1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:47,360 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:47,360 --> 00:00:50,280 OUR PRESENTERS TODAY INCLUDE DR. 12 00:00:50,280 --> 00:00:51,720 CHRISTINA ANNUNZIATA, SENIOR 13 00:00:51,720 --> 00:00:54,920 VISITOR IN WOMEN'S MALIGNANCIES 14 00:00:54,920 --> 00:00:56,440 BRANCH CENTER FOR CANCER 15 00:00:56,440 --> 00:00:57,160 RESEARCH NCI. 16 00:00:57,160 --> 00:00:59,920 DR. ELAINE JAFFE, NIH 17 00:00:59,920 --> 00:01:01,440 DISTINGUISHED INVESTIGATOR, 18 00:01:01,440 --> 00:01:02,960 LABORATORY OF PATHOLOGY, ALSO AT 19 00:01:02,960 --> 00:01:05,120 NCI. 20 00:01:05,120 --> 00:01:07,600 DR. ASHKAN MALAYERI, LEAD 21 00:01:07,600 --> 00:01:09,640 RADIOLOGIST FOR BODY MRI NIH 22 00:01:09,640 --> 00:01:13,360 CLINICAL CENTER. 23 00:01:13,360 --> 00:01:18,000 DR. DIANENA BAN BIANCHI, NHGRI 24 00:01:18,000 --> 00:01:19,240 AND DIRECTOR OF THE NATIONAL 25 00:01:19,240 --> 00:01:20,840 INSTITUTE OF CHILD HEALTH AND 26 00:01:20,840 --> 00:01:22,480 HUMAN DEVELOPMENT. 27 00:01:22,480 --> 00:01:24,400 AND MS. AMY TURRIFF, GENETIC 28 00:01:24,400 --> 00:01:26,240 COUNSELOR IN THE CENTER FOR 29 00:01:26,240 --> 00:01:28,720 PRECISION HEALTH RESEARCH NHGRI. 30 00:01:28,720 --> 00:01:30,680 WE ARE GOING TO HEAR TODAY ABOUT 31 00:01:30,680 --> 00:01:33,480 WHAT NOT TO EXPECT WHEN 32 00:01:33,480 --> 00:01:35,040 EXPECTING, THE IDENTIFY STUDY. 33 00:01:35,040 --> 00:01:38,120 WITH THAT I'LL HAND IT OVER. 34 00:01:38,120 --> 00:01:41,840 >> THANKS SO MUCH, DR. BAROCHIA. 35 00:01:41,840 --> 00:01:44,040 TODAY WE WILL PRESENT TO YOU A 36 00:01:44,040 --> 00:01:45,400 CASE WHICH IS A PATIENT WHO 37 00:01:45,400 --> 00:01:48,640 ENROLLED ON OUR IDENTIFY STUDY. 38 00:01:48,640 --> 00:01:51,080 NEXT SLIDE. 39 00:01:51,080 --> 00:01:52,520 JUST TO NOTE THAT NONE OF US 40 00:01:52,520 --> 00:01:53,880 HAVE FINANCIAL DISCLOSURES. 41 00:01:53,880 --> 00:01:56,200 THE OUTLINE OF OUR PRESENTATION 42 00:01:56,200 --> 00:01:57,640 TODAY WILL START WITH THE CASE 43 00:01:57,640 --> 00:01:59,400 PRESENTATION, GO THROUGH 44 00:01:59,400 --> 00:02:01,480 IMAGING, THEN PATHOLOGY, THEN DO 45 00:02:01,480 --> 00:02:03,720 A CLINICAL FOLLOW-UP AND THEN A 46 00:02:03,720 --> 00:02:05,880 DISCUSSION OF THE BACKGROUND AND 47 00:02:05,880 --> 00:02:10,040 FUTURE RESEARCH FOR THE STUDY. 48 00:02:10,040 --> 00:02:11,440 SO THE CASE PRESENTATION STARTS 49 00:02:11,440 --> 00:02:14,000 WITH A 31-YEAR-OLD WOMAN, THIS 50 00:02:14,000 --> 00:02:15,000 WAS HER FIRST PREGNANCY. 51 00:02:15,000 --> 00:02:16,240 SHE WAS OTHERWISE HEALTHY 52 00:02:16,240 --> 00:02:18,840 WITHOUT ANY OTHER SYMPTOMS. 53 00:02:18,840 --> 00:02:21,640 IN APRIL 2021 AT 12 WEEKS 54 00:02:21,640 --> 00:02:23,520 PREGNANT SHE UNDERWENT 55 00:02:23,520 --> 00:02:25,560 NON-INVASIVE PRE-NATAL TEST OR 56 00:02:25,560 --> 00:02:29,960 NIPT THAT SHOWED MON SEWMY 1 AND 57 00:02:29,960 --> 00:02:30,280 TRY SEWMY TWO. 58 00:02:30,280 --> 00:02:32,000 I WILL GET INTO THOSE DETAILS IN 59 00:02:32,000 --> 00:02:32,480 A BIT. 60 00:02:32,480 --> 00:02:36,240 IN MAY OF 2021, WHEN SHE WAS 16 61 00:02:36,240 --> 00:02:39,680 WEEKS PREGNANT SHE UNDERWENT 62 00:02:39,680 --> 00:02:41,640 AMNIOCENTESIS AND FOUND TO HAVE 63 00:02:41,640 --> 00:02:45,720 NORMAL FETAL KARYOTYPE. 64 00:02:45,720 --> 00:02:48,840 SO WHAT IS THE NIPT TEST? 65 00:02:48,840 --> 00:02:52,040 THERE ARE SEVERAL TESTS FOR 66 00:02:52,040 --> 00:02:54,440 PRE-NATAL TESTS FOR FETAL 67 00:02:54,440 --> 00:02:55,040 AANYPLOIDIES. 