TY - JOUR
T1 - Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients
AU - Koomen, Bregje M.
AU - Voorham, Quirinus J.M.
AU - Epskamp-Kuijpers, Chantal C.H.J.
AU - van Dooijeweert, Carmen
AU - van Lindert, Anne S.R.
AU - Deckers, Ivette A.G.
AU - Willems, Stefan M.
N1 - Funding Information:
This work was supported by AstraZeneca, MSD and Roche (grant numbers not applicable). None of the grant suppliers were involved in the study design, collection, analysis and interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.
Funding Information:
SM Willems received research grants from Amgen, AstraZeneca, Bayer, BMS, MSD, NextCure, Pfizer and Roche, all outside the submitted work. ASR van Lindert reports consultation fees (paid to the institution) from AstraZeneca and Roche, outside the submitted work. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Publisher Copyright:
© 2021 The Authors
PY - 2021/9
Y1 - 2021/9
N2 - Objectives: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%−71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%−40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%−73.4%) and 29.2% (14.7%−43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data.
AB - Objectives: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%−71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%−40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%−73.4%) and 29.2% (14.7%−43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data.
KW - Clinical pathology
KW - Immunohistochemistry
KW - Interlaboratory variation
KW - Non-small cell lung cancer
KW - Programmed death-ligand 1
UR - https://www.scopus.com/pages/publications/85111255171
U2 - 10.1016/j.lungcan.2021.07.012
DO - 10.1016/j.lungcan.2021.07.012
M3 - Article
AN - SCOPUS:85111255171
SN - 0169-5002
VL - 159
SP - 117
EP - 126
JO - Lung Cancer
JF - Lung Cancer
ER -