutant ( L833V / H835L ) lung adenocarcinoma patient: a case report.

Although uncommon epidermal growth factor receptor (EGFR) mutations account for 10-15% EGFR mutant non-small cell lung cancer (NSCLC) patients, clinical evidence for uncommon EGFR mutations, such as complex mutations remain limited. In this study, we reported a NSCLC patient harboring complex EGFR L833V / H835L mutation in exon 21, who had a complete response to first-line osimertinib monotherapy. The patient admitted to our hospital for space-occupying lesions of right lower lung during an annual health checkup, and was diagnosed as stage IIIA lung adenocarcinoma. Targeted next-generation sequencing (NGS) on tumor samples showed a complex EGFR mutation: L833V / H835L in exon 21. Therefore, she was treated with osimertinib monotherapy and complete remission achieved soon. During follow-up period, no metastasis was found and serum carcinoembryonic antigen returned to normal. In addition, NGS monitoring of mutations in circulating tumor DNA maintained negative. The patient remain benefitted for osimertinib monotherapy over 22 months with no disease progression. Our case firstly provided clinical evidences of first-line osimertinib therapy in lung cancer patients with rare L833V / H835L EGFR mutation.

Watershed analysis in wedge resection of pulmonary pure ground-glass nodules hardly localized by CT-guided puncture.

BACKGROUND: To investigate the feasibility and safety of watershed analysis after target pulmonary vascular occlusion for the wedge resection in patients with non-palpable and non-localizable pure ground-glass nodules during uniport thoracoscopic surgery. METHODS: A total of 30 patients with pure ground-glass nodules < 1 cm in diameter, localized in the lateral third of the lung parenchyma, were enrolled. Three-dimensional reconstruction of thin-section computed tomography (CT) data was performed using Mimics software before surgery to observe and identify the target pulmonary vessels supplying the lung tissue in the area where the pulmonary nodules were localized and to temporarily block the target pulmonary vessels during surgery. Next, the extent of the watershed was determined with the expansion-collapse method, and finally, wedge resection was performed. After wedge resection of the target lung tissue, the blocked pulmonary vessel was released, thus allowing operators to complete the procedure without damaging pulmonary vessels. RESULTS: None of the patients experienced postoperative complications. The chest CT of all patients was reviewed six months after the operation, revealing no tumor recurrence. CONCLUSIONS: Our results suggest that watershed analysis following target pulmonary vascular occlusion for wedge resection in pulmonary pure ground-glass nodules is a safe and feasible approach.

Inhalation Lenalidomide-Loaded Liposome for Bleomycin-Induced Pulmonary Fibrosis Improvement.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease with unclear etiology and increasing prevalence. Pulmonary administration can make the drug directly reach the lung lesion location and reduce systemic toxic and side effects. The effectiveness of lenalidomide (Len) liposomal lung delivery in idiopathic pulmonary fibrosis was investigated. Len liposomes (Len-Lip) were prepared from soybean lecithin, cholesterol (Chol), and medicine in different weight ratios by thin film hydration method. The Len-Lip were spherical in shape with an average size of 226.7 ± 1.389 nm. The liposomes with a higher negative zeta potential of around - 34 mV, which was conducive to improving stability by repelling each other. The drug loading and encapsulation rate were 2.42 ± 0.07% and 85.47 ± 2.42%. Len-Lip had little toxicity at the cellular level and were well taken up by cells. At bleomycin-induced pulmonary fibrosis model mice, inhalation Len-Lip could improve lung function and decrease lung hydroxyproline contents, and alleviate pulmonary fibrosis state. Inhalation Len-Lip provided a reference for the treatment of idiopathic pulmonary fibrosis.

The Role of Surveillance Inspections in Reducing False-Positives of SARS-CoV-2 Omicron Variants during the COVID-19 Epidemic.

Objective: This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. Method: The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. Results: The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Conclusion: Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

[Evaluation of the value of 7th editions of UICC-AJCC esophageal and gastric cancer TNM staging systems for prognostic prediction of adenocarcinoma of esophagogastric junction (Siewert type II)].

