BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To assess the dosimetric impact on the target volumes and organs at risk ( OARs) using simultaneous integrated boost ( SIB ) for the hypoxic regions of the pancreatic cancer patients treated with stereotactic body radiotherapy ( SBRT ) , and to predict an optimal way of SIB. Methods The setup corrections guided by 100 sets of CBCT scans of 10 patients previously treated with SBRT were imported to the treatment planning system ( TPS ) to recalculate the dose to the target and OARs. Two tumor control probability ( TCP ) models were applied to calculate the TCP under various hypoxic situations. The correlations between the TCP and target dose were analyzed. Results Without setup corrections, the PTV and ITV were underdosed by 8. 9％ and 9. 2％ on average respectively relative to planed dose. With setup corrections, the mean dose to PTV and ITV coverage were 1. 6％ and 1. 3％lower than planned respectively. The mean deviations of OAR dose were between -0. 11 Gy and 0. 26 Gy for all plans. The predictive values of Dmean on hypoxic regions were 31. 4, 34. 0 and 37. 2 Gy (Niemierko model) or 31. 6, 33. 9 and 37. 2 Gy (Poisson model) when the oxygen enhancement ratios (OERs) were 1, 1. 5 and 3 respectively. Conclusions With CBCT setup corrections, the dosimetric impacts of setup errors on the target and OARs can be neglected. Significant deviations of TCP calculation were observed without accounting for tumor hypoxia. To counteract the impacts of hypoxia, the mean dose to the hypoxic regions should be at least 1. 24 times of prescribed dose.

The 13th World Congress of the International Hepato-Pancreato-Biliary Association was held from 4th to 7th September 2018 in Geneva,Switzerland.Thousands of wellknown specialists and scholars from 96 countries around the world were invited for the great event.The congress aimed to explore the latest achievements of diagnosis and treatment of hepatobiliary and pancreatic diseases from both the clinical and basic perspective.In this article,authors reviewed and analyzed the up-to-date research information and combined clinical researches of the author team,in order to share the experience and achievements in the field of hepato-pancreato-biliary surgery with colleagues and provide new information and inference for optimization of diagnosis and treatment in this field.

Objective To investigate the radiosensitizing effects of cyclooxygenase-2 selective inhibitor LM-1685 on A549 cells in vitro.Methods A549 human lung adenocarcinoma cell line was used in this study.Cell growth kinetics Was determined using MTT assay.Cell survival was analyzed by clonogenic assay.The change of cell cycle Was measured by flow cytometry.Results LM-1685 inhibited the growth of A549 cells,showing a dose-dependent and time-dependent manner.LM-1685(50/μmol/L),either with or without IL-1β,showed the radiosensitizing effects on A549 cells,and the sensitizing enhancement ratio(SER)was 1.12 and 1.06,respectively.LM-1685(50 μmol/L)abrogated radiation-induced G2/M arrest of the tested A549 cells.Conclusions Cyclooxygenase-2 selective inhibitor can enhance the radiosensitivity of A549 cell line.Abrogation of radiation-induced G2/M arrest could be part of the mechanism.