68 00:02:55,040 --> 00:02:58,800 WE ARE LOOKING FOR COMMON FETAL 69 00:02:58,800 --> 00:03:02,480 ANE UPLOIDE IRKS SERKS. 70 00:03:02,480 --> 00:03:04,240 THESE ARE INCREASED RISK OF 71 00:03:04,240 --> 00:03:05,920 HAVING THESE WITH INCREASING 72 00:03:05,920 --> 00:03:08,000 MATERNAL AGE BUT ALSO OTHER 73 00:03:08,000 --> 00:03:08,640 FACTORS. 74 00:03:08,640 --> 00:03:10,600 THE SCREENING TEST THAT ARE 75 00:03:10,600 --> 00:03:15,080 AVAILABLE FOR FETAL ANEUPLOIDY 76 00:03:15,080 --> 00:03:17,200 INCLUDE FIRST TRIMESTER, IS 10 77 00:03:17,200 --> 00:03:19,600 TO 14 WEEKS HAVE A SERUM ANOLYTE 78 00:03:19,600 --> 00:03:22,480 TEST DRAWN WHICH IS THE BETA HCG 79 00:03:22,480 --> 00:03:28,080 AND THE PATH A AND ALSO 80 00:03:28,080 --> 00:03:28,800 ULTRASOUND. 81 00:03:28,800 --> 00:03:31,880 AT 15 TO 22 WEEKS, SECOND 82 00:03:31,880 --> 00:03:33,880 TRIMESTER WOMEN WITH UNDERGO 83 00:03:33,880 --> 00:03:35,200 QUADRUPLE SCREEN WHICH INCLUDES 84 00:03:35,200 --> 00:03:42,800 THE BETA HCG AFP, ESTRADIOL AND 85 00:03:42,800 --> 00:03:43,160 DIA. 86 00:03:43,160 --> 00:03:45,360 THROUGHOUT THE PREGNANCY THOUGH 87 00:03:45,360 --> 00:03:47,600 FROM TEN TO 40 WEEKS PATIENTS 88 00:03:47,600 --> 00:03:49,800 WITH CAN UNDERGO THE 89 00:03:49,800 --> 00:03:50,920 NON-INVASIVE PRE-NATAL TEST 90 00:03:50,920 --> 00:03:53,520 WHICH IS SELF RADON -- CELL FREE 91 00:03:53,520 --> 00:03:55,400 DNA. 92 00:03:55,400 --> 00:03:58,400 SO THE NIPT TEST IS AS I 93 00:03:58,400 --> 00:03:59,840 MENTIONED A SCREENING TEST FOR 94 00:03:59,840 --> 00:04:03,040 FETAL CHROMOSOMAL ABNORMALITIES 95 00:04:03,040 --> 00:04:07,760 OR ANEUPLOIDY, IT HAS A HIGHER 96 00:04:07,760 --> 00:04:09,280 POSITIVE PREDICTIVE VALUE THAN 97 00:04:09,280 --> 00:04:10,520 SERUM ANOLYTE TESTING. 98 00:04:10,520 --> 00:04:11,640 THE OTHER BENEFIT IS IT CAN 99 00:04:11,640 --> 00:04:14,080 IDENTIFY THE SEX OF THE BABY SO 100 00:04:14,080 --> 00:04:16,640 THIS MAKES IT A VERY ATTRACTIVE 101 00:04:16,640 --> 00:04:18,920 TEST FOR BOTH PREGNANT WOMAN, 102 00:04:18,920 --> 00:04:20,800 PREGNANT FAMILY AND THE 103 00:04:20,800 --> 00:04:23,200 PHYSICIAN TREATING THE PATIENT. 104 00:04:23,200 --> 00:04:25,040 THIS TEST CAN BE OFFERED TO ALL 105 00:04:25,040 --> 00:04:27,600 PREGNANT PATIENTS REGARDLESS OF 106 00:04:27,600 --> 00:04:27,760 AGE. 107 00:04:27,760 --> 00:04:29,840 IT IS AS I MENTIONED A CELL FREE 108 00:04:29,840 --> 00:04:31,080 DNA TEST SO IT IS BASICALLY 109 00:04:31,080 --> 00:04:33,400 LOOKING FOR THE FETAL FRACTION 110 00:04:33,400 --> 00:04:36,400 OF CELL FREE DNA IN THE MATERNAL 111 00:04:36,400 --> 00:04:36,760 CIRCULATION. 112 00:04:36,760 --> 00:04:38,640 CELL FREE DNA FROM FETUS CAN BE 113 00:04:38,640 --> 00:04:40,960 DETECTED STARTING AT 9 TO 10 114 00:04:40,960 --> 00:04:43,160 WEEKS GESTATION, AND IT DOES 115 00:04:43,160 --> 00:04:43,640 INCREASE THROUGHOUT THE 116 00:04:43,640 --> 00:04:45,000 PREGNANCY. 117 00:04:45,000 --> 00:04:46,200 BY END OF THE PREGNANCY IT CAN 118 00:04:46,200 --> 00:04:49,160 BE AS MUCH AS 13% OF THE TOTAL 119 00:04:49,160 --> 00:04:52,800 CELL FREE DNA IN THE MATERNAL 120 00:04:52,800 --> 00:04:55,760 BLOOD. 121 00:04:55,760 --> 00:04:57,360 WHEN ONE OF THESE SCREENING 122 00:04:57,360 --> 00:05:00,120 TESTS IS ABNORMAL, A WOMAN WILL 123 00:05:00,120 --> 00:05:02,360 THEN PROCEED TO A DIAGNOSTIC 124 00:05:02,360 --> 00:05:02,560 TEST. 125 00:05:02,560 --> 00:05:06,720 SO THE DIAGNOSTIC TEST CAN BE AN 126 00:05:06,720 --> 00:05:10,760 AMNIOCENTESIS OR CORIONIC 127 00:05:10,760 --> 00:05:13,360 SAMPLING THAT CAN LOOK AT FETAL 128 00:05:13,360 --> 00:05:14,480 KARYOTYPES THE CELLSOMES IN MORE 129 00:05:14,480 --> 00:05:15,080 DETAIL. 