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Van Bockstal MR, François A, Altinay S, et al. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study. Mod Pathol. 2021;34(12):2130-2140doi: 10.1038/s41379-021-00865-z.
Van Bockstal, M. R., François, A., Altinay, S., Arnould, L., Balkenhol, M., Broeckx, G., Burguès, O., Colpaert, C., Dedeurwaerdere, F., Dessauvagie, B., Duwel, V., Floris, G., Fox, S., Gerosa, C., Hastir, D., Jaffer, S., Kurpershoek, E., Lacroix-Triki, M., Laka, A., Lambein, K., MacGrogan, G. M., Marchiò, C., Martin Martinez, M. D., Nofech-Mozes, S., Peeters, D., Ravarino, A., Reisenbichler, E., Resetkova, E., Sanati, S., Schelfhout, A. M., Schelfhout, V., Shaaban, A., Sinke, R., Stanciu-Pop, C. M., van Deurzen, C. H. M., Van de Vijver, K. K., Van Rompuy, A. S., Vincent-Salomon, A., Wen, H. Y., Wong, S., Bouzin, C., & Galant, C. (2021). Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 34(12), 2130-2140. https://doi.org/10.1038/s41379-021-00865-z
Van Bockstal, Mieke R, et al. "Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study." Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc vol. 34,12 (2021): 2130-2140. doi: https://doi.org/10.1038/s41379-021-00865-z
Van Bockstal MR, François A, Altinay S, Arnould L, Balkenhol M, Broeckx G, Burguès O, Colpaert C, Dedeurwaerdere F, Dessauvagie B, Duwel V, Floris G, Fox S, Gerosa C, Hastir D, Jaffer S, Kurpershoek E, Lacroix-Triki M, Laka A, Lambein K, MacGrogan GM, Marchiò C, Martin Martinez MD, Nofech-Mozes S, Peeters D, Ravarino A, Reisenbichler E, Resetkova E, Sanati S, Schelfhout AM, Schelfhout V, Shaaban A, Sinke R, Stanciu-Pop CM, van Deurzen CHM, Van de Vijver KK, Van Rompuy AS, Vincent-Salomon A, Wen HY, Wong S, Bouzin C, Galant C. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study. Mod Pathol. 2021 Dec;34(12):2130-2140. doi: 10.1038/s41379-021-00865-z. Epub 2021 Jul 03. PMID: 34218258; PMCID: PMC8595512.
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Mod Pathol. 2021 Dec;34(12):2130-2140. doi: 10.1038/s41379-021-00865-z. Epub 2021 Jul 03.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

Mieke R Van Bockstal, Aline François, Serdar Altinay, Laurent Arnould, Maschenka Balkenhol, Glenn Broeckx, Octavio Burguès, Cecile Colpaert, Franceska Dedeurwaerdere, Benjamin Dessauvagie, Valérie Duwel, Giuseppe Floris, Stephen Fox, Clara Gerosa, Delfyne Hastir, Shabnam Jaffer, Eline Kurpershoek, Magali Lacroix-Triki, Andoni Laka, Kathleen Lambein, Gaëtan Marie MacGrogan, Caterina Marchiò, Maria-Dolores Martin Martinez, Sharon Nofech-Mozes, Dieter Peeters, Alberto Ravarino, Emily Reisenbichler, Erika Resetkova, Souzan Sanati, Anne-Marie Schelfhout, Vera Schelfhout, Abeer Shaaban, Renata Sinke, Claudia M Stanciu-Pop, Carolien H M van Deurzen, Koen K Van de Vijver, Anne-Sophie Van Rompuy, Anne Vincent-Salomon, Hannah Y Wen, Serena Wong, Caroline Bouzin, Christine Galant

Affiliations

  1. Department of Pathology, Cliniques universitaires Saint-Luc Bruxelles, Woluwé-Saint-Lambert, Belgium. [email protected].
  2. Department of Pathology, Cliniques universitaires Saint-Luc Bruxelles, Woluwé-Saint-Lambert, Belgium.
  3. Department of Pathology, University of Health Sciences, Bakirköy Dr. Sadi Konuk Health Application and Research Center, Istanbul, Turkey.
  4. Département de Biologie et de Pathologie des Tumeurs, Centre George-François Leclerc, Dijon, France.
  5. Department of Pathology, Radboud University Medical Center, HB, Nijmegen, The Netherlands.
  6. Department of Pathology, University Hospital Antwerp, Edegem, Belgium.
  7. Department of Pathology, Hospital Clínico Universitario de Valencia, València, Spain.
  8. Department of Pathology, AZ Turnhout Campus Sint-Jozef, Turnhout, Belgium.
  9. Department of Pathology, AZ Delta, Roeselare, Belgium.
  10. Division of Pathology and Laboratory Medicine, Medical School, The University of Western Australia, Crawley, WA, Australia.
  11. Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, Australia.
  12. Department of pathology, AZ Klina Brasschaat, Brasschaat, Belgium.
  13. Department of Pathology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium.
  14. Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium.
  15. Department of Pathology, Peter MacCallum Cancer Center and the University of Melbourne, Melbourne, VIC, Australia.
  16. Department of Pathology, University of Cagliari, AOU San Giovanni di Dio, Cagliari, Italy.
  17. Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
  18. Department of Pathology, Mount Sinai Hospital and Icahn School of Medicine, New York, NY, USA.
  19. Pathan BV, PM, Rotterdam, The Netherlands.
  20. Department of Pathology, Gustave-Roussy Cancer Campus, Villejuif, France.
  21. Department of Pathology, Clinique Notre-Dame de Grâce (CNDG), Gosselies, Belgium.
  22. Department of Pathology, AZ St Lucas Hospital, Ghent, Belgium.
  23. Surgical Pathology Unit, Department of Pathobiology, Institut Bergonié, Bordeaux, France.
  24. Department of Medical Sciences, University of Turin, Torino, Italy.
  25. Pathology Unit, FPO-IRCCS, Candiolo Cancer Institute, Candiolo, Italy.
  26. Institut de Pathologie et de Génétique, Charleroi, Belgium.
  27. Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
  28. Department of Pathology, AZ St Maarten, Mechelen, Belgium.
  29. Histopathology, Imaging and Quantification Unit, HistoGeneX, Antwerp, Belgium.
  30. Department of Pathology, Yale School of Medicine, Yale New Haven Hospital, New Haven, USA.
  31. The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  32. Department of Pathology and Lab Medicine, Cedars-Sinai Medical Center, Los Angeles, USA.
  33. Department of Pathology, Onze-Lieve-Vrouwziekenhuis Aalst, Aalst, Belgium.
  34. Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham, University of Birmingham, Birmingham, UK.
  35. Department of Pathology, CHU UCL Namur, Site Godinne, Yvoir, Belgium.
  36. Department of Pathology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
  37. Department of Pathology, Ghent University Hospital, Ghent, Belgium.
  38. Pôle de Médicine Diagnostique & Théranostique, INSERM U934, Institut Curie, Paris Cedex 05, France.
  39. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  40. 2IP IREC Imaging Platform, Institute of Clinical and Experimental Research (IREC), Université catholique de Louvain, Brussels, Belgium.
  41. Institute of Clinical and Experimental Research (IREC), Université catholique de Louvain, Brussels, Belgium.

PMID: 34218258 PMCID: PMC8595512 DOI: 10.1038/s41379-021-00865-z

Abstract

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.

© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.

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