Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Mohamed Amgad; Elisabeth Specht Stovgaard; Eva Balslev; Jeppe Thagaard; Weijie Chen; Sarah Dudgeon; Ashish Sharma; Jennifer K. Kerner; Carsten Denkert; Yinyin Yuan; Khalid AbdulJabbar; Stephan Wienert; Peter Savas; Leonie Voorwerk; Andrew H. Beck; Anant Madabhushi; Johan Hartman; Manu M. Sebastian; Hugo M. Horlings; Jan Hudecek; Francesco Ciompi; David A. Moore; Rajendra Singh; Elvire Roblin; Marcelo Luiz Balancin; Marie-Christine Mathieu; Jochen K. Lennerz; Pawan Kirtani; I-Chun Chen; Jeremy P. Braybrooke; Giancarlo Pruneri; Sandra Demaria; Sylvia Adams; Stuart J. Schnitt; Sunil R. Lakhani; Federico Rojo; Laura Comerma; Sunil S. Badve; Mehrnoush Khojasteh; W. Fraser Symmans; Christos Sotiriou; Paula Gonzalez-Ericsson; Katherine L. Pogue-Geile; Rim S. Kim; David L. Rimm; Giuseppe Viale; Stephen M. Hewitt; John M. S. Bartlett; Frederique Penault-Llorca; Loes F. S. Kooreman; International Immuno-Oncology Biomarker Working Group; Lee A. D. Cooper; Roberto Salgado

doi:10.1038/s41523-020-0154-2

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Mohamed Amgad, Elisabeth Specht Stovgaard, Eva Balslev, Jeppe Thagaard, Weijie Chen, Sarah Dudgeon, Ashish Sharma, Jennifer K. Kerner, Carsten Denkert, Yinyin Yuan, Khalid AbdulJabbar, Stephan Wienert, Peter Savas, Leonie Voorwerk, Andrew H. Beck, Anant Madabhushi, Johan Hartman, Manu M. Sebastian, Hugo M. Horlings, Jan HudecekFrancesco Ciompi, David A. Moore, Rajendra Singh, Elvire Roblin, Marcelo Luiz Balancin, Marie-Christine Mathieu, Jochen K. Lennerz, Pawan Kirtani, I-Chun Chen, Jeremy P. Braybrooke, Giancarlo Pruneri, Sandra Demaria, Sylvia Adams, Stuart J. Schnitt, Sunil R. Lakhani, Federico Rojo, Laura Comerma, Sunil S. Badve, Mehrnoush Khojasteh, W. Fraser Symmans, Christos Sotiriou, Paula Gonzalez-Ericsson, Katherine L. Pogue-Geile, Rim S. Kim, David L. Rimm, Giuseppe Viale, Stephen M. Hewitt, John M. S. Bartlett, Frederique Penault-Llorca, Loes F. S. Kooreman, International Immuno-Oncology Biomarker Working Group, Lee A. D. Cooper^*, Roberto Salgado^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Original language	English
Article number	16
Number of pages	13
Journal	npj Breast Cancer
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41523-020-0154-2
Publication status	Published - 12 May 2020

Keywords

BREAST-CANCER
STANDARDIZED METHOD
DIGITAL PATHOLOGY
QUALITY-CONTROL
IMAGE-ANALYSIS
SOLID TUMORS
T-CELLS
IN-SITU
TILS
CLASSIFICATION

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Cite this

Amgad, M., Stovgaard, E. S., Balslev, E., Thagaard, J., Chen, W., Dudgeon, S., Sharma, A., Kerner, J. K., Denkert, C., Yuan, Y., AbdulJabbar, K., Wienert, S., Savas, P., Voorwerk, L., Beck, A. H., Madabhushi, A., Hartman, J., Sebastian, M. M., Horlings, H. M., ... Salgado, R. (2020). Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group. npj Breast Cancer, 6(1), Article 16. https://doi.org/10.1038/s41523-020-0154-2

