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

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Abstract
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.

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MLA
Kos, Zuzana, et al. “Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (STILs) in Breast Cancer.” NPJ BREAST CANCER, vol. 6, 2020.
APA
Kos, Z., Roblin, E., Kim, R. S., Michiels, S., Gallas, B. D., Chen, W., … Salgado, R. (2020). Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. NPJ BREAST CANCER, 6.
Chicago author-date
Kos, Zuzana, Elvire Roblin, Rim S Kim, Stefan Michiels, Brandon D Gallas, Weijie Chen, Koen Van de Vijver, et al. 2020. “Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (STILs) in Breast Cancer.” NPJ BREAST CANCER 6.
Chicago author-date (all authors)
Kos, Zuzana, Elvire Roblin, Rim S Kim, Stefan Michiels, Brandon D Gallas, Weijie Chen, Koen Van de Vijver, Shom Goel, Sylvia Adams, Sandra Demaria, Giuseppe Viale, Torsten O Nielsen, Sunil S Badve, W Fraser Symmans, Christos Sotiriou, David L Rimm, Stephen Hewitt, Carsten Denkert, Sibylle Loibl, Stephen J Luen, John M S Bartlett, Peter Savas, Giancarlo Pruneri, Deborah A Dillon, Maggie Chon U Cheang, Andrew Tutt, Jacqueline A Hall, Marleen Kok, Hugo M Horlings, Anant Madabhushi, Jeroen van der Laak, Francesco Ciompi, Anne-Vibeke Laenkholm, Enrique Bellolio, Tina Gruosso, Stephen B Fox, Juan Carlos Araya, Giuseppe Floris, Jan Hudecek, Leonie Voorwerk, Andrew H Beck, Jen Kerner, Denis Larsimont, Sabine Declercq, Gert Van den Eynden, Lajos Pusztai, Anna Ehinger, Wentao Yang, Khalid AbdulJabbar, Yinyin Yuan, Rajendra Singh, Crispin Hiley, Maise Al Bakir, Alexander J Lazar, Stephen Naber, Stephan Wienert, Miluska Castillo, Giuseppe Curigliano, Maria-Vittoria Dieci, Fabrice Andre, Charles Swanton, Jorge Reis-Filho, Joseph Sparano, Eva Balslev, I-Chun Chen, Elisabeth Ida Specht Stovgaard, Katherine Pogue-Geile, Kim R M Blenman, Frederique Penault-Llorca, Stuart Schnitt, Sunil R Lakhani, Anne Vincent-Salomon, Federico Rojo, Jeremy P Braybrooke, Matthew G Hanna, M Teresa Soler-Monso, Daniel Bethmann, Carlos A Castaneda, Karen Willard-Gallo, Ashish Sharma, Huang-Chun Lien, Susan Fineberg, Jeppe Thagaard, Laura Comerma, Paula Gonzalez-Ericsson, Edi Brogi, Sherene Loi, Joel Saltz, Frederick Klaushen, Lee Cooper, Mohamed Amgad, David A Moore, and Roberto Salgado. 2020. “Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (STILs) in Breast Cancer.” NPJ BREAST CANCER 6.
Vancouver
1.
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, et al. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. NPJ BREAST CANCER. 2020;6.
IEEE
[1]
Z. Kos et al., “Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer,” NPJ BREAST CANCER, vol. 6, 2020.
@article{8662484,
  abstract     = {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.},
  articleno    = {17},
  author       = {Kos, Zuzana and Roblin, Elvire and Kim, Rim S and Michiels, Stefan and Gallas, Brandon D and Chen, Weijie and Van de Vijver, Koen and Goel, Shom and Adams, Sylvia and Demaria, Sandra and Viale, Giuseppe and Nielsen, Torsten O and Badve, Sunil S and Symmans, W Fraser and Sotiriou, Christos and Rimm, David L and Hewitt, Stephen and Denkert, Carsten and Loibl, Sibylle and Luen, Stephen J and Bartlett, John M S and Savas, Peter and Pruneri, Giancarlo and Dillon, Deborah A and Cheang, Maggie Chon U and Tutt, Andrew and Hall, Jacqueline A and Kok, Marleen and Horlings, Hugo M and Madabhushi, Anant and van der Laak, Jeroen and Ciompi, Francesco and Laenkholm, Anne-Vibeke and Bellolio, Enrique and Gruosso, Tina and Fox, Stephen B and Araya, Juan Carlos and Floris, Giuseppe and Hudecek, Jan and Voorwerk, Leonie and Beck, Andrew H and Kerner, Jen and Larsimont, Denis and Declercq, Sabine and Van den Eynden, Gert and Pusztai, Lajos and Ehinger, Anna and Yang, Wentao and AbdulJabbar, Khalid and Yuan, Yinyin and Singh, Rajendra and Hiley, Crispin and Bakir, Maise Al and Lazar, Alexander J and Naber, Stephen and Wienert, Stephan and Castillo, Miluska and Curigliano, Giuseppe and Dieci, Maria-Vittoria and Andre, Fabrice and Swanton, Charles and Reis-Filho, Jorge and Sparano, Joseph and Balslev, Eva and Chen, I-Chun and Stovgaard, Elisabeth Ida Specht and Pogue-Geile, Katherine and Blenman, Kim R M and Penault-Llorca, Frederique and Schnitt, Stuart and Lakhani, Sunil R and Vincent-Salomon, Anne and Rojo, Federico and Braybrooke, Jeremy P and Hanna, Matthew G and Soler-Monso, M Teresa and Bethmann, Daniel and Castaneda, Carlos A and Willard-Gallo, Karen and Sharma, Ashish and Lien, Huang-Chun and Fineberg, Susan and Thagaard, Jeppe and Comerma, Laura and Gonzalez-Ericsson, Paula and Brogi, Edi and Loi, Sherene and Saltz, Joel and Klaushen, Frederick and Cooper, Lee and Amgad, Mohamed and Moore, David A and Salgado, Roberto},
  issn         = {2374-4677},
  journal      = {NPJ BREAST CANCER},
  language     = {eng},
  title        = {Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer},
  url          = {http://dx.doi.org/10.1038/s41523-020-0156-0},
  volume       = {6},
  year         = {2020},
}

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