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Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (Stils) in Breast Cancer Publisher



Kos Z1 ; Roblin E2, 3 ; Kim RS4 ; Michiels S2, 3 ; Gallas BD5 ; Chen W5 ; Van De Vijver KK8, 9 ; Goel S10, 11 ; Adams S12 ; Demaria S13 ; Viale G14 ; Nielsen TO15 ; Badve SS16 ; Symmans WF17 Show All Authors
Authors
  1. Kos Z1
  2. Roblin E2, 3
  3. Kim RS4
  4. Michiels S2, 3
  5. Gallas BD5
  6. Chen W5
  7. Van De Vijver KK8, 9
  8. Goel S10, 11
  9. Adams S12
  10. Demaria S13
  11. Viale G14
  12. Nielsen TO15
  13. Badve SS16
  14. Symmans WF17
  15. Sotiriou C18
  16. Rimm DL19
  17. Hewitt S20
  18. Denkert C21
  19. Loibl S22
  20. Luen SJ11, 23
  21. Bartlett JMS24, 25
  22. Savas P11, 23
  23. Pruneri G26
  24. Dillon DA27, 28
  25. Cheang MCU29
  26. Tutt A30
  27. Hall JA31
  28. Kok M32
  29. Horlings HM8, 33
  30. Madabhushi A34, 35
  31. Van Der Laak J36
  32. Ciompi F36
  33. Laenkholm AV37
  34. Bellolio E38
  35. Gruosso T39
  36. Fox SB10, 40
  37. Araya JC41
  38. Floris G42
  39. Hudecek J43
  40. Voorwerk L44
  41. Beck AH45
  42. Kerner J45
  43. Larsimont D46
  44. Declercq S47
  45. Van Den Eynden G47
  46. Pusztai L48
  47. Ehinger A49
  48. Yang W50
  49. Abduljabbar K51
  50. Yuan Y51
  51. Singh R53
  52. Hiley C54
  53. Bakir M54
  54. Lazar AJ55
  55. Naber S56
  56. Wienert S57
  57. Castillo M58
  58. Curigliano G59
  59. Dieci MV60, 61
  60. Andre F62
  61. Swanton C54, 63
  62. Reisfilho J64, 65
  63. Sparano J66
  64. Balslev E67
  65. Chen IC68, 69, 70
  66. Stovgaard EIS67
  67. Poguegeile K4
  68. Blenman KRM48
  69. Penaultllorca F71
  70. Schnitt S27
  71. Lakhani SR72
  72. Vincentsalomon A73
  73. Rojo F74, 75
  74. Braybrooke JP76
  75. Hanna MG64
  76. Solermonso MT77
  77. Bethmann D78
  78. Castaneda CA58
  79. Willardgallo K79
  80. Sharma A80
  81. Lien HC81
  82. Fineberg S82
  83. Thagaard J83
  84. Comerma L75, 85
  85. Gonzalezericsson P86
  86. Brogi E64
  87. Loi S11, 23
  88. Saltz J87
  89. Klaushen F88
  90. Cooper L89
  91. Amgad M90
  92. Moore DA91, 92
  93. Salgado R23, 47
  94. Hyytiainen A93
  95. Hida AI94
  96. Thompson A95
  97. Lefevre A96
  98. Gown A97
  99. Lo A98
  100. Sapino A99
  101. Moreira AM100
  102. Richardson A101
  103. Vingiani A102
  104. Bellizzi AM103
  105. Guerrero A104
  106. Grigoriadis A105, 106
  107. Garridocastro AC107, 108
  108. Ciminomathews A109
  109. Srinivasan A4
  110. Acs B110
  111. Singh B111
  112. Calhoun B112
  113. Haibekans B113
  114. Solomon B11
  115. Thapa B114
  116. Nelson BH115
  117. Ballesteroesmerino C116
  118. Criscitiello C117
  119. Boeckx C96
  120. Colpaert C118
  121. Quinn C119
  122. Chennubhotla CS120
  123. Solinas C121
  124. Drubay D2, 3
  125. Sabanathan D122
  126. Peeters D123
  127. Zardavas D124
  128. Hoflmayer D125
  129. Johnson DB126
  130. Thompson EA127
  131. Perez E128
  132. Elgabry EA129
  133. Blackley EF11
  134. Reisenbichler E19
  135. Chmielik E130
  136. Gaire F131
  137. Lu FI132
  138. Azmoudehardalan F133
  139. Peale F134
  140. Hirsch FR135
  141. Acostahaab G136
  142. Farshid G137
  143. Broeckx G138
  144. Koeppen H98
  145. Haynes HR139
  146. Mcarthur H140
  147. Joensuu H141
  148. Olofsson H142
  149. Cree I143
  150. Nederlof I33
  151. Frahm I144
  152. Brcic I145
  153. Chan J146
  154. Ziai J98
  155. Brock J27
  156. Weseling J8
  157. Giltnane J98
  158. Lemonnier J147
  159. Zha J148
  160. Ribeiro J149
  161. Lennerz JK150
  162. Carter JM151
  163. Hartman J152
  164. Hainfellner J153
  165. Le Quesne J154
  166. Juco JW155
  167. Van Den Berg J8
  168. Sanchez J58
  169. Cucherousset J156
  170. Adam J157
  171. Balko JM158
  172. Saeger K159
  173. Siziopikou K160
  174. Sikorska K161
  175. Weber K22
  176. Steele KE148
  177. Emancipator K155
  178. El Bairi K162
  179. Allison KH163
  180. Korski K131
  181. Buisseret L79
  182. Shi L164
  183. Kooreman LFS165
  184. Molinero L134
  185. Estrada MV166
  186. Van Seijen M33
  187. Lacroixtriki M167
  188. Sebastian MM168
  189. Balancin ML169
  190. Mathieu MC171
  191. Van De Vijver M172
  192. Rebelatto MC148
  193. Piccart M173
  194. Goetz MP128
  195. Preusser M153
  196. Khojasteh M174
  197. Sanders ME175
  198. Regan MM108, 176
  199. Barnes M177
  200. Christie M178
  201. Misialek M179
  202. Ignatiadis M18
  203. De Maaker M33
  204. Van Bockstal M180
  205. Harbeck N181
  206. Tung N182
  207. Laudus N183
  208. Sirtaine N184
  209. Burchardi N22
  210. Ternes N2
  211. Radosevicrobin N185
  212. Gluz O186
  213. Grimm O131
  214. Nuciforo P187
  215. Jank P188
  216. Kirtani P189
  217. Watson PH15
  218. Jelinic P155
  219. Francis PA10, 11
  220. Russell PA190
  221. Pierce RH191
  222. Hills R192
  223. Leonferre R128
  224. De Wind R184
  225. Shui R50
  226. Leung S15
  227. Tabbarah S193
  228. Souza SC156
  229. Otoole S194
  230. Swain S195
  231. Dudgeon S5
  232. Willis S196
  233. Ely S197
  234. Bedri S198
  235. Irshad S199
  236. Liu S201
  237. Hendry S40
  238. Bianchi S202
  239. Braganca S203
  240. Paik S4
  241. Luz S204
  242. Gevaert T205
  243. Dalfons T64
  244. John T206
  245. Sugie T207
  246. Kurkure U174
  247. Bossuyt V150
  248. Manem V113
  249. Camaea VP208
  250. Tong W209
  251. Tran WT193
  252. Wang Y210
  253. Allory Y211
  254. Husain Z212
  255. Bagohorvath Z213

Source: npj Breast Cancer Published:2020


Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls. © 2020, The Author(s).
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