OBJECTIVE: To compare the value of applicability of the 7th edition of UICC-AJCC esophageal and gastric cancer TNM staging system in the prognostic prediction of adenocarcinoma of esophagogastric junction (EGJ). METHODS: During June 1, 2007 through Dec. 31, 2010, a total of 199 patients with adenocarcinoma of esophagogastric junction (Siewert type II) underwent R0-intent resection from June 1, 2007 to Dec 31, 2010 in our hospital. Their clinicopathological and survival data were retrospectively analyzed with Kaplan-Meier and Cox regression models. They were restaged according to the 7th edition of UICC/AJCC TNM stage systems for esophageal adenocarcinoma and gastric cancer, respectively. Then the likelihood ratio chi-square test related to the Cox regression model and Akaike information criterion (AIC) were used for measuring goodness of fit for both staging systems. RESULTS: 199 patients with Siewert type II esophagogastric junction adenocarcinoma were identified in this study. Out of them, there were 162 males and 37 females. Their age range was from 38 to 79 years, with a median age of 62 years. 176 cases underwent transthoracic surgery, and other 23 cases underwent transabdominal surgery. TNM-EC and TNM-GC classified 4 patients to stage T1, 39 to T2, 139 to T3, and 17 to T4a, respectively, and classified 76 patients to stage N0, 58 to N1, 49 to N2, 16 to N3, respectively. The median follow-up period was 30 months. The 1-, 3-, and 5-year survival rates were 95.0%, 52.7% and 39.2%, respectively. Univariate analysis indicated that age at surgery (P = 0.009), surgical approach (P = 0.002), cell differentiation (P = 0.030), preoperative co-morbidity implications (P = 0.026), depth of tumor invasion (P < 0.001) and number of metastatic lymph nodes (P < 0.001) were significantly influencing factors of postoperative overall survival. Multivariate analysis showed that the independent prognostic factors for adenocarcinoma of esophagogastric junction were only T stage, N stage and preoperative co-morbidity and morbidities according to the 7th edition of esophageal cancer or gastric cancer TNM staging systems. The AIC value was 961.4 for the 7th edition of esophageal adenocarcinoma caner staging system, and 965.7 for the 7th edition of gastric cancer staging system. CONCLUSIONS: The UICC/AJCC 7th edition of esophageal adenocarcinoma cancer TNM classification staging system is superior to the 7th edition of gastric cancer TNM staging system for adenocarcinoma of esophagogastric junction.

Application of a Comprehensive Model Based on CT Radiomics and Clinical Features for Postoperative Recurrence Risk Prediction in Non-small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: We constructed a comprehensive model by combining the radiomics and clinical features of tumors to predict the recurrence risk of patients with operable stage IA-IIIA non-small cell lung cancer (NSCLC). Our aim was to improve the accuracy of prognostic prediction and provide personalized treatment plans to enhance patient outcomes. MATERIALS AND METHODS: We retrospectively analyzed 152 surgically treated patients with pathologically confirmed stage IA-IIIA NSCLC. These patients were randomly divided into a training cohort and a test cohort in an 8:2 ratio. Using the 3D Slicer image computing platform, we manually delineated the regions of interest (ROI) for all lesions and extracted radiomics features using Python. We used the Least Absolute Shrinkage and Selection Operator (LASSO) to select the radiomics features, while the COX multivariate regression model was employed to identify independent clinical risk factors for recurrence. Finally, we utilized logistic regression (LR) to build the model and validated it using the receiver operating characteristic curve (ROC). The predictive performance of the model was evaluated using the concordance index (C-index), and the clinical value of the model was compared through decision curve analysis (DCA). RESULTS: We extracted a total of 1562 radiomics features. After feature selection, we retained 29 features. The COX multivariate regression model demonstrated that the N stage was an independent risk factor for postoperative recurrence. In the training and test cohorts, the area under the curve (AUC) values of the radiomics-clinical comprehensive model were 0.972 and 0.937, respectively, while the C-index values were 0.815 and 0.847. These values surpassed those of the standalone clinical model or radiomics model. CONCLUSION: Our study demonstrates that a comprehensive model based on CT radiomics and clinical features can effectively stratify the risk of postoperative recurrence in patients with operable NSCLC. It provides a powerful tool for accurately stratifying the risk of high-risk patients after surgery.

