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  • C6 NBD Ceramide b iframe width height src https www youtube


    r> We aimed to investigate the association between the C6 NBD Ceramide use and response to IO in patients with metastatic NSCLC treated with IO at our Institution. The impact of antibiotics on outcome was analyzed considering not only the simple antibiotic use in the Early IO Period (EIOP), but also the cumulative exposure to antibiotics in the Whole IO Period (WIOP). For this purpose, we coined a new variable called Antibiotic-Immunotherapy Exposure Ratio (AIER), defined as “days of antibiotic/days of IO” during the WIOP.
    2. Materials and methods
    We analyzed data about all consecutive patients with metastatic  Lung Cancer 132 (2019) 72–78
    NSCLC treated with ICIs at Istituto Nazionale dei Tumori, Milan, Italy, between April 2013 and January 2018.
    All the patients signed a written informed consent declaring their agreement to the use of personal data for research purposes at some time of their disease history.
    Clinical data were retrospectively collected from institutional da-tabase and included age, gender, performance status (PS) according to Eastern Cooperative Oncology Group (ECOG) [32], smoking habits, histology, tumor molecular characterization whenever performed, line of IO, ICI prescribed, response to IO according to Response Evaluation Criteria for Solid Tumors (RECIST) [33], number of metastatic sites at the beginning of IO, and details of antibiotic use (including specific drug, route of administration, dosage, and duration).
    For the purpose of the analysis concerning the EIOP, antibiotic use was considered relevant when it happened between 1 month before and 3 months after starting IO. Patients receiving antibiotics outside this time frame were considered as non-antibiotic treated patients. The AIER was defined as the rate “days of antibiotic therapy/days of IO” during the WIOP. First, the AIER was considered as a continuous variable for statistical analyses. Then, the median value of AIER was used as cut-off and patients with an AIER lower than the cut-off were included in the control group as those never receiving antibiotics.
    All ICIs were considered, irrespective of mechanism of action. Cases who received only the first dose of drug and then discontinued for toxicity, worsening of general conditions or death were excluded from the basidiomycetes analysis. Patients receiving at least two doses of ICI and then dis-continued treatment for unequivocal clinical progression were included in the analyses and accounted as patients with progressive disease at first evaluation.
    2.2. Statistical analysis
    Descriptive statistics were used to analyze and report clinical vari-ables.
    All patients were followed until death, loss at follow-up or time C6 NBD Ceramide of data lock, which was set on the 1st March 2018. PFS was calculated as the time from the beginning of IO to the time of disease progression, or death for any cause. Disease response was assessed using RECIST, at the last version applicable at the time of IO administration (ranging from 2013 to 2018). Overall survival (OS) was calculated as the time from the beginning of IO to death for any cause. Alive patients were right-censored at the time of last contact. PFS and OS were estimated using the Kaplan-Meier method. Duration of follow-up was calculated using the reverse Kaplan-Meier method. Differences between survival curves were analyzed with the log-rank test.
    Fisher’s exact test was used to compare discrete qualitative vari-ables. Differences between continuous ordinal variables were tested using the Mann-Whitney non-parametric U test. Univariate analyses were performed according to sex (male versus female), age (< 70 years versus ≥70 years), smoking status (current or former smoker versus never smoker), tumor histology (squamous NSCLC versus non-squamous NSCLC), ICI (anti-PD1 versus anti-PD-L1 versus anti-CTLA4 and combi-nations), line of IO (first versus second versus third or more), basal ECOG PS (0 versus 1 or 2), and number of metastatic sites at the beginning of IO (0 or 1 versus 2 or more). χ square test was used for univariate analyses. Cox proportional hazard model was applied for multivariate analyses, which were calculated for the significant variables at uni-variate test. All analyses were two-sided and values of p < 0.05 were considered statistically significant.
    Statistical analyses were performed using SAS (version 9.4, SAS Institute, Cary, NC, USA).
    High Low Negative Unknown 1 Number. 2 Performance Status. 3 Immunotherapy. 4 Central Nervous System. 5 Non Small Cell Lung Cancer.
    Rearranged Wild type Unknown PD-L1 expression
    Mutated Wild type Unknown ALK status
    Squamous NSCLC EGFR status
    Former / current smoker Never smoker