Author of

• 17398

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  P2.01 - Poster Session with Presenters Present (ID 461)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 2
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17446

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    P2.01-048 - Paired Comparison of PDL1 Assessment on Cytology and Histology from Malignancies in the Lung (ID 4355)

    14:30 - 14:30  |  Author(s): T. Skov
    • Abstract

    Background:
    PD-L1 tests have been approved on histological specimens only. More than 1/3 of NSCLC patients are diagnosed on cytology alone. The hypothesis of this study is that cytological cell block material is as good as histological material for PD-L1 analysis.
    
    Methods:
    86 paired samples of malignancies from the lung (NSCLC = 72, other primary malignancies and metastases = 14), where cytological cell block and histological material were available from the same lesion within 6 weeks were stained for PD-L1 on serial sections with PD-L1 IHC 28-8 pharmDx (28-8pharmDx) and PD-L1 IHC 22C3 pharmDx (22C3pharmDx). The partial or complete membrane staining on malignant cells regardless of intensity was assessed as >1%, >5%, >10% and hereafter in 10% increments. Number of malignant cells (< or > 100) and staining heterogeneity were recorded. The pathologist was blinded to previous evaluations of pair members. Overall (OA) and Average Positive (APA) and Negative (ANA) agreement were calculated as well as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with histology as the non-reference standard. CIs were bootstrapped.
    
    Results:
    Agreement statistics for PD-L1 positivity with different cutoffs in cytology and histology specimens, % (95% CI)

    22C3pharmDx
    	≥ 1% positive	≥ 50% positive
    OA	85 (77–92)	94 (88–99)
    APA	83 (73–91)	82 (61–96)
    ANA	86 (78–93)	97 (93–99)
    PPA	80 (67–92)	100
    NPA	89 (79–98)	93 (87–99)
    28-8pharmDx
    	≥ 1% positive	≥ 5% positive	≥ 10 % positive
    OA	87 (80–94)	95 (91–99)	90 (83–95)
    APA	86 (77–94)	94 (86–99)	84 (71–93)
    ANA	88 (80–94)	96 (92–99)	92 (87–97)
    PPA	81 (69–92)	91 (79–100)	79 (63–93)
    NPA	93 (85–100)	98 (94–100)	95 (88–100)

    There was high agreement between the cytological and histological scores, applying to both pharmDx kits and all cutoffs (Table), not changing by exclusion of cytological cell blocks containing <100 cells nor by exclusion of non-NSCLC. Pearson r[2 ]were 0.87-0.89. Paired samples with PD-L1 staining heterogeneity on histological material seemed to have lower agreement than samples with homogenous staining
    
    Conclusion:
    High correlation between staining on cytological cell block material and histological specimens was observed using PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx, suggesting that cytological material is as good as histological material for PD-L1 IHC analysis. Intra-tumor heterogeneity may contribute to disagreement and more research on the influence of staining heterogeneity is warranted.
    
    

  • 17447

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    P2.01-049 - A Comparative Study of PD-L1 IHC 28-8 pharmDx and PD-L1 IHC 22C3 pharmDx on Malignancies from the Lung (ID 4356)

    14:30 - 14:30  |  Author(s): T. Skov
    • Abstract

    Background:
    PD-L1 tests as predictive biomarkers for anti-PD-1 immunotherapy for NSCLC have been developed independently and use different assays and cutoffs for positivity. A more flexible PD-L1 testing would allow for efficient use of sparse tissue and pathology resources. The aim of this study was to evaluate the agreement between PD-L1 IHC 28-8 pharmDx (28-8 pharmDx) and PD-L1 IHC 22C3pharmDx (22C3pharmDx) assays in patients with malignancy in the lung. The comparison was made on cytological cell blocks as well as on histological material.
    
    Methods:
    Paired samples of malignancies from the lung (NSCLC = 73, other primary malignancies and metastases = 14) where cytological cell block material (N=86) and histologic material (N=87) were available from the same lesion within 6 weeks were stained for PD-L1 on serial sections with 28-8pharmDx and 22C3pharmDx. The partial or complete membrane staining on malignant cells regardless of intensity was assessed as >1%, >5%, >10% and hereafter in 10% increments. The pathologist was blinded to previous evaluations of pair members. Overall Agreement (OA) and Average Positive (APA) and Negative Agreement (ANA) were calculated
    
    Results:
    Agreement statistics for 28-8 pharmDx and 22C3 pharmDx with different cutoffs for PD-L1 positivity in cytology and histology specimens, % (95% CI)

    PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx on cytological cell blocks
    	≥ 1%	≥ 5%	≥ 10 %	≥ 50%
    OA	94 (90–99)	98 (94–100)	97 (92–100)	93 (87-98)
    APA	93 (87-97)	97 (91-100)	94 (85-100)	80 (61-94)
    ANA	95 (90-99)	98 (95-100)	98 (94-100)	96 (92-99)
    PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx on histological material
    	≥ 1%	≥ 5%	≥ 10 %	≥ 50%
    OA	97 (92-100)	99 (97-100)	95 (91-99)	93 (86-97)
    APA	96 (92-100)	98 (95-100)	93 (84-98)	80 (62-94)
    ANA	97 (92-100)	99 (97-100)	97 (93-99)	96 (92-99)

    High OA, APA and ANA were found for agreement between 22C3pharmDx and 28-8pharmDx on cytological clot material, as well as on histological tissue for all cutoffs. The APA at cutoff 50% positivity was the lowest (80%); the CIs were however wide due to small number of positive samples at this cutoff. Pearson r[2 ]were 0.96-0.97
    
    Conclusion:
    High correlation between PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx was observed on both cytological and histological specimens, suggesting that these assays may be used interchangeably in testing of lung tumors for PD-L1 expression. However, more data is needed to alter current guidelines.