Molecular characteristics of multiple primary pulmonary nodules under a three-dimensional reconstruction model and relevant multi-omics analyses: a case report.

Background: In addition to CT images and pathological features, many other molecular characteristics remain unknown about multiple primary lung cancer (MPLC) from intrapulmonary metastatic lung cancer. Case presentation: In this study, we reported a patient with an early-stage MPLC with both adenocarcinoma in situ (AIS) subtype and minimally invasive adenocarcinoma (MIA) subtype. The patient was diagnosed with more than 10 nodules and underwent precise surgery assisted by three-dimensional (3D) reconstruction at the left upper lung lobe. Whole-exome sequencing (WES) and multiple immunohistochemistry (mIHC) were performed to reveal the genomic profiling and tumor microenvironments of multiple nodules in this patient with MPLC. Based on 3D reconstruction location information, we found that the genomic and pathological results of adjacent lymph nodes were quite different. On the other hand, PD-L1 expression and the proportion of infiltrating lymphocytes in tumor microenvironments were all at a low status and did not vary in adjacent lymph nodes. Additionally, maximum diameter and tumor mutational burden levels were found to be significantly associated with CD8+ T cell proportion (p<0.05). Besides, CD163+ macrophages and CD4+ T cell proportion were higher in MIA nodules than in AIS nodules (p<0.05). This patient reached a recurrence-free survival of 39 months. Conclusion: Generally, in addition to CT imaging and pathological results, genomic profiling and tumor microenvironments may facilitate identifying the potential molecular mechanisms and clinical outcomes in patients with early-stage MPLC.

The Association between the Risk of Esophageal Cancer and Type 2 Diabetes Mellitus: An Updated Meta-Analysis.

Background: A large amount of publications had reported the association between incidence of esophageal cancer (EC) and type 2 diabetes mellitus (T2DM) in the past decade. However, those papers' results are inconsistent on relationships between T2DM the incidence of EC. Therefore, the objective of this meta-analysis was to determine the relationship between T2DM and the risk of EC (including 2 histological types, esophageal adenocarcinoma [EADC] and esophageal squamous cell carcinoma [ESCC]). Method: We finally extracted 19 articles though Pubmed, Embased, and Cochrane library. Those identify extraction date including 14,312 cases and 24,959,067 control records and then mixed the relative risks (RRs) and corresponding 95% confidence intervals (95%CIs) through STATA. Results: We observed that there are significantly positive correlation between T2DM and EC risk (RR = 1.28, 95% CI: 1.05-1.57, P = 0.015).Also, our study showed positive correlation between T2DM and EADC (esophageal adenocarcinoma) risk (RR = 1.28, 95% CI: 1.05-1.57, P < 0.001). What's more, subgroup analysis based on ethnicity represented the Caucasian is more susceptible to EC (RR = 1.28 ,95% CI: 1.10-1.49, P = 0.001). Conclusion: Those results offer a recent epidemiological and integrated evidence to ascertain the correlations between T2DM and incidence of EC. Those results take public health implications on preventing T2DM and then depress the occurrence of EC. Our study also provides referenced information for the prevention. However, some data is still insufficient, and more research should be carried out.

Green credit and enterprise green operation: Based on the perspective of enterprise green transformation.

This paper uses panel data of listed heavily polluting enterprises from 2007 to 2021, based on the perspective of transformation and upgrading of heavy polluters, innovatively studies the impact of green credit on the green operation of enterprises. At the micro level, the research results of this paper verify the effectiveness of green credit policy on the transformation of green enterprises. It is also found that the two intermediary paths of debt cost and government subsidy play a partial intermediary role in the process of green credit promoting green enterprise transformation and upgrading. Green credit policy also moderates the green transformation of enterprises through debt cost and government subsidies. Based on the research results, this paper puts forward targeted policy suggestions from the aspects of financing constraints, government subsidy policies, enterprise technological innovation and green operation, and provides empirical support for the current expansion of green credit policies in China.