@article{8b2b022fb2ef4b708351ef2ea2336298,

title = "Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group",

abstract = "Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.",

keywords = "BREAST-CANCER, STANDARDIZED METHOD, DIGITAL PATHOLOGY, QUALITY-CONTROL, IMAGE-ANALYSIS, SOLID TUMORS, T-CELLS, IN-SITU, TILS, CLASSIFICATION",

author = "Mohamed Amgad and Stovgaard, {Elisabeth Specht} and Eva Balslev and Jeppe Thagaard and Weijie Chen and Sarah Dudgeon and Ashish Sharma and Kerner, {Jennifer K.} and Carsten Denkert and Yinyin Yuan and Khalid AbdulJabbar and Stephan Wienert and Peter Savas and Leonie Voorwerk and Beck, {Andrew H.} and Anant Madabhushi and Johan Hartman and Sebastian, {Manu M.} and Horlings, {Hugo M.} and Jan Hudecek and Francesco Ciompi and Moore, {David A.} and Rajendra Singh and Elvire Roblin and Balancin, {Marcelo Luiz} and Marie-Christine Mathieu and Lennerz, {Jochen K.} and Pawan Kirtani and I-Chun Chen and Braybrooke, {Jeremy P.} and Giancarlo Pruneri and Sandra Demaria and Sylvia Adams and Schnitt, {Stuart J.} and Lakhani, {Sunil R.} and Federico Rojo and Laura Comerma and Badve, {Sunil S.} and Mehrnoush Khojasteh and Symmans, {W. Fraser} and Christos Sotiriou and Paula Gonzalez-Ericsson and Pogue-Geile, {Katherine L.} and Kim, {Rim S.} and Rimm, {David L.} and Giuseppe Viale and Hewitt, {Stephen M.} and Bartlett, {John M. S.} and Frederique Penault-Llorca and Kooreman, {Loes F. S.} and {International Immuno-Oncology Biomarker Working Group} and Cooper, {Lee A. D.} and Roberto Salgado",

note = "Funding Information: L.A.D.C. is supported in part by the National Institutes of Health National Cancer Institute (NCI) grants U01CA220401 and U24CA19436201. R.S. is supported by the Breast Cancer Research Foundation (BCRF), grant No. 17-194. J.S. is supported in part by NCI grants UG3CA225021 and U24CA215109. A.M. is supported in part by NCI grants 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01, National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University. S.G. is supported by Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance. T.O.N. receives funding support from the Canadian Cancer Society. M.M.S. is supported by P30 CA16672 DHHS/NCI Cancer Center Support Grant (CCSG). A.S. is supported in part by NCI grants 1UG3CA225021, 1U24CA215109, and Leidos 14 × 138. This work includes contributions from, and was reviewed by, individuals at the F.D.A. This work has been approved for publication by the agency, but it does not necessarily reflect official agency policy. Certain commercial materials and equipment are identified in order to adequately specify experimental procedures. In no case does such identification imply recommendation or endorsement by the FDA, nor does it imply that the items identified are necessarily the best available for the purpose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs, the Department of Defense, the United States Government, or other governments or entities. The following is a list of current members of the International Immuno-Oncology Working Group (TILs Working Group). Members contributed to the manuscript through discussions, including at the yearly TIL-WG meeting, and have reviewed and provided input on the manuscript. The authors alone are responsible for the views expressed in the work of the TILs Working Group and they do not necessarily represent the decisions, policy or views of their employer. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = may,

day = "12",

doi = "10.1038/s41523-020-0154-2",

language = "English",

volume = "6",

journal = "npj Breast Cancer",

issn = "2374-4677",

publisher = "Nature Publishing Group",

number = "1",

}

Amgad, M, Stovgaard, ES, Balslev, E, Thagaard, J, Chen, W, Dudgeon, S, Sharma, A, Kerner, JK, Denkert, C, Yuan, Y, AbdulJabbar, K, Wienert, S, Savas, P, Voorwerk, L, Beck, AH, Madabhushi, A, Hartman, J, Sebastian, MM, Horlings, HM, Hudecek, J, Ciompi, F, Moore, DA, Singh, R, Roblin, E, Balancin, ML, Mathieu, M-C, Lennerz, JK, Kirtani, P, Chen, I-C, Braybrooke, JP, Pruneri, G, Demaria, S, Adams, S, Schnitt, SJ, Lakhani, SR, Rojo, F, Comerma, L, Badve, SS, Khojasteh, M, Symmans, WF, Sotiriou, C, Gonzalez-Ericsson, P, Pogue-Geile, KL, Kim, RS, Rimm, DL, Viale, G, Hewitt, SM, Bartlett, JMS, Penault-Llorca, F, Kooreman, LFS, International Immuno-Oncology Biomarker Working Group, Cooper, LAD & Salgado, R 2020, 'Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group', npj Breast Cancer, vol. 6, no. 1, 16. https://doi.org/10.1038/s41523-020-0154-2

TY - JOUR

T1 - Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

AU - Amgad, Mohamed

AU - Stovgaard, Elisabeth Specht

AU - Balslev, Eva

AU - Thagaard, Jeppe

AU - Chen, Weijie

AU - Dudgeon, Sarah

AU - Sharma, Ashish

AU - Kerner, Jennifer K.

