Xueqin Yang

Background This trail is an open-label, single-arm, phase II study that aims to observe the efficacy and safety of toripalimab combined with anlotinib and platinum-etoposide (EP) chemotherapy as first-line treatment in ES-SCLC (Clinical trial information: NCT04731909). The preliminary results of the study have been presented in 2020 ASCO abstract e20570, which demonstrated 100% objective response rate (ORR) and tolerable safety. Here we report PFS analysis results of the study. Methods The study enrolled treatment-naïve ES-SCLC patients (18–75 years, ECOG PS ≤2) who have measurable target lesion evaluated by RECIST v1.1. All enrolled patients received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1–3) plus carboplatin (AUC=5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1–14) of a 21-day cycle. After 4–6 cycles of the treatment, patients who achieved complete response (CR), partial response (PR) or stable disease (SD) could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). ORR, disease control rate (DCR), progression-free survival (PFS) and safety were set as secondary endpoints. Results As of July 16, 2021, the median follow-up was 13.7 months. 9 disease progression events occurred of the enrolled 16 treatment-naïve ES-SCLC patients (14 males, 2 females, median age 63). The investigator-assessed median PFS was 13.3 months (95%CI: 5.0–21.6). The PFS rate at 6 months was 81.3% and the PFS rate at 12 months was 31.3%. 15 patients were still alive and the study treatments for 7 patients were still ongoing. At the data cutoff, there was only 1 patient dead with 37.6 months OS and the median OS was not reached. No new unexpected adverse events were observed. Conclusions Combined with preliminary data at 2020 ASCO, toripalimab combined with anlotinib and EP chemotherapy showed excellent ORR and PFS as well as tolerable safety in treatment-naïve ES-SCLC. The combination therapy is expected to provide clinically meaningful OS benefit and become a promising treatment option. Trial Registration This study is registered with ClinicalTrials.gov (National Institutes of Health), number NCT04731909. Ethics Approval The program was approved by the ethics committee of Army Medical Center (Daping Hospital ).

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94–3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.

Despite the success of anti‑HER2 therapy in patients with breast cancer with HER2 amplification or HER2 overexpression, the results of clinical trials on anti‑HER2 therapy for lung cancer have not been satisfactory. The aim of the present study was to report a case of a non‑smoker, female patient diagnosed with stage IIIA lung adenocarcinoma harboring HER2 amplification. The disease progressed despite surgery and multiple lines of chemotherapy, plus trastuzumab or lapatinib. The pan‑ErbB inhibitor pyrotinib (400 mg/day) was commenced as a fourth‑line regimen, and the patient achieved complete response with a time to progression (TTP) of 6 months. After the lung adenocarcinoma progressed, pyrotinib was continued, along with anlotinib and nivolumab. The patient achieved stable disease (SD) status with another 6 months of TTP. The overall survival of the patient was 28 months. Therefore, the present case suggests that the development of novel drugs may provide new and effective therapeutic regimens for lung cancer with HER2 amplification.

Background: The responsiveness to preoperative neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) is significantly related to the surgical effect and long-term prognosis of patients. Biomarkers for predicting the effect of preoperative neoadjuvant therapy of ESCC are urgently needed in clinical practice. M2 macrophage in the tumor microenvironment (TME) has been confirmed to have a definite correlation with neoadjuvant therapy. However, the research on the potential functional genes of M2 macrophage has not been carried out. The purpose of this study is to systematically screen the potential functional genes of M2 macrophages and verify the correlation between the expression of screened genes and responsiveness to neoadjuvant therapy in ESCC.Methods: The Cancer Genome Atlas (TCGA) database was used to screen the potential functional genes of M2 macrophages systematically. The correlation between the screened genes and responsiveness to neoadjuvant therapy in ESCC was analyzed in the training set GSE45670 and the validation set GSE104958. The correlation of the screened genes was confirmed in a cohort of 27 patients using immunohistochemistry (IHC).Results: A total of 11 M2 macrophage potential functional genes were screened out. The suppressor of cytokine signaling 1 (SOCS1) and ORAI calcium release-activated calcium modulator 3 (ORAI3) were selected for subsequent verification. The expression of SOCS1 and ORAI3 in 27 cases of ESCC was evaluated by the H-score system. The result showed that the high expression of SOCS1 was significantly correlated with favourable responsiveness to preoperative neoadjuvant therapy (AUC = 0.830, 95% CI: 0.647-1, P = 0.006). No significant correlation was found between the expression of ORAI3 and neoadjuvant therapy in ESCC (AUC=0.688, 95% CI: 0.478-0.899, P=0.117).Conclusion: The high expression of SOCS1 in the local tumor microenvironment is significantly correlated with favourable responsiveness to neoadjuvant therapy in patients with ESCC, which can be used as a biomarker to predict the responsiveness to neoadjuvant therapy, and has certain clinical value.

