a b/processing/MACCROBAT/20146086.ann
1
T1  Age 2 13    54-year-old
2
T2  Sex 14 19   woman
3
T3  Disease_disorder 34 39  NSCLC
4
E1  Disease_disorder:T3 
5
T4  Detailed_description 25 33  stage IV
6
R1  MODIFY Arg1:T4 Arg2:E1  
7
T5  Medication 57 68    carboplatin
8
E2  Medication:T5 
9
T6  Medication 73 83    paclitaxel
10
E3  Medication:T6 
11
T8  Diagnostic_procedure 110 128    Molecular analysis
12
E4  Diagnostic_procedure:T8 
13
T9  Diagnostic_procedure 132 144    tumor tissue
14
E5  Diagnostic_procedure:T9 
15
R2  SUB_PROCEDURE Arg1:E5 Arg2:E4   
16
T10 Detailed_description 149 160    unavailable
17
R3  MODIFY Arg1:T10 Arg2:E4 
18
T12 Personal_background 209 214 Asian
19
T13 History 224 239 smoking history
20
T14 Severity 216 223    minimal
21
R4  MODIFY Arg1:T14 Arg2:T13    
22
T16 Medication 387 396  erlotinib
23
E7  Medication:T16 
24
T17 Lab_value 398 404   150 mg
25
R5  MODIFY Arg1:T17 Arg2:T15    
26
T18 Detailed_description 362 370    standard
27
R7  MODIFY Arg1:T18 Arg2:T15    
28
R8  BEFORE Arg1:E1 Arg2:E2  
29
*   OVERLAP E2 E3 E4
30
T19 Coreference 410 421 her disease
31
E9  Coreference:T19 
32
T20 Date 433 458    Twenty-eight months later
33
E10 Date:T20 
34
T21 Medication 487 496  erlotinib
35
E11 Medication:T21 
36
T22 Coreference 517 524 disease
37
E12 Coreference:T22 
38
T23 Detailed_description 525 537    systemically
39
T24 Sign_symptom 4114 4122  survived
40
E13 Sign_symptom:T24 
41
T25 Date 4123 4171  14 months following the diagnosis of CNS disease
42
E14 Date:T25 
43
T26 Disease_disorder 4160 4171  CNS disease
44
E15 Disease_disorder:T26 
45
*   OVERLAP E13 E14
46
T27 Date 3959 3974  One month later
47
E16 Date:T27 
48
T28 Medication 4032 4041    cetixumab
49
E17 Medication:T28 
50
T29 Medication 4046 4055    erlotinib
51
E18 Medication:T29 
52
T30 Lab_value 4095 4101 100 mg
53
T31 Dosage 4085 4093;4103 4108  low dose daily
54
R13 MODIFY Arg1:T30 Arg2:T31    
55
T33 Dosage 3933 3947    1500 mg weekly
56
T35 Medication 3948 3957    erlotinib
57
E19 Medication:T35 
58
R14 MODIFY Arg1:T33 Arg2:E19    
59
R16 MODIFY Arg1:T31 Arg2:E18    
60
A3  TREND E18 DEC
61
R18 BEFORE Arg1:E19 Arg2:E16    
62
T36 Disease_disorder 3988 4010  intra-thoracic disease
63
E20 Disease_disorder:T36 
64
T37 Detailed_description 3976 3987  progressive
65
R19 MODIFY Arg1:T37 Arg2:E20    
66
*   OVERLAP E16 E20
67
R20 BEFORE Arg1:E20 Arg2:E17    
68
*   OVERLAP E17 E18
69
R21 BEFORE Arg1:E18 Arg2:E13    
70
T38 Diagnostic_procedure 256 265    histology
71
E21 Diagnostic_procedure:T38 
72
T39 Detailed_description 241 255    non-small cell
73
R22 MODIFY Arg1:T39 Arg2:E21    
74
T40 Coreference 277 288 her disease
75
E22 Coreference:T40 
76
R23 IDENTICAL Arg1:E22 Arg2:E1  
77
A4  POLARITY E4 NEG
78
T47 History 256 265 histology
79
T48 Diagnostic_procedure 302 326    EGFR TKI sensitive cells
80
E23 Diagnostic_procedure:T48 
