Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

被引：134

作者：

Kos, Zuzana ^{[1
]}

Roblin, Elvire ^{[2
,3
]}

Kim, Rim S. ^{[4
]}

Michiels, Stefan ^{[2
,3
]}

Gallas, Brandon D. ^{[5
,6
,7
]}

Chen, Weijie ^{[5
,6
,7
]}

van de Vijver, Koen K. ^{[8
,9
]}

Goel, Shom ^{[10
,11
]}

Adams, Sylvia ^{[12
]}

Demaria, Sandra ^{[13
,14
]}

Viale, Giuseppe ^{[15
]}

Nielsen, Torsten O. ^{[16
]}

Badve, Sunil S. ^{[17
]}

Symmans, W. Fraser ^{[18
]}

Sotiriou, Christos ^{[19
]}

Rimm, David L. ^{[20
]}

Hewitt, Stephen ^{[21
]}

Denkert, Carsten ^{[22
,23
]}

Loibl, Sibylle ^{[24
]}

Luen, Stephen J. ^{[11
,25
]}

Bartlett, John M. S. ^{[26
,27
]}

Savas, Peter ^{[11
,25
]}

Pruneri, Giancarlo ^{[28
,29
]}

Dillon, Deborah A. ^{[30
,31
]}

Cheang, Maggie Chon U. ^{[32
]}

Tutt, Andrew ^{[31
,33
]}

Hall, Jacqueline A. ^{[34
]}

Kok, Marleen ^{[35
,36
]}

Horlings, Hugo M. ^{[8
,37
]}

Madabhushi, Anant ^{[38
,39
]}

van der Laak, Jeroen ^{[40
]}

Ciompi, Francesco ^{[40
]}

Laenkholm, Anne-Vibeke ^{[41
]}

Bellolio, Enrique ^{[42
]}

Gruosso, Tina ^{[43
]}

Fox, Stephen B. ^{[10
,44
]}

Araya, Juan Carlos ^{[45
]}

Floris, Giuseppe ^{[46
,47
]}

Hudecek, Jan ^{[48
]}

Voorwerk, Leonie ^{[49
]}

Beck, Andrew H. ^{[50
]}

Kerner, Jen ^{[50
]}

Larsimont, Denis ^{[51
]}

Declercq, Sabine ^{[52
]}

Van den Eynden, Gert ^{[52
]}

Pusztai, Lajos ^{[53
]}

Ehinger, Anna ^{[54
]}

Yang, Wentao ^{[55
]}

AbdulJabbar, Khalid ^{[56
]}

Yuan, Yinyin ^{[56
]}

机构：

[1] BC Canc Vancouver, Dept Pathol, Vancouver, BC, Canada

[2] Univ Paris Saclay, Gustave Roussy, Dept Biostat & Epidemiol, Villejuif, France

[3] Univ Paris Saclay, Oncostat U1018, INSERM, Labeled Ligue Canc, Villejuif, France

[4] Natl Surg Adjuvant Breast & Bowel Project NSABP N, Pittsburgh, PA USA

[5] US FDA, Div Imaging Diagnost & Software Reliabil DIDSR, Silver Spring, MD USA

[6] US FDA, Off Sci & Engn Labs OSEL, Silver Spring, MD USA

[7] US FDA, Ctr Devices & Radiol Hlth CDRH, Silver Spring, MD USA

[8] Univ Hosp Antwerp, Dept Pathol, Antwerp, Belgium

[9] Ghent Univ Hosp, Canc Res Inst Ghent CRIG, Dept Pathol, Ghent, Belgium

[10] Sir Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[11] Univ Melbourne, Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[12] NYU, Sch Med, Perlmutter Canc Ctr, New York, NY USA

[13] Weill Cornell Med, Dept Radiat Oncol, New York, NY USA

[14] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY USA

[15] Univ Milan, Ist Europeo Oncol, Dept Pathol, Milan, Italy

[16] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[17] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA

[18] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[19] Univ Libre Bruxelles, Inst Jules Bordet, Dept Med Oncol, Brussels, Belgium

[20] Yale Sch Med, Dept Pathol, New Haven, CT USA

[21] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA

[22] Univ Klinikum Giessen & Marburg GmbH, Inst Pathol, Standort Marburg, Marburg, Germany

[23] Philipps Univ Marburg, Marburg, Germany

[24] German Breast Grp, Neu Isenburg, Germany

[25] Univ Melbourne, Peter MacCallum Canc Ctr, Div Res & Canc Med, Melbourne, Vic, Australia

