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.

Van Bockstal, Mieke R, François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer M, Sinke, Renata, Stanciu-Pop, Claudia M, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline and Galant, Christine (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. ISSN 1530-0285. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: http://www.nature.com/modpathol/

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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
WN Medical imaging. Radiology
WO Surgery
Divisions: Clinical Support > Pathology
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Depositing User: Jamie Edgar
Date Deposited: 14 Jul 2021 11:29
Last Modified: 14 Jul 2021 11:29
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4477

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