Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

被引：13

作者：

Hudecek, Jan ^{[1
]}

Voorwerk, Leonie ^{[2
]}

van Seijen, Maartje ^{[3
]}

Nederlof, Iris ^{[2
]}

de Maaker, Michiel ^{[3
]}

van den Berg, Jose ^{[4
]}

van de Vijver, Koen K. ^{[5
]}

Sikorska, Karolina ^{[6
]}

Adams, Sylvia ^{[7
]}

Demaria, Sandra ^{[8
,9
]}

Viale, Giuseppe ^{[10
,11
]}

Nielsen, Torsten O. ^{[12
]}

Badve, Sunil S. ^{[13
]}

Michiels, Stefan ^{[14
,15
]}

Symmans, William Fraser ^{[16
]}

Sotiriou, Christos ^{[17
]}

Rimm, David L. ^{[18
,19
]}

Hewitt, Stephen M. ^{[20
]}

Denkert, Carsten ^{[21
,22
]}

Loibl, Sibylle ^{[23
]}

Loi, Sherene ^{[24
]}

Bartlett, John M. S. ^{[25
,26
,27
]}

Pruneri, Giancarlo ^{[28
,29
]}

Dillon, Deborah A. ^{[30
]}

Cheang, Maggie C. U. ^{[31
]}

Tutt, Andrew ^{[32
]}

Hall, Jacqueline A. ^{[33
]}

Kos, Zuzana ^{[34
]}

Salgado, Roberto ^{[24
,35
]}

Kok, Marleen ^{[2
,36
]}

Horlings, Hugo M. ^{[3
,4
]}

机构：

[1] Netherlands Canc Inst, Dept Res IT, Amsterdam, Netherlands

[2] Netherlands Canc Inst, Div Tumor Biol & Immunol, Amsterdam, Netherlands

[3] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands

[4] Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands

[5] Ghent Univ Hosp, Dept Pathol, Ghent, Belgium

[6] Netherlands Canc Inst, Dept Biometr, Amsterdam, Netherlands

[7] NYU, Sch Med, Dept Med, Perlmutter Canc Ctr, New York, NY USA

[8] Weill Cornell Med, Dept Radiat Oncol, New York, NY USA

[9] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY USA

[10] IEO European Inst Oncol IRCCS, Dept Pathol & Lab Med, Int Breast Canc Study Grp, Cent Pathol Off, Milan, Italy

[11] Univ Milan, Milan, Italy

[12] Univ British Columbia, Genet Pathol Evaluat Ctr, Dept Pathol & Lab Med, Vancouver, BC, Canada

[13] Indiana Univ, Simon Canc Ctr, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA

[14] Univ Paris Saclay, Univ Paris Sud, CESP, Serv Biostat & Epidemiol,Gustave Roussy, Villejuif, France

[15] Univ Paris Saclay, Univ Paris Sud, INSERM, Fac Med UVSQ,CESP, Villejuif, France

[16] MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[17] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, U CRC, Brussels, Belgium

[18] Yale Sch Med, Dept Pathol, New Haven, CT USA

[19] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA

[20] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA

[21] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany

[22] Philipps Univ Marburg, Inst Pathol, Marburg, Germany

[23] German Breast Grp, Neu Isenburg, Germany

[24] Univ Melbourne, Peter MacCallum Canc Ctr, Div Res & Clin Med, Melbourne, Vic, Australia

[25] Ontario Inst Canc Res, Toronto, ON, Canada

[26] IGMM, Edinburgh, Midlothian, Scotland

[27] Western Gen Hosp, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland

[28] Fdn Inst Nazl Tumori, IRCCS, Dept Pathol & Lab Med, Milan, Italy

[29] Univ Milan, Sch Med, Milan, Italy

[30] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[31] Inst Canc Res, Clin Trials & Stat Unit, Surrey, England

[32] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London, England

[33] Vivactiv Ltd, Res & Dev, Chesham, Bucks, England

[34] Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON, Canada

[35] GZA ZNA Ziekenhuizen, Dept Pathol, Antwerp, Belgium

[36] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands

来源：

NPJ BREAST CANCER | 2020年 / 6卷 / 01期

基金：

英国医学研究理事会;

关键词：

BIOMARKERS;

D O I：

10.1038/s41523-020-0155-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

引用

页数：8

共 22 条

[1] Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group [J].

