Standardized assessment of tumor-infiltrating lymphocytes in breast cancer

an evaluation of inter-observer agreement between pathologists

Trine Tramm, Tina Di Caterino, Anne-Marie B Jylling, Giedrius Lelkaitis, Anne-Vibeke Lænkholm, Péter Ragó, Tomasz P Tabor, Maj-Lis M Talman, Emmanouela Vouza, Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG)

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

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Resumé

INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.

MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.

RESULTS: Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%.

DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

OriginalsprogEngelsk
TidsskriftActa Radiologica Open
Vol/bind57
Udgave nummer1
Sider (fra-til)90-94
ISSN2058-4601
DOI
StatusUdgivet - jan. 2018
Begivenhed16th Acta Oncologica Symposium - Aarhus , Danmark
Varighed: 18. jan. 201819. jan. 2018

Konference

Konference16th Acta Oncologica Symposium
LandDanmark
ByAarhus
Periode18/01/201819/01/2018

Fingeraftryk

Tumor-Infiltrating Lymphocytes
Pathologists
Hematoxylin
Eosine Yellowish-(YS)

Citer dette

Tramm, T., Di Caterino, T., Jylling, A-M. B., Lelkaitis, G., Lænkholm, A-V., Ragó, P., ... Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG) (2018). Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists. Acta Radiologica Open, 57(1), 90-94. https://doi.org/10.1080/0284186X.2017.1403040
Tramm, Trine ; Di Caterino, Tina ; Jylling, Anne-Marie B ; Lelkaitis, Giedrius ; Lænkholm, Anne-Vibeke ; Ragó, Péter ; Tabor, Tomasz P ; Talman, Maj-Lis M ; Vouza, Emmanouela ; Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG). / Standardized assessment of tumor-infiltrating lymphocytes in breast cancer : an evaluation of inter-observer agreement between pathologists. I: Acta Radiologica Open. 2018 ; Bind 57, Nr. 1. s. 90-94.
@inproceedings{25e50eb0b94543f49d993f7ff8060317,
title = "Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists",
abstract = "INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.RESULTS: Evaluation of TILs led to an ICC of 0.71 (95{\%} CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60{\%}.DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.",
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author = "Trine Tramm and {Di Caterino}, Tina and Jylling, {Anne-Marie B} and Giedrius Lelkaitis and Anne-Vibeke L{\ae}nkholm and P{\'e}ter Rag{\'o} and Tabor, {Tomasz P} and Talman, {Maj-Lis M} and Emmanouela Vouza and {Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG)}",
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pages = "90--94",
journal = "Acta Radiologica Open",
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Tramm, T, Di Caterino, T, Jylling, A-MB, Lelkaitis, G, Lænkholm, A-V, Ragó, P, Tabor, TP, Talman, M-LM, Vouza, E & Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG) 2018, 'Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists', Acta Radiologica Open, bind 57, nr. 1, s. 90-94. https://doi.org/10.1080/0284186X.2017.1403040

Standardized assessment of tumor-infiltrating lymphocytes in breast cancer : an evaluation of inter-observer agreement between pathologists. / Tramm, Trine; Di Caterino, Tina; Jylling, Anne-Marie B; Lelkaitis, Giedrius; Lænkholm, Anne-Vibeke; Ragó, Péter; Tabor, Tomasz P; Talman, Maj-Lis M; Vouza, Emmanouela; Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG).

I: Acta Radiologica Open, Bind 57, Nr. 1, 01.2018, s. 90-94.

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

TY - GEN

T1 - Standardized assessment of tumor-infiltrating lymphocytes in breast cancer

T2 - an evaluation of inter-observer agreement between pathologists

AU - Tramm, Trine

AU - Di Caterino, Tina

AU - Jylling, Anne-Marie B

AU - Lelkaitis, Giedrius

AU - Lænkholm, Anne-Vibeke

AU - Ragó, Péter

AU - Tabor, Tomasz P

AU - Talman, Maj-Lis M

AU - Vouza, Emmanouela

AU - Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG)

PY - 2018/1

Y1 - 2018/1

N2 - INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.RESULTS: Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%.DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

AB - INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.RESULTS: Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%.DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

KW - Breast Neoplasms/immunology

KW - Carcinoma, Ductal, Breast/immunology

KW - Carcinoma, Lobular/immunology

KW - Female

KW - Humans

KW - Lymphocytes, Tumor-Infiltrating/pathology

KW - Pathology, Clinical/standards

KW - Reproducibility of Results

KW - Staining and Labeling

U2 - 10.1080/0284186X.2017.1403040

DO - 10.1080/0284186X.2017.1403040

M3 - Conference article

VL - 57

SP - 90

EP - 94

JO - Acta Radiologica Open

JF - Acta Radiologica Open

SN - 2058-4601

IS - 1

ER -