81
R24 MODIFY Arg1:E23 Arg2:E22    
82
R25 BEFORE Arg1:E23 Arg2:E7 
83
R26 IDENTICAL Arg1:E12 Arg2:E9  
84
T53 Detailed_description 502 513    progression
85
R27 MODIFY Arg1:T53 Arg2:E12    
86
*   OVERLAP E11 E12
87
T54 Medication 593 615  angiogenesis inhibitor
88
E24 Medication:T54 
89
T55 Detailed_description 580 592    experimental
90
R28 MODIFY Arg1:T55 Arg2:E24    
91
T56 Medication 631 641  pemetrexed
92
E25 Medication:T56 
93
T57 Coreference 654 677 standard dose erlotinib
94
E26 Coreference:T57 
95
*   OVERLAP E25 E26
96
T60 Date 703 718    11 months later
97
E27 Date:T60 
98
T61 Coreference 720 731 her disease
99
E28 Coreference:T61 
100
R29 IDENTICAL Arg1:E28 Arg2:E12 
101
T62 Detailed_description 738 748    progressed
102
R30 MODIFY Arg1:T62 Arg2:E28    
103
*   OVERLAP E28 E27 E30
104
R31 BEFORE Arg1:E26 Arg2:E27    
105
T67 Other_event 473 483 resistance
106
E29 Other_event:T67 
107
*   OVERLAP E10 E29
108
R32 MODIFY Arg1:E11 Arg2:E29    
109
R33 BEFORE Arg1:E12 Arg2:E24    
110
R34 BEFORE Arg1:E24 Arg2:E25    
111
T68 Diagnostic_procedure 773 779    biopsy
112
E30 Diagnostic_procedure:T68 
113
T69 Diagnostic_procedure 887 904    Direct sequencing
114
E31 Diagnostic_procedure:T69 
115
T70 Diagnostic_procedure 950 954    EGFR
116
E32 Diagnostic_procedure:T70 
117
T71 Detailed_description 933 946    kinase domain
118
R35 MODIFY Arg1:T71 Arg2:E32    
119
T72 Diagnostic_procedure 968 982    L858R mutation
120
E33 Diagnostic_procedure:T72 
121
R36 SUB_PROCEDURE Arg1:E33 Arg2:E32 
122
R37 SUB_PROCEDURE Arg1:E32 Arg2:E31 
123
T73 Diagnostic_procedure 1058 1072  T790M mutation
124
E34 Diagnostic_procedure:T73 
125
T74 Biological_structure 750 753    DNA
126
R38 MODIFY Arg1:T74 Arg2:E30    
127
T75 Disease_disorder 802 808    lesion
128
E35 Disease_disorder:T75 
129
T76 Biological_structure 797 801    lung
130
T77 Detailed_description 785 796    progressing
131
R39 MODIFY Arg1:T76 Arg2:E35    
132
R40 MODIFY Arg1:T77 Arg2:E35    
133
T78 Diagnostic_procedure 867 881    EGFR mutations
134
E36 Diagnostic_procedure:T78 
135
T79 Sign_symptom 1150 1159  headaches
136
E37 Sign_symptom:T79 
137
T80 Disease_disorder 1207 1217  metastases
138
E38 Disease_disorder:T80 
139
T81 Biological_structure 1203 1206  CNS
140
R41 MODIFY Arg1:T81 Arg2:E38    
141
A5  POLARITY E38 MAYBE_POS
142
T82 Diagnostic_procedure 1235 1242  imaging
143
E39 Diagnostic_procedure:T82 
144
T83 Lab_value 1226 1234 negative
145
R42 MODIFY Arg1:T83 Arg2:E39    
146
A6  POLARITY E39 NEG
147
T84 Detailed_description 908 919    exons 18–21
148
R43 MODIFY Arg1:T84 Arg2:T71    
149
T85 Detailed_description 999 1019   EGFR TKI sensitivity
150
R44 MODIFY Arg1:T85 Arg2:E33    
151
T86 Detailed_description 1089 1117  acquired EGFR TKI resistance
152
R45 MODIFY Arg1:T86 Arg2:E34    
153
T87 Therapeutic_procedure 1270 1285 lumbar puncture
154
E40 Therapeutic_procedure:T87 
155
A7  POLARITY E40 NEG
156
T88 Medication 1309 1321    temozolomide
157
E41 Medication:T88 
158
T89 Detailed_description 1301 1308  empiric
159
R46 MODIFY Arg1:T89 Arg2:E41    
160
R47 MODIFY Arg1:T23 Arg2:E12    
161
R50 MODIFY Arg1:E35 Arg2:E30    
162
T90 Detailed_description 1327 1340  standard dose
163
T92 Medication 1341 1350    erlotinib
164
E6  Medication:T92 
165
T93 Dosage 1352 1364    150 mg daily
166
T91 Disease_disorder 1379 1390  CNS disease
167
E42 Disease_disorder:T91 
168
A8  POLARITY E42 MAYBE_POS
169
T94 Time 1396 1411  after one cycle
170
E43 Time:T94 
171
T95 Sign_symptom 1416 1425  headaches
172
E44 Sign_symptom:T95 
173
T96 Lab_value 1426 1434 worsened
174
R51 MODIFY Arg1:T96 Arg2:E44    
175
T97 Sign_symptom 1454 1460  nausea
176
E45 Sign_symptom:T97 
177
T98 Sign_symptom 1465 1473  vomiting
178
E46 Sign_symptom:T98 
179
T99 Disease_disorder 1489 1503  CNS metastases
180
E47 Disease_disorder:T99 
181
T100    Diagnostic_procedure 1527 1548  intracranial pressure
182
E48 Diagnostic_procedure:T100 
183
T101    Lab_value 1520 1526 raised
184
R52 MODIFY Arg1:T101 Arg2:E48   
185
T102    Diagnostic_procedure 1550 1576  Magnetic resonance imaging
186
E49 Diagnostic_procedure:T102 
187
T103    Diagnostic_procedure 1577 1582  (MRI)
188
E50 Diagnostic_procedure:T103 
189
R53 IDENTICAL Arg1:E50 Arg2:E49 
190
T104    Biological_structure 1590 1595  brain
191
T105    Diagnostic_procedure 1637 1649  CSF cytology
192
E51 Diagnostic_procedure:T105 
193
R54 MODIFY Arg1:T104 Arg2:E50   
194
R55 SUB_PROCEDURE Arg1:E51 Arg2:E50 
195
T106    Disease_disorder 1613 1615  LM
196
E52 Disease_disorder:T106 
197
T107    Biological_structure 1685 1688  DNA
198
T108    Diagnostic_procedure 1673 1683  sequencing
199
E53 Diagnostic_procedure:T108 
200
T109    Detailed_description 1666 1672  direct
201
R56 MODIFY Arg1:T109 Arg2:E53   
202
T110    Diagnostic_procedure 1694 1703  CSF cells
203
E54 Diagnostic_procedure:T110 
204
T111    Diagnostic_procedure 1713 1718  L858R
205
E55 Diagnostic_procedure:T111 
206
T112    Diagnostic_procedure 1730 1750  EGFR TKI sensitivity
207
E56 Diagnostic_procedure:T112 
208
T113    Diagnostic_procedure 1783 1808  T790M resistance mutation
209
E57 Diagnostic_procedure:T113 
210
T114    Diagnostic_procedure 1850 1855  T790M
211
E58 Diagnostic_procedure:T114 
212
A9  POLARITY E58 NEG
213
T115    Lab_value 1860 1868 negative
214
R57 MODIFY Arg1:T115 Arg2:E58   
215
A10 POLARITY E56 MAYBE_POS
216
A11 POLARITY E57 MAYBE_NEG
217
T116    Coreference 1872 1883   this sample
218
E59 Coreference:T116 
219
R58 IDENTICAL Arg1:E59 Arg2:E54 
220
T117    Diagnostic_procedure 1948 1953  assay
221
E60 Diagnostic_procedure:T117 
222
T118    Lab_value 1900 1914 more sensitive
223
T119    Detailed_description 1915 1937  fluorescence detection
224
T120    Detailed_description 1938 1947  PCR-based