130 00:05:15,080 --> 00:05:17,640 WHEN THE RESULTS OF THE NIPT 131 00:05:17,640 --> 00:05:20,760 TESTS ARE NON-REPORTABLE, THE 132 00:05:20,760 --> 00:05:21,720 LABORATORY THIS MEANS THE 133 00:05:21,720 --> 00:05:24,040 LABORATORY IS REALLY UNABLE TO 134 00:05:24,040 --> 00:05:25,680 RETURN THE FETAL RISK 135 00:05:25,680 --> 00:05:26,200 ASSESSMENT. 136 00:05:26,200 --> 00:05:28,720 THIS ACTUALLY CAN MEAN THAT 137 00:05:28,720 --> 00:05:30,640 THERE IS ACTUALLY INCREASE RISK 138 00:05:30,640 --> 00:05:32,720 OF FETAL CHROMOSOMAL 139 00:05:32,720 --> 00:05:34,520 ABNORMALITIES BUT THESE MIGHT BE 140 00:05:34,520 --> 00:05:37,320 OTHER THAN THE 13, 18 OR 21 THAT 141 00:05:37,320 --> 00:05:38,840 IS INVOLVED. 142 00:05:38,840 --> 00:05:41,840 SO IF IF THE WOMAN UNDERGOES A 143 00:05:41,840 --> 00:05:43,200 DIAGNOSTIC TEST AFTER 144 00:05:43,200 --> 00:05:46,160 NON-REPORTABLE NIPT, AND THE 145 00:05:46,160 --> 00:05:47,240 DIAGNOSTIC TEST THEN SHOWS 146 00:05:47,240 --> 00:05:49,120 NORMAL FETAL CHROMOSOMES, THERE 147 00:05:49,120 --> 00:05:50,800 IS NO STANDARD RECOMMENDATIONS 148 00:05:50,800 --> 00:05:53,440 FOR WHAT TO DO FOR THE MATERNAL 149 00:05:53,440 --> 00:05:54,080 EVALUATION. 150 00:05:54,080 --> 00:05:57,320 WHAT'S GOING ON IN THE MATERNAL 151 00:05:57,320 --> 00:05:57,720 CIRCULATION. 152 00:05:57,720 --> 00:05:59,960 NEXT SLIDE. 153 00:05:59,960 --> 00:06:05,040 SO AS I MENTION R BP AT 12 WEEKS 154 00:06:05,040 --> 00:06:08,280 PREGNANT UNDERWENT NIPT AND HER 155 00:06:08,280 --> 00:06:09,840 RESULTS WERE INITIALLY DELIVERED 156 00:06:09,840 --> 00:06:13,680 AS NON-REPORTABLE. 157 00:06:13,680 --> 00:06:16,480 SO THIS IS WHAT SHE GOT 158 00:06:16,480 --> 00:06:19,560 RETURNED, SHE HAD NORMAL 13, 18 159 00:06:19,560 --> 00:06:21,760 AND 21 BUT THERE WAS A LITTLE 160 00:06:21,760 --> 00:06:25,320 SORT OF FINE PRINT BOX THERE 161 00:06:25,320 --> 00:06:28,480 SAYING THAT THESE REGIONS ARE 162 00:06:28,480 --> 00:06:31,240 NEGATIVE BUT THESE MIGHT REFLECT 163 00:06:31,240 --> 00:06:34,360 OTHER CHROMOSOMAL FETAL 164 00:06:34,360 --> 00:06:38,040 ABNORMALITIES, PLACENTAL AND/OR 165 00:06:38,040 --> 00:06:39,600 THE PATIENT HERSELF MAY BE DUE 166 00:06:39,600 --> 00:06:41,040 TO MATERNAL CONDITIONS OR MAYBE 167 00:06:41,040 --> 00:06:41,760 A FALSE POSITIVE. 168 00:06:41,760 --> 00:06:44,600 SO BASICALLY THEN THE LITTLE 169 00:06:44,600 --> 00:06:46,280 FINE PRINT UNDER THAT IS THAT 170 00:06:46,280 --> 00:06:47,240 GENETIC COUNSELING IS 171 00:06:47,240 --> 00:06:50,840 RECOMMENDED. 172 00:06:50,840 --> 00:06:52,840 SO WHEN WE INQUIRED A LITTLE BIT 173 00:06:52,840 --> 00:06:54,040 MORE WHEN SHE INQUIRED A LITTLE 174 00:06:54,040 --> 00:06:57,040 BIT MORE ABOUT WHAT WERE THESE 175 00:06:57,040 --> 00:06:58,600 OTHER FINDINGS, TURNED OUT WHAT 176 00:06:58,600 --> 00:07:01,600 THEY HAD FOUND ON THE SCREENING 177 00:07:01,600 --> 00:07:04,320 TEST WAS A MONOSOMY OF 178 00:07:04,320 --> 00:07:07,000 CHROMOSOME 1 AND TRISOMY OF 179 00:07:07,000 --> 00:07:11,280 CHROMOSOME 2. 180 00:07:11,280 --> 00:07:14,440 SO SHE DID UNDERGO AMNIOCENTESIS 181 00:07:14,440 --> 00:07:15,640 AT 16 WEEKS PREGNANT AND THAT 182 00:07:15,640 --> 00:07:19,240 SHOWED A NORMAL FETAL KARYOTYPE. 183 00:07:19,240 --> 00:07:20,680 SO BASED ON THAT SHE WAS 184 00:07:20,680 --> 00:07:23,000 ELIGIBLE TO ENROLL IN OUR STUDY, 185 00:07:23,000 --> 00:07:25,240 THE IDENTIFY STUDY, WHEN SHE WAS 186 00:07:25,240 --> 00:07:26,400 28 WEEKS PREGNANT. 