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. ;

Hudecek, 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, Frederique ;

Goel, Shom .

NPJ BREAST CANCER, 2020, 6 (01)

[2] QuPath: Open source software for digital pathology image analysis [J].

Bankhead, Peter ;

Loughrey, Maurice B. ;

Fernandez, Jose A. ;

Dombrowski, Yvonne ;

Mcart, Darragh G. ;

Dunne, Philip D. ;

McQuaid, Stephen ;

Gray, Ronan T. ;

Murray, Liam J. ;

Coleman, Helen G. ;

James, Jacqueline A. ;

Salto-Tellez, Manuel ;

Hamilton, Peter W. .

SCIENTIFIC REPORTS, 2017, 7

[3] Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy [J].

Denkert, Carsten ;

von Minckwitz, Gunter ;

Darb-Esfahani, Silvia ;

Lederer, Bianca ;

Heppner, Barbara I. ;

Weber, Karsten E. ;

Budczies, Jan ;

Huober, Jens ;

Klauschen, Frederick ;

Furlanetto, Jenny ;

Schmitt, Wolfgang D. ;

Blohmer, Jens-Uwe ;

Karn, Thomas ;

Pfitzner, Berit M. ;

Kuemmel, Sherko ;

Engels, Knut ;

Schneeweiss, Andreas ;

Hartmann, Arndt ;

Noske, Aurelia ;

Fasching, Peter A. ;

Jackisch, Christian ;

van Mackelenbergh, Marion ;

Sinn, Peter ;

Schem, Christian ;

Hanusch, Claus ;

Untch, Michael ;

Loibl, Sibylle .

LANCET ONCOLOGY, 2018, 19 (01) :40-50

[4] Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+breast cancer [J].

Dieci, M. V. ;

Conte, P. ;

Bisagni, G. ;

Brandes, A. A. ;

Frassoldati, A. ;

Cavanna, L. ;

Musolino, A. ;

Giotta, F. ;

Rimanti, A. ;

Garrone, O. ;

Bertone, E. ;

Cagossi, K. ;

Sarti, S. ;

Ferro, A. ;

Piacentini, F. ;

Maiorana, A. ;

Orvieto, E. ;

Sanders, M. ;

Miglietta, F. ;

Balduzzi, S. ;

D'Amico, R. ;

Guarneri, V. .

ANNALS OF ONCOLOGY, 2019, 30 (03) :418-423

[5] Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer A Phase 1 Study [J].

Emens, Leisha A. ;

Cruz, Cristina ;

Eder, Joseph Paul ;

Braiteh, Fadi ;

Chung, Cathie ;

Tolaney, Sara M. ;

Kuter, Irene ;

Nanda, Rita ;

Cassier, Philippe A. ;

Delord, Jean-Pierre ;

Gordon, Michael S. ;

ElGabry, Ehab ;

Chang, Ching-Wei ;

Sarkar, Indrani ;

Grossman, William ;

O'Hear, Carol ;

Fasso, Marcella ;

Molinero, Luciana ;

Schmid, Peter .

JAMA ONCOLOGY, 2019, 5 (01) :74-82

[6]

Fleiss JL., 1981, STAT METHODS RATES P, V2

[7] A risk-management approach for effective integration of biomarkers in clinical trials: perspectives of an NCI, NCRI, and EORTC working group [J].

Hall, Jacqueline Anne ;

Salgado, Roberto ;

Lively, Tracy ;

Sweep, Fred ;

Schuh, Anna .

LANCET ONCOLOGY, 2014, 15 (04) :E184-E193

[8] Breaking a Vicious Cycle [J].