225
R59 MODIFY Arg1:T120 Arg2:E60   
226
R60 MODIFY Arg1:T119 Arg2:E60   
227
R61 MODIFY Arg1:T118 Arg2:E60   
228
T121    Diagnostic_procedure 1980 2024  PCR restriction fragment length polymorphism
229
E61 Diagnostic_procedure:T121 
230
T122    Coreference 2038 2068   the specific missense mutation
231
E62 Coreference:T122 
232
T123    Coreference 2120 2131   That result
233
E63 Coreference:T123 
234
A12 POLARITY E63 NEG
235
T124    Lab_value 2141 2149 negative
236
R62 MODIFY Arg1:T124 Arg2:E63   
237
T125    Diagnostic_procedure 2163 2177  wild type peak
238
E64 Diagnostic_procedure:T125 
239
A13 POLARITY E64 POS
240
R63 IDENTICAL Arg1:E63 Arg2:E60 
241
R64 SUB_PROCEDURE Arg1:E62 Arg2:E61 
242
R65 IDENTICAL Arg1:E62 Arg2:E57 
243
T155    Diagnostic_procedure 3025 3049  Pharmacokinetic analysis
244
E76 Diagnostic_procedure:T155 
245
T156    Biological_structure 3053 3056  CSF
246
R81 MODIFY Arg1:T156 Arg2:E76   
247
T157    Subject 3062 3077   another patient
248
T158    Disease_disorder 3089 3091  LM
249
E77 Disease_disorder:T158 
250
T159    Disease_disorder 3083 3088  NSCLC
251
E78 Disease_disorder:T159 
252
R82 MODIFY Arg1:E78 Arg2:E77    
253
T160    Dosage 3117 3124;3135 3141  1500 mg weekly
254
T162    Medication 3125 3134    erlotinib
255
E79 Medication:T162 
256
R88 MODIFY Arg1:T160 Arg2:E79   
257
R90 MODIFY Arg1:T93 Arg2:T90    
258
R91 MODIFY Arg1:T90 Arg2:E6 
259
T165    Lab_value 3186 3195 11,300 nM
260
T166    Diagnostic_procedure 3157 3182  peak plasma concentration
261
E80 Diagnostic_procedure:T166 
262
T169    Lab_value 3235 3241 130 nM
263
T170    Diagnostic_procedure 3214 3231  CSF concentration
264
E81 Diagnostic_procedure:T170 
265
R75 MODIFY Arg1:T169 Arg2:E81   
266
R92 MODIFY Arg1:T165 Arg2:E80   
267
T172    Detailed_description 3333 3351  exceeding the IC50
268
R93 MODIFY Arg1:T172 Arg2:T169  
269
T178    Dosage 3458 3474    high-dose weekly
270
T179    Medication 3475 3484    erlotinib
271
E87 Medication:T179 
272
T180    Lab_value 3488 3495 1000 mg
273
T181    Lab_value 3501 3508 1200 mg
274
R96 MODIFY Arg1:T178 Arg2:E87   
275
R98 MODIFY Arg1:T180 Arg2:T178  
276
R99 MODIFY Arg1:T181 Arg2:T178  
277
R100    MODIFY Arg1:T178 Arg2:E87   
278
T182    Sign_symptom 3521 3527  nausea
279
E88 Sign_symptom:T182 
280
T183    Detailed_description 3510 3520  persistent
281
R102    MODIFY Arg1:T183 Arg2:E88   
282
T184    Diagnostic_procedure 3552 3576  Pharmacokinetic analysis
283
E89 Diagnostic_procedure:T184 
284
A15 POLARITY E89 NEG
285
T186    Disease_disorder 3758 3771  hydrocephalus
286
E91 Disease_disorder:T186 
287
T187    Sign_symptom 3787 3795  symptoms
288
E92 Sign_symptom:T187 
289
T188    Detailed_description 3776 3786  persistent
290
R104    MODIFY Arg1:T188 Arg2:E92   
291
T189    Diagnostic_procedure 3819 3840  intracranial pressure
292
E93 Diagnostic_procedure:T189 
293
