Search

Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR -mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797. Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8–73·7) in the icotinib group and 32·5% (21·3–44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42–1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group. Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR -mutant stage II–IIIA NSCLC after complete tumour resection. Betta Pharmaceuticals For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy has offered novel therapeutic options for patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Depicting the landscape of genomic and immune profiles is critical in predicting therapeutic responses., Methods: We integrated whole-exome sequencing, single-cell RNA sequencing, and immunofluorescence data of ESCC samples from 24 patients who received neoadjuvant treatment with PD-1 inhibitors plus paclitaxel and platinum-based chemotherapy to identify correlations with therapeutic responses., Findings: An elevation of small insertions and deletions was observed in responders. DNA mismatch repair (MMR) pathway alternations were highly frequent in patients with optimal responses and correlated with tumour infiltrating lymphocytes (TILs). Among the TILs in ESCC, dichotomous developing trajectories of B cells were identified, with one lineage differentiating towards LMO2 + germinal centre B cells and another lineage differentiating towards CD55 + memory B cells. While LMO2 + germinal centre B cells were enriched in responding tumours, CD55 + memory B cells were found to correlate with inferior responses to combination therapy, exhibiting immune-regulating features and impeding the cytotoxicity of CD8 + T cells. The comprehensive evaluation of transcriptomic B cell lineage features was validated to predict responses to immunotherapy in patients with cancer., Interpretation: This comprehensive evaluation of tumour MMR pathway alternations and intra-tumoural B cell features will help to improve the selection and management of patients with ESCC to receive neoadjuvant chemoimmunotherapy., Funding: National Science Foundation of China (82373371, 82330053), Eastern Scholar Program at Shanghai Institutions of Higher Learning, National Science and Technology Major Project of China (2023YFA1800204, 2020YFC2008402), and Science and Technology Commission of Shanghai Municipality (22ZR1410700, 20ZR1410800)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Seven rare oxylipins, siegesbeckins A-G (1-7) representing further bioactive constituents different from the general terpenyl compounds found in Siegesbeckia species, have been obtained from the aerial parts of Siegesbeckia glabrescens. These isolates were identified to be a series of methyl 4-methylpentanoates incorporating fatty acid moieties of different chain lengths, based on spectroscopic techniques, and their absolute configurations were determined via chemical degradation and comparison of experimental and theoretically calculated ECD spectra. With respect to bioactivity, antibacterial, anti-inflammatory and cytotoxic properties of selected compounds were evaluated. Compounds 1 and 5 showed moderate antibacterial activity against two Gram-positive bacteria with MIC values of 4.3 μg/mL, while 3 showed no pronounced activity in these assays., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

The purpose of this study was to establish and characterize patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mice for utilization in antitumor drug discovery. A total of 96 esophageal squamous cell carcinoma (ESCC) tissues from Chinese patients were transplanted subcutaneously into immunodeficient mice. Histology, EGFR, K-ras, B-raf, and PIK3CA mutations, and HER2 gene amplifications were analyzed in both patient tumors and mouse xenograft tissues using immunohistochemistry, mutant-enriched liquid chip sequencing and fluorescence in situ hybridization assays, respectively. Furthermore, in vivo efficacy studies using five PDECX mice harboring a variety of genetic aberrations were performed using the chemotherapy agents 5-fluorouracil (5-FU) and cisplatin. Thirty-seven PDECX mouse models were successfully established in immunodeficient mice. Pathological analysis revealed similar histological architecture and degrees of differentiation between patient ESCC and xenografted tumors. No mutations were identified in EGFR, K-ras, and B-raf genes in either xenograft models or patient ESCC tissues. In contrast, PIK3CA gene mutations were detected in 12.5% (12/96) ESCC patients and 18.9% (7/37) PDECX models. Interestingly, patient ESCC tissues exhibiting HER2 overexpression or gene amplification were unable to survive in immunodeficient mice. Further analysis showed that PDECX models carrying HER2 2+ expression had no response to 5-FU/cisplatin, compared with HER2-negative models. In conclusion, a panel of PDECX mouse models, which include PIK3CA mutant and HER2-positive models, was established and characterized thus mimicking the current clinical genetic setting of esophageal carcinoma. The sensitivity of HER2-negative ESCC models to chemotherapy supports stratification approaches in the treatment of esophageal carcinoma patients and warrants further investigation of the impact of PI3KCA on treatment response.

Background: A new classification of pulmonary adenocarcinoma has been recently proposed by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS). This study was undertaken in an attempt to explore the clinical implication of this new classification in Chinese patients., Methods: Two hundred ninety-two lung adenocarcinomas were reclassified strictly according to the IASLC/ATS/ERS classification by two pathologists, independently. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the new classification and patients' prognosis., Results: We confirmed three groups with different outcomes. Both AIS and MIA had 100% 5-year disease-free survival rate and 100% 5-year overall survival rate. Lepidic, acinar, and papillary as well as variants of invasive adenocarcinoma had intermediate prognosis. Solid and micropapillary cases had poor prognosis (DFS: P < 0.001, OS: P = 0.002). After controlling the clinicopathological factors, the new classification was identified as an independent prognostic factor in patients' disease-free survival and overall survival., Conclusions: We have demonstrated a valuable prognostic role of the new classification in Chinese patients. This new classification is valuable of screening out patients with high risk of recurrence to receive postoperative adjuvant therapy., (Copyright © 2012 Wiley Periodicals, Inc.)