[26] Ontario Inst Canc Res, Toronto, ON, Canada

[27] Univ Edinburgh, Canc Res Ctr, Edinburgh, Midlothian, Scotland

[28] Fdn Inst Nazl Tumori, IRCCS, Dept Pathol, Milan, Italy

[29] Univ Milan, Sch Med, Milan, Italy

[30] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[31] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA

[32] Inst Canc Res, Clin Trials & Stat Unit, Surrey, England

[33] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London, England

[34] Vivactiv Ltd, Bellingdon, Bucks, England

[35] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands

[36] Netherlands Canc Inst, Div Tumor Biol & Immunol, Amsterdam, Netherlands

[37] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands

[38] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA

[39] Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH USA

[40] Radboud Univ Nijmegen, Med Ctr, Computat Pathol Grp, Dept Pathol, Nijmegen, Netherlands

[41] Zealand Univ Hosp, Dept Surg Pathol, Koge, Denmark

[42] Univ La Frontera, Dept Anat Patol, Temuco, Chile

[43] Forbius, Montreal, PQ, Canada

[44] Peter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic, Australia

[45] Univ La Frontera, Dept Pathol, Temuco, Chile

[46] KU Leuven Univ Leuven, Dept Imaging & Pathol, Lab Translat Cell & Tissue Res, Leuven, Belgium

[47] KU Leuven Univ Hosp Leuven, Dept Pathol, Leuven, Belgium

[48] Netherlands Canc Inst, Dept Res IT, Amsterdam, Netherlands

[49] Netherlands Canc Inst, Div Tumor Biol & Immunol, Amsterdam, Netherlands

[50] PathAI Inc, Boston, MA USA

来源：

NPJ BREAST CANCER | 2020年 / 6卷 / 01期

基金：

英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会; 欧洲研究理事会; 欧盟地平线“2020”;

关键词：

PROGNOSTIC VALUE; CHEMOTHERAPY; IMMUNITY; THERAPY; SYSTEM;

D O I：

10.1038/s41523-020-0156-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

引用

页数：16

共 47 条

[1] Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].

Adams, Sylvia ;

Gray, Robert J. ;

Demaria, Sandra ;

Goldstein, Lori ;

Perez, Edith A. ;

Shulman, Lawrence N. ;

Martino, Silvana ;

Wang, Molin ;

Jones, Vicky E. ;

Saphner, Thomas J. ;

Wolff, Antonio C. ;

Wood, William C. ;

Davidson, Nancy E. ;

Sledge, George W. ;

Sparano, Joseph A. ;

Badve, Sunil S. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+

[2] Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group [J].

Amgad, Mohamed ;

Stovgaard, Elisabeth Specht ;

Balslev, Eva ;

Thagaard, Jeppe ;

Chen, Weijie ;

Dudgeon, Sarah ;

Sharma, Ashish ;

Kerner, Jennifer K. ;

Denkert, Carsten ;

Yuan, Yinyin ;

AbdulJabbar, Khalid ;

Wienert, Stephan ;

Savas, Peter ;

Voorwerk, Leonie ;

Beck, Andrew H. ;

Madabhushi, Anant ;

Hartman, Johan ;

Sebastian, Manu M. ;

Horlings, Hugo M. ;

Hudecek, Jan ;

Ciompi, Francesco ;

Moore, David A. ;

Singh, Rajendra ;

Roblin, Elvire ;

Balancin, Marcelo Luiz ;

Mathieu, Marie-Christine ;

Lennerz, Jochen K. ;

Kirtani, Pawan ;

Chen, I-Chun ;

Braybrooke, Jeremy P. ;

Pruneri, Giancarlo ;

Demaria, Sandra ;

Adams, Sylvia ;

Schnitt, Stuart J. ;

Lakhani, Sunil R. ;

Rojo, Federico ;

Comerma, Laura ;

Badve, Sunil S. ;

Khojasteh, Mehrnoush ;

Symmans, W. Fraser ;

Sotiriou, Christos ;

Gonzalez-Ericsson, Paula ;

Pogue-Geile, Katherine L. ;

Kim, Rim S. ;

Rimm, David L. ;

Viale, Giuseppe ;

Hewitt, Stephen M. ;

Bartlett, John M. S. ;

Penault-Llorca, Frederique ;

Goel, Shom .

NPJ BREAST CANCER, 2020, 6 (01)

[3] PD-1 and PD-L1 antibodies in cancer: current status and future directions [J].

