Bregje M Koomen1, Quirinus J M Voorham2, Chantal C H J Epskamp-Kuijpers3, Carmen van Dooijeweert4, Anne S R van Lindert5, Ivette A G Deckers2, Stefan M Willems6. 1. Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. Electronic address: b.m.koomen@umcutrecht.nl. 2. PALGA Foundation, De Bouw 123, 3991 SZ, Houten, the Netherlands. 3. Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands; PALGA Foundation, De Bouw 123, 3991 SZ, Houten, the Netherlands. 4. Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. 5. Department of Pulmonology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. 6. Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Abstract
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.
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 NSCLCpatients 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.
Authors: Henri B Wolff; Elisabeth M P Steeghs; Zakile A Mfumbilwa; Harry J M Groen; Eddy M Adang; Stefan M Willems; Katrien Grünberg; Ed Schuuring; Marjolijn J L Ligtenberg; Bastiaan B J Tops; Veerle M H Coupé Journal: JCO Precis Oncol Date: 2022-07