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5. PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer

Author

Rugo, Hope S, Loi, Sherene, Adams, Sylvia, Schmid, Peter, Schneeweiss, Andreas, Barrios, Carlos H, Iwata, Hiroji, Diéras, Véronique, Winer, Eric P, Kockx, Mark M, Peeters, Dieter, Chui, Stephen Y, Lin, Jennifer C, Duc, Anh Nguyen, Viale, Giuseppe, Molinero, Luciana, and Emens, Leisha A

Subjects
Cancer, Breast Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Humans, B7-H1 Antigen, Biomarkers, Tumor, Immunohistochemistry, Triple Negative Breast Neoplasms, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundIn the phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced or metastatic triple-negative breast cancer patients who were programmed death-ligand 1 (PD-L1)+ (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry assay. Here we evaluate 2 other PD-L1 assays for analytical concordance with SP142 and patient-associated clinical outcomes.MethodsSamples from 614 patients (68.1% of intention-to-treat population) were centrally evaluated by immunohistochemistry for PD-L1 status on IC (VENTANA SP142, SP263, Dako 22C3) or as a combined positive score (CPS; 22C3).ResultsUsing SP142, SP263, and 22C3 assays, PD-L1 IC ≥1% prevalence was 46.4% (95% confidence interval [CI] = 42.5% to 50.4%), 74.9% (95% CI = 71.5% to 78.3%), and 73.1% (95% CI = 69.6% to 76.6%), respectively; 80.9% were 22C3 CPS ≥1. At IC ≥1% (+), the analytical concordance between SP142 and SP263 and 22C3 was 69.2% and 68.7%, respectively. Almost all SP142+ cases were captured by other assays (double positive), but several SP263+ (29.6%) or 22C3+ (29.0%) cases were SP142- (single positive). A+nP clinical activity vs placebo+nP in SP263+ and 22C3+ patients (progression-free survival [PFS] hazard ratios [HRs] = 0.64 to 0.68; overall survival [OS] HRs = 0.75 to 0.79) was driven by double-positive cases (PFS HRs = 0.60 to 0.61; OS HRs = 0.71 to 0.75) rather than single-positive cases (PFS HRs = 0.68 to 0.81; OS HRs = 0.87 to 0.95). Concordance for harmonized cutoffs for SP263 (IC ≥4%) and 22C3 (CPS ≥10) to SP142 (IC ≥1%) was subpar (approximately 75%).Conclusions22C3 and SP263 assays identified more patients as PD-L1+ (IC ≥1%) than SP142. No inter-assay analytical equivalency was observed. Consistent improved A+nP efficacy was captured by the SP142 PD-L1 IC ≥1% subgroup nested within 22C3 and SP263 PD-L1+ (IC ≥1%) populations.

Published
2021

7. Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer: Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria? An International Interobserver Study

Author

Baez-Navarro, Ximena, van Bockstal, Mieke R., Nawawi, Diënna, Broeckx, Glenn, Colpaert, Cecile, Doebar, Shusma C., Hogenes, Marieke C.H., Koop, Esther, Lambein, Kathleen, Peeters, Dieter J.E., Sinke, Renata H.J.A., Bastiaan van Brakel, Johannes, van der Starre-Gaal, José, van der Vegt, Bert, van de Vijver, Koen, Vreuls, Celien P.H., Vreuls, Willem, Westenend, Pieter J., and van Deurzen, Carolien H.M.

Published
2023
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10. 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

Author

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, 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

Published
2021
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11. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

Author

Dano, Hélène, Altinay, Serdar, Arnould, Laurent, Bletard, Noella, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchió, Caterina, Martinez, Dolores Martin, 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 Maria, Stobbe, Claudia, van Deurzen, Carolien H.M., Van de Vijver, Koen, Van Rompuy, Anne-Sophie, Verschuere, Stephanie, Vincent-Salomon, Anne, Wen, Hannah, Bouzin, Caroline, Galant, Christine, and Van Bockstal, Mieke R.

Published
2020
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12. Training pathologists to assess stromal tumour‐infiltrating lymphocytes in breast cancer synergises efforts in clinical care and scientific research

Author

Ly, Amy, primary, Garcia, Victor, additional, Blenman, Kim R M, additional, Ehinger, Anna, additional, Elfer, Katherine, additional, Hanna, Matthew G, additional, Li, Xiaoxian, additional, Peeters, Dieter J E, additional, Birmingham, Ryan, additional, Dudgeon, Sarah, additional, Gardecki, Emma, additional, Gupta, Rajarsi, additional, Lennerz, Jochen, additional, Pan, Tony, additional, Saltz, Joel, additional, Wharton, Keith A, additional, Ehinger, Daniel, additional, Acs, Balazs, additional, Dequeker, Elisabeth M C, additional, Salgado, Roberto, additional, and Gallas, Brandon D, additional

Published
2024
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14. The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper

Author

Cristofanilli, Massimo, Pierga, Jean-Yves, Reuben, James, Rademaker, Alfred, Davis, Andrew A., Peeters, Dieter J., Fehm, Tanja, Nolé, Franco, Gisbert-Criado, Rafael, Mavroudis, Dimitrios, Grisanti, Salvatore, Giuliano, Mario, Garcia-Saenz, Jose A., Stebbing, Justin, Caldas, Carlos, Gazzaniga, Paola, Manso, Luis, Zamarchi, Rita, de Lascoiti, Angela Fernandez, De Mattos-Arruda, Leticia, Ignatiadis, Michail, Cabel, Luc, van Laere, Steven J., Meier-Stiegen, Franziska, Sandri, Maria-Teresa, Vidal-Martinez, Jose, Politaki, Eleni, Consoli, Francesca, Generali, Daniele, Cappelletti, Maria Rosa, Diaz-Rubio, Eduardo, Krell, Jonathan, Dawson, Sarah-Jane, Raimondi, Cristina, Rutten, Annemie, Janni, Wolfgang, Munzone, Elisabetta, Carañana, Vicente, Agelaki, Sofia, Almici, Camillo, Dirix, Luc, Solomayer, Erich-Franz, Zorzino, Laura, Darrigues, Lauren, Reis-Filho, Jorge S., Gerratana, Lorenzo, Michiels, Stefan, Bidard, François-Clément, and Pantel, Klaus