187 00:07:26,400 --> 00:07:28,240 SO THE IDENTIFY STUDY WE HAVE 188 00:07:28,240 --> 00:07:31,880 OPEN HERE IN THE CLINICAL CENTER 189 00:07:31,880 --> 00:07:36,440 IS 19C 0132, IT IS AN NCI STUDY. 190 00:07:36,440 --> 00:07:38,840 AND IT IS CALLED INCIDENTAL 191 00:07:38,840 --> 00:07:40,640 DETECTION OF MATERNAL NEOPLASIA 192 00:07:40,640 --> 00:07:42,640 THROUGH NON-INVASIVE CELL FREE 193 00:07:42,640 --> 00:07:44,360 DNA ANALYSIS. 194 00:07:44,360 --> 00:07:48,400 NEXT SLIDE. 195 00:07:48,400 --> 00:07:49,960 JUST BRIEFLY TO EMPHASIZE THIS 196 00:07:49,960 --> 00:07:52,320 WAS A HEALTHY PATIENT SHE HAD 197 00:07:52,320 --> 00:07:53,520 REALLY NO OTHER PAST MEDICAL 198 00:07:53,520 --> 00:07:56,240 HISTORY. 199 00:07:56,240 --> 00:07:59,960 SHE HAD FAMILY HISTORY 200 00:07:59,960 --> 00:08:02,280 SIGNIFICANT WITH MATERNAL 201 00:08:02,280 --> 00:08:05,840 GRANDMOTHER ENDOMETRIAL EARLY 202 00:08:05,840 --> 00:08:08,760 STAGE CANCER LIST RECKTOMY BUT 203 00:08:08,760 --> 00:08:10,800 NO FURTHER ADJUVANT THERAPY. 204 00:08:10,800 --> 00:08:12,560 A PATERNAL GRANDFATHER HAD LUNG 205 00:08:12,560 --> 00:08:14,640 CANCER AFTER HEAVY SMOKING 206 00:08:14,640 --> 00:08:16,440 HISTORY, AGAIN EARLY STAGE AND 207 00:08:16,440 --> 00:08:23,280 HAS BEEN IN REMISSION 10 YEARS. 208 00:08:23,280 --> 00:08:25,280 REST OF HISTORY WAS NEGATIVE, 209 00:08:25,280 --> 00:08:26,880 REVIEW OF SYSTEMS WAS NEGATIVE, 210 00:08:26,880 --> 00:08:30,560 ASYMPTOMATIC. 211 00:08:30,560 --> 00:08:32,960 LABORATORIES SHOW MILD ANEMIA 212 00:08:32,960 --> 00:08:35,720 PREGNANCY 11.5 HEMOGLOBIN 213 00:08:35,720 --> 00:08:39,440 OTHERWISE NORMAL. 214 00:08:39,440 --> 00:08:42,640 SO NOW I WILL TURN IT OVER TO 215 00:08:42,640 --> 00:08:44,640 DR. MALAYERI TOLL DISCUSS MRI 216 00:08:44,640 --> 00:08:47,480 FINDINGS. 217 00:08:47,480 --> 00:08:48,240 >> THANK YOU VERY MUCH. 218 00:08:48,240 --> 00:08:50,120 I WILL GO OVER THE MRI AND WHAT 219 00:08:50,120 --> 00:08:51,920 WE DO FOR SCREENING PATIENTS FOR 220 00:08:51,920 --> 00:08:53,600 HIGH RISK AT NIH. 221 00:08:53,600 --> 00:08:56,680 WE HAVE A LOT OF EXPERIENCE WITH 222 00:08:56,680 --> 00:08:58,440 THESE PATIENTS AND DOING WHOLE 223 00:08:58,440 --> 00:08:59,240 BODY MRI. 224 00:08:59,240 --> 00:09:00,400 I WILL SPECIFICALLY TALK ABOUT 225 00:09:00,400 --> 00:09:03,360 WHAT WE DO IN PATIENTS WHO ARE 226 00:09:03,360 --> 00:09:05,160 ENROLLED IN IDENTIFY STUDY. 227 00:09:05,160 --> 00:09:06,960 THIS IS AN OUTLINE OF SOME OF 228 00:09:06,960 --> 00:09:09,040 THE SEQUENCES WE RUN IN THIS 229 00:09:09,040 --> 00:09:12,280 PATIENTS, AS YOU CAN SEE ON THE 230 00:09:12,280 --> 00:09:15,960 LEFT THERE ARE TWO CHORONAL 231 00:09:15,960 --> 00:09:18,040 IMAGES STITCHED TOGETHER TO GIVE 232 00:09:18,040 --> 00:09:19,560 A SEAMLESS VIEW OF PATIENT AS IF 233 00:09:19,560 --> 00:09:21,360 THE PATIENT IS STANDING IN FRONT 234 00:09:21,360 --> 00:09:24,240 OF YOU. 235 00:09:24,240 --> 00:09:26,440 AND WE SCAN THE ENTIRE BODY FOR 236 00:09:26,440 --> 00:09:28,800 ANY ABNORMAL SIGNAL. 237 00:09:28,800 --> 00:09:31,080 AND IN ORDER TO GET A MORE 238 00:09:31,080 --> 00:09:34,240 DETAIL LOOK INSIDE BODY, WE 239 00:09:34,240 --> 00:09:36,480 ACQUIRED THE AXIAL IMAGES ON THE 240 00:09:36,480 --> 00:09:41,120 RIGHT SIDE OF THE SCREEN, T 1 241 00:09:41,120 --> 00:09:43,440 SEQUENCES DESIGNED TO GIVE A LOT 242 00:09:43,440 --> 00:09:45,520 OF ANATOMICAL INFORMATION. 