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425126 Background: Adjuvant and neoadjuvant immunotherapy have been approved by US FDA to treat early-stage NSCLC. However, the optimal neoadjuvant and adjuvant treatment, including duration of treatment, are unknown. We present the interim results of a randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy in resectable stage III NSCLC. Methods: Patients with stage II/III resectable NSCLC, without EGFR/ALK alterations for non-squamous NSCLC, were randomly assigned 1:1 to receive 240 mg toripalimab or placebo combined with chemotherapy Q3W for 3 cycles before surgery and one cycle after surgery, followed by toripalimab or placebo monotherapy Q3W for 13 cycles. Stratification variables for randomization included disease stage, histopathologic subtype, PD-L1 expression and surgical procedure. Primary endpoints were EFS by investigator and major pathological response (MPR) rate by a blinded independent pathologic review (BIPR) in the stage III and the ITT populations. Secondary endpoints included overall survival (OS), pathologic complete response (pCR) rate, EFS by independent review committee (IRC), and safety. A planned interim analysis was performed on the primary endpoint of EFS in the stage III subjects. Results: A total of 404 patients with stage III NSCLC were randomly assigned to toripalimab (n=202) or placebo (n=202). By the data cutoff date (November 30, 2022), the median follow-up was 18.3 months. Baseline characteristics were well balanced between the two arms. EFS was significantly improved in the toripalimab arm, HR=0.40, 95% CI (0.277-0.565), P<0.0001, and crossed the pre-specified efficacy boundary. The median EFS was not reached in the toripalimab arm and 15.1 months in the placebo arm. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups. The MPR and pCR rates per BIPR were also higher in the toripalimab arm, 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The OS results showed a trend favoring toripalimab. The incidence of Grade ≥3 adverse events (AEs) (63.4% vs 54.0%), fatal AEs related to toripalimab/placebo (0.5% vs 0%) and AEs leading to discontinuation of toripalimab/placebo (9.4% vs 7.4%) were comparable between the two arms. However, the incidence of immune-related AEs (42.1% vs 22.8%) was more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to perioperative chemotherapy showed statistically significant improvements in EFS for patients with stage III NSCLC with a manageable safety profile. Patients will be followed for overall survival. Clinical trial information: NCT04158440 .

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Background: Various reports showed some conflicting data on survival at different ages. This study aimed to investigate the main cause of death in older patients with lung cancer and to perform a comparison with younger patients in order to observe the differences between these two cohorts.Methods: Outcomes of patients with stage IA non-small cell lung cancer (NSCLC) ≤3 cm who underwent lobectomy without induction therapy in the Surveillance, Epidemiology, and End Results-18 (SEER-18; January 2004 to December 2016) database were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.Results: A total of 16,672 eligible NSCLC cases were found in the SEER database. The number of patients aged ≤60, 61-70, and ≥71 years was 3,930, 6,391, and 6,351, respectively. Among these patient groups, 527 (13.4%), 1,018 (15.9%), and 1,235 (19.4%) died of lung cancer during follow-up, while 357 (9.1%), 964 (15.1%) and 1,579 (25.2%) died of non-lung cancer diseases, respectively. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of younger patients showed a significant survival advantage over older patients. After propensity-score matching (PSM) of patients aged ≤60 and ≥71 years using a ratio of 1:1, we found that 403 (12.9%) and 584 (18.7%) patients in the ≤60 and ≥71 years age groups died of lung cancer, respectively. The OS and LCSS rates of younger patients still exhibited a significant survival advantage over older patients.Conclusions: Older patients with stage IA NSCLC have a worse prognosis compared with younger patients. Also, cancer-related causes were more frequent in older patients than non-cancer-related causes.

Circular RNA (circRNA) plays an important role in cancer progression. Here, we investigated the function of circ_0086414 in the malignant progression of esophageal cancer (EC). RNA expression of circ_0086414, microRNA-1290 (miR-1290), and SPARC like 1 ( SPARCL1 ) was detected by quantitative real-time polymerase chain reaction. The protein levels of N-cadherin, E-cadherin, and SPARCL1 were checked by Western blotting analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-29-deoxyuridine (EdU), and cell colony formation assays. Cell invasion and apoptosis were analyzed by transwell invasion assay and flow cytometry analysis, respectively. Glycolysis was evaluated by analyzing glucose consumption and lactate production. In an xenograft mouse model, the effect of circ_0086414 on tumor tumorigenesis was investigated. The interactions among circ_0086414, miR-1290, and SPARCL1 were identified by dual-luciferase reporter and RNA pull-down assays. Results showed that circ_0086414 and SPARCL1 expression were significantly downregulated, while miR-1290 was upregulated in EC tissues and cells. EC patients with low circ_0086414 expression had a poor prognosis. Increasing circ_0086414 expression led to decreased EC cell proliferation, invasion and glycolysis and increased cell apoptosis, accompanied by a decrease of N-cadherin expression and an increase of E-cadherin expression. Also, the enforced expression of circ_0086414 delayed tumor tumorigenesis. Besides, circ_0086414 acted as a miR-1290 sponge and regulated EC cell processes by binding to the miRNA. MiR-1290 also participated in EC malignant progression through SPARCL1 . Further, circ_0086414 stimulated SPARCL1 production by negatively regulating miR-1290. Thus, circ_0086414 inhibited EC cell malignancy through the miR-1290/ SPARCL1 pathway, providing a reliable target for the therapy of EC.

Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel three gene methylation panel and validated the diagnostic efficiency from a total of 351 subjects (197 controls, 154 cases). DNA methylation of short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) could be used as a panel of biomarkers to distinguish between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2-91.5%], 98.0% specificity [95% CI 94.9-99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.

Introduction Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore. Methods The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology. Results A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively. Conclusion Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.

BackgroundLung cancer remains the leading cause of cancer deaths across the world. Early detection of lung cancer by low-dose computed tomography (LDCT) can reduce the mortality rate. However, making a definitive preoperative diagnosis of malignant pulmonary nodules (PNs) found by LDCT is a clinical challenge. This study aimed to develop a prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant pulmonary nodules from benign PNs. MethodsWe assessed three DNA methylation biomarkers (PTGER4, RASSF1A, and SHOX2) in a training cohort of 110 individuals with PNs. Using univariate and multivariate logistic regression analysis, we developed a prediction model based on the three DNA methylation biomarkers and one radiological characteristic for identifying malignant from benign PNs. The performance of the prediction model with that of the methylation biomarkers and the Mayo Clinic model were compared using the non-parametric approach of DeLong et al. with the area under a receiver operator characteristic curve (AUC) analysis. ResultsThe developed prediction model achieved a sensitivity of 87.3% and a specificity of 95.7% with an AUC value of 0.951 in malignant PNs diagnosis, being significantly higher than the three DNA methylation biomarkers (84.1% sensitivity and 89.4% specificity, p=0.013) or clinical/radiological characteristics (76.2% sensitivity and 87.2% specificity, p=0.001) alone. Validation of the prediction model in the testing cohort of 100 subjects with PNs confirmed the diagnostic value.ConclusionWe have shown that integrating DNA methylation biomarkers and radiological characteristics could more accurately identify lung cancer in subjects with CT-found PNs. The prediction model developed in our study may provide clinical utility in combination with LDCT to improve the over-all diagnosis of lung cancer.