Rogier Butter1, Liesbeth M Hondelink2, Lisette van Elswijk3, Johannes L G Blaauwgeers4, Elisabeth Bloemena5, Rieneke Britstra5, Nicole Bulkmans6, Anna Lena van Gulik7, Kim Monkhorst8, Mathilda J de Rooij9, Ivana Slavujevic-Letic9, Vincent T H B M Smit2, Ernst-Jan M Speel10, Erik Thunnissen5, Jan H von der Thüsen11, Wim Timens12, Marc J van de Vijver1, David C Y Yick13, Aeilko H Zwinderman14, Danielle Cohen2, Nils A 't Hart15, Teodora Radonic16. 1. Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, The Netherlands. 2. Department of Pathology, Leiden University Medical Center, Leiden University, The Netherlands. 3. Independent Operating Psychologist, The Netherlands. 4. Department of Pathology, OLVG LAB BV, Amsterdam, The Netherlands. 5. Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, The Netherlands. 6. Department of Pathology, Spaarne Gasthuis, Haarlem, The Netherlands. 7. Department of Pathology, University Hospital Cologne, Germany. 8. Department of Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 9. Department of Pathology, Symbiant Pathology Expert Center, Alkmaar, The Netherlands. 10. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, University of Maastricht, The Netherlands. 11. Department of Pathology, Erasmus University Medical Center, Erasmus University Rotterdam, The Netherlands. 12. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands. 13. Department of Pathology, Amphia Hospital, Breda, The Netherlands. 14. Department of Clinical Epidemiology and Biostatistics, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands. 15. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Pathology, Isala Hospitals, Zwolle, The Netherlands. 16. Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, The Netherlands; Department of Pathology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, The Netherlands. Electronic address: t.radonic@amsterdamumc.nl.
Abstract
OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring. MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness. RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009). CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.
OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring. MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness. RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009). CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.
Authors: D Gompelmann; K Sinn; J Brugger; D Bernitzky; B Mosleh; H Prosch; S Geleff; A Blessing; A Tiefenbacher; K Hoetzenecker; M Idzko; M A Hoda Journal: J Cancer Res Clin Oncol Date: 2022-06-16 Impact factor: 4.553