Balar, Arjun Vasant ;

Weber, Jeffrey S. .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2017, 66 (05) :551-564

[4]

Bera Kaustav, 2018, Am Soc Clin Oncol Educ Book, V38, P1008, DOI 10.1200/EDBK_199747

[5] An update on the validation of whole slide imaging systems following FDA approval of a system for a routine pathology diagnostic service in the United States [J].

Boyce, B. F. .

BIOTECHNIC & HISTOCHEMISTRY, 2017, 92 (06) :381-389

[6] Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019 [J].

Burstein, H. J. ;

Curigliano, G. ;

Loibl, S. ;

Dubsky, P. ;

Gnant, M. ;

Poortmans, P. ;

Colleoni, M. ;

Denkert, C. ;

Piccart-Gebhart, M. ;

Regan, M. ;

Senn, H. -J. ;

Winer, E. P. ;

Thurlimann, B. .

ANNALS OF ONCOLOGY, 2019, 30 (10) :1541-1557

[7] Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: a retrospective analysis [J].

Cha, Yoon Jin ;

Ahn, Sung Gwe ;

Bae, Soong June ;

Yoon, Chang Ik ;

Seo, Jayeong ;

Jung, Woo Hee ;

Son, Eun Ju ;

Jeong, Joon .

BREAST CANCER RESEARCH AND TREATMENT, 2018, 171 (02) :295-302

[8] Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non-Small Cell Lung Cancer [J].

Corredor, German ;

Wang, Xiangxue ;

Zhou, Yu ;

Lu, Cheng ;

Fu, Pingfu ;

Syrigos, Konstantinos ;

Rimm, David L. ;

Yang, Michael ;

Romero, Eduardo ;

Schalper, Kurt A. ;

Velcheti, Vamsidhar ;

Madabhushi, Anant .

CLINICAL CANCER RESEARCH, 2019, 25 (05) :1526-1534

[9] Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy [J].

Denkert, Carsten ;

von Minckwitz, Gunter ;

Darb-Esfahani, Silvia ;

Lederer, Bianca ;

Heppner, Barbara I. ;

Weber, Karsten E. ;

Budczies, Jan ;

Huober, Jens ;

Klauschen, Frederick ;

Furlanetto, Jenny ;

Schmitt, Wolfgang D. ;

Blohmer, Jens-Uwe ;

Karn, Thomas ;

Pfitzner, Berit M. ;

Kuemmel, Sherko ;

Engels, Knut ;

Schneeweiss, Andreas ;

Hartmann, Arndt ;

Noske, Aurelia ;

Fasching, Peter A. ;

Jackisch, Christian ;

van Mackelenbergh, Marion ;

Sinn, Peter ;

Schem, Christian ;

Hanusch, Claus ;

Untch, Michael ;

Loibl, Sibylle .

LANCET ONCOLOGY, 2018, 19 (01) :40-50

[10] Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group [J].

Denkert, Carsten ;

Wienert, Stephan ;

Poterie, Audrey ;

Loibl, Sibylle ;

Budczies, Jan ;

Badve, Sunil ;

Bago-Horvath, Zsuzsanna ;

Bane, Anita ;

Bedri, Shahinaz ;

Brock, Jane ;

Chmielik, Ewa ;

Christgen, Matthias ;

Colpaert, Cecile ;

Demaria, Sandra ;

Van den Eynden, Gert ;

Floris, Giuseppe ;

Fox, Stephen B. ;

Gao, Dongxia ;

Heppner, Barbara Ingold ;

Kim, S. Rim ;

Kos, Zuzana ;

Kreipe, Hans H. ;

Lakhani, Sunil R. ;

Penault-Llorca, Frederique ;

Pruneri, Giancarlo ;

Radosevic-Robin, Nina ;

Rimm, David L. ;

Schnitt, Stuart J. ;

Sinn, Bruno V. ;

Sinn, Peter ;

Sirtaine, Nicolas ;

O'Toole, Sandra A. ;

Viale, Giuseppe ;

Van de Vijver, Koen ;

de Wind, Roland ;

von Minckwitz, Gunter ;

Klauschen, Frederick ;

Untch, Michael ;

Fasching, Peter A. ;

Reimer, Toralf ;

Willard-Gallo, Karen ;

Michiels, Stefan ;

Loi, Sherene ;

Salgado, Roberto .

MODERN PATHOLOGY, 2016, 29 (10) :1155-1164

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