T190    Therapeutic_procedure 3850 3858 VP shunt
294
E94 Therapeutic_procedure:T190 
295
T191    Lab_value 3809 3818 increased
296
R105    MODIFY Arg1:T191 Arg2:E93   
297
T192    Therapeutic_procedure 3875 3892 radiation therapy
298
E95 Therapeutic_procedure:T192 
299
T193    Biological_structure 3863 3874  whole-brain
300
R106    MODIFY Arg1:T193 Arg2:E95   
301
T7  Detailed_description 84 108 without disease response
302
R9  MODIFY Arg1:T7 Arg2:E2  
303
R10 MODIFY Arg1:T7 Arg2:E3  
304
A2  POLARITY E23 MAYBE_POS
305
*   OVERLAP E5 E23
306
R11 IDENTICAL Arg1:E9 Arg2:E22  
307
R12 BEFORE Arg1:E7 Arg2:E9  
308
T11 Detailed_description 422 431    responded
309
R107    MODIFY Arg1:T11 Arg2:E9 
310
R108    BEFORE Arg1:E9 Arg2:E10 
311
#1  AnnotatorNotes E29  Not sure how to label drug resistance 
312
R109    SUB_PROCEDURE Arg1:E36 Arg2:E30 
313
R110    SUB_PROCEDURE Arg1:E31 Arg2:E36 
314
R111    SUB_PROCEDURE Arg1:E34 Arg2:E8  
315
T41 Coreference 1033 1035   It
316
E8  Coreference:T41 
317
R112    IDENTICAL Arg1:E8 Arg2:E31  
318
*   OVERLAP E34 E37 E38 E39 E40 E41 E6 E42
319
R113    BEFORE Arg1:E42 Arg2:E43    
320
*   OVERLAP E43 E44 E45 E46 E47
321
A1  POLARITY E47 MAYBE_POS
322
R114    MODIFY Arg1:E48 Arg2:E47    
323
*   OVERLAP E48 E49
324
R115    MODIFY Arg1:E52 Arg2:E50    
325
R116    MODIFY Arg1:E52 Arg2:E51    
326
*   OVERLAP E51 E53
327
R117    MODIFY Arg1:T107 Arg2:E54   
328
R118    SUB_PROCEDURE Arg1:E54 Arg2:E53 
329
R119    SUB_PROCEDURE Arg1:E55 Arg2:E54 
330
R120    SUB_PROCEDURE Arg1:E56 Arg2:E55 
331
R121    SUB_PROCEDURE Arg1:E57 Arg2:E54 
332
*   OVERLAP E57 E58 E60
333
R122    SUB_PROCEDURE Arg1:E61 Arg2:E60 
334
*   OVERLAP E62 E63
335
R123    SUB_PROCEDURE Arg1:E64 Arg2:E63 
336
R66 MODIFY Arg1:T157 Arg2:E76   
337
R67 MODIFY Arg1:E77 Arg2:T157   
338
*   OVERLAP E77 E79 E80 E81
339
*   OVERLAP E64 E76
340
R68 BEFORE Arg1:E81 Arg2:E87    
341
*   OVERLAP E87 E88 E89
342
T42 Date 3613 3626  After 1 month
343
E65 Date:T42 
344
R69 BEFORE Arg1:E89 Arg2:E65    
345
T43 Diagnostic_procedure 3684 3687  MRI
346
E66 Diagnostic_procedure:T43 
347
T44 Biological_structure 3678 3683  brain
348
R70 MODIFY Arg1:T44 Arg2:E66    
349
T45 Date 3701 3715  after 2 months
350
E67 Date:T45 
351
T46 Biological_structure 3723 3735  cauda equina
352
R71 BEFORE Arg1:E66 Arg2:E67    
353
T49 Disease_disorder 3672 3674  LM
354
E68 Disease_disorder:T49 
355
T50 Diagnostic_procedure 3639 3668  partial radiographic response
356
E69 Diagnostic_procedure:T50 
357
R72 MODIFY Arg1:E68 Arg2:E69    
358
*   OVERLAP E65 E69
359
R73 SUB_PROCEDURE Arg1:E69 Arg2:E66 
360
*   OVERLAP E67 E91 E66 E92 E93
361
R74 MODIFY Arg1:T46 Arg2:E66    
362
R76 BEFORE Arg1:E93 Arg2:E94    
363
*   OVERLAP E94 E95
364
R77 BEFORE Arg1:E95 Arg2:E19    
365
T15 Dosage 371 383  daily dosing
366
R6  MODIFY Arg1:T15 Arg2:E7 
367
R48 IDENTICAL Arg1:E26 Arg2:E7