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Takanori Kawabata



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-41 - Clinical and Immunological Factors Associated with Mutation Burden in Non-Small Cell Lung Cancer (ID 1313)

      10:15 - 18:15  |  Author(s): Takanori Kawabata

      • Abstract

      Background

      It is unclear whether factors including clinical and immune microenvironment (IME) are associated with tumor mutation burden (TMB) in patients with non-small cell lung cancer (NSCLC). We aimed to develop a prediction model to identify the association between these factors and TMB in patients with NSCLC.

      Method

      We assessed somatic mutation burden in surgical tumor specimens with whole exome sequencing (WES) using an ion torrent proton platform (Thermo Fisher Scientific). The IME profiles including PD-L1 tumor proportion score (TPS), stromal CD8 tumor infiltrating T cell (TIL) density, and stromal Foxp3 TIL were quantified by digital pathology using a machine learning algorithm. To detect factors associated with TMB, factors including clinical and IME were assessed using a multipul regression model. Two hundred NSCLC patients, for whom both WES and clinical data from Project HOPE (High-Tech-Omics-based Patient Evaluation) were available, excluding those with low tumor purity (less than 20%), were assessed in this study.

      Result

      Out of 250 NSCLC patients with tumors surgically resected between September 2014 and September 2015, we analyzed tumors from 200 patients. Patient background: median age (range) 70 (39-87), male 37.5%, smoker 27.5%, pathological stage (p-stage) (I/ II/ III) 63.5/22.5/14.0% respectively, histological type (Ad/Sq) 77.0/23.0%, primary tumor location (upper/lower) 58.5/41.5%, median standardized uptake value (SUV) 7.5 (0.86-29.8), median serum CEA level (range) 3.4 ng/ml (0.5-144.3), median serum CYFRA 21-1 level 1.2 ng/ml (1.0-38.0), median TMB 2.19/ Mb (0.12-64.38), median PD-L1 TPS 15.1% (0.09-77.4), median stromal CD8 TIL 582.1/mm2 (120.0-4967.6), and median stromal Foxp3 TIL 183.7/mm2 (6.3-544.0).

      In simple regression analysis, gender (male/female), smoking status (yes/no), p-stage (I/II,III,IV), age (< 70, ≥70), primary tumor location (lower/upper), serum CEA level (low [< 5.0ng/ml], high [≥ 5.0 ng/ml]), serum CYFRA level (low [< 3.5ng/ml], high [≥3.5 ng/ml]), and actionable mutation status (Mt+/Mt-) were favorable prognostic factors (p < .0001, p = .0001, p = .072, p = .027, p = .045, p = .002, p = .009, and p = .069 respectively).

      Multiple regression analysis identified five factors [smoking status: smoker, age: less than 70, primary tumor location: lower, serum CEA level (greater than 5ng/ml), and serum CYFRA level (greater than 3.5ng/ml)] associated with higher TMB (p = .002, p = .045, p = .03, p = .046 and p = .016 respectively).

      Conclusion

      IME factors did not associate with tumor mutation burden. However, along with smoking, lower primary location, elevated CEA and CYFRA level may be independent predictors of high TMB.