Skip to main content
Top
Published in: Diagnostic Pathology 1/2020

Open Access 01-12-2020 | NSCLC | Research

Evaluation of an online training tool for scoring programmed cell death ligand-1 (PD-L1) diagnostic tests for lung cancer

Authors: Bharat Jasani, Gudrun Bänfer, Rebecca Fish, Wim Waelput, Yves Sucaet, Craig Barker, Jessica L. Whiteley, Jill Walker, Rudy Hovelinck, Rolf Diezko

Published in: Diagnostic Pathology | Issue 1/2020

Login to get access

Abstract

Background

Numerous studies indicate that higher tumour programmed cell death ligand-1 (PD-L1) expression is associated with greater response to anti-programmed cell death-1 (PD-1)/PD-L1 immunotherapy in non-small cell lung cancer (NSCLC). In the era of precision medicine, there is a need to provide reliable, standardised training for pathologists to improve their accuracy of interpretation and scoring, as the results are used directly to inform clinical decisions. Here we present findings regarding reader reproducibility of PD-L1 tumour cell (TC) staining scoring for NSCLC using a PD-L1 e-trainer tool as part of a PD-L1 immunohistochemistry reader training course.

Methods

The PD-L1 training course was developed based on the use of VENTANA PD-L1 (SP263) and Dako PD-L1 IHC PharmDx 22C3 stained NSCLC samples in combination with a PD-L1 e-trainer tool. Five-hundred formalin-fixed, paraffin-embedded archival samples were obtained from commercial sources and stained for PD-L1. Slides were scored by two expert pathologists, then scanned to produce digital images and re-scored. Thirty-three cases were selected and sorted into three sets: a training set and two self-assessment tests (pre-test and ‘competence’ test). Participants (all selected board-certified pathologists) received face-to-face training including use of an e-trainer tool. Statistical analyses were performed using the competence test set. Overall percentage agreement (OPA) was assessed between the participant pathologists’ registered scores and the reference scores assigned by expert pathologists at clinically relevant PD-L1 cut-offs (≥1%, ≥25% and ≥ 50%).

Results

Seven sessions were held and 69 participant pathologists completed the training. Inter-reader concordance indicated high OPA (85–95%) for PD-L1 TC scoring at clinically relevant cut-offs, with Fleiss’ Kappa > 0.5.

Conclusions

Use of this web-based training tool incorporated into classroom-style training was associated with an overall moderately good level of inter-reader reproducibility at key cut-offs for TC PD-L1 expression testing in NSCLC. Overall, the online training tool offers a means of standardised training for practising pathologists in a clinical setting.
Literature
1.
go back to reference Lantuejoul S, Damotte D, Hofman V, Adam J. Programmed death ligand 1 immunohistochemistry in non-small cell lung carcinoma. J Thorac Dis. 2019;11(Suppl 1):S89–S101.CrossRef Lantuejoul S, Damotte D, Hofman V, Adam J. Programmed death ligand 1 immunohistochemistry in non-small cell lung carcinoma. J Thorac Dis. 2019;11(Suppl 1):S89–S101.CrossRef
2.
go back to reference Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. On behalf of the KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375:1823–33.CrossRef Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. On behalf of the KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375:1823–33.CrossRef
3.
go back to reference Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–50.CrossRef Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–50.CrossRef
4.
go back to reference Garassino MC, Cho BC, Kim JH, Mazières J, Vansteenkiste J, Lena H, on behalf of the ATLANTIC Investigators, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19:521–36.CrossRef Garassino MC, Cho BC, Kim JH, Mazières J, Vansteenkiste J, Lena H, on behalf of the ATLANTIC Investigators, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19:521–36.CrossRef
5.
go back to reference Sarode VR, Xiang QD, Christie A, Collins R, Rao R, Leitch AM, et al. Evaluation of HER2/neu status by immunohistochemistry using computer-based image analysis and correlation with gene amplification by fluorescence in situ hybridization assay: a 10-year experience and impact of test standardization on concordance rate. Arch Pathol Lab Med. 2015;139:922–8.CrossRef Sarode VR, Xiang QD, Christie A, Collins R, Rao R, Leitch AM, et al. Evaluation of HER2/neu status by immunohistochemistry using computer-based image analysis and correlation with gene amplification by fluorescence in situ hybridization assay: a 10-year experience and impact of test standardization on concordance rate. Arch Pathol Lab Med. 2015;139:922–8.CrossRef
7.
go back to reference Rebelatto MC, Midha A, Mistry A, Sabalos C, Schechter N, Li X, et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol. 2016;11:95.CrossRef Rebelatto MC, Midha A, Mistry A, Sabalos C, Schechter N, Li X, et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol. 2016;11:95.CrossRef
8.
go back to reference Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3:1051–8.CrossRef Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3:1051–8.CrossRef
9.
go back to reference Scheel AH, Dietel M, Heukamp LC, Jöhrens K, Kirchner T, Reu S, et al. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol. 2016;29:1165–72.CrossRef Scheel AH, Dietel M, Heukamp LC, Jöhrens K, Kirchner T, Reu S, et al. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol. 2016;29:1165–72.CrossRef
10.
go back to reference Brunnström H, Johansson A, Westbom-Fremer S, Backman M, Djureinovic D, Patthey A, et al. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Mod Pathol. 2017;30:1411–21.CrossRef Brunnström H, Johansson A, Westbom-Fremer S, Backman M, Djureinovic D, Patthey A, et al. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Mod Pathol. 2017;30:1411–21.CrossRef
Metadata
Title
Evaluation of an online training tool for scoring programmed cell death ligand-1 (PD-L1) diagnostic tests for lung cancer
Authors
Bharat Jasani
Gudrun Bänfer
Rebecca Fish
Wim Waelput
Yves Sucaet
Craig Barker
Jessica L. Whiteley
Jill Walker
Rudy Hovelinck
Rolf Diezko
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
Diagnostic Pathology / Issue 1/2020
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-020-00953-9

Other articles of this Issue 1/2020

Diagnostic Pathology 1/2020 Go to the issue