@article{baa54e2c27ea4aee89446497428f1701,
title = "Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials",
abstract = "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.",
author = "{International Immuno-Oncology Biomarker Working Group} and Jan Hude{\v c}ek and Leonie Voorwerk and {van Seijen}, Maartje and Iris Nederlof and {de Maaker}, Michiel and {van den Berg}, Jose and {van de Vijver}, {Koen K.} and Karolina Sikorska and Sylvia Adams and Sandra Demaria and Giuseppe Viale and Nielsen, {Torsten O.} and Badve, {Sunil S.} and Stefan Michiels and Symmans, {William Fraser} and Christos Sotiriou and Rimm, {David L.} and Hewitt, {Stephen M.} and Carsten Denkert and Sibylle Loibl and Sherene Loi and Bartlett, {John M.S.} and Giancarlo Pruneri and Dillon, {Deborah A.} and Cheang, {Maggie C.U.} and Andrew Tutt and Hall, {Jacqueline A.} and Zuzana Kos and Roberto Salgado and Marleen Kok and Horlings, {Hugo M.} and Aini Hyyti{\"a}inen and Hida, {Akira I.} and Alastair Thompson and Alex Lefevre and Lazar, {Alexander J.} and Allen Gown and Amy Lo and Anna Sapino and Anant Madabhushi and Andre Moreira and Andrea Richardson and Andrea Vingiani and Beck, {Andrew H.} and Bellizzi, {Andrew M.} and Angel Guerrero and Anna Ehinger and Thompson, {E. Aubrey} and Carter, {Jodi M.} and Goetz, {Matthew P.}",
note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41523-020-0155-1",
language = "English (US)",
volume = "6",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}