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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

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).
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