Can China's ecological civilization strike a balance between economic benefits and green efficiency? A preliminary province-based quasi-natural experiment.

To encourage the building of a development route for ecological civilization construction which commensurates with China's unique national conditions, early demonstration and pilot ecological civilization zones should be built. This study aims to investigate the effects of ecological civilization construction policies on regional total factor productivity, green total factor productivity, and the methods of action by using panel data from 30 provinces in Mainland China from 2005 to 2020. Our findings indicate that the pilot eco-civilization policies have a more significant effect on the promotion of green total factor production, while the effect on total factor productivity is average. Furthermore, the main purpose of the ecological civilization construction pilot is to improve the level of green innovation, optimise the industrial structure and promote the allocation of factors to achieve a win-win situation for regional economic development and green benefits. Moreover, under different levels of economic growth, the pilot eco-civilization policies have a more significant effect on the promotion of green total factor at various stages of economic growth and industrialization. There are also clear discrepancies in how well ecological civilization construction programmes are implemented. Thus, in order to support high-quality regional economic development, it is crucial to continue to advance and promote the pilot eco-civilization initiatives.

The Impact of Social Media on Employee Mental Health and Behavior Based on the Context of Intelligence-Driven Digital Data.

With the rapid development and widespread popularity of the Internet, employee social media use at work has become an increasingly common phenomenon in organizations. This paper analyzes 105 related papers from the Social Science Citation Index in Web of Science through Scoping Review to clarify the definition and characteristics of employee social media use and the types of social media and summarizes the current research methods. Then, the reasons for employees' willingness and refusal to use social media and the positive and negative effects of employee social media use on employees' work attitudes, behaviors, and performance are discussed. Then, the mediating variables, moderating variables, and theoretical frameworks used in the relevant studies are described, and a comprehensive model of employee social media use is constructed. Finally, this paper indicates future research directions based on the latest research results in 2020-2022, i.e., improving research methods, increasing antecedent studies, expanding consequence research, and expanding mediating variables, moderating variables, and theoretical perspectives.

Epidemiological Evidence Between Variants in Matrix Metalloproteinases-2, -7, and -9 and Cancer Risk.

Background: Matrix metalloproteinases (MMPs), a kind of proteases, have a critical function in cancer occurrence, invasion, and migration. MMP gene variants (e.g., MMP-2, MMP-7, and MMP-9) can affect the biological functions of these enzymes and lead to the occurrence and progression of cancer, which has become a hot topic in recent years, but the corresponding results are still controversial. In this context, here, the meta-analysis was conducted for assessing the relations of variants in MMP-2, MMP-7, and MMP-9 with the risk of various cancers. Methods: PubMed, Web of Science, and Medline were systemically searched, and data were extracted from all eligible studies so as to investigate the susceptibility of MMP-2, MMP-7, and MMP-9 to different types of cancers. The association between a variant in MMP and cancer susceptibility was analyzed through odds ratios (ORs) as well as 95% CIs. The Venice criteria and false-positive report probability (FPRP) were adopted to evaluate epidemiological evidence of significant associations discovered. Results: The associations between the variants of MMPs and cancer risk in 36,530 cases and 41,258 controls were found, with 12 associations (MMP-2 rs243865 with esophageal cancer and lung cancer, MMP-7 rs11568818 with bladder and cervical cancer, and MMP-9 rs3918242 with breast cancer) rated as strong associations for cancer risk and 7 and 15 as moderate and weak associations, respectively. These significant associations were mostly found in Asians. Conclusions: These findings support the relations between variants of MMP-2, MMP-7, and MMP-9 and various cancers risk, demonstrating the credibility of these relations.

Transcription factor NFIC functions as a tumor suppressor in lung squamous cell carcinoma progression by modulating lncRNA CASC2.

