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Application of a Risk-Management Framework for Integration of Stromal Tumor-Infiltrating Lymphocytes in Clinical Trials Publisher



Hudecek J1 ; Voorwerk L2 ; Van Seijen M3 ; Nederlof I2 ; De Maaker M3 ; Van Den Berg J4 ; Van De Vijver KK5 ; Sikorska K6 ; Adams S7 ; Demaria S8, 9 ; Viale G10, 11 ; Nielsen TO12 ; Badve SS13 ; Michiels S14, 15 Show All Authors
Authors
  1. Hudecek J1
  2. Voorwerk L2
  3. Van Seijen M3
  4. Nederlof I2
  5. De Maaker M3
  6. Van Den Berg J4
  7. Van De Vijver KK5
  8. Sikorska K6
  9. Adams S7
  10. Demaria S8, 9
  11. Viale G10, 11
  12. Nielsen TO12
  13. Badve SS13
  14. Michiels S14, 15
  15. Symmans WF16
  16. Sotiriou C17
  17. Rimm DL18, 19
  18. Hewitt SM20
  19. Denkert C21, 22
  20. Loibl S23, 191
  21. Loi S24
  22. Bartlett JMS25, 26, 27
  23. Pruneri G28, 29
  24. Dillon DA30
  25. Cheang MCU31
  26. Tutt A32
  27. Hall JA33
  28. Kos Z34
  29. Salgado R24, 35
  30. Kok M2, 36
  31. Horlings HM3, 4
  32. Hyytiainen A37
  33. Hida AI38
  34. Thompson A39
  35. Lefevre A40, 74
  36. Lazar AJ41
  37. Gown A42
  38. Lo A43
  39. Sapino A44
  40. Madabhushi A45, 46
  41. Moreira A47
  42. Richardson A48
  43. Vingiani A49
  44. Beck AH50
  45. Bellizzi AM51
  46. Guerrero A52
  47. Grigoriadis A53, 54
  48. Ehinger A55
  49. Garridocastro A56
  50. Vincentsalomon A57
  51. Laenkholm AV58
  52. Sharma A59
  53. Ciminomathews A60
  54. Srinivasan A61, 217
  55. Acs B62
  56. Singh B63
  57. Calhoun B64
  58. Haibekans B65
  59. Solomon B66
  60. Thapa B67
  61. Nelson BH68
  62. Gallas BD69
  63. Castaneda C70, 71, 150
  64. Ballesterosmerino C72
  65. Criscitiello C73
  66. Boeckx C40, 74
  67. Colpaert C75
  68. Quinn C76
  69. Chennubhotla CS77
  70. Swanton C78
  71. Solinas C79
  72. Hiley C78
  73. Drubay D80, 81
  74. Bethmann D82
  75. Moore DA83, 84
  76. Larsimont D85
  77. Sabanathan D86
  78. Peeters D87
  79. Zardavas D88
  80. Hoflmayer D89
  81. Johnson DB90
  82. Thompson EA91
  83. Brogi E92, 233
  84. Perez E93
  85. Elgabry EA94
  86. Stovgaard ES95
  87. Blackley EF66
  88. Roblin E96, 97
  89. Reisenbichler E18
  90. Bellolio E98, 99
  91. Balslev E95
  92. Chmielik E100
  93. Gaire F101
  94. Andre F102
  95. Lu FI103
  96. Azmoudehardalan F104
  97. Rojo F105, 106
  98. Gruosso T107
  99. Ciompi F108
  100. Peale F109
  101. Hirsch FR110
  102. Klauschen F21
  103. Penaultllorca F111
  104. Acosta Haab G112
  105. Farshid G113
  106. Van Den Eynden G114
  107. Curigliano G115, 116
  108. Floris G117, 118
  109. Broeckx G119
  110. Koeppen H43
  111. Haynes HR121
  112. Mcarthur H122
  113. Joensuu H123
  114. Olofsson H124
  115. Lien HC125
  116. Chen IC126, 127
  117. Cree I128
  118. Frahm I129
  119. Brcic I130
  120. Chan J131
  121. Ziai J43
  122. Brock J132
  123. Wesseling J133
  124. Giltnane J43
  125. Kerner JK134
  126. Thagaard J135, 136
  127. Braybrooke JP137, 138
  128. Van Der Laak JAWM108
  129. Lemonnier J139
  130. Zha J140
  131. Ribeiro J141
  132. Lennerz JK142, 237
  133. Carter JM143
  134. Saltz J144
  135. Hartman J145
  136. Hainfellner J146
  137. Quesne JL147
  138. Juco JW148
  139. Reisfilho J92, 149, 233
  140. Sanchez J71, 150
  141. Sparano J151
  142. Cucherousset J152
  143. Araya JC98
  144. Adam J153
  145. Balko JM154
  146. Saeger K155
  147. Siziopikou K156
  148. Willardgallo K157
  149. Weber K23, 191
  150. Poguegeile KL158
  151. Steele KE140
  152. Emancipator K148
  153. Abduljabbar K159
  154. El Bairi K160
  155. Blenman KRM161
  156. Allison KH162
  157. Korski K163
  158. Pusztai L161
  159. Comerma L106, 164
  160. Buisseret L157
  161. Cooper LAD165
  162. Shi L166
  163. Kooreman LFS167
  164. Molinero L109
  165. Estrada MV168
  166. Lacroixtriki M169
  167. Al Bakir M78
  168. Sebastian MM170
  169. Van De Vijver M171
  170. Balancin ML172, 173
  171. Dieci MV174
  172. Mathieu MC175
  173. Rebelatto MC140
  174. Piccart M176
  175. Hanna MG92, 233
  176. Goetz MP93
  177. Preusser M146
  178. Khojasteh M177, 236
  179. Sanders ME178
  180. Regan MM179, 180
  181. Barnes M181
  182. Christie M182
  183. Misialek M183
  184. Ignatiadis M184
  185. Van Bockstal M185
  186. Castillo M71, 150
  187. Amgad M186
  188. Harbeck N187
  189. Tung N188
  190. Laudus N189
  191. Sirtaine N190
  192. Burchardi N23, 191
