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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., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

This study aimed to summarize the efficacy and safety of neoadjuvant chemoimmunotherapy in resectable esophageal squamous cell carcinoma (ESCC).Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in resectable ESCC published before June 2022 was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool. Subgroup and sensitivity analyses were further performed.A total of 452 patients from 15 studies were included in this meta-analysis. All of the studies explored the efficacy and safety of neoadjuvant chemoimmunotherapy. The pooled major pathological response (MPR) rate and pathological complete response (PCR) rate were 58.3% and 32.9%, respectively. The pooled incidence of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were 91.6% and 19.4%, respectively. The pooled R0 resection rate was 92.8%, and the resection rate was 81.1%. Incidence of anastomotic leakage, pulmonary infection, and postoperative hoarseness were 10.7%, 21.3%, and 13.0%, respectively. Compared with 2 cycles of neoadjuvant therapy, patients who received2 cycles of neoadjuvant therapy showed higher MPR rate (57.3% vs. 61.1%) and PCR rate (30.6% vs. 37.9%), and the incidence of TRAEs (89.2% vs. 98.9%) tended to be higher. However, no significant difference was found (P0.05). Two cycles of neoadjuvant therapy showed higher R0 resection rate and resection rate (R0 resection rate: 96.0% vs. 87.8%, P = 0.02; resection rate: 85.6% vs. 74.7%, P = 0.01). Pembrolizumab- and tislelizumab-based neoadjuvant therapy showed higher MPR rate (72.4% and 72.2%) and PCR rate (41.5 % and 50.0%). Compared with other ICIs, tislelizumab-based neoadjuvant therapy showed lower R0 resection rate (80.5%). The pooled incidence of SAEs for pembrolizumab-based neoadjuvant therapy (2.0%) was lower. Camrelizumab-based neoadjuvant therapy showed lower incidence of pulmonary infection (11.5%).Neoadjuvant chemoimmunotherapy is effective and safe for resectable ESCC.

IntroductionThe 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 methodsTissue 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.ResultsDEK 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).ConclusionsDEK expression is positively correlated with reduced survival in ESCC patients. DEK has potential to be an independent biomarker in predicting prognosis of ESCC patients.

250 Background: Camrelizumab, a fully humanized monoclonal anti-PD-1 antibody, has shown promising efficacy with good tolerance in neoadjuvant therapy of resectable locally advanced esophageal cancer (EC). The present study aimed to investigate the effectiveness and safety of camrelizumab-based neoadjuvant therapy in a comparatively larger number of resectable EC patients in a real-world setting and initial results were reported here. Methods: In this prospective multicenter observational study (ChiCTR2000039170), patients with histologically confirmed resectable EC who were scheduled for camrelizumab-based neoadjuvant therapy at the discretion of treating physicians/ oncologists were included. Eligible patients were aged ≥ 18 years, had ECOG PS of 0-1, measurable disease per RECIST v1.1, adequate organ function, and expected survival time of ≥ 3 months, as well as provided written informed consent. The primary endpoint was safety. The secondary endpoints were major pathologic response (MPR), pathologic complete response (pCR), R0 resection rate, overall response rate (ORR), one-year overall survival (OS) rate, and disease-free survival (DFS). Results: At total of 166 patients (62.9 ± 9.2 years, and 84.2% male) were enrolled between October 20 2020 and August 26 2021. All patients received neoadjuvant camrelizumab plus chemotherapies (primarily nab-paclitaxel and nedaplatin) except one receiving camrelizumab alone. Overall, 109 patients (65.7%) experienced treatment-related adverse events (TRAEs), most commonly reactive cutaneous capillary endothelial proliferation (RCCEP, 45.3%), cough (10.4%), and pneumonia (8.5%). Thirteen (7.8%) patients experienced grade 3-4 TRAEs. There was no grade 5 toxicity. At the data cutoff, 141 (84.9%) patients were evaluable for radiological response, 82 (69.5%) patients underwent surgical resection. The ORR was 70.9% (100/141) and the R0 resection rate was 97.5% (79/82). Among the 81 patients available for pathologic assessment, 51 (63.0%) patients achieved MPR and of which, 15 (18.5%) had pCR. The median survival times have not been reached at the time of data analysis. Conclusions: The real-world data of our resectable EC patients showed effectiveness and safety profiles of camrelizumab-based neoadjuvant therapy consistent with those observed in previous trials.