Hayes, Daniel F. ;

Allen, Jef ;

Compton, Carolyn ;

Gustavsen, Gary ;

Leonard, Debra G. B. ;

McCormack, Robert ;

Newcomer, Lee ;

Pothier, Kristin ;

Ransohof, David ;

Schilsky, Richard L. ;

Sigal, Ellen ;

Taube, Sheila E. ;

Tunis, Sean R. .

SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (196)

[9] Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research [J].

Hendry, Shona ;

Salgado, Roberto ;

Gevaert, Thomas ;

Russell, Prudence A. ;

John, Tom ;

Thapa, Bibhusal ;

Christie, Michael ;

van de Vijver, Koen ;

Estrada, M. V ;

Gonzalez-Ericsson, Paula I ;

Sanders, Melinda ;

Solomon, Benjamin sss ;

Solinas, Cinzia ;

Van den Eynden, Gert G. G. M. ;

Allory, Yves ;

Preusser, Matthias ;

Hainfellner, Johannes ;

Pruneri, Giancarlo ;

Vingiani, Andrea ;

Demaria, Sandra ;

Symmans, Fraser ;

Nuciforo, Paolo ;

Comerma, Laura ;

Thompson, E. A. ;

Lakhani, Sunil ;

Kim, Seong-Rim ;

Schnitt, Stuart ;

Colpaert, Cecile ;

Sotiriou, Christos ;

Scherer, Stefan J. ;

Ignatiadis, Michail ;

Badve, Sunil ;

Pierce, Robert H. ;

Viale, Giuseppe ;

Sirtaine, Nicolas ;

Penault-Llorca, Frederique ;

Sugie, Tomohagu ;

Fineberg, Susan ;

Paik, Soonmyung ;

Srinivasan, Ashok ;

Richardson, Andrea ;

Wang, Yihong ;

Chmielik, Ewa ;

Brock, Jane ;

Johnson, Douglas B. ;

Balko, Justin ;

Wienert, Stephan ;

Bossuyt, Veerle ;

Michiels, Stefan ;

Ternes, Nils .

ADVANCES IN ANATOMIC PATHOLOGY, 2017, 24 (05) :235-251

[10] Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer [J].

Kos, Zuzana ;

Roblin, Elvire ;

Kim, Rim S. ;

Michiels, Stefan ;

Gallas, Brandon D. ;

Chen, Weijie ;

van de Vijver, Koen K. ;

Goel, Shom ;

Adams, Sylvia ;

Demaria, Sandra ;

Viale, Giuseppe ;

Nielsen, Torsten O. ;

Badve, Sunil S. ;

Symmans, W. Fraser ;

Sotiriou, Christos ;

Rimm, David L. ;

Hewitt, Stephen ;

Denkert, Carsten ;

Loibl, Sibylle ;

Luen, Stephen J. ;

Bartlett, John M. S. ;

Savas, Peter ;

Pruneri, Giancarlo ;

Dillon, Deborah A. ;

Cheang, Maggie Chon U. ;

Tutt, Andrew ;

Hall, Jacqueline A. ;

Kok, Marleen ;

Horlings, Hugo M. ;

Madabhushi, Anant ;

van der Laak, Jeroen ;

Ciompi, Francesco ;

Laenkholm, Anne-Vibeke ;

Bellolio, Enrique ;

Gruosso, Tina ;

Fox, Stephen B. ;

Araya, Juan Carlos ;

Floris, Giuseppe ;

Hudecek, Jan ;

Voorwerk, Leonie ;

Beck, Andrew H. ;

Kerner, Jen ;

Larsimont, Denis ;

Declercq, Sabine ;

Van den Eynden, Gert ;

Pusztai, Lajos ;

Ehinger, Anna ;

Yang, Wentao ;

AbdulJabbar, Khalid ;

Yuan, Yinyin .

NPJ BREAST CANCER, 2020, 6 (01)

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