  193. Ternes N14
  194. Radosevicrobin N192
  195. Gluz O193
  196. Grimm O101
  197. Nuciforo P194
  198. Jank P195
  199. Gonzalezericsson P196
  200. Kirtani P197
  201. Jelinic P148
  202. Watson PH198
  203. Savas P24, 199
  204. Francis PA200, 201
  205. Russell PA202
  206. Singh R203
  207. Kim RS204
  208. Pierce RH205
  209. Hills R206
  210. Leonferre R93
  211. De Wind R190
  212. Shui R207
  213. De Clercq S208
  214. Leung S209
  215. Tabbarah S210
  216. Souza SC211
  217. Otoole S212
  218. Swain S213
  219. Dudgeon S214
  220. Willis S215
  221. Ely S216
  222. Kim SR61, 217
  223. Bedri S218
  224. Irshad S219, 220
  225. Liu SW221
  226. Goel S200, 201
  227. Hendry S222
  228. Bianchi S223
  229. Braganca S224
  230. Paik S61, 217
  231. Wienert S225
  232. Fox SB222
  233. Luen SJ24
  234. Naber S226
  235. Schnitt SJ30, 227
  236. Sua LF228
  237. Lakhani SR229
  238. Fineberg S230
  239. Soler T231
  240. Gevaert T232
  241. Dalfonso T92, 233
  242. John T234
  243. Sugie T235
  244. Kurkure U177, 236
  245. Bossuyt V142, 237
  246. Manem V65
  247. Camara VP238
  248. Tong W239
  249. Chen W69
  250. Yang W207
  251. Tran WT210
  252. Wang Y240
  253. Yuan Y159
  254. Allory Y241
  255. Husain Z242
  256. Bagohorvath Z243
Show Affiliations
Authors Affiliations
  1. 1. Department of Research IT, The Netherlands Cancer Institute, Amsterdam, Netherlands
  2. 2. Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  3. 3. Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  4. 4. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  5. 5. Department of Pathology, Ghent University Hospital, Ghent, Belgium
  6. 6. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, Netherlands
  7. 7. Department of Medicine, Perlmutter Cancer Center, New York University School of Medicine, New York, NY, United States
  8. 8. Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, United States
  9. 9. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States
  10. 10. International Breast Cancer Study Group Central Pathology Office, Department of Pathology and Laboratory Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy
  11. 11. University of Milan, Milan, Italy
  12. 12. Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC, Canada
  13. 13. Department of Pathology and Laboratory Medicine, Indiana University Simon Cancer Center, Indianapolis, IN, United States
  14. 14. Service de Biostatistique et d’Epidemiologie, Gustave Roussy, CESP, Universite-Paris Sud, Universite Paris-Saclay, Villejuif, France
  15. 15. CESP, Fac. de medecine - Univ. Paris-Sud, Fac. de medecine - UVSQ, INSERM, Universite Paris-Saclay, Villejuif, France
  16. 16. Department of Pathology, M.D. Anderson Cancer Center, Houston, TX, United States
  17. 17. Breast Cancer Translational Research Laboratory, Institut Jules Bordet, U-CRC, Universite Libre de Bruxelles, Brussels, Belgium
  18. 18. Department of Pathology, Yale School of Medicine, New Haven, CT, United States
  19. 19. Department of Medicine, Yale University School of Medicine, New Haven, CT, United States
  20. 20. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States
  21. 21. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany
  22. 22. Institute of Pathology, Philipps-University Marburg, Marburg, Germany
  23. 23. German Breast Group, Neu-Isenburg, Germany
  24. 24. Division of Research and Clinical Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia
  25. 25. Ontario Institute for Cancer Research, Toronto, ON, Canada
  26. 26. IGMM, Edinburgh, United Kingdom
  27. 27. Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, United Kingdom
  28. 28. Department of Pathology and Laboratory Medicine, IRCCS Fondazion - Instituto Nazionale Tumori, Milan, Italy
  29. 29. School of Medicine, University of Milan, Milan, Italy
  30. 30. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  31. 31. Clinical Trials and Statistics Unit, The Institute of Cancer Research, Surrey, United Kingdom
  32. 32. Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom
  33. 33. Research and Development, Vivactiv Ltd, Chesham, Buckinghamshire, United Kingdom
  34. 34. Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada
  35. 35. Department of Pathology, GZA-ZNA Ziekenhuizen, Antwerp, Belgium
  36. 36. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  37. 37. Department of Oral and Maxillofacial Diseases, Helsinki, Finland
  38. 38. Department of Pathology, Matsuyama Shimin Hospital, Matsuyama, Japan
  39. 39. Surgical Oncology, Baylor College of Medicine, Houston, TX, United States
  40. 40. Roche Diagnostics, Mechelen, Belgium
  41. 41. Departments of Pathology, Genomic Medicine, Dermatology, and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
  42. 42. PhenoPath Laboratories, Seattle, WA, United States
  43. 43. Research Pathology, Genentech Inc., South San Francisco, CA, United States
  44. 44. University of Turin/Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy
  45. 45. Case Western Reserve University, Cleveland, OH, United States
  46. 46. Louis Stokes Cleveland Veterans Health Administration Medical Center, Cleveland, OH, United States
  47. 47. Pulmonary Pathology, New York University Center for Biospecimen Research and Development, New York University, New York, NY, United States
  48. 48. Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, United States
  49. 49. Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan, Italy
  50. 50. PathAI, Inc, Cambridge, MA, United States
  51. 51. Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
  52. 52. Department of Oncology, IVO, Valencia, Spain
  53. 53. Cancer Bioinformatics Lab, Cancer Centre at Guy’s Hospital, London, United Kingdom
  54. 54. School of Life Sciences and Medicine, King’s College London, London, United Kingdom
  55. 55. Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Oncology and Pathology, Lund, Sweden
  56. 56. Dana Farber Cancer Institute, Boston, MA, United States
  57. 57. Institut Curie, Paris Sciences Lettres Universite, Inserm U934, Department of Pathology, Paris, France
  58. 58. Department of Surgical Pathology, Zealand University Hospital, Koge, Denmark
  59. 59. Department of Biomedical Informatics, Emory University, GA, United States
  60. 60. Departments of Pathology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, United States
  61. 61. National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA, United States
  62. 62. Department of Pathology, Karolinska Institutet, Karolinska, Sweden
  63. 63. Department of Pathology, New York University Langone Medical Centre, New York, NY, United States
  64. 64. Department of Pathology and Laboratory Medicine, UNC School of Medicine, Chapel Hill, NC, United States
  65. 65. Bioinformatics and Computational Genomics Laboratory, Princess Margaret Cancer Center, Toronto, ON, Canada
  66. 66. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  67. 67. Department of Medicine, University of Melbourne, Parkville, VIC, Australia
  68. 68. Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
  69. 69. Division of Imaging, Diagnostics, and Software Reliability (DIDSR), Office of Science and Engineering Laboratories (OSEL), Center for Devices and Radiological Health (CDRH), Rockville, MD, United States
  70. 70. Department of Research, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
  71. 71. Department of Research, Instituto Nacional de Enfermedades Neoplasicas, Lima, 15038, Peru
  72. 72. Providence Cancer Research Center, Portland, Oregon, United States
  73. 73. Department of Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy
  74. 74. Roche Diagnostics, Mechelen, Belgium
  75. 75. Department of Pathology, AZ Turnhout, Turnhout, Belgium
  76. 76. Department of Pathology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland
  77. 77. Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, United States
  78. 78. Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, United Kingdom
  79. 79. Azienda AUSL, Regional Hospital of Aosta, Aosta, Italy
  80. 80. Universite Paris-Sud, Institut National de la Sante et de la Recherche Medicale, Villejuif, France
  81. 81. Gustave Roussy, Universite Paris-Saclay, Villejuif, France
  82. 82. University Hospital Halle (Saale), Institute of Pathology, Halle, (Saale), Germany
  83. 83. Department of Pathology, UCL Cancer Institute, UCL, London, United Kingdom
  84. 84. University College Hospitals NHS Trust, London, United Kingdom
  85. 85. Department of Pathology, Jules Bordet Institute, Brussels, Belgium
  86. 86. Department of Clinical Medicine, Macquarie University, Sydney, Australia
