Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial

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 \u3c .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 \u3c .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

Application of engineering- R&D integrated thinking mode for innovative talents cultivation of intelligent navigation experimental class

In view of the four prominent contradictions in the traditional engineering thinking teaching system of surveying and mapping engineering, which are difficult to meet the new requirements of innovative talents cultivation, a new talent training mode based on the integration of engineering and re-search thinking is proposed. Taking surveying and mapping engineering (intelligent navigation experimental class) as the research object, the multi-level training system of “thinking transformation - professional development - model transformation” was designed, and the reform and practice were carried out from the multiple links of “curriculum system - textbook construction - practical teaching - innovation credits”. The teaching practice in the past four years shows that the integrated thinking mode of engineering and research has been well applied in the cultivation of innovative talents in the intelligent navigation experimental class, and has achieved remarkable results in many aspects, such as the improvement of innovation ability, the promotion of teaching and practice system, the construction and application of teaching materials, and the development of disciplines and specialties, laying a solid foundation for the output of top innovative talents in the intelligent navigation experimental class

Strength and Deformation Characteristics of Fiber and Cement-Modified Waste Slurry

Using fiber and cement to modify waste slurry and apply it to roads is an effective way to recycle waste slurry. A new type of road material, fiber–cement-modified waste slurry (FRCS), was prepared in this study. The static and dynamic characteristics of the cement soil were studied using an unconfined compressive strength test and dynamic triaxial test. The results show that the optimum fiber content of FRCS is 0.75%. In the unconfined compressive strength test, under this fiber content, the unconfined compressive strength (UCS) of the FRCS is the largest, and the elastic modulus and modulus strength ratio are both the smallest, indicating that the tensile properties of the cement slurry have been enhanced. In the dynamic triaxial test, the hysteretic curve of the FRCS tends to be stable with the increase in the number of cycles, the dynamic elastic modulus of the FRCS decreases first and then increases with the increase in the dosage, while the damping ratio becomes stable after a rapid decline, and the fiber incorporation increases the cumulative strain of the soil–cement under low-stress cycles, indicating that the ductility of the FRCS is improved. In addition, a cumulative strain prediction model of the FRCS is established in this paper, which can provide a reference for the resource application of waste slurry in road engineering

Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial

Abstract Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5–6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64–30.36) and 11.60 (95% CI: 8.28–13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34–0.64, p < 0.0001). IRC-assessed confirmed objective response rate (ORR) was higher (81.68% vs. 70.68%, p = 0.056) and duration of response was longer (median, 25.79 [95% CI, 16.53–29.47] vs. 11.14 [95% CI, 9.23–16.59] months, p = 0.0003) in the envonalkib group compared with the crizotinib group. In participants with baseline brain target lesions, IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib (78.95% vs. 23.81%). Overall survival (OS) data were immature, and median OS was not reached in either group (HR = 0.84, 95% CI: 0.48–1.47, p = 0.5741). The 12-month OS rates were 90.6% (95% CI, 84.0%–94.5%) and 89.4% (95% CI, 82.8%–93.6%) in the envonalkib and crizotinib groups, respectively. Grade ≥3 treatment-related adverse events were observed in 55.73% and 42.86% of participants in the envonalkib and crizotinib groups, respectively. Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC