Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer.
Kos Z., Roblin E., Kim RS., Michiels S., Gallas BD., Chen W., van de Vijver KK., Goel S., Adams S., Demaria S., Viale G., Nielsen TO., Badve SS., Symmans WF., Sotiriou C., Rimm DL., Hewitt S., Denkert C., Loibl S., Luen SJ., Bartlett JMS., Savas P., Pruneri G., Dillon DA., Cheang MCU., Tutt A., Hall JA., Kok M., Horlings HM., Madabhushi A., van der Laak J., Ciompi F., Laenkholm A-V., Bellolio E., Gruosso T., Fox SB., Araya JC., Floris G., Hudeček J., Voorwerk L., Beck AH., Kerner J., Larsimont D., Declercq S., Van den Eynden G., Pusztai L., Ehinger A., Yang W., AbdulJabbar K., Yuan Y., Singh R., Hiley C., Bakir MA., Lazar AJ., Naber S., Wienert S., Castillo M., Curigliano G., Dieci M-V., André F., Swanton C., Reis-Filho J., Sparano J., Balslev E., Chen I-C., Stovgaard EIS., Pogue-Geile K., Blenman KRM., Penault-Llorca F., Schnitt S., Lakhani SR., Vincent-Salomon A., Rojo F., Braybrooke JP., Hanna MG., Soler-Monsó MT., Bethmann D., Castaneda CA., Willard-Gallo K., Sharma A., Lien H-C., Fineberg S., Thagaard J., Comerma L., Gonzalez-Ericsson P., Brogi E., Loi S., Saltz J., Klaushen F., Cooper L., Amgad M., Moore DA., Salgado R., International Immuno-Oncology Biomarker Working Group None.
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 .