Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer

Simple Summary The stromal tumour infiltrating lymphocytes (sTILs) within a tumour are a strong predictor of outcome for patients with triple negative breast cancer (TNBC). However, the assessment of sTILs is subject to variation and needs to be standardized in order for it to be used more widely as...

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Autores: Kilmartin, D, O'Loughlin, M, Andreu, X, Bago-Horvath, Z, Bianchi, S, Chmielik, E, Cserni, G, Figueiredo, P, Floris, G, Foschini, MP, Kovacs, A, Heikkila, P, Kulka, J, Laenkholm, AV, Liepniece-Karele, I, Marchio, C, Provenzano, E, Regitnig, P, Reiner, A, Ryska, A, Sapino, A, Stovgaard, ES, Quinn, C, Zolota, V, Webber, M, Roshan, D, Glynn, SA, Callagy, G
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p2229
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/2229
Access Level:acceso abierto
Palabra clave:TILs
sTILs
triple negative
breast cancer
reproducibility
international immuno-oncology biomarker working group
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network_name_str España
repository_id_str
spelling Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast CancerKilmartin, DO'Loughlin, MAndreu, XBago-Horvath, ZBianchi, SChmielik, ECserni, GFigueiredo, PFloris, GFoschini, MPKovacs, AHeikkila, PKulka, JLaenkholm, AVLiepniece-Karele, IMarchio, CProvenzano, ERegitnig, PReiner, ARyska, ASapino, AStovgaard, ESQuinn, CZolota, VWebber, MRoshan, DGlynn, SACallagy, GTILssTILstriple negativebreast cancerreproducibilityinternational immuno-oncology biomarker working groupSimple Summary The stromal tumour infiltrating lymphocytes (sTILs) within a tumour are a strong predictor of outcome for patients with triple negative breast cancer (TNBC). However, the assessment of sTILs is subject to variation and needs to be standardized in order for it to be used more widely as a biomarker. The aim of this study was to determine the level of consistency that can be achieved when an internet-based scoring aid is used to assist with evaluation of sTILs. Twenty-three breast pathologists across Europe scored sTILs in 49 cases of TNBC taken from a routine diagnostic practice using this aid. The consistency of scoring sTILs was good. However, variation in the distribution of sTILs within the tumour resulted in discordance between pathologists scoring cases, particularly as it caused variability in the selection of regions of the tumour to score. More rigorous training of pathologists is needed for standardization of sTILs assessment, which may potentially be improved using automated approaches. Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539-0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727-0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561-0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546-0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/2229CancersISSN: 20726694reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p22292026-06-21T15:30:37Z
dc.title.none.fl_str_mv Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
title Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
spellingShingle Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
Kilmartin, D
TILs
sTILs
triple negative
breast cancer
reproducibility
international immuno-oncology biomarker working group
title_short Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
title_full Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
title_fullStr Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
title_full_unstemmed Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
title_sort Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer
dc.creator.none.fl_str_mv Kilmartin, D
O'Loughlin, M
Andreu, X
Bago-Horvath, Z
Bianchi, S
Chmielik, E
Cserni, G
Figueiredo, P
Floris, G
Foschini, MP
Kovacs, A
Heikkila, P
Kulka, J
Laenkholm, AV
Liepniece-Karele, I
Marchio, C
Provenzano, E
Regitnig, P
Reiner, A
Ryska, A
Sapino, A
Stovgaard, ES
Quinn, C
Zolota, V
Webber, M
Roshan, D
Glynn, SA
Callagy, G
author Kilmartin, D
author_facet Kilmartin, D
O'Loughlin, M
Andreu, X
Bago-Horvath, Z
Bianchi, S
Chmielik, E
Cserni, G
Figueiredo, P
Floris, G
Foschini, MP
Kovacs, A
Heikkila, P
Kulka, J
Laenkholm, AV
Liepniece-Karele, I
Marchio, C
Provenzano, E
Regitnig, P
Reiner, A
Ryska, A
Sapino, A
Stovgaard, ES
Quinn, C
Zolota, V
Webber, M
Roshan, D
Glynn, SA
Callagy, G
author_role author
author2 O'Loughlin, M
Andreu, X
Bago-Horvath, Z
Bianchi, S
Chmielik, E
Cserni, G
Figueiredo, P
Floris, G
Foschini, MP
Kovacs, A
Heikkila, P
Kulka, J
Laenkholm, AV
Liepniece-Karele, I
Marchio, C
Provenzano, E
Regitnig, P
Reiner, A
Ryska, A
Sapino, A
Stovgaard, ES
Quinn, C
Zolota, V
Webber, M
Roshan, D
Glynn, SA
Callagy, G
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TILs
sTILs
triple negative
breast cancer
reproducibility
international immuno-oncology biomarker working group
topic TILs
sTILs
triple negative
breast cancer
reproducibility
international immuno-oncology biomarker working group
description Simple Summary The stromal tumour infiltrating lymphocytes (sTILs) within a tumour are a strong predictor of outcome for patients with triple negative breast cancer (TNBC). However, the assessment of sTILs is subject to variation and needs to be standardized in order for it to be used more widely as a biomarker. The aim of this study was to determine the level of consistency that can be achieved when an internet-based scoring aid is used to assist with evaluation of sTILs. Twenty-three breast pathologists across Europe scored sTILs in 49 cases of TNBC taken from a routine diagnostic practice using this aid. The consistency of scoring sTILs was good. However, variation in the distribution of sTILs within the tumour resulted in discordance between pathologists scoring cases, particularly as it caused variability in the selection of regions of the tumour to score. More rigorous training of pathologists is needed for standardization of sTILs assessment, which may potentially be improved using automated approaches. Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539-0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727-0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561-0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546-0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://i3pt.portalinvestigacion.com/publicaciones/2229
url https://i3pt.portalinvestigacion.com/publicaciones/2229
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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