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Dong-Mei Lin



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    ES17 - The New WHO Classification of Lung Tumors (ID 239)

    • Event: WCLC 2020
    • Type: Educational Session
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
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      ES17.02 - Chair (ID 4080)

      15:30 - 16:30  |  Presenting Author(s): Dong-Mei Lin

      • Abstract

      Abstract not provided

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    FP07 - Pathology (ID 109)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP07.03 - Landscape Heterogeneity of PD-L1 Expression and Immune Cells Predicts Prognosis of Metastatic Non-Small Cell Lung Cancer (ID 878)

      00:00 - 00:00  |  Presenting Author(s): Dong-Mei Lin

      • Abstract
      • Presentation
      • Slides

      Introduction

      Immune microenvironment evolution may occur during tumor progression. The purpose of this study is to quantitatively access the heterogeneity and its significance of PD-L1 expression and immune cells (ICs) during the metastatic progression of non-small cell lung cancer (NSCLC).

      Methods

      Matched 64 resected specimens of paired primary tumors (PTs) and metastatic tumors (MTs) were obtained from 28 NSCLC patients. PD-L1 co-expression on tumor cells (TCs) and ICs (CD8+ cytotoxic T cells and CD68+ macrophages) as well as the density and spatial distance of ICs were analyzed by DNA-tagged multiplex staining on whole sections using HALO@ platform. The prognostic significance of the heterogeneity between MTs and corresponding PTs were concerned.

      Results

      Heterogeneity in the tumor proportion score (TPS) of PD-L1 expression on TCs, density of ICs, and spatial distance between ICs and TCs was observed between MTs and PTs. Importantly, subgroup analysis showed that significant discrepancies of TPS and ICs between MTs and PTs were associated with treatment (Figure 1). It was also novelty found that the alterations in PD-L1 expression on ICs during metastasis were closely associated with overall survival (OS) in NSCLC. Compared to corresponding PTs, an increase in TPS on MTs was slightly related to poor prognosis, while an increase in the density of PD-L1+ ICs and decrease in spatial distance between PD-L1+/CD8+ T cells and TCs was significantly correlated with prolonged OS as a positive immune response (Figure 2).

      Figure 1. Represented multiplex figures and quantitative analysis of the heterogeneity between MTs and PTs, Wilcoxon-signed-rank-test.

      figure 1.png

      Figure 2. The change status of PD-L1 expression and ICs on MTs compared to corresponding PTs was closely related with overall survival (OS).

      figure 2.png

      Conclusion

      Landscape of PD-L1 expression and ICs in MT and corresponding PT to highlight the change status of immune microenvironment predicts prognosis of metastatic NSCLC.

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    P33 - Pathology - Immunotherapy Biomarker (ID 101)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P33.12 - Real-World Prevalence of PD-L1 Expression in Chinese Patients with Advanced or Metastatic NSCLC: Express II Study (ID 3057)

      00:00 - 00:00  |  Presenting Author(s): Dong-Mei Lin

      • Abstract
      • Slides

      Introduction

      Evaluation of PD-L1 expression is fundamental to identify candidates for anti-PD-L1/PD-L1 therapy. PD-L1 prevalence in multi-national EXPRESS1 study was 48% with PD-L1 TPS < 1%, 30% with TPS 1-49% and 22% with TPS≥50%. Due to limited data on PD-L1 expression in China, we conducted a multicenter, observational study to determine the real-world prevalence of tumor PD-L1 expression in Chinese patients with NSCLC.

      Methods

      Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤3 years old) obtained before treatment were identified in 10 centers where PD-L1 expression was evaluated by pathologists using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). Tumor samples from eligible patients were selected consecutively.

      Results

      In this study, 1023 patient tumor samples were screened, of which 122 did not meet the inclusion criteria while 22 were unevaluable due to inadequate tumor cells. Among 879 samples analyzed, 424 (48.2%) had PD-L1 TPS < 1%, 266 (30.3%) had TPS 1-49%, and 189(21.5%) had TPS≥50%.

      Samples with TPS≥1% and ≥50% were less common among patients with sensitizing EGFR mutations (43.8%/14.3%). Conversely, samples without EGFR mutation had 49.8% and 27.4% with TPS≥1% and ≥50% respectively. PD-L1 prevalence was consistent across subgroups defined by ALK translocation status and the reference value may be limited owing to the small size of samples with ALK positive. Further, among those with both EGFR mutation negative and ALK negative, there were 50.2% samples with TPS≥1% and 28.0% with TPS≥50%.

      Current and former smokers with TPS≥50% were more than never smokers(31.7% and 24.4% vs 15.7%). Women with TPS≥50% is less than men (14.2% vs 25.6%). PD-L1 prevalence in other demographic and clinicopathological characteristics is listed in Table 1.

      Table 1 Prevalence of PD-L1 by Baseline Demographic and Clinicopathologic Characteristics

      Characteristic, n (%)

      N

      TPS < 1%

      TPS 1-49%

      TPS≥50%

      All patients

      879

      424 (48.2)

      266 (30.3)

      189(21.5)

      Sex

      　

      　

      　

      　

      Male

      562

      250 (44.5)

      168 (29.9)

      144 (25.6)

      Female

      317

      174 (54.9)

      98 (30.9)

      45 (14.2)

      Smoking status

      Never

      447

      237 (53.0)

      140 (31.3)

      70 (15.7)

      Former

      209

      91 (43.5)

      67 (32.1)

      51 (24.4)

      Current

      145

      56 (38.6)

      43 (29.7)

      46 (31.7)

      Unknown

      78

      40 (51.3)

      16 (20.5)

      22 (28.2)

      Specimen type

      Surgical resection

      314

      161 (51.3)

      82 (26.1)

      71 (22.6)

      Biopsy

      564

      263(46.6)

      183 (32.4)

      118(20.9)

      Unknown

      1

      0

      1 (100)

      0

      Specimen source

      Primary

      584

      273 (46.7)

      190 (32.5)

      121 (20.7)

      Metastases

      295

      151 (51.2)

      76 (25.8)

      68 (23.1)

      Unknown

      0

      0

      0

      0

      Histology

      Squamous

      207

      85 (41.1)

      71 (34.3)

      51 (24.6)

      Non-squamous

      657

      331 (50.4)

      193 (29.4)

      133 (20.2)

      Unknown

      15

      8 (53.3)

      2 (13.3)

      5 (33.3)

      AJCC stage

      IIIB

      225

      95 (42.2)

      73 (32.4)

      57 (25.3)

      IV

      624

      314 (50.3)

      184 (29.5)

      126 (20.2)

      others

      30

      15(50.0)

      9(30.0)

      6(20.0)

      ALK translocation status

      Positive

      32

      17 (53.1)

      8 (25.0)

      7 (21.9)

      Negative

      500

      261 (52.2)

      128 (25.6)

      111 (22.2)

      Unknown

      347

      146 (42.1)

      130 (37.5)

      71 (20.5)

      EGFR mutation status

      Positive

      210

      118 (56.2)

      62 (29.5)

      30 (14.3)

      Negative

      277

      139 (50.2)

      62 (22.4)

      76 (27.4)

      Unknown

      392

      167 (42.6)

      142 (36.2)

      83 (21.2)

      ALK translocation and EGFR mutation negative

      225

      112 (49.8)

      50 (22.2)

      63 (28.0)
      Conclusion

      PD-L1 prevalence in this study was generally consistent with multi-national EXPRESS1 study. The low testing failure rate (2.44%) is indicative of the reliability of PD-L1 IHC 22C3 pharmDx assay. This study may assist with clinical decision making in immunotherapy for Chinese patients with advanced NSCLC.

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