243 00:09:45,520 --> 00:09:49,400 AND AXIAL DWI IS CONSIDERED A 244 00:09:49,400 --> 00:09:51,320 FUNCTIONAL IMAGE THAT IS VERY 245 00:09:51,320 --> 00:09:54,240 SENSITIVE TO DETECT MALIGNANCY. 246 00:09:54,240 --> 00:09:57,120 ALL THESE SCANS ARE DONE ON A 247 00:09:57,120 --> 00:10:02,280 LOW POWER SCANNER THAT IS 1.5 248 00:10:02,280 --> 00:10:07,040 TESLA SCANNER COMPARED TO 3T 249 00:10:07,040 --> 00:10:09,720 SCANS THAT WE HAVE AND HAY TAKE 250 00:10:09,720 --> 00:10:11,400 APPROXIMATELY 45 MINUTES TO 251 00:10:11,400 --> 00:10:12,680 ACQUIRE. 252 00:10:12,680 --> 00:10:15,960 SO COUPLE OF WORDS FOR PATIENTS 253 00:10:15,960 --> 00:10:22,560 WHO ARE PREGNANT UNDERGOING MRI. 254 00:10:22,560 --> 00:10:27,640 FIRST IS STRENGTHS OF MAGNETIC 255 00:10:27,640 --> 00:10:28,000 FIELD. 256 00:10:28,000 --> 00:10:29,440 SOME OF THESE FROM MESH COLLEGE 257 00:10:29,440 --> 00:10:31,120 OF RADIOLOGY MANUAL ON MRI 258 00:10:31,120 --> 00:10:31,520 SAFETY. 259 00:10:31,520 --> 00:10:37,000 WE USE MRI ROUTINELY FOR 260 00:10:37,000 --> 00:10:39,360 PATIENTS WHO ARE PREGNANT TO 261 00:10:39,360 --> 00:10:41,640 DEMONSTRATE FETAL ABNORMALITIES 262 00:10:41,640 --> 00:10:42,800 OR ANSWER CLINICAL QUESTIONS, 263 00:10:42,800 --> 00:10:45,880 THERE ARE NO CLINICAL DATA 264 00:10:45,880 --> 00:10:48,520 SHOWING EXPOSURE TO MR HAS 265 00:10:48,520 --> 00:10:49,640 DELETERIOUS AFFECTS ON 266 00:10:49,640 --> 00:10:51,640 DEVELOPING FETUS. 267 00:10:51,640 --> 00:10:53,120 IF PREGNANCY IS ESTABLISHED 268 00:10:53,120 --> 00:10:55,440 DECISION TO PROCEED WITH A 269 00:10:55,440 --> 00:10:58,640 NON-CONTRAST MR STUDY AT 1.5 T 270 00:10:58,640 --> 00:11:01,600 SCANNER SIMILAR TO ONE WE USE, 271 00:11:01,600 --> 00:11:03,400 SHOULD BE BASED ON MEDICAL 272 00:11:03,400 --> 00:11:05,440 BENEFIT WEIGHTED AGAINST UNKNOWN 273 00:11:05,440 --> 00:11:07,920 POTENTIAL REIS. 274 00:11:07,920 --> 00:11:11,840 MRI IS VERY SAFE IN PREGNANCY 275 00:11:11,840 --> 00:11:13,520 AND DONE ON ROUTINE BASIS. 276 00:11:13,520 --> 00:11:17,400 NEXT SLIDE. 277 00:11:17,400 --> 00:11:19,400 HOWEVER CONTRAST IS ANOTHER 278 00:11:19,400 --> 00:11:21,160 ISSUE IN MR AND WE DON'T USE 279 00:11:21,160 --> 00:11:24,640 CONTRAST FOR PROTOCOL AND THERE 280 00:11:24,640 --> 00:11:27,840 IS TYPE OF CONTRAST WE USE FOR 281 00:11:27,840 --> 00:11:30,320 MRI IS A CONTRAST AGENT. 282 00:11:30,320 --> 00:11:32,960 THESE HAVE SHOWN TO CROSS THE 283 00:11:32,960 --> 00:11:35,400 PLACENTA, BLOOD BARRIER AND GET 284 00:11:35,400 --> 00:11:41,160 INTO THE FETUS CIRCULATION. 285 00:11:41,160 --> 00:11:43,240 MRI CONTRAST PATIENTS SHOULD NOT 286 00:11:43,240 --> 00:11:45,040 BE USED TO PREGNANT PATIENTS. 287 00:11:45,040 --> 00:11:46,880 AS A RESULT THERE IS WIDESPREAD 288 00:11:46,880 --> 00:11:49,120 CONSENSUS THAT AVOIDING GAD LYNN 289 00:11:49,120 --> 00:11:52,080 YUM BASED CONTRAST AGENTS IN 290 00:11:52,080 --> 00:11:55,920 PREGNANCY IS PRUDENT. 291 00:11:55,920 --> 00:11:58,920 GOING BACK TO OUR PATIENTS, 292 00:11:58,920 --> 00:12:01,440 THESE ARE IMAGES WE DISCUSSED 293 00:12:01,440 --> 00:12:01,840 BEFORE. 294 00:12:01,840 --> 00:12:04,840 AS YOU CAN SEE THE PATIENT IS 295 00:12:04,840 --> 00:12:07,600 PREGNANT WITH A FETUS IN THE 296 00:12:07,600 --> 00:12:09,480 UTERUS AND YOU CAN SEE THE 297 00:12:09,480 --> 00:12:12,240 YELLOW ARROW IS POINTING TOWARDS 298 00:12:12,240 --> 00:12:14,640 SIGNAL ABNORMALITY IN THE 299 00:12:14,640 --> 00:12:21,480 INTERIOR MEDIA STEINUM, IT 300 00:12:21,480 --> 00:12:23,120 APPEARS IN THE STY NUMBER IN THE 301 00:12:23,120 --> 00:12:25,960 ANTERIOR WEIGHTED IMAGES. 