The impact of a pathologist’s personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

Butter, Rogier; Hondelink, Liesbeth M.; Elswijk, Lisette van; Blaauwgeers, J. L. G.; Bloemena, Elisabeth; Britstra, Rieneke; Bulkmans, Nicole W.J.; Gullik, Anna Lena van; Monkhorst, Kim; Rooij, Mathilda de; Slavujevic-Letic, Ivana; Speel, Ernst-Jan; Thunnissen, Erik; Thüsen, Jan von der; Timens, Wim; Vijver, M. van de; Yick, David C Y; Zwinderman, Aeilko H.; Cohen, Daniëlle; Hart, Nils ’t; Radonic, Teodora

doi:10.1016/j.lungcan.2022.03.002

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…It must be noted, that our study in comparison to the other study reflects the real-life situation. The demonstration of a statistically significant correlation in this study is even more significant because it is known that interpretation of PD-L1 expression does have its peculiarities with varying interobserver agreement (Butter et al 2022 ).…”

Section: Discussionsupporting

confidence: 50%

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment

Gompelmann

Sinn

Brugger

et al. 2022

J Cancer Res Clin Oncol

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Purposes Programmed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour. Methods In this retrospective study, PD-L1 expression on tumour cells derived from bronchoscopy brush cytology, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy, transbronchial biopsy (TBB) and computed tomography (CT)-guided transthoracic biopsy was compared to the PD-L1 expression of the corresponding surgical resection in lung cancer patients with regard to neoadjuvant treatment in-between. Results A quantitative comparison between the diagnostic biopsy of the primary tumour with corresponding resected surgical specimens in a total of 113 lung cancer patients (60% male, mean age 65 ± 9 years) revealed a statistically significant correlation of PD-L1 expression on tumour cells (r = 0.58, p< 0.001), for patients without neoadjuvant treatment in-between and for patients who underwent neoadjuvant treatment (both p < 0.001). Using a cut-off value of ≥ 50% PD-L1 TPS for comparing the biopsy samples and resected specimens, the concordance rate was 78% with a Cohen’s Kappa of 0.45. Conclusion A statistically significant concordance for PD-L1 expression on tumour cells between biopsies from primary lung tumour and resected specimen was found, but of uncertain clinical accuracy. The use of a cut-off value of ≥ 50% PD-L1 TPS resulted only in a moderate agreement. Therefore, the interpretation of the PD-L1 determined form biopsy specimens status should only be considered with caution for treatment decisionsQuery.

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Section: Discussionsupporting

confidence: 50%

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment

Gompelmann

Sinn

Brugger

et al. 2022

J Cancer Res Clin Oncol

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“…It also overcomes the common problem of interobserver variability in assessing the positive fraction of IHC stains. 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

Validation of automated positive cell and region detection of immunohistochemically stained laryngeal tumor tissue using digital image analysis

Smits

Swartz

Philippens

et al. 2023

Journal of Pathology Informatics

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“…Panels of IHC markers are used typically as an adjunctive to standard pathological diagnosis ( Painter et al, 2010 ), and help answer questions relevant to a specific clinical scenario. While a pathologist is capable of interpreting histological staining patterns using biological context, and naturally compensating for staining and tissue variability or artifacts to assess relative protein expression levels, they are not as well suited to making quantitative measurements of expression level or cellular percent positivity (e.g., Troncone and Gridelli, 2017 ; Tsutsumi, 2021 ; Butter et al, 2022 ). Conversely, IA is dependent on digitizing and measuring specific image features that relate to biology in question and are therefore very reproducible.…”

Section: 21 Clinical Decision Points—cutoff Valuesmentioning

confidence: 99%

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Locke

Hoyt

2023

Front. Mol. Biosci.

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Immunohistochemistry has long been held as the gold standard for understanding the expression patterns of therapeutically relevant proteins to identify prognostic and predictive biomarkers. Patient selection for targeted therapy in oncology has successfully relied upon standard microscopy-based methodologies, such as single-marker brightfield chromogenic immunohistochemistry. As promising as these results are, the analysis of one protein, with few exceptions, no longer provides enough information to draw effective conclusions about the probability of treatment response. More multifaceted scientific queries have driven the development of high-throughput and high-order technologies to interrogate biomarker expression patterns and spatial interactions between cell phenotypes in the tumor microenvironment. Such multi-parameter data analysis has been historically reserved for technologies that lack the spatial context that is provided by immunohistochemistry. Over the past decade, technical developments in multiplex fluorescence immunohistochemistry and discoveries made with improving image data analysis platforms have highlighted the importance of spatial relationships between certain biomarkers in understanding a patient’s likelihood to respond to, typically, immune checkpoint inhibitors. At the same time, personalized medicine has instigated changes in both clinical trial design and its conduct in a push to make drug development and cancer treatment more efficient, precise, and economical. Precision medicine in immuno-oncology is being steered by data-driven approaches to gain insight into the tumor and its dynamic interaction with the immune system. This is particularly necessary given the rapid growth in the number of trials involving more than one immune checkpoint drug, and/or using those in combination with conventional cancer treatments. As multiplex methods, like immunofluorescence, push the boundaries of immunohistochemistry, it becomes critical to understand the foundation of this technology and how it can be deployed for use as a regulated test to identify the prospect of response from mono- and combination therapies. To that end, this work will focus on: 1) the scientific, clinical, and economic requirements for developing clinical multiplex immunofluorescence assays; 2) the attributes of the Akoya Phenoptics workflow to support predictive tests, including design principles, verification, and validation needs; 3) regulatory, safety and quality considerations; 4) application of multiplex immunohistochemistry through lab-developed-tests and regulated in vitro diagnostic devices.

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The impact of a pathologist’s personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

Cited by 18 publications

References 38 publications

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment

Validation of automated positive cell and region detection of immunohistochemically stained laryngeal tumor tissue using digital image analysis

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

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