Nuclear factor I (NFI) family is emerging found playing oncogenic or tumor-suppressive potential in cancers. However, the function and underlying mechanisms of NFIC, in the progression of Lung Squamous Cell Carcinoma (LUSC) remain unclear. Therefore, this study aims to probe into the function of NFIC in the development of LUSC. In the present study, we reported that NFIC was low expressed in human LUSC tissues and cell lines. NFIC inhibited LUSC cell proliferation and promoted cell apoptosis in vitro and in vivo. Moreover, NFIC also inhibited LUSC cell migration and invasion. Furthermore, we found that there were binding sites between lncRNA cancer susceptibility candidate 2 (CASC2) and NFIC, whose relationship was confirmed by the luciferase reporter assay. The expression of CASC2 and the expression of NFIC were positively correlated, and the function of CASC2 overexpression is similar to that of NFIC overexpression, which suggested that CASC2 may play a key role in LUSC development. Our study provided a new perspective for NFIC acting as an antioncogene in LUSC tumorigenesis, and NFIC and CASC2 may serve as novel potential targets for the treatment of LUSC.

Rupture of contralateral mainstem bronchus during uniportal video-assisted thoracoscopy surgery lobectomy and 3 successful cases of repair.

BACKGROUND: Our goal was to discuss the treatment for rupture of contralateral mainstem bronchus during uniportal video-assisted thoracoscopy surgery (uniportal VATS) lobectomy. CASE PRESENTATION: We analyzed clinical data of 3 cases of rupture of contralateral mainstem bronchus during uniportal VATS. Surgical repair was performed immediately under an uniportal VATS during operation, as a result, 3 cases of bronchial rupture all were repaired successfully, and we continued to complete lobectomy and systemic lymph node dissection. Reexamination was performed after 1 week, and no fistula was found in trachea and bronchi through a fiberoptic bronchoscopy. The time range for indwelling the chest tube is 6-9 days, and the hospital stay is 8-10 days. No abnormality was observed on chest radiography when the 3 patients returned to the hospital 1 month after the operation for the second reexamination. CONCLUSIONS: Instant surgical repair is recommended to the treatment of bronchial rupture in thoracic surgery. It is safe and feasible to repair bronchial tear with uniportal VATS.

Characteristics of Oral Microbiota in Patients with Esophageal Cancer in China.

Gut microbiota dysbiosis is closely associated with intestinal carcinogenesis, but the oral microbiota of patients with esophageal squamous cell carcinoma who live in high-risk regions in China has not been fully characterized. In the current study, oral microbial diversity was investigated in 33 patients with esophageal squamous cell carcinoma and 35 healthy controls in Chongqing, China, by sequencing 16S rRNA of V3-V4 gene regions. There were statistically significant differences in oral microbiota between esophageal squamous cell carcinoma patients and controls as determined via unweighted pair-group analysis with arithmetic means. At the phylum level, in esophageal squamous cell carcinoma patients, there were comparatively greater amounts of Firmicutes (34.0% vs. 31.1%) and Bacteroidetes (25.3% vs. 24.9%) and lower amounts of Proteobacteria (17.0% vs. 20.1%). At the genus level, esophageal squamous cell carcinoma patients exhibited comparatively greater amounts of Streptococcus (17.3% vs. 14.5%) and Prevotella_7 (8.6% vs. 8.5%) and lower amounts of Neisseria (8.1% vs. 10.7%). Using a linear discriminant analysis effect size method, Planctomycetes and Verrucomicrobia were identified in the esophageal squamous cell carcinoma group. 10 genera were higher abundances identified in the healthy control group, and different 10 genera were identified in the esophageal squamous cell carcinoma group. In the present study, there were significant differences in oral microbial compositions of esophageal squamous cell carcinoma patients and healthy controls. Further longitudinal and mechanistic studies are needed to further characterize relationships between oral microbiota and esophageal squamous cell carcinoma.

