Liangming Zhu

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

BACKGROUND: Microwave ablation (MWA) has recently become an established treatment option for topical therapy of lung cancer patients. In this study, we evaluated whether MWA combined with chemotherapy could improve progression-free survival (PFS) of patients with stage IV lung adenocarcinoma compared with chemotherapy alone. METHODS: A total of 49 patients were enrolled into the study; 21 patients accepted MWA therapy combined with chemotherapy, 28 patients accepted only chemotherapy. Enumeration data were analyzed using χ2 test or Fisher's exact probability test and univariate analysis was analyzed using Kaplan-Meier survival curves. Multivariate analysis was carried out with the Cox proportional hazard model. RESULTS: The treatment regimen was not correlated with clinical features of the patients, which included gender, age, smoking history, tumor site, tumor size and Eastern Cooperative Oncology Group (ECOG). The patients' 3-year overall survival (OS) was 12.5%, and median survival time was 19.3 months. The median PFS was 6.1 months and the 1-year PFS was 0.0%. The PFS was significantly associated with tumor size (P < 0.05), ECOG (P < 0.01) and treatment regimen (P < 0.01). The median time to local progression (TTLP) was 8.4 months and the 3-year TTLP was 2.0%. The TTLP was significantly associated with tumor size (P < 0.05) and treatment regimen (P < 0.01). Cox multivariate regression demonstrated that MWA combined with chemotherapy was the independent factor for both the PFS and TTLP. CONCLUSION: MWA, as a topical treatment method, when combined with chemotherapy improved the PFS and TTLP of patients with stage IV lung adenocarcinoma.

Recent studies have demonstrated that deregulated microRNA (miRNA/miR) expression has a profound impact on biological and pathological processes; abnormal miR-1469 expression was detected in several human malignancies. In the present study, the clinicopathological and prognostic significance of miR-1469 was assessed in 129 patients with esophageal squamous cell cancer (ESCC) who successfully underwent esophagectomy and esophagogastrostomy. Low miR-1469 expression was identified to be significantly associated with tumor invasion depth (P=0.026), lymph node metastasis status (P<0.001) and pathological tumor stage (P<0.001). Survival analysis demonstrated that patients with low miR-1469 expression had significantly poorer disease-free survival (DFS) (18.2 vs. 43.2%; P=0.004) and overall survival (29.1 vs. 47.3%; P=0.029) 5 years following surgery compared with patients with high miR-1469 expression. Univariate survival analysis demonstrated that low miR-1469 expression significantly predicted unfavorable 5-year DFS among patients with N1-3 disease (7.1 vs. 31.8%; P=0.043). The results from the present study indicate that miR-1469 expression could be used in the clinic to predict ESCC progression and prognosis. This will aid in the identification of high-risk patients with ESCC that require more aggressive therapeutic interventions.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Background/Aim: To investigate the clinical and prognostic significance of MUC1 expression in patients with esophageal squamous cell carcinoma (ESCC) after radical resection. Materials and Methods: A total of 108 ESCC specimens were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1 at the mRNA level and were evaluated by immunohistochemistry (IHC) to detect MUC1 at the protein level. Results: MUC1 mRNA was found in 74 cases by RT-PCR and MUC1 protein expression was found by IHC in 70 cases. Both MUC1 mRNA and protein expression correlated with pT (<0.05), pN (P < 0.01), and pTNM (<0.01). The 5-year survival rates of the patients were 39.8%. In univariate analysis, the 5-year survival rate in the ESCC patients was significantly associated with pT (P < 0.01), pN (P < 0.01), pTNM stage (P < 0.01), and MUC1 mRNA and protein expression (P < 0.05). In multivariate analysis, pN and MUC1 expression were the independent relevant factors. Conclusion: MUC1 expression can become a useful marker to predict poor prognostic factors for 5-year survival rate in patients with ESCC after radical resection.