  87. 87. HistoGeneX NV, Antwerp, Belgium and AZ Sint-Maarten Hospital, Mechelen, Belgium
  88. 88. Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, United States
  89. 89. Institut fur Pathologie, UK Hamburg, Germany
  90. 90. Department of Medicine, Vanderbilt University Medical Centre, Nashville, TN, United States
  91. 91. Department of Cancer CV, Jacksonville, FL, United States
  92. 92. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  93. 93. Department of Oncology, Mayo Clinic, Rochester, MN, United States
  94. 94. Roche, Tucson, AZ, United States
  95. 95. Department of Pathology, Herlev and Gentofte Hospital, Gentofte, Denmark
  96. 96. Universite Paris-Saclay, Univ. Paris-Sud, Villejuif, France
  97. 97. Service de biostatistique et d’epidemiologie, Gustave Roussy, Villejuif, France
  98. 98. Department of Pathology, Universidad de La Frontera, Temuco, Chile
  99. 99. Departamento de Anatomia Patologica, Universidad de La Frontera, Temuco, Chile
  100. 100. Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland
  101. 101. Pathology and Tissue Analytics, Roche, Neuherberg, Germany
  102. 102. Department of Medical Oncology, Gustave Roussy, Villejuif, France
  103. 103. Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  104. 104. Tehran University of Medical Sciences, Tehran, Iran
  105. 105. Pathology Department, Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz (IIS-FJD), Madrid, Spain
  106. 106. GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain
  107. 107. Translational Research, Montreal, Canada
  108. 108. Computational Pathology Group, Department of Pathology, Nijmegen, Radboud University Medical Center, Netherlands
  109. 109. Oncology Biomarker Development, Genentech-Roche, Neuherberg, Germany
  110. 110. Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
  111. 111. Centre de Lutte Contre le cancer - Centre Jean Perrin, Clermont-Ferrand, France
  112. 112. Department of Pathology, Hospital de Oncologia Maria Curie, Buenos Aires, Argentina
  113. 113. Directorate of Surgical Pathology, SA Pathology, Adelaide, Australia
  114. 114. Department of Pathology, GZA-ZNA Ziekenhuizen, Wilrijk, Belgium
  115. 115. University of Milano, Instituto Europeo di Oncologia, IRCCS, Milano, Italy
  116. 116. Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS, Milan, Italy
  117. 117. Department of Imaging and Pathology, Laboratory of TranslCal Cell & Tissue Research, Leuven, Belgium
  118. 118. KU Leuven- University Hospitals Leuven, Department of Pathology, Leuven, Belgium
  119. 119. Department of Pathology, University Hospital of Antwerp, Antwerp, Belgium
  120. 120. Paula I, Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, TN, United States
  121. 121. Translational Health Sciences, Department of Cellular Pathology, North Bristol NHS Trust, University of Bristol, Bristol, United Kingdom
  122. 122. Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
  123. 123. Helsinki University Central Hospital, Helsinki, Finland
  124. 124. Department of Clinical Pathology, Akademiska University Hospital, Uppsala, Sweden
  125. 125. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
  126. 126. Department of Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
  127. 127. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
  128. 128. International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
  129. 129. Department of Pathology, Sanatorio Mater Dei, Buenos Aires, Argentina
  130. 130. Institute of Pathology, Medical University of Graz, Graz, Austria
  131. 131. Department of Oncology, National Cancer Centre Singapore, Singapore, Singapore
  132. 132. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, United States
  133. 133. Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands
  134. 134. PathAI Inc, Cambridge, MA, United States
  135. 135. Visiopharm A/S, Horsholm, Denmark
  136. 136. DTU Compute, Department of Applied Mathematics, Technical University of Denmark, Lyngby, Denmark
  137. 137. Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  138. 138. Department of Medical Oncology, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
  139. 139. R&D UNICANCER, Paris, France
  140. 140. Translational Sciences, MedImmune, Gaithersberg, MD, United States
  141. 141. Breast Unit, Champalimaud Clinical Centre, Lisboa, Portugal