Published
2019
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15. Supplementary Tables S1-S2 from mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Author

Sieuwerts, Anieta M., primary, Mostert, Bianca, primary, Bolt-de Vries, Joan, primary, Peeters, Dieter, primary, de Jongh, Felix E., primary, Stouthard, Jacqueline M.L., primary, Dirix, Luc Y., primary, van Dam, Peter A., primary, Van Galen, Anne, primary, de Weerd, Vanja, primary, Kraan, Jaco, primary, van der Spoel, Petra, primary, Ramírez-Moreno, Raquel, primary, van Deurzen, Carolien H.M., primary, Smid, Marcel, primary, Yu, Jack X., primary, Jiang, John, primary, Wang, Yixin, primary, Gratama, Jan W., primary, Sleijfer, Stefan, primary, Foekens, John A., primary, and Martens, John W.M., primary

Published
2023
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16. Supplementary Figures S1-S2 from mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Author

Sieuwerts, Anieta M., primary, Mostert, Bianca, primary, Bolt-de Vries, Joan, primary, Peeters, Dieter, primary, de Jongh, Felix E., primary, Stouthard, Jacqueline M.L., primary, Dirix, Luc Y., primary, van Dam, Peter A., primary, Van Galen, Anne, primary, de Weerd, Vanja, primary, Kraan, Jaco, primary, van der Spoel, Petra, primary, Ramírez-Moreno, Raquel, primary, van Deurzen, Carolien H.M., primary, Smid, Marcel, primary, Yu, Jack X., primary, Jiang, John, primary, Wang, Yixin, primary, Gratama, Jan W., primary, Sleijfer, Stefan, primary, Foekens, John A., primary, and Martens, John W.M., primary

Published
2023
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17. Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

Author

Onstenk, Wendy, Sieuwerts, Anieta M., Weekhout, Marleen, Mostert, Bianca, Reijm, Esther A., van Deurzen, Carolien H.M., Bolt-de Vries, Joan B., Peeters, Dieter J., Hamberg, Paul, Seynaeve, Caroline, Jager, Agnes, de Jongh, Felix E., Smid, Marcel, Dirix, Luc Y., Kehrer, Diederik F.S., van Galen, Anne, Ramirez-Moreno, Raquel, Kraan, Jaco, Van, Mai, Gratama, Jan W., Martens, John W.M., Foekens, John A., and Sleijfer, Stefan

Published
2015
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20. Imaging Three-Dimensional Airway Morphology in Congenital Pulmonary Airway Malformation Using Hierarchical Phase-Contrast Tomography.

Author

Verleden, Stijn E., Urban, Theresa, Brunet, Joseph, Wen, Wen, Peeters, Dieter J. E., Lapperre, Therese S., Walsh, Claire, Tafforeau, Paul, Dejea, Hector, Jonigk, Danny, Ackermann, Maximilian, Van Hoorenbeeck, Kim, Lee, Peter D., Jacob, Joseph, and Hendriks, Jeroen M. H.

Subjects
BRONCHIAL arteries, SCANNING electron microscopy, MEDICAL ethics committees, THREE-dimensional imaging, ASYMPTOMATIC patients
Abstract

The article explores congenital pulmonary airway malformation (CPAM) in a 2-year-old boy's right lower lobe, detected during routine pregnancy follow-up. Using hierarchical phase-contrast tomography (HiP-CT), researchers observed cystic changes and abnormal airway development in the lung. The study revealed details of CPAM pathogenesis, including misconnected airways, intact arterial supply, and increased collateral ventilation, providing insights into lung diseases that are difficult to study otherwise. The research was conducted ethically with parental consent and hospital approval. [Extracted from the article]

Published
2024
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21. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data

Author

Bidard, François-Clément, Peeters, Dieter J, Fehm, Tanja, Nolé, Franco, Gisbert-Criado, Rafael, Mavroudis, Dimitrios, Grisanti, Salvatore, Generali, Daniele, Garcia-Saenz, Jose A, Stebbing, Justin, Caldas, Carlos, Gazzaniga, Paola, Manso, Luis, Zamarchi, Rita, de Lascoiti, Angela Fernandez, De Mattos-Arruda, Leticia, Ignatiadis, Michail, Lebofsky, Ronald, van Laere, Steven J, Meier-Stiegen, Franziska, Sandri, Maria-Teresa, Vidal-Martinez, Jose, Politaki, Eleni, Consoli, Francesca, Bottini, Alberto, Diaz-Rubio, Eduardo, Krell, Jonathan, Dawson, Sarah-Jane, Raimondi, Cristina, Rutten, Annemie, Janni, Wolfgang, Munzone, Elisabetta, Carañana, Vicente, Agelaki, Sofia, Almici, Camillo, Dirix, Luc, Solomayer, Erich-Franz, Zorzino, Laura, Johannes, Helene, Reis-Filho, Jorge S, Pantel, Klaus, Pierga, Jean-Yves, and Michiels, Stefan