302 00:12:25,960 --> 00:12:27,120 WE REQUIRE AXIAL IMAGES NEXT 303 00:12:27,120 --> 00:12:28,080 SLIDE PLEASE. 304 00:12:28,080 --> 00:12:29,440 AND HERE YOU CAN SEE CLEARLY 305 00:12:29,440 --> 00:12:31,520 THAT THERE IS A SIGNAL 306 00:12:31,520 --> 00:12:33,720 ABNORMALITY IN THE ANTERIOR 307 00:12:33,720 --> 00:12:37,640 MEDIA STINUM CLOSE TO THYMUS ON 308 00:12:37,640 --> 00:12:39,920 THE STIR AND T 1 IMAGES AND ON 309 00:12:39,920 --> 00:12:41,920 AXIAL DWI IMAGE YOU CAN SEE THIS 310 00:12:41,920 --> 00:12:44,880 SHOWING INCREASED SIGNAL. 311 00:12:44,880 --> 00:12:47,560 DWI IMAGES ARE AS I SAID BEFORE, 312 00:12:47,560 --> 00:12:51,480 FUNCTIONAL IMAGES AND THEY LOOK 313 00:12:51,480 --> 00:12:54,560 AT MOTION OF WATER MOLECULES IN 314 00:12:54,560 --> 00:13:00,120 MICROENVIRONMENTMENT SO IF HIGH 315 00:13:00,120 --> 00:13:02,120 CYTOPLASMIC NUCLEUS RATIO OR 316 00:13:02,120 --> 00:13:04,120 CELL WALS ARE NOT FUNCTIONING 317 00:13:04,120 --> 00:13:05,680 PROPERLY SUCH ASTHMA LEG 318 00:13:05,680 --> 00:13:07,920 FANTASTIC TISSUE, YOU WOULD END 319 00:13:07,920 --> 00:13:10,800 UP WITH INCREASE SIGNAL ON DWI 320 00:13:10,800 --> 00:13:15,840 IMAGE. 321 00:13:15,840 --> 00:13:22,760 >> SO THIS PATIENT HAD OPTED TO 322 00:13:22,760 --> 00:13:25,920 UNDERGO FIRST WORK UP AFTER 323 00:13:25,920 --> 00:13:28,160 DELIVERY SO IN OCTOBER 2021 SHE 324 00:13:28,160 --> 00:13:29,240 DELIVERED HEALTHY BABY AND IN 325 00:13:29,240 --> 00:13:32,880 NOVEMBER OF 2021 SHE RETURNED TO 326 00:13:32,880 --> 00:13:36,840 NIH AND UNDERWENT A PET CT SCAN. 327 00:13:36,840 --> 00:13:40,480 >> SO WE PERFORM THE FDG PET 328 00:13:40,480 --> 00:13:41,640 AFTER PREGNANCY AND AS YOU CAN 329 00:13:41,640 --> 00:13:44,600 SEE HERE THERE IS A ON THE IMAGE 330 00:13:44,600 --> 00:13:47,840 ON THE LEFT THERE IS AVID FDG 331 00:13:47,840 --> 00:13:50,600 UPTAKE IN MASS WE SAW BEFORE. 332 00:13:50,600 --> 00:13:51,840 AND IMAGE ON THE RIGHT WHICH IS 333 00:13:51,840 --> 00:13:55,560 A MIP IMAGE YOU CAN SEE INCREASE 334 00:13:55,560 --> 00:13:57,680 ACTIVITY IN THE MASS NICELY HERE 335 00:13:57,680 --> 00:13:59,800 BUT YOU DON'T SEE ANY OTHER 336 00:13:59,800 --> 00:14:02,840 SORTS OF -- ANY OTHER ACTIVITY 337 00:14:02,840 --> 00:14:03,680 THROUGHOUT THE BODY. 338 00:14:03,680 --> 00:14:05,160 THERE IS A LOT OF ACTIVITY IN 339 00:14:05,160 --> 00:14:06,400 THE BREAST TISSUE BECAUSE 340 00:14:06,400 --> 00:14:13,240 PATIENT IS POSTPARTUM. 341 00:14:13,240 --> 00:14:16,320 SO ON DECEMBER 21, PATIENT 342 00:14:16,320 --> 00:14:17,880 UNDERWENT SURGICAL BIOPSY AND 343 00:14:17,880 --> 00:14:19,360 RESECTION FOR DIAGNOSIS. 344 00:14:19,360 --> 00:14:22,240 I WILL TURN IT OVER TO DR. JAFFE 345 00:14:22,240 --> 00:14:24,240 TO GO OVER PATHOLOGY. 346 00:14:24,240 --> 00:14:24,800 THANK YOU. 347 00:14:24,800 --> 00:14:26,800 >> SO AS YOU HAVE HEARD, THE 348 00:14:26,800 --> 00:14:32,840 PATIENT HAD AN INTERIOR 349 00:14:32,840 --> 00:14:35,480 MEDIASTINAL MASS LEADING TO 350 00:14:35,480 --> 00:14:36,720 SURGICAL EXCISION OF THYMUS 351 00:14:36,720 --> 00:14:37,200 GLAND. 352 00:14:37,200 --> 00:14:38,760 THE WEIGHT WAS 49 GRAMS, 353 00:14:38,760 --> 00:14:39,840 SOMEWHAT ENLARGED FOR AN 354 00:14:39,840 --> 00:14:43,080 INDIVIDUAL AT HER AGE. 355 00:14:43,080 --> 00:14:45,640 THE THYMUS WAS LARGELY NORMAL 356 00:14:45,640 --> 00:14:47,600 BUT A SINGLE MASS SEEN WITHIN 357 00:14:47,600 --> 00:14:51,440 THE THYMUS MEASURING 358 00:14:51,440 --> 00:14:52,360 APPROXIMATELY 3 BY 359 00:14:52,360 --> 00:14:54,600 3-CENTIMETERS. 