Durable Response to Immunotherapy With Antiangiogenic Drug in Large-Cell Lung Carcinoma With Multiple Fulminant Postoperative Metastases: A Case Report.

Immunotherapy alone or chemo-immunotherapy has recently been recommended for treating advanced lung carcinoma in patients without driver mutations. However, the efficacy of immunotherapy and molecular mechanism in large-cell lung cancer (LCLC) remains unclear. Here, we reported a rare case of multiple fulminant postoperative body and mouth metastases in LCLC treating with combination immunotherapy. Initially, the patient was diagnosed as early stage LCLC and underwent a radical resection of the right lower lobe. Just one month later, multiple fulminant body and mouth lesions appeared in the right upper arm, right elbow, right waist, and tongue root. Meanwhile, serum neuron specific enolase (NSE) concentration dramatically increased from 12.12 to 30.14 ng/ml. Immumohistochemistry findings demonstrated moderate PD-L1 expressions with tumor proportion score (TPS), while next-generation sequencing indicated moderate tumor mutational burden (TMB) levels and gene mutations in PBRM1 L1230P and TP53 L194R of both foci. Besides, loss of heterozygosity (LOH) at human leukocyte antigen (HLA) class I (HLA-A*02:03, HLA-B*55:02 and HLA-C*12:03) were detected in the right upper arm metastasis, which may facilitate malignant postoperative metastases in this case. Notably, this patient received combination therapy with anti-PD-1 antibody sintilimab plus anlotinib, and achieved a partial response for at least 12 months. Using an integrated computational method, the mutant peptide TEIPENDIPL derived from PBRM1 L1230P was predicted to be a specific neoantigen and could still be presented by HLA-B*40:01. This case suggests that immunotherapy plus antiangiogenic drug may provide an alternative therapeutic option for advanced LCLC patients without common gene mutations.

A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study).

BACKGROUND: Preoperative chemotherapy or chemoradiotherapy is the standard treatment for resectable esophageal cancer (EC); however, it is associated with increased postoperative complications and mortality. Recently, Immune Checkpoint inhibitors have been incorporated in the treatment of advanced EC. Its role in the preoperative setting has not been established yet. In this multicenter, single-arm study, we evaluated the efficacy and safety of neoadjuvant therapy with sintilimab in combination with chemotherapy in treating EC. METHODS: Patients received neoadjuvant therapy with 3 cycles of sintilimab 200 mg Q3W in combination with platinum-based chemotherapy. Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoints of the trial were pathological complete response (pCR) and safety. RESULTS: A total of 23 patients (21 men and 2 women) were enrolled. Surgery was completed in 17 participants, with 16 achieving R0 resection and 1 had R1 resection, 5 participants refused surgery. One patient progressed prior to surgery. Twenty one patients (91%) had significant improvement in their dysphagia following treatment as assessed by Stooler's criteria. The majority of patients who underwent resection have a good pathological response and downstaging rate was 76.5% (13/17). A pCR was achieved in 6 cases (6/17, 35.3%) and major pathological response (MPR) in 9 cases (9/17, 52.9%). The main preoperative adverse events (AEs) were vomiting (13/23, 56.5%), leukopenia (12/23, 52.2%), neutropenia (9/23, 39.1%), and malaise (8/23, 34.8%). Immune-related AEs were mild and included hypothyroidism (2/23, 8.7%) and rash (4/23, 17.4%). The incidence of ≥ grade 3 treatment related AEs was 30.4% (7/23). There were no ≥ grade 4 AEs. CONCLUSIONS: Sintilimab in combination with chemotherapy in the neoadjuvant treatment of EC is safe and lead to a high pCR. Therefore, further testing is warranted.

Neoadjuvant programmed cell death protein 1 inhibitors combined with chemotherapy in resectable non-small cell lung cancer: an open-label, multicenter, single-arm study.