  142. 142. Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
  143. 143. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
  144. 144. Biomedical Informatics Department, Stony Brook University, Stony Brook, NY, United States
  145. 145. Department of Oncology and Pathology, Karolinska Institutet and University Hospital, Solna, Sweden
  146. 146. Department of Medicine, Clinical Division of Oncology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria
  147. 147. Leicester Cancer Research Centre, University of Leicester, Leicester, and MRC Toxicology Unit, University of Cambridge, Cambridge, United Kingdom
  148. 148. Merck & Co., Inc, Kenilworth, United States
  149. 149. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  150. 150. Department of Research, Instituto Nacional de Enfermedades Neoplasicas, Lima, 15038, Peru
  151. 151. Department of Medicine, Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein Medical Center, Bronx, United States
  152. 152. GHI Le Raincy-Montfermeil, Chelles, Ile-de-France, France
  153. 153. Department of Pathology, Gustave Roussy, Grand Paris, France
  154. 154. Departments of Medicine and Cancer Biology, Vanderbilt University Medical Centre, Nashville, TN, United States
  155. 155. VMscope GmbH, Berlin, Germany
  156. 156. Department of Pathology, Breast Pathology Section, Northwestern University, Chicago, IL, United States
  157. 157. Molecular Immunology Unit, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  158. 158. NSABP/NRG Oncology, Pittsburgh, PA, United States
  159. 159. Division of Molecular Pathology, Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom
  160. 160. Cancer Biomarkers Working Group, Faculty of Medicine and Pharmacy, Universite Mohamed Premier, Oujda, Morocco
  161. 161. Yale Cancer Center Genetics, Genomics and Epigenetics Program, Yale School of Medicine, New Haven, CT, United States
  162. 162. Pathology Department, Stanford University Medical Centre, Stanford, CA, United States
  163. 163. Pathology and Tissue Analytics, Roche Innovation Centre Munich, Penzberg, Germany
  164. 164. Pathology Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
  165. 165. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  166. 166. Center for Pharmacogenomics and Fudan-Zhangjiang, Center for Clinical Genomics School of Life Sciences and Shanghai Cancer Center, Fudan University, Fudan, China
  167. 167. GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre and Department of Pathology, Maastricht University Medical Centre, Maastricht, Netherlands
  168. 168. Biorepository and Tissue Technology Shared Resources, University of California San Diego, San Diego, CA, United States
  169. 169. Department of Pathology, Gustave Roussy, Villejuif, France
  170. 170. Departments of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
  171. 171. Department of Pathology, Academic Medical Center, Amsterdam, Netherlands
  172. 172. Department of Pathology, University of Sao Paulo, Sao Paulo, Brazil
  173. 173. Hospital das Clinicas, Sao Paulo, Brazil
  174. 174. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
  175. 175. Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France
  176. 176. Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  177. 177. Roche Tissue Diagnostics, Digital Pathology, Santa Clara, CA, United States
  178. 178. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Centre, Nashville, TN, United States
  179. 179. Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, United States
  180. 180. Harvard Medical School, Boston, MA, United States
  181. 181. Roche Diagnostics Information Solutions, Belmont, CA, United States
  182. 182. Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia
  183. 183. Vernon Cancer Center, Newton-Wellesley Hospital, Newton, MA, United States
  184. 184. Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  185. 185. Service de pathologique, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
  186. 186. Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, United States
  187. 187. Breast Center, Dept. OB&GYN and CCC (LMU), University of Munich, Munich, Germany
  188. 188. Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States
  189. 189. University of Leuven, Leuven, Belgium
  190. 190. Department of Pathology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  191. 191. German Breast Group, Neu-Isenburg, Germany