360 00:14:54,600 --> 00:14:57,760 HERE YOU CAN SEE THE NORMAL 361 00:14:57,760 --> 00:14:59,800 THYMUS GLAND WITH BOTH CORTICAL 362 00:14:59,800 --> 00:15:05,040 AND MEDULLARY AREAS. 363 00:15:05,040 --> 00:15:07,280 AND WITHIN THE THYMUS THERE WAS 364 00:15:07,280 --> 00:15:11,040 A SINGLE MASS, THE MASS WAS 365 00:15:11,040 --> 00:15:14,240 LIMITED BY FIBROUS TISSUE. 366 00:15:14,240 --> 00:15:16,240 DELIMITED BY FIBROUS TISSUE AND 367 00:15:16,240 --> 00:15:19,200 NO EXTENSION BEYOND THE THYMUS 368 00:15:19,200 --> 00:15:20,040 GLAND. 369 00:15:20,040 --> 00:15:20,560 NEXT PLEASE. 370 00:15:20,560 --> 00:15:22,960 HERE AT HIGHER POWER WITHIN THE 371 00:15:22,960 --> 00:15:24,760 MASS LESION YOU CAN SEE SHEETS 372 00:15:24,760 --> 00:15:27,440 OF LARGE LYMPHOID CELLS. 373 00:15:27,440 --> 00:15:29,240 THERE ARE FREQUENT MITOTIC 374 00:15:29,240 --> 00:15:30,720 FIGURES AS NOTED BY THE RED 375 00:15:30,720 --> 00:15:37,560 ARROW. 376 00:15:37,560 --> 00:15:40,800 IMMUNOHISTOCHEMICAL STUDIES 377 00:15:40,800 --> 00:15:43,320 SHOWED CD 20 EXPRESSION 378 00:15:43,320 --> 00:15:44,640 INDICATING THAT THIS WAS A B 379 00:15:44,640 --> 00:15:46,840 CELL LYMPHOMA, THE TUMOR WAS 380 00:15:46,840 --> 00:15:50,640 POSITIVE FOR BCL 6 AND CD 30. 381 00:15:50,640 --> 00:15:54,800 THE OVERALL MORPHOLOGY AND 382 00:15:54,800 --> 00:15:58,080 IMMUNOPHENOTYPE WAS 383 00:15:58,080 --> 00:16:00,040 CHARACTERISTIC OF PRIMARY 384 00:16:00,040 --> 00:16:02,160 MEDIASTINAL B CELL LYMPHOMA 385 00:16:02,160 --> 00:16:13,320 REFERRED TO AS PRIMARY MEDIA 386 00:16:13,320 --> 00:16:15,000 MEDIASTINAL, AND CLASSIC 387 00:16:15,000 --> 00:16:16,840 HODGKIN'S LYMPHOMA OF THE 388 00:16:16,840 --> 00:16:18,280 NODULAR TYPE, SHARE MANY 389 00:16:18,280 --> 00:16:19,840 FEATURES IN COMMON BOTH DISEASE 390 00:16:19,840 --> 00:16:22,160 ARE MORE COMMON IN FEMALES THAN 391 00:16:22,160 --> 00:16:24,240 MALES AND TYPICALLY PRESENT IN 392 00:16:24,240 --> 00:16:27,240 ADOLESCENCE OR YOUNG ADULTS. 393 00:16:27,240 --> 00:16:30,440 THE CLASSIC PRESENTATION IS A 394 00:16:30,440 --> 00:16:33,280 MEDIASTINAL MASS WITH OR WITHOUT 395 00:16:33,280 --> 00:16:37,080 INVOLVEMENT OF CLAVICULAR LYMPH 396 00:16:37,080 --> 00:16:38,720 NODES. 397 00:16:38,720 --> 00:16:41,440 TUMORS SHARE COMMON CYTOGENETIC 398 00:16:41,440 --> 00:16:44,400 ABNORMALITIES INCLUDING GAINS AT 399 00:16:44,400 --> 00:16:48,560 9P 24 AND GAINS AT 2P 16. 400 00:16:48,560 --> 00:16:51,360 INTERESTINGLY AS YOU HEARD, THIS 401 00:16:51,360 --> 00:16:54,240 PATIENT HAD EVIDENCE OF 402 00:16:54,240 --> 00:16:59,000 ANEUPLOIDY ON CHROMOSOME 2 IN 403 00:16:59,000 --> 00:17:02,200 HER PRE-CLINICAL -- 404 00:17:02,200 --> 00:17:04,200 PRE-PREGNANCY TEST. 405 00:17:04,200 --> 00:17:05,640 BOTH DISEASES SHOW SIMILAR 406 00:17:05,640 --> 00:17:11,000 PATTERN OF GENE EXPRESSION WITH 407 00:17:11,000 --> 00:17:14,080 ACTIVATION OF NF KAPPA B PATHWAY 408 00:17:14,080 --> 00:17:17,320 AND BOTH LYMPHOMAS ARISE FROM B 409 00:17:17,320 --> 00:17:19,520 CELL. 410 00:17:19,520 --> 00:17:21,640 TURN BACK TO DR. ANNUNZIATA FOR 411 00:17:21,640 --> 00:17:26,560 FURTHER FOLLOW-UP. 412 00:17:26,560 --> 00:17:27,280 >> THANK YOU. 413 00:17:27,280 --> 00:17:28,440 TO CONTINUE WITH FOLLOW-UP ON 414 00:17:28,440 --> 00:17:30,440 THIS PATIENT, SHE WAS DIAGNOSED 415 00:17:30,440 --> 00:17:33,080 WITH PRIMARY MEDIASTINAL 416 00:17:33,080 --> 00:17:34,960 LYMPHOMA, LIMITED STAGE WHERE IT 417 00:17:34,960 --> 00:17:36,440 WAS CONTAINED IN ONE POTENTIAL 418 00:17:36,440 --> 00:17:38,760 RADIATION FIELD. 