Non-small cell lung cancer (NSCLC) is a major type of lung cancer, with the highest mortality rate in all cancers. For all stages of NSCLC, the five-year survival is less than fifteen percent. Epithelial-mesenchymal transition (EMT) is a significant process in tumor occurrence and development, in which microRNAs may play an important role. In many cancers, microRNA-15's family member can act as suppressors or oncogenes of tumors; however, the relation between these microRNAs and EMT in lung cancer remains unclear. According to our study, miR-15a expression decreased in tumor tissues compared with than that in adjacent tissue samples. Knocking down miR-15a expression in NSCLC cells inhibited apoptosis and facilitated cell proliferation and invasion, and. Moreover, down-regulating miR-15a decreased the expression of an EMT-associated protein, E-cadherin, while increased those of vimentin, N-cadherin, and slug.

Aim: To investigate whether plasma miR-19a can serve as a biomarker for esophageal squamous cell carcinoma (ESCC) diagnosis and prognosis. Materials & methods: Plasma samples from 89 ESCC, 45 benign lesion patients and 80 healthy controls were subjected to RT-qPCR analyses for miR-19a. In addition, plasma samples from 30 patients were collected before and after surgery for the same analyses. Results: Plasma miR-19a was significantly increased in ESCC patients compared with healthy controls. The sensitivity of miR-19a for early stages of ESCC was 68.09%. Combination of miR-19a and cytokeratin 19 fragment 21–1 (Cyfra21-1) further improved the sensitivity to 78.70%. Moreover, plasma miR-19a level was decreased in patients after surgery. Conclusion: Plasma miR-19a may serve as a potential biomarker that complements Cyfra21-1 in detecting early stages of ESCC.

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.

Changes in the expression profiles of microRNAs (miRNAs) have been found in many cancers. The study was aimed to investigate the expression of miR-25, miR-223, and miR-375 in the serum of patients with esophageal squamous cell carcinoma (ESCC) and its effect on survival outcome. We examined the expression levels of miR-25, miR-223, and miR-375 in 20 pairs of ESCC cancer and matched paracancerous tissues, serum samples from 94 healthy volunteers and 194 patients with ESCC using quantitative reverse transcription polymerase chain reaction, and analyzed the relationship between expressions of serum miR-25, miR-223, and miR-375 and ESCC clinicopathological parameters as well as survival. Expressions of miR-25 and miR-223 were significantly increased in ESCC tissues compared with paracancerous tissues (P = 0.008 and 0.009, respectively), whereas the expression of miR-375 was significantly decreased in ESCC tissues compared with paracancerous tissues (P = 0.006). Expressions of serum miR-25 and miR-223 were significantly higher in ESCC patients than those in healthy controls, and, inversely, expression of serum miR-375 was significantly lower in ESCC patients than those in healthy controls (P = 0.007). High expression of serum miR-25 was significantly associated with lymph node metastasis (P = 0.01). Survival analysis showed that high expression of serum miR-223 and low expression of serum miR-375 were associated with poor survival in ESCC patients [hazard ratio (HR) = 1.717, 95% confidence intervals (CI) 1.139-2.588, P = 0.01; HR = 1.750, 95% CI 1.111-2.756, P = 0.016, respectively). Furthermore, Patients with high miR-223 and low miR-375 expression had higher risk of death than those with low miR-223 and high miR-375 expression (HR = 3.599, 95% CI 1.800-7.195, P = 2.92 × 10(-4)). In conclusion, miR-25, miR-223, and miR-375 were abnormally expressed in ESCC tissues and sera. Serum miR-223 and miR-375 are potential prognostic biomarkers for ESCC.

MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and prognosis. The aim of this study was to evaluate the effects of miRNA polymorphisms on clinical outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) treated with platinum-based chemotherapy. Five polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR-125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes and drug response, toxicity, and overall survival were analyzed. miR-146a rs2910164 was significantly associated with an increased risk of severe hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171–0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 % CI 1.112–2.165, P = 0.010; HR = 2.171, 95 % CI 1.173–4.017, P = 0.014, respectively]. Combined analysis revealed a 4.073-fold increased risk of death in patients carrying two unfavorable genotypes (P = 0.002). Taken together, these findings indicate that miRNA polymorphisms may predict prognosis in advanced ESCC patients receiving platinum-based chemotherapy.

The study presented a case of esophageal cancer presenting as intermittent fever with markedly elevated serum leukocyte and C-reactive protein. The patient's symptoms had not improved with antibiotic treatment. However, after thoracic esophagectomy, the fever faded and leukocyte serum levels rapidly normalized.

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.