Traditional nursing operations have many disadvantages, such as low inefficiency, high risk, and large cost. Utilizing the existing simulation technology, a nursing virtual simulation laboratory characterized by informatization can be established. Nursing operations virtual simulation training system includes two major parts: simulation equipment, nursing virtual training and evaluation systems. It truly reproduces the first-line clinical nursing work scenarios, meets features of clinical practice teaching, that is, real, visual, and repeatable, greatly enhancing the practical ability of nursing students. It is an effective complement to the teaching methods with human as practical teaching object in nursing education, and has extensive development and application prospects.

Although originally identified as a putative metastasis suppressor, increasing studies have confirmed a possible role for Nm23-H1 in DNA repair, through the base excision repair and nucleotide excision repair pathways. In this study, we explored whether Nm23-H1 was also involved in double-strand break repair (DSBR). We constructed a stable A549-shNm23-H1 cell line with doxycycline-regulated expression of Nm23-H1, and a A549-nNm23-H1 cell line that over expressed a nucleus-localized version of Nm23-H1. Results from both lines confirmed that Nm23-H1 participated in the repair of double-strand breaks induced by X-rays, using Comet and γ-H2AX foci assays. Subsequent studies showed that Nm23-H1 activated the phosphorylation of checkpoint-related proteins including ATM serine/threonine kinase (on S1981), tumor protein p53 (on S15), and checkpoint kinase 2 (Chk2) (on T68). We also detected interactions between Nm23-H1 and the MRE11-RAD50-NBS1 (MRN) complex, as well as Ku80. Moreover, NBS1 and Ku80 levels were comparably higher in Nm23-H1 overexpressing cells than in control cells (t = 14.462, p < 0.001 and t = 5.347, p = 0.006, respectively). As Ku80 is the keystone of the non-homologous end joining (NHEJ) pathway, we speculate that Nm23-H1 promotes DSBR through NHEJ. The results indicate that Nm23-H1 participates in multiple steps of DSBR.

Stereotactic body radiation therapy (SBRT) is an important modality in treatment of tumors. We hypothesized that SBRT can achieve excellent local control with limited toxicity in patients with thymic tumors. A single-institution prospective study was performed with 32 patients who underwent SBRT of thymoma and thymic carcinoma between 2005 and 2014. Thirty-two patients including 39 target lesions were analyses in this study. Almost half of the patients (46.9%) were type C by histopathology and more than half (56.3%) were classified into stage IVA or IVB. The median dose of SBRT for gross tumor volume (GTV) was 56 Gy (range 49–70 Gy). Results showed that the response rate was 96.9% after SBRT and the median tumor shrinkage rate was 62.2% (range 3.8–100%). For the patients with both stage II–III and type A-B (n = 6), the median PFS was 28 months. In-field failure was only observed in 4 patients, and outside-field failure was seen in 2 patients. The local control rate was 81.25%. Patients treated with SBRT had an excellent local control with mild toxicities, which suggests that SBRT is feasible for the patients with thymic tumors who are unable to undergo either surgery or conventionally fractionated radiation therapy.