419 00:17:38,760 --> 00:17:40,800 ADVANCE STAGE DISEASE IF SHE HAD 420 00:17:40,800 --> 00:17:43,600 THAT WOULD HAVE BEEN DIAGNOSED 421 00:17:43,600 --> 00:17:45,920 -- WOULD HAVE BEEN GREATER THAT 422 00:17:45,920 --> 00:17:47,040 THAN TEN CENTIMETERS FOR 423 00:17:47,040 --> 00:17:47,720 WIDESPREAD. 424 00:17:47,720 --> 00:17:50,400 TYPICAL TREATMENT FOR LIMITED 425 00:17:50,400 --> 00:17:52,040 STAGE DISEASE IS OUR TOP 426 00:17:52,040 --> 00:17:55,280 CHEMOTHERAPY FOR SIX CYCLES PLUS 427 00:17:55,280 --> 00:17:57,040 FIELD RADIATION OR DOSES 428 00:17:57,040 --> 00:17:59,840 ADJUSTED EPOCR FOR 6 TO 8 CYCLES 429 00:17:59,840 --> 00:18:03,080 WITHOUT RADIATION. 430 00:18:03,080 --> 00:18:05,840 OUR PATIENT BECAUSE SHE WAS 431 00:18:05,840 --> 00:18:08,160 DIAGNOSED SO EARLY, EXCUSE ME GO 432 00:18:08,160 --> 00:18:08,560 BACK. 433 00:18:08,560 --> 00:18:11,080 BECAUSE SHE WAS DIAGNOSED EARLY 434 00:18:11,080 --> 00:18:16,480 SHE HAD THE MASS SURGICALLY 435 00:18:16,480 --> 00:18:17,960 REMOVED, FOR DIAGNOSTIC PURPOSES 436 00:18:17,960 --> 00:18:19,720 SHE IS UNDERGOING FOUR CYCLES OF 437 00:18:19,720 --> 00:18:23,000 TOP CHEMOTHERAPY, ABBREVIATED 438 00:18:23,000 --> 00:18:26,440 DUE TO TEXT OF HER DISEASE. 439 00:18:26,440 --> 00:18:28,440 I WILL TURN IT OVER TO DR. 440 00:18:28,440 --> 00:18:29,040 BIANCHI. 441 00:18:29,040 --> 00:18:31,880 >> THANK YOU, DR. ANNUNZIATA. 442 00:18:31,880 --> 00:18:34,240 SO WE TITLED THIS WHAT NOT TO 443 00:18:34,240 --> 00:18:36,040 EXPECT WHEN YOU ARE EXPECTING 444 00:18:36,040 --> 00:18:38,880 BECAUSE WE CERTAINLY DIDN'T 445 00:18:38,880 --> 00:18:40,880 EXPECT THAT A ROUTINE PRE-NATAL 446 00:18:40,880 --> 00:18:45,040 SCREEN FOR ANEUPLOIDY WOULD 447 00:18:45,040 --> 00:18:45,840 DETECT CANCER. 448 00:18:45,840 --> 00:18:47,960 STEPPING BACK, CELL FREE DNA 449 00:18:47,960 --> 00:18:51,280 SEQUENCING OF MATERNAL PLASMA IS 450 00:18:51,280 --> 00:18:52,480 ROUTINELY OVERRED TO PREGNANT 451 00:18:52,480 --> 00:18:54,320 WELL AS DR. ANNUNZIATA SAID. 452 00:18:54,320 --> 00:18:57,840 THE DIFFERENCE IS THAT MANAGED 453 00:18:57,840 --> 00:19:01,240 CARE INSURANCE PLANS PAY FOR THE 454 00:19:01,240 --> 00:19:03,720 TEST GENERALLY IF THE WOMAN IS 455 00:19:03,720 --> 00:19:05,400 HIGH RISK AND WE ARE MOVING OVER 456 00:19:05,400 --> 00:19:10,000 TO SOME SCENARIOS TO HAVE IT 457 00:19:10,000 --> 00:19:11,440 PAID FOR BY INSURANCE FOR WOMEN 458 00:19:11,440 --> 00:19:13,800 OF LOW RISK OR GENERAL RISK. 459 00:19:13,800 --> 00:19:16,920 AS YOU HEARD FROM DR. ANNUNZIATA 460 00:19:16,920 --> 00:19:19,600 EARLIER, POSITIVE SCREENS REALLY 461 00:19:19,600 --> 00:19:22,000 REQUIRE DIAGNOSTIC CONFIRMATION. 462 00:19:22,000 --> 00:19:23,520 SOME WOMEN CHOOSE NOT TO DO THAT 463 00:19:23,520 --> 00:19:25,840 BUT THAT IS THE OFFICIAL 464 00:19:25,840 --> 00:19:26,240 RECOMMENDATION. 465 00:19:26,240 --> 00:19:27,920 WHAT WE WILL BE TALKING ABOUT 466 00:19:27,920 --> 00:19:32,120 HERE, THE FALSE POSITIVE RESULTS 467 00:19:32,120 --> 00:19:33,360 WHICH MEANS THAT THE RESULTS 468 00:19:33,360 --> 00:19:37,400 WERE ABOUT NORMAL OR 469 00:19:37,400 --> 00:19:38,440 NON-REPORTABLE, AND YOU HAVE 470 00:19:38,440 --> 00:19:40,760 NORMAL FETAL DIAGNOSTIC 471 00:19:40,760 --> 00:19:44,400 KARYOTYPE OR MICROARRAY OBTAINED 472 00:19:44,400 --> 00:19:50,320 FROM AMNIOCENTESIS OR CHORIONI 473 00:19:50,320 --> 00:19:50,880 SAMPLING. 474 00:19:50,880 --> 00:19:53,320 BOTH MOTHER AND FETUS PRