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Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

PurposeThe present study aims to identify factors related to anastomotic leakage before esophagectomy and to construct a prediction model.MethodsA retrospective analysis of 285 patients who underwent minimally invasive esophagectomy (MIE). An absolute shrinkage and selection operator was applied to screen the variables, and predictive models were developed using binary logistic regression.ResultsA total of 28 variables were collected in this study. LASSO regression analysis, combined with previous literature and clinical experience, finally screened out four variables, including aortic calcification, heart disease, BMI, and FEV1. A binary logistic regression was conducted on the four predictors, and a prediction model was established. The prediction model showed good discrimination and calibration, with a C-statistic of 0.67 (95% CI, 0.593–0.743), a calibration curve fitting a 45° slope, and a Brier score of 0.179. The DCA demonstrated that the prediction nomogram was clinically useful. In the internal validation, the C-statistic still reaches 0.66, and the calibration curve has a good effect.ConclusionsWhen patients have aortic calcification, heart disease, obesity, and a low FEV1, the risk of anastomotic leakage is higher, and relevant surgical techniques can be used to prevent it. Therefore, the clinical prediction model is a practical tool to guide surgeons in the primary prevention of anastomotic leakage.

Abstract Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting.

Background: The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% CIs, were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and subgroup analysis and sensitivity analysis were conducted to investigate the findings further. Results: A total of nine studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response and major pathologic response in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% (P <0.00001) and 48.1% versus 24.6% (P <0.00001), respectively. The ORs for achieving pathologic complete response and major pathologic response were 4.24 (95% CI, 2.84-6.32, I2=14%) and 3.30 (95% CI, 2.31-4.71, I2= 0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events and serious adverse events in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of treatment-related adverse events (OR= 0.67, 95% CI, 0.29-1.54, P=0.35, I2=58%) or serious adverse events (OR= 1.28, 95% CI, 0.69-2.36, P= 0.43, I2=0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness. Conclusions: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable oesophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients' short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. Methods: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper =0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. Results: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups (P=0.68, after PSM; P=0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P =0.01), chylothorax (5.79 0.30%, P =0.001), and cardiac events (19.53 vs. 9.20%, P= 0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P =0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P =0.31) and cardiac events (19.51 vs. 14.63%, P =0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR = 0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group (P= 0.003, PSM; P=0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. Conclusions: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up. [ABSTRACT FROM AUTHOR]

Introduction: The DEK gene encodes a nuclear phosphoprotein which is involved in multiple cell metabolic processes, such as DNA damage repair, mRNA splicing, modifying chromatin structure and transcription regulation. DEK has been shown to be overexpressed in various solid human tumors and associated with patient prognosis. In this study, our aim was to investigate DEK protein expression and its relationship with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC).Material and Methods: Tissue samples were collected from 120 routinely diagnosed ESCC patients who underwent surgical resection at the Zhongshan Hospital, Xiamen University in the period from June 2011 to May 2013. The expression of DEK was determined by immunohistochemistry.Results: DEK protein was ubiquitously distributed in the nucleus of ESCC cells, and its positive rate (71.7%) was significantly higher in cancer samples than those of para-carcinoma (21.4%) or normal esophageal (13.9%) tissues (p < 0.001). Similarly, significantly more cells overexpressing DEK were found in ESCC tissues (57.5%) in comparison with para-carcinoma samples (11.4%) and normal esophageal mucosa (0%, p < 0.001). The DEK overexpression rate was significantly different between patients with different tumor-node-metastasis (TNM) stages and differentiation degrees (p < 0.001). ESCC cases with elevated DEK amounts showed reduced disease-free and 5-year survival rates compared with those expressing low DEK amounts (p < 0.001). DEK overexpression was also confirmed to independently predict prognosis in ESCC (HR = 4.121, 95% CI: 1.803-9.42, p = 0.001).Conclusions: DEK expression is positively correlated with reduced survival in ESCC patients. DEK has potential to be an independent biomarker in predicting prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]

Flail chest is caused by complex fractures of multiple ribs as a result of severe chest injuries, which results in paradoxical chest movements that severely compromise respiratory function. We report our experience of thoracoscopically assisted, minimally invasive surgical stabilization of massive anterolateral flail chest using a Nuss bar in three patients. This technique offers effective stabilization while having the advantages of short surgical time, minimal blood loss, less trauma, quicker recovery, and small and inconspicuous incisions. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinum-based chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC. [ABSTRACT FROM AUTHOR]