BACKGROUND: Neoadjuvant therapy has significantly improved the 5-year overall survival (OS) of patients with resectable non-small cell lung cancer (NSCLC). The CheckMate 159 trial showed that neoadjuvant therapy with a single-drug programmed cell death protein 1 (PD-1) inhibitor (nivolumab) achieved major pathological response (MPR) and pathological complete response (pCR) in 45% and 15%of participants, respectively. We conducted an open-label single-arm study to evaluate the safety and efficacy of neoadjuvant PD-1 inhibitors in combination with chemotherapy in the treatment of resectable NSCLC. METHODS: This study was conducted in a total of 2 hospitals in the Chinese cities of Xi'an and Chongqing, and included eligible patients over 18 years of age with clinically staged IIA-IIIB NSCLC. All patients were scheduled to receive surgery within 4-6 weeks after neoadjuvant treatment (3-4 cycles) consisting of PD-1 inhibitors combined with a conventional chemotherapy regimen on day 1 of each 21-day cycle. RESULTS: Twenty-three patients, 22 males, and 1 female with just one of them with no smoking habits) were diagnosed with NSCL C in a stage IIA (3 cases), IIB (3 cases), IIIA (8 cases), and IIIB (9cases) and no druggable driver mutations/translocations were addressed to receive neoadjuvant treatment between June 2018 and June 2020. The treatment was well tolerated with just 3 typical immune-related adverse events (hyperthyroidism, hyperglycemia, and rash) recorded. There was a partial response (PR) and stable disease (SD) in 17 (73.9%) and 6 (26.1%) patients, with an overall response rate (ORR) of 73.9% according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). Six of these patients resulted in pCR (30%) while ten of them showed a MPR (50%). Twenty patients underwent surgical resection after treatment, while further 3 refused surgery. Surgical procedure included video-assisted thoracoscopic resection (10 cases), Vinci Robot surgery (4 cases), and thoracotomy in 4 cases while there were secondary compliance-related thoracotomy in two cases. The pathology analysis revealed a R0 in 19 cases (19/20, 95%). CONCLUSIONS: Our results suggest that the neoadjuvant approach with chemotherapy and PD-1 blocking mAbs is safe and active in patients with resectable NSCLC where is associated with a promising high ORR, MPR and pCR.

Tanshinone IIA Reverses Gefitinib-Resistance In Human Non-Small-Cell Lung Cancer Via Regulation Of VEGFR/Akt Pathway.

BACKGROUND: Gefitinib-resistance is a primary obstacle for the treatment of non-small-cell lung cancer (NSCLC). It has been shown that tanshinone IIA (Tan IIA) could induce apoptosis of NSCLC cells. However, the role of combination of gefitinib with Tan IIA on gefitinib-resistance NSCLC cells remains unclear. Thus, this study aimed to investigate the role of combination on the proliferation, apoptosis and invasion of gefitinib-resistance NSCLC cells. METHODS: CCK-8, flow cytometric and transwell assays were applied to detect proliferation, apoptosis and invasion in gefitinib-resistance NSCLC cells, respectively. In addition, Western blotting assay was used to detect the expressions of p-EGFR, p-VEGFR2, and p-Akt in HCC827/gefitinib cells. RESULTS: In this study, Tan IIA enhanced the cytotoxic effect of gefitinib in gefitinib-resistance NSCLC cells. In addition, the inhibitory effects of gefitinib on the proliferation, migration and invasion of gefitinib-resistance NSCLC cells were enhanced in the presence of Tan IIA. Moreover, Tan IIA enhanced the pro-apoptotic effect of gefitinib in gefitinib-resistance NSCLC cells via increasing the level of cleaved caspase 3. Meanwhile, Tan IIA enhanced the sensitivity of HCC827/gefitinib cells to gefitinib via downregulation of the VEGFR2/Akt pathway. In vivo experiments further confirmed that combination of gefitinib with Tan IIA inhibited tumor growth in mouse xenograft model of HCC827/gefitinib. CONCLUSION: We found that Tan IIA could enhance gefitinib sensitivity in gefitinib-resistance NSCLC cells. Therefore, combination of gefitinib with Tan IIA might be considered as a therapeutic approach for the treatment of gefitinib-resistant NSCLC.