  192. 192. Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France
  193. 193. Johanniter GmbH - Evangelisches Krankenhaus Bethesda Monchengladbach, West German Study Group, Monchengladbach, Germany
  194. 194. Molecular Oncology Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain
  195. 195. Department of Pathology, University of Marburg, Marburg, Germany
  196. 196. Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
  197. 197. Department of Histopathology, Manipal Hospitals Dwarka, New Delhi, India
  198. 198. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
  199. 199. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  200. 200. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  201. 201. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  202. 202. Department of Anatomical Pathology, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
  203. 203. Icahn School of Medicine at Mt. Sinai, New York, NY, United States
  204. 204. NRG Oncology/NSABP, Pittsburgh, PA, United States
  205. 205. Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  206. 206. Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom
  207. 207. Department of Pathology, Fudan University Cancer Center, Shanghai, China
  208. 208. Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium
  209. 209. University of British Columbia, Vancouver, BC, Canada
  210. 210. Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Research Institute, Toronto, ON, Canada
  211. 211. Merck Oncology, Kenilworth, NJ, United States
  212. 212. The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  213. 213. Georgetown University Medical Center, Washington, DC, United States
  214. 214. FDA/CDRH/OSEL/Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States
  215. 215. Department of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD, United States
  216. 216. Translational Medicine, Bristol-Myers Squibb, Princeton, NJ, United States
  217. 217. National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA, United States
  218. 218. Anatomic Pathology, Boston, MA, United States
  219. 219. Guy’s Hospital, London, United Kingdom
  220. 220. King’s College London, London, United Kingdom
  221. 221. Peking University First Hospital Breast Disease Center, Beijing, China
  222. 222. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  223. 223. Dipartimento di Scienze della Salute (DSS), Firenze, Italy
  224. 224. Department of Oncology, Champalimaud Clinical Centre, Lisbon, Portugal
  225. 225. Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health, Institute of Pathology, Berlin, Germany
  226. 226. Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, United States
  227. 227. Dana-Farber Cancer Institute, Boston, MA, United States
  228. 228. Department of Pathology, Fundacion Valle del Lili, Cali, Valle del Cauca, Colombia
  229. 229. The University of Queensland Centre for Clinical Research and Pathology Queensland, Brisbane, QLD, Australia
  230. 230. Department of Pathology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, United States
  231. 231. Department of Pathology, University Hospital of Bellvitge, Oncobell, IDIBELL, L’Hospitalet del Llobregat, Barcelona, 08908, Catalonia, Spain
  232. 232. Department of Development and Regeneration, Laboratory of Experimental Urology, KU Leuven, Leuven, Belgium
  233. 233. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  234. 234. Department of Medical Oncology, Austin Health, Heidelberg, VIC, Australia
  235. 235. Department of Surgery, Kansai Medical School, Hirakata, Japan
  236. 236. Roche Tissue Diagnostics, Digital Pathology, Santa Clara, CA, United States
  237. 237. Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
  238. 238. Pathology Department, H.U. Vall d’Hebron, Barcelona, Spain
  239. 239. Division of Bioinformatics and Biostatistics, US Food and Drug Administration, Silver Spring, MD, United States
  240. 240. Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Providence, RI, United States
  241. 241. Universite Paris-Est, Creteil, France
  242. 242. Praava Health, Dhaka, Bangladesh
  243. 243. Department of Pathology, Medical University of Vienna, Vienna, Austria

Source: npj Breast Cancer Published:2020


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. © 2020, The Author(s).