AU - Denkert, Carsten

AU - Yuan, Yinyin

AU - AbdulJabbar, Khalid

AU - Wienert, Stephan

AU - Savas, Peter

AU - Voorwerk, Leonie

AU - Beck, Andrew H.

AU - Madabhushi, Anant

AU - Hartman, Johan

AU - Sebastian, Manu M.

AU - Horlings, Hugo M.

AU - Hudecek, Jan

AU - Ciompi, Francesco

AU - Moore, David A.

AU - Singh, Rajendra

AU - Roblin, Elvire

AU - Balancin, Marcelo Luiz

AU - Mathieu, Marie-Christine

AU - Lennerz, Jochen K.

AU - Kirtani, Pawan

AU - Chen, I-Chun

AU - Braybrooke, Jeremy P.

AU - Pruneri, Giancarlo

AU - Demaria, Sandra

AU - Adams, Sylvia

AU - Schnitt, Stuart J.

AU - Lakhani, Sunil R.

AU - Rojo, Federico

AU - Comerma, Laura

AU - Badve, Sunil S.

AU - Khojasteh, Mehrnoush

AU - Symmans, W. Fraser

AU - Sotiriou, Christos

AU - Gonzalez-Ericsson, Paula

AU - Pogue-Geile, Katherine L.

AU - Kim, Rim S.

AU - Rimm, David L.

AU - Viale, Giuseppe

AU - Hewitt, Stephen M.

AU - Bartlett, John M. S.

AU - Penault-Llorca, Frederique

AU - Kooreman, Loes F. S.

AU - International Immuno-Oncology Biomarker Working Group

AU - Cooper, Lee A. D.

AU - Salgado, Roberto

N1 - Funding Information: L.A.D.C. is supported in part by the National Institutes of Health National Cancer Institute (NCI) grants U01CA220401 and U24CA19436201. R.S. is supported by the Breast Cancer Research Foundation (BCRF), grant No. 17-194. J.S. is supported in part by NCI grants UG3CA225021 and U24CA215109. A.M. is supported in part by NCI grants 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01, National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University. S.G. is supported by Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance. T.O.N. receives funding support from the Canadian Cancer Society. M.M.S. is supported by P30 CA16672 DHHS/NCI Cancer Center Support Grant (CCSG). A.S. is supported in part by NCI grants 1UG3CA225021, 1U24CA215109, and Leidos 14 × 138. This work includes contributions from, and was reviewed by, individuals at the F.D.A. This work has been approved for publication by the agency, but it does not necessarily reflect official agency policy. Certain commercial materials and equipment are identified in order to adequately specify experimental procedures. In no case does such identification imply recommendation or endorsement by the FDA, nor does it imply that the items identified are necessarily the best available for the purpose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs, the Department of Defense, the United States Government, or other governments or entities. The following is a list of current members of the International Immuno-Oncology Working Group (TILs Working Group). Members contributed to the manuscript through discussions, including at the yearly TIL-WG meeting, and have reviewed and provided input on the manuscript. The authors alone are responsible for the views expressed in the work of the TILs Working Group and they do not necessarily represent the decisions, policy or views of their employer. Publisher Copyright: © 2020, The Author(s).

PY - 2020/5/12

Y1 - 2020/5/12

N2 - Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

AB - Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

KW - BREAST-CANCER

KW - STANDARDIZED METHOD

KW - DIGITAL PATHOLOGY

KW - QUALITY-CONTROL

KW - IMAGE-ANALYSIS

KW - SOLID TUMORS

KW - T-CELLS

KW - IN-SITU

KW - TILS

KW - CLASSIFICATION

U2 - 10.1038/s41523-020-0154-2

DO - 10.1038/s41523-020-0154-2

M3 - (Systematic) Review article

C2 - 32411818

SN - 2374-4677

VL - 6

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 16

ER -