Published
2014
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22. External Quality Assessment 2.0: The Importance of a Standardized Implementation of TILs for Daily and Trial Practices

Author

Nauwelaers, Inne, primary, Laudus, Nele, additional, Peeters, Dieter, additional, Acs, Balazs, additional, Denkert, Carsten, additional, Michiels, Stefan, additional, Horlings, Hugo, additional, Siziopikou, Kalliopi P., additional, Ely, Scott, additional, Zardavas, Dimitrios, additional, Mustimbo, Roberts, additional, Bartlett, John, additional, Floris, Giuseppe, additional, Hartman, Johan, additional, van Deurzen, Carolien H. M., additional, Ceusters, Dorien, additional, Dequeker, Els, additional, and Salgado, Roberto, additional

Published
2022
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23. Interobserver variation in the assessment of HER2 low expression in breast cancer: can we improve by adjusting criteria? An international interobserver study.

Author

Navarro, Ximena Baez, primary, Bockstal, Mieke Rosalie van, additional, Nawawi, Diënna, additional, Broeckx, Glenn, additional, Colpaert, Cecile, additional, Doebar, Shusma Charlane, additional, Hogenes, Marieke C.H., additional, Koop, Esther, additional, Lambein, Kathleen, additional, Peeters, Dieter J.E., additional, Sinke, Renata, additional, Brakel, Johannes Bastiaan van, additional, Starre-Gaal, José van der, additional, Vegt, Bert Van der, additional, de Vijver, Koen Van, additional, Vreuls, Celien P.H., additional, Vreuls, Willem, additional, Westenend, Pieter, additional, and Deurzen, Carolien van, additional

Published
2022
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24. Pilot study to evaluate tools to collect pathologist annotations for validating machine learning algorithms

Author

Elfer, Katherine, primary, Dudgeon, Sarah, additional, Garcia, Victor, additional, Blenman, Kim, additional, Hytopoulos, Evangelos, additional, Wen, Si, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Werness, Bruce, additional, Sheth, Manasi S., additional, Amgad, Mohamed, additional, Gupta, Rajarsi, additional, Saltz, Joel, additional, Hanna, Matthew G., additional, Ehinger, Anna, additional, Peeters, Dieter, additional, Salgado, Roberto, additional, and Gallas, Brandon D., additional

Published
2022
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25. External Quality Assessment 2.0:The Importance of a Standardized Implementation of TILs for Daily and Trial Practices

Author

Nauwelaers, Inne, Laudus, Nele, Peeters, Dieter, Acs, Balazs, Denkert, Carsten, Michiels, Stefan, Horlings, Hugo, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Mustimbo, Roberts, Bartlett, John, Floris, Giuseppe, Hartman, Johan, van Deurzen, Carolien H.M., Ceusters, Dorien, Dequeker, Els, Salgado, Roberto, Nauwelaers, Inne, Laudus, Nele, Peeters, Dieter, Acs, Balazs, Denkert, Carsten, Michiels, Stefan, Horlings, Hugo, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Mustimbo, Roberts, Bartlett, John, Floris, Giuseppe, Hartman, Johan, van Deurzen, Carolien H.M., Ceusters, Dorien, Dequeker, Els, and Salgado, Roberto

Abstract

New assays are developed regularly to improve health care for patients. It is important to ensure that assays are performed correctly. Therefore, it is advised to participate in training and proficiency (competence assessment) programs. Tumor infiltrating lymphocytes (TILs) might improve the estimates of response to therapy and prognosis. Herewith, we propose a new training and proficiency program in which each pathologist can train and test themselves regarding TILs (and PDL1) scoring.

Published
2022

27. Development of Training Materials for Pathologists to Provide Machine Learning Validation Data of Tumor-Infiltrating Lymphocytes in Breast Cancer

Author

Garcia, Victor, primary, Elfer, Katherine, additional, Peeters, Dieter J. E., additional, Ehinger, Anna, additional, Werness, Bruce, additional, Ly, Amy, additional, Li, Xiaoxian, additional, Hanna, Matthew G., additional, Blenman, Kim R. M., additional, Salgado, Roberto, additional, and Gallas, Brandon D., additional

Published
2022
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28. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Author

Van Bockstal, Mieke R., primary, Cooks, Maxine, additional, Nederlof, Iris, additional, Brinkhuis, Mariël, additional, Dutman, Annemiek, additional, Koopmans, Monique, additional, Kooreman, Loes, additional, van der Vegt, Bert, additional, Verhoog, Leon, additional, Vreuls, Celine, additional, Westenend, Pieter, additional, Kok, Marleen, additional, van Diest, Paul J., additional, Nauwelaers, Inne, additional, Laudus, Nele, additional, Denkert, Carsten, additional, Rimm, David, additional, Siziopikou, Kalliopi P., additional, Ely, Scott, additional, Zardavas, Dimitrios, additional, Roberts, Mustimbo, additional, Floris, Giuseppe, additional, Hartman, Johan, additional, Acs, Balazs, additional, Peeters, Dieter, additional, Bartlett, John M.S., additional, Dequeker, Els, additional, Salgado, Roberto, additional, Giudici, Fabiola, additional, Michiels, Stefan, additional, Horlings, Hugo, additional, and van Deurzen, Carolien H. M., additional

Published
2021
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29. Dynamic changes of PD-L1 and T-cell activation in ECLIPSE : A phase II study investigating preoperative immune combination strategies in untreated, operable ER+ primary breast cancer

Author

Schmid, Peter, Kockx, Mark, Kim, Sung-Bae, Wheatley, Duncan, Phillips, Melissa Mary, Hoffmann, Oliver, Blohmer, Jens U., Im, Seock-Ah, Schneeweiss, Andreas, Zamora, Esther, Waumans, Yannick, Van Dam, Pieter-Jan, Peeters, Dieter, Wimalasingham, Akhila, Marosics, Patricia, Prendergast, Aaron, Mousa, Kelly, Cortes, Javier, and Kuemmel, Sherko

Subjects
Medizin, ComputingMethodologies_GENERAL
Abstract

Poster-Abstract

Published
2021

30. 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.

Author

UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, 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, Sinke, Renata, Stanciu-Pop, Claudia, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, Galant, Christine, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, 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, Sinke, Renata, Stanciu-Pop, Claudia, 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

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

Published
2021

31. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group.

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'anatomie pathologique, Van Bockstal, Mieke, Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariël, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J, Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P, Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M S, Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, van Deurzen, Carolien H M, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'anatomie pathologique, Van Bockstal, Mieke, Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariël, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J, Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P, Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M S, Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, and van Deurzen, Carolien H M

Abstract

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs.

Published
2021

32. 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.

Author

UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (MGD) Service d'anatomie pathologique, Van Bockstal, Mieke, Francois, 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, Sinke, Renata, Stanciu-Pop, Claudia Maria, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, Galant, Christine, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (MGD) Service d'anatomie pathologique, Van Bockstal, Mieke, Francois, 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, Sinke, Renata, Stanciu-Pop, Claudia Maria, 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

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

Published
2021

33. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Author

Van Bockstal, Mieke R., Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariel, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J., Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M. S., Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, van Deurzen, Carolien H.M., Van Bockstal, Mieke R., Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariel, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J., Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M. S., Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, and van Deurzen, Carolien H.M.

Abstract

Patients with advanced triple‐negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD‐L1/SP142‐positive immune cells. Numbers of tumor‐infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter‐pathologist agreement in the assessment of PD‐L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD‐L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD‐L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD‐ L1 status (positive versus negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD‐L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD‐L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD‐L1 status of primary TNBCs.

Published
2021

34. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Author

Pathologie, Cancer, Van Bockstal, Mieke R., Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariel, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J., Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M. S., Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, van Deurzen, Carolien H. M., Pathologie, Cancer, Van Bockstal, Mieke R., Cooks, Maxine, Nederlof, Iris, Brinkhuis, Mariel, Dutman, Annemiek, Koopmans, Monique, Kooreman, Loes, van der Vegt, Bert, Verhoog, Leon, Vreuls, Celine, Westenend, Pieter, Kok, Marleen, van Diest, Paul J., Nauwelaers, Inne, Laudus, Nele, Denkert, Carsten, Rimm, David, Siziopikou, Kalliopi P., Ely, Scott, Zardavas, Dimitrios, Roberts, Mustimbo, Floris, Giuseppe, Hartman, Johan, Acs, Balazs, Peeters, Dieter, Bartlett, John M. S., Dequeker, Els, Salgado, Roberto, Giudici, Fabiola, Michiels, Stefan, Horlings, Hugo, and van Deurzen, Carolien H. M.

Published
2021

35. PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer

Author

Rugo, Hope S, primary, Loi, Sherene, additional, Adams, Sylvia, additional, Schmid, Peter, additional, Schneeweiss, Andreas, additional, Barrios, Carlos H, additional, Iwata, Hiroji, additional, Diéras, Véronique, additional, Winer, Eric P, additional, Kockx, Mark M, additional, Peeters, Dieter, additional, Chui, Stephen Y, additional, Lin, Jennifer C, additional, Nguyen-Duc, Anh, additional, Viale, Giuseppe, additional, Molinero, Luciana, additional, and Emens, Leisha A, additional

Published
2021
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36. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

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., Hudeček, 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, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., van der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, Cooper, Lee A. D., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Tutt, Andrew, Guerrero-Zotano, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Anna C., Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Castaneda, Carlos, Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Dillon, Deborah A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Bellolio, Enrique, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Gruosso, Forbius Tina, Peale, Franklin, Hirsch, Fred R., Klaushen, Frederick, Acosta-Haab, Gabriela, Farshid, Gelareh, van den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Hall, Jacqueline A., Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, M. Ribeiro, Joana, Carter, Jodi M., Hainfellner, Johannes, Quesne, John Le, Juco, Jonathan W., Reis-Filho, Jorge, van den Berg, Jose, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., van de Vijver, Koen K., Korski, Konstanty, Pusztai, Lajos, Buisseret, Laurence, Shi, Leming, Shi-wei, Liu, Molinero, Luciana, Estrada, M. Valeria, van Seijen, Maartje, Lacroix-Triki, Magali, Cheang, Maggie C. U., Bakir, Maise al, van de Vijver, Marc, Dieci, Maria Vittoria, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Sanders, Melinda E., Regan, Meredith M., Christie, Michael, Misialek, Michael, Ignatiadis, Michail, de Maaker, Michiel, van Bockstal, Mieke, Castillo, Miluska, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Jelinic, Petar, Watson, Peter H., Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, de Wind, Roland, Shui, Ruohong, Declercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Willis, Scooter, Ely, Scott, Kim, Seong- Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Luz, Sua, Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, d’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Yang, Wentao, Tran, William T., Wang, Yihong, Allory, Yves, Husain, Zaheed, Amgad, Mohamed [0000-0001-7599-6162], Sharma, Ashish [0000-0002-1011-6504], Savas, Peter [0000-0001-5999-428X], Hudeček, Jan [0000-0003-1071-5686], Braybrooke, Jeremy P. [0000-0003-1943-7360], Demaria, Sandra [0000-0003-4426-0499], Comerma, Laura [0000-0002-0249-4636], Badve, Sunil S. [0000-0001-8861-9980], Symmans, W. Fraser [0000-0002-1526-184X], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Rimm, David L. [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hanna, Matthew G. [0000-0002-7536-1746], Lazar, Alexander J. [0000-0002-6395-4499], Bago-Horvath, Zsuzsanna [0000-0002-8555-7806], van der Laak, Jeroen A. W. M. [0000-0001-7982-0754], Gallas, Brandon D. [0000-0001-7332-1620], Kurkure, Uday [0000-0002-8273-7334], Cooper, Lee A. D. [0000-0002-3504-4965], and Apollo - University of Cambridge Repository

Subjects
631/67/580, 692/4028/67/1857, 631/67/2321, 692/53/2422, review-article, Review Article, 631/67/1347
Abstract

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Published
2020

37. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice

Author

Gonzalez-Ericsson, Paula, Stovgaard, Elisabeth, Sua, Luz, Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi, Michiels, Stefan, Le Quesne, John, Nielsen, Torsten, Laenkholm, Anne-Vibeke, Fox, Stephen, Adam, Julien, Bartlett, John MS, Rimm, David, Quinn, Cecily, Peeters, Dieter, Dieci, Maria, Vincent-Salomon, Anne, Cree, Ian, Hida, Akira, Balko, Justin, Haynes, Harry, Frahm, Isabel, Acosta-Haab, Gabriela, Balancin, Marcelo, Bellolio, Enrique, Yang, Wentao, Kirtani, Pawan, Sugie, Tomoharu, Ehinger, Anna, Castaneda, Carlos, Kok, Marleen, McArthur, Heather, Siziopikou, Kalliopi, Badve, Sunil, Fineberg, Susan, Gown, Allen, Viale, Giuseppe, Schnitt, Stuart, Pruneri, Giancarlo, Penault-Llorca, Frédérique, Hewitt, Stephen, Thompson, E Aubrey, Allison, Kimberly, Symmans, William, Bellizzi, Andrew, Brogi, Edi, Moore, David, Larsimont, Denis, Dillon, Deborah, Lazar, Alexander, Lien, Huangchun, Goetz, Matthew, Broeckx, Glenn, El Bairi, Khalid, Harbeck, Nadia, Cimino-Mathews, Ashley, Sotiriou, Christos, Adams, Sylvia, Liu, Shi-Wei, Loibl, Sibylle, Chen, I-Chun, Lakhani, Sunil, Juco, Jonathan, Denkert, Carsten, Blackley, Elizabeth, Demaria, Sandra, Leon-Ferre, Roberto, Gluz, Oleg, Zardavas, Dimitrios, Emancipator, Kenneth, Ely, Scott, Loi, Sherene, Salgado, Roberto, Sanders, Melinda, Gonzalez‐Ericsson, Paula, Lænkholm, Anne‐Vibeke, Vincent‐Salomon, Anne, Acosta‐Haab, Gabriela, Penault‐Llorca, Frederique, Cimino‐Mathews, Ashley, Liu, Shi‐wei, Chen, I‐Chun, Leon‐Ferre, Roberto, Int Immuno-Oncology Biomarker Work, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University of Leicester, Department of Pathology, Odense University Hospital, Universita degli Studi di Padova, Pharmacogenomics Unit [Paris], Department of Genetics [Paris], Institut Curie [Paris]-Institut Curie [Paris], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Helsingborg Hospital, Ctr Biomol Struct & Org, University of Maryland [College Park], University of Maryland System-University of Maryland System, The Netherlands Cancer Institute, Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), European Institute of Oncology [Milan] (ESMO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), The University of Texas M.D. Anderson Cancer Center [Houston], Université Mohamed 1 Oujda MAROC, Frauenklinik, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Breast Group, University of Southern Queensland (USQ), Charité, Institute of Pathology, Translational Tumorpathology Unit, West German Study Group, Breast International Group [Brussels, Belgium] (BIG aisbl), Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), and German Breast Group (GBG)

Subjects
0301 basic medicine, Oncology, PD-L1, medicine.medical_specialty, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Triple Negative Breast Neoplasms, Pembrolizumab, biomarker risk-management, B7-H1 Antigen, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, Lymphocytes, Tumor-Infiltrating, Atezolizumab, Internal medicine, Biomarkers, Tumor, Medicine, Humans, TILs, Triple-negative breast cancer, Tumor marker, Cancer immunology, Risk Management, business.industry, Médecine pathologie humaine, Sciences bio-médicales et agricoles, immunotherapy, medicine.disease, 3. Good health, Clinical trial, Cancérologie, 030104 developmental biology, 030220 oncology & carcinogenesis, Human medicine, Nivolumab, business
Abstract

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer. TILs can be easily assessed on hematoxylin and eosin stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Since TILs and PD-L1 are parts of an immunological spectrum in breast cancer, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immune-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with breast cancer. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in breast cancer. This article is protected by copyright. All rights reserved., info:eu-repo/semantics/published

Published
2020
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38. The path to a better biomarker:application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice

Author

Gonzalez-Ericsson, Paula I., Stovgaard, Elisabeth S., Sua, Luz F., Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi M., Michiels, Stefan, Le Quesne, John, Nielsen, Torsten O., Lænkholm, Anne Vibeke, Fox, Stephen B., Adam, Julien, Bartlett, John M.S., Rimm, David L., Quinn, Cecily, Peeters, Dieter, Dieci, Maria V., Vincent-Salomon, Anne, Cree, Ian, Hida, Akira I., Balko, Justin M., Haynes, Harry R., Frahm, Isabel, Acosta-Haab, Gabriela, Balancin, Marcelo, Bellolio, Enrique, Yang, Wentao, Kirtani, Pawan, Sugie, Tomoharu, Ehinger, Anna, Castaneda, Carlos A., Kok, Marleen, McArthur, Heather, Siziopikou, Kalliopi, Badve, Sunil, Fineberg, Susan, Gown, Allen, Viale, Giuseppe, Schnitt, Stuart J., Pruneri, Giancarlo, Penault-Llorca, Frederique, Hewitt, Stephen, Thompson, E. Aubrey, Allison, Kimberly H., Symmans, William F., Bellizzi, Andrew M., Brogi, Edi, Moore, David A., Larsimont, Denis, Dillon, Deborah A., Lazar, Alexander, Lien, Huangchun, Goetz, Matthew P., Broeckx, Glenn, El Bairi, Khalid, Harbeck, Nadia, Cimino-Mathews, Ashley, Sotiriou, Christos, Adams, Sylvia, Liu, Shi wei, Loibl, Sibylle, Chen, I. Chun, Lakhani, Sunil R., Juco, Jonathan W., Denkert, Carsten, Blackley, Elizabeth F., Demaria, Sandra, Leon-Ferre, Roberto, Gluz, Oleg, Zardavas, Dimitrios, Emancipator, Kenneth, Ely, Scott, Loi, Sherene, Salgado, Roberto, Sanders, Melinda, Gonzalez-Ericsson, Paula I., Stovgaard, Elisabeth S., Sua, Luz F., Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi M., Michiels, Stefan, Le Quesne, John, Nielsen, Torsten O., Lænkholm, Anne Vibeke, Fox, Stephen B., Adam, Julien, Bartlett, John M.S., Rimm, David L., Quinn, Cecily, Peeters, Dieter, Dieci, Maria V., Vincent-Salomon, Anne, Cree, Ian, Hida, Akira I., Balko, Justin M., Haynes, Harry R., Frahm, Isabel, Acosta-Haab, Gabriela, Balancin, Marcelo, Bellolio, Enrique, Yang, Wentao, Kirtani, Pawan, Sugie, Tomoharu, Ehinger, Anna, Castaneda, Carlos A., Kok, Marleen, McArthur, Heather, Siziopikou, Kalliopi, Badve, Sunil, Fineberg, Susan, Gown, Allen, Viale, Giuseppe, Schnitt, Stuart J., Pruneri, Giancarlo, Penault-Llorca, Frederique, Hewitt, Stephen, Thompson, E. Aubrey, Allison, Kimberly H., Symmans, William F., Bellizzi, Andrew M., Brogi, Edi, Moore, David A., Larsimont, Denis, Dillon, Deborah A., Lazar, Alexander, Lien, Huangchun, Goetz, Matthew P., Broeckx, Glenn, El Bairi, Khalid, Harbeck, Nadia, Cimino-Mathews, Ashley, Sotiriou, Christos, Adams, Sylvia, Liu, Shi wei, Loibl, Sibylle, Chen, I. Chun, Lakhani, Sunil R., Juco, Jonathan W., Denkert, Carsten, Blackley, Elizabeth F., Demaria, Sandra, Leon-Ferre, Roberto, Gluz, Oleg, Zardavas, Dimitrios, Emancipator, Kenneth, Ely, Scott, Loi, Sherene, Salgado, Roberto, and Sanders, Melinda

Abstract

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC.

Published
2020

39. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers into breast cancer clinical trials and daily practice.

Author

Gonzalez-Ericsson, Paula I, Stovgaard, Elisabeth ES, Sua, Luz F, Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi M, Michiels, Stefan, Le Quesne, John, Nielsen, Torsten O, Laenkholm, Anne-Vibeke, Fox, Stephen B, Adam, Julien, Bartlett, John Ms, Rimm, David L, Quinn, Cecily, Peeters, Dieter, Dieci, Maria V, Vincent-Salomon, Anne, Cree, Ian, Hida, Akira I, Balko, Justin M, Haynes, Harry HR, Frahm, Isabel, Acosta-Haab, Gabriela, Balancin, Marcelo, Bellolio, Enrique, Yang, Wentao, Kirtani, Pawan, Sugie, Tomoharu, Ehinger, Anna, Castaneda, Carlos Altamirano, Kok, Marleen, McArthur, Heather, Siziopikou, Kalliopi, Badve, Sunil, Fineberg, Susan, Gown, Allen A.M., Viale, Giuseppe, Schnitt, Stuart J, Pruneri, Giancarlo, Penault-Llorca, Frederique, Hewitt, Stephen M, Thompson, E Aubrey, Allison, Kimberly H, Symmans, William Fraser, Bellizzi, Andrew M, Brogi, Edi, Moore, David A, Larsimont, Denis, Dillon, Deborah A, Lazar, Alexander, Lien, Huangchun, Goetz, Matthew P, Broeckx, Glenn, El Bairi, Khalid, Harbeck, Nadia, Cimino-Mathews, Ashley, Sotiriou, Christos, Adams, Sylvia, Liu, Shi-Wei, Loibl, Sibylle, Chen, I-Chun, Lakhani, Sunil R, Juco, Jonathan W, Denkert, Carsten, Blackley, Elizabeth EF, Demaria, Sandra, Leon-Ferre, Roberto, Gluz, Oleg, Zardavas, Dimitrios, Emancipator, Kenneth, Ely, Scott, Loi, Sherene, Salgado, Roberto, Sanders, Melinda M.E., International Immuno-Oncology Biomarker Working Group, Gonzalez-Ericsson, Paula I, Stovgaard, Elisabeth ES, Sua, Luz F, Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi M, Michiels, Stefan, Le Quesne, John, Nielsen, Torsten O, Laenkholm, Anne-Vibeke, Fox, Stephen B, Adam, Julien, Bartlett, John Ms, Rimm, David L, Quinn, Cecily, Peeters, Dieter, Dieci, Maria V, Vincent-Salomon, Anne, Cree, Ian, Hida, Akira I, Balko, Justin M, Haynes, Harry HR, Frahm, Isabel, Acosta-Haab, Gabriela, Balancin, Marcelo, Bellolio, Enrique, Yang, Wentao, Kirtani, Pawan, Sugie, Tomoharu, Ehinger, Anna, Castaneda, Carlos Altamirano, Kok, Marleen, McArthur, Heather, Siziopikou, Kalliopi, Badve, Sunil, Fineberg, Susan, Gown, Allen A.M., Viale, Giuseppe, Schnitt, Stuart J, Pruneri, Giancarlo, Penault-Llorca, Frederique, Hewitt, Stephen M, Thompson, E Aubrey, Allison, Kimberly H, Symmans, William Fraser, Bellizzi, Andrew M, Brogi, Edi, Moore, David A, Larsimont, Denis, Dillon, Deborah A, Lazar, Alexander, Lien, Huangchun, Goetz, Matthew P, Broeckx, Glenn, El Bairi, Khalid, Harbeck, Nadia, Cimino-Mathews, Ashley, Sotiriou, Christos, Adams, Sylvia, Liu, Shi-Wei, Loibl, Sibylle, Chen, I-Chun, Lakhani, Sunil R, Juco, Jonathan W, Denkert, Carsten, Blackley, Elizabeth EF, Demaria, Sandra, Leon-Ferre, Roberto, Gluz, Oleg, Zardavas, Dimitrios, Emancipator, Kenneth, Ely, Scott, Loi, Sherene, Salgado, Roberto, Sanders, Melinda M.E., and International Immuno-Oncology Biomarker Working Group

Abstract

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer. TILs can be easily assessed on hematoxylin and eosin stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Since TILs and PD-L1 are parts of an immunological spectrum in breast cancer, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immune-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with breast cancer. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in breast cancer. This article is protected by copyright. All rights reserved., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2020

40. Abstract PD14-06: Dynamic changes of PD-L1 and T-cell activation in ECLIPSE: A phase II study investigating preoperative immune combination strategies in untreated, operable ER+ primary breast cancer

Author

Schmid, Peter, primary, Kockx, Mark, additional, Kim, Sung-Bae, additional, Wheatley, Duncan, additional, Phillips, Melissa Mary, additional, Hoffmann, Oliver, additional, Blohmer, Jens U., additional, Im, Seock-Ah, additional, Schneeweiss, Andreas, additional, Zamora, Esther, additional, Waumans, Yannick, additional, Van Dam, Pieter-Jan, additional, Peeters, Dieter, additional, Wimalasingham, Akhila, additional, Marosics, Patricia, additional, Prendergast, Aaron, additional, Mousa, Kelly, additional, Cortes, Javier, additional, and Kuemmel, Sherko, additional

Published
2021
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42. Abstract OT3-18-02: A comparative study of two detection platforms of circulating tumour cells in patients with metastatic breast cancer

Author

Peeters, Dieter, primary, Buys, Andy, additional, Ledegen, Hannah, additional, Moehlig, Kathlyn, additional, Oeyen, Steffi, additional, Rondas, Dieter, additional, De Beukelaer, Alexia, additional, Van Laere, Steven, additional, Vervoort, Liesbet, additional, Vermeulen, Peter, additional, Ung, Christopher, additional, Kockx, Mark, additional, and Dirix, Luc, additional

Published
2020
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43. Abstract PD1-07: Exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple-negative breast cancer: A retrospective substudy of IMpassion130

Author

Rugo, Hope, primary, Loi, Sherene, additional, Adams, Sylvia, additional, Schmid, Peter, additional, Schneeweiss, Andreas, additional, Barrios, Carlos H, additional, Iwata, Hiroji, additional, Diéras, Véronique, additional, Winer, Eric P, additional, Kockx, Mark M, additional, Peeters, Dieter, additional, Chui, Stephen Y, additional, Lin, Jennifer C, additional, Duc, Anh Nguyen, additional, Viale, Guiseppe, additional, Molinero, Luciana, additional, and Emens, Leisha A, additional

Published
2020
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44. Abstract P5-02-04: Upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast to reduce inter-observer variability: The DCISion study

Author

Van Bockstal, Mieke Rosalie, primary, Dano, Hélène, additional, Altinay, Serdar, additional, Arnould, Laurent, additional, Bletard, Noella, additional, Colpaert, Cecile, additional, Dedeurwaerdere, Franceska, additional, Dessauvagie, Benjamin, additional, Duwel, Valérie, additional, Floris, Giuseppe, additional, Fox, Stephen, additional, Gerosa, Clara, additional, Jaffer, Shabnam, additional, Kurpershoek, Eline, additional, Lacroix-Triki, Magali, additional, Laka, Andoni, additional, Lambein, Kathleen, additional, MacGrogan, Gaëtan Marie, additional, Marchió, Caterina, additional, Martinez, Dolores Martin, additional, Nofech-Mozes, Sharon, additional, Peeters, Dieter, additional, Ravarino, Alberto, additional, Reisenbichler, Emily, additional, Resetkova, Erika, additional, Sanati, Souzan, additional, Schelfhout, Anne-Marie, additional, Schelfhout, Vera, additional, Shaaban, Abeer M, additional, Sinke, Renata, additional, Stanciu-Pop, Claudia Maria, additional, Stobbe, Claudia, additional, van Deurzen, Carolien HM, additional, de Vijver, Koen Van, additional, Van Rompuy, Anne-Sophie, additional, Verschuere, Stephanie, additional, Vincent-Salomon, Anne, additional, Wen, Hannah, additional, Bouzin, Caroline, additional, and Galant, Christine, additional

Published
2020
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47. HER-2 status of circulating tumor cells in a metastatic breast cancer cohort: A comparative study on characterization techniques

Author

Brouwer, Anja, primary, De Laere, Bram, additional, van Dam, Pieter-Jan, additional, Peeters, Dieter, additional, Van Haver, Jasper, additional, Sluydts, Ellen, additional, El Moussaoui, Ali, additional, Mendelaar, Pauline, additional, Kraan, Jaco, additional, Peeters, Marc, additional, Van Laere, Steven, additional, and Dirix, Luc, additional

Published
2019
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48. Dichotomous histopathological assessment of ductal carcinoma in situ of the breast results in substantial interobserver concordance

Author

UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Erasmus Medical Center Rotterdam - Department of Pathology, Van Bockstal, Mieke, Baldewijns, Marcella, Colpaert, Cécile, Dano, Hélène, Floris, Giuseppe, Galant, Christine, Lambein, Kathleen, Peeters, Dieter, Van Renterghem, Sofie, Van Rompuy, Anne-Sophie, Verbeke, Sofie, Verschuere, Stephanie, Van Dorpe, Jo, UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Erasmus Medical Center Rotterdam - Department of Pathology, Van Bockstal, Mieke, Baldewijns, Marcella, Colpaert, Cécile, Dano, Hélène, Floris, Giuseppe, Galant, Christine, Lambein, Kathleen, Peeters, Dieter, Van Renterghem, Sofie, Van Rompuy, Anne-Sophie, Verbeke, Sofie, Verschuere, Stephanie, and Van Dorpe, Jo

Abstract

AIMS: Robust prognostic markers for ductal carcinoma in situ (DCIS) of the breast require high reproducibility and thus low interobserver variability. The aim of this study was to compare interobserver variability among 13 pathologists, in order to enable the identification of robust histopathological characteristics. METHODS AND RESULTS: One representative haematoxylin and eosin-stained slide was selected for 153 DCIS cases. All pathologists independently assessed nuclear grade, intraductal calcifications, necrosis, solid growth, stromal changes, stromal inflammation, and apocrine differentiation. All characteristics were assessed categorically. Krippendorff's alpha was calculated to assess overall interobserver concordance. Cohen's kappa was calculated for every observer duo to further explore interobserver variability. The highest concordance was observed for necrosis, calcifications, and stromal inflammation. Assessment of solid growth, nuclear grade and stromal changes resulted in lower concordance. Poor concordance was observed for apocrine differentiation. Kappa values for each observer duo identified the 'ideal' cut-off for dichotomisation of multicategory variables. For instance, concordance was higher for 'non-high versus high' nuclear grade than for 'low versus non-low' nuclear grade. 'Absent/mild' versus 'moderate/extensive' stromal inflammation resulted in substantially higher concordance than other dichotomous cut-offs. CONCLUSIONS: Dichotomous assessment of the histopathological features of DCIS resulted in moderate to substantial agreement among pathologists. Future studies on prognostic markers in DCIS should take into account this degree of interobserver variability to define cut-offs for categorically assessed histopathological features, as reproducibility is paramount for robust prognostic markers in daily clinical practice. A new prognostic index for DCIS might be considered, based on two-tier grading of histopathological features. Future resear

Published
2018

49. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immunooncology biomarkers in breast cancer clinical trials and daily practice.

Author

Gonzalez-Ericsson, Paula I., Stovgaard, Elisabeth S., Sua, Luz F., Reisenbichler, Emily, Kos, Zuzana, Carter, Jodi M., Michiels, Stefan, Le Quesne, John, Nielsen, Torsten O., Lnkholm, Anne-Vibeke, Fox, Stephen B., Adam, Julien, Bartlett, John MS, Rimm, David L., Quinn, Cecily, Peeters, Dieter, Dieci, Maria V., Vincent-Salomon, Anne, Cree, Ian, and Hida, Akira I.

Subjects
PACLITAXEL, PROGRAMMED death-ligand 1, TRIPLE-negative breast cancer, IMMUNE checkpoint inhibitors, TRIAL practice, BREAST cancer
Abstract

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying =1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a riskmanagement framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. [ABSTRACT FROM AUTHOR]

Published
2020
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50. Dichotomous histopathological assessment of ductal carcinomain situof the breast results in substantial interobserver concordance

Author

Van Bockstal, Mieke, primary, Baldewijns, Marcella, additional, Colpaert, Cécile, additional, Dano, Hélène, additional, Floris, Giuseppe, additional, Galant, Christine, additional, Lambein, Kathleen, additional, Peeters, Dieter, additional, Van Renterghem, Sofie, additional, Van Rompuy, Anne-Sophie, additional, Verbeke, Sofie, additional, Verschuere, Stephanie, additional, and Van Dorpe, Jo, additional

Published
2018
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