Virtual Library

Start Your Search

Ugo Pastorino



Author of

  • +

    MA05 - Lung Cancer Screening (ID 174)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Screening and Early Detection
    • Presentations: 1
    • +

      MA05.03 - Differential Frequency of Blood Immune Cells as Biomarkers for Risks Assessment in bioMILD Lung Cancer Screening Trial (ID 2197)

      11:45 - 12:45  |  Author(s): Ugo Pastorino

      • Abstract
      • Presentation
      • Slides

      Introduction

      The role of adaptive and innate systemic immunity in lung carcinogenesis is poorly understood both in murine and clinical settings. Nevertheless, studying peripheral blood immune cells could provide insights into the pathogenesis of this process and allow the identification of novel biomarkers for early diagnosis and intervention. In line with this hypothesis is our previous finding that circulating microRNAs deriving from peripheral immune cells compose a three level miRNA signature risk Classifier (high, intermediate, low MSC) able to predict cancer development in heavy smokers. In this study we aimed to test whether differential frequencies of specific immune cell subsets in the peripheral blood of subjects enrolled in the bioMILD screening trial could help identifying high risk subjects and implement the accuracy of the MSC test.

      Methods

      Peripheral blood mononuclear cells (PBMC) prospectively isolated and stored from blood of volunteers enrolled in the bioMILD screening trial were analyzed by multiparametric flow cytometry (Cytoflex) using a total of 23 antibodies specific for markers encompassing monocyte and myeloid-derived suppressor cells (MDSC) subsets, regulatory T cells, cytolytic NK cells and activated/exhausted/hyperexausted T cells. To maximize the chances of detecting differential phenotypic patterns, the analysis was initially performed in a first training set of samples of the bioMILD trial including 20 Low Dose Computed Tomography (LDCT)-detected lung cancers and 20 matched cancer-free heavy smokers controls. Data were then validated in PBMC from 80 LDCT-detected lung cancer patients and 80 matched (1:1) cancer-free controls of the bioMILD trial. The C-reactive protein (CRP) plasma level was also measured in all subjects as inflammation marker.

      Results

      An increase of pro-angiogenic monocytes (CD14+CX3CR1+) and monocytic-MDSC (M-MDSC, CD14+HLA-DRneg) was observed in the patients group compared to controls. Conversely, intermediate monocytes (CD14+CD16+), which are associated with cancer immunosurveillance, and activated cytotoxic T (CD3+CD8+PD-1+) were instead reduced in lung cancer patients compared to controls. The plasma level of CRP did not differ in cases vs controls and showed no correlation with any of the analyzed immune cell subpopulations.The majority of these cell subsets were able to discriminate patients and controls independently from MSC risk level. However, specific cell subsets were differentially expressed in MSC high compared to low/intermediate risk patients. Among them, hyper-exhausted T cells (CD3+CD8+PD-1+LAG3+) and M-MDSC were increased in MSC high risk patients, while CD16highCD56+CD3+ NKT cells, protective elements mediating antibody-dependent cell cytotoxicity, were instead reduced.

      Conclusion

      Altogether, these findings suggest that MSC risk might associate with a immunosuppressed systemic immunity that could predispose to lung carcinogenesis. Hence, the characterization of the peripheral myeloid/lymphoid compartments can help distinguishing lung cancer screening cases and controls and may thus implement the accuracy of the blood miRNA-based MSC test.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA09 - Prognosis and Staging (ID 187)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Staging
    • Presentations: 1
    • +

      MA09.11 - Surgical Outcome of Lung Cancer Volumetric Screening According to Ldct Intervals in Two Prospective Trials (ID 1795)

      09:15 - 10:15  |  Presenting Author(s): Ugo Pastorino

      • Abstract
      • Slides

      Introduction

      The publication of Dutch-Belgian volumetric LDCT screening (NELSON) trial results at 10 years, confirming a significant lung cancer (LC) mortality reduction in heavy smokers, opens a new phase of implementation of worldwide LC screening policies. The impact of LDCT intervals on surgical performance represents one of the crucial factors, and the experience accumulated by prospective trials focused on this specific issue can contribute to improve future screening programs.

      Methods

      From 2005 to 2016, MILD and BioMILD trials enrolled a total of 6495 subjects (36% females, median age 59, median pack-years 41, 75% current smokers), applying volumetric nodule measurement and volume doubling time (VDT) +/- PET, with three planned screening intervals: A) annual LDCT (1,190, MILD); B) biennial LDCT (1,186, MILD); and C) individually targeted LDCT, 1 vs. 3 years, according to radiomic features and blood microRNA value at baseline examination (4,119, BioMILD). Median follow-up was 75 months overall; 124 A, 124 B and 64 C. Cumulative person/years were 46,027 overall; 11,777 A, 11,818 B and 22,431 C. The average number of LDCT performed in each subject was 3.7 overall, 6.2 A, 4.3 B and 2.8 C.

      Results
      We recorded a total of 283 lung cancers (LC) from 266 subjects in the study cohorts, including 16 second primaries and 1 third primary, and specifically 74 A, 44 B and 165 C.
      The LC resection rate was: 71% overall (202, 2 pneumonectomy, 145 lobectomy, 48 segmentectomy, and 7 wedge), 68% (50) A, 52% (23) B and 78% (129) C (Figure 1). The proportion of Stage I LC was 56% (159) overall, 51% (38) A, 45% (20) B and 61% (101) C. Minimally invasive thoracoscopic approach (VATS) was applied to 37% (106) of LC overall, 18% (13) A, 11% (5) B, and 53% (88) C; corresponding to 53% of all LC resections (26% A, 22% B and 68% C). Segmentectomy was chosen in 29% of stage I LC (26% A, 15% B and 33% C). Overall post-operative mortality was 1% (2/202) at 30-days, and 2% (4/202) at 90-days. Lung resections for benign histology were performed in 4.7% overall (10/212; 3 B and 7 C).

      figure 1.png Conclusion
      In our experience, LDCT intervals could be safely adjusted by individual risk profile, to reduce unnecessary LDCT repeats in volumetric LC screening. Risk-based LDCT intervals did not cause a detrimental effect on LC detection, stage I proportion or surgical outcomes.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
    • +

      PS01.03 - Discussant (ID 4250)

      07:00 - 09:00  |  Presenting Author(s): Ugo Pastorino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
    • +

      PS02.03 - Discussant (ID 4284)

      18:00 - 20:00  |  Presenting Author(s): Ugo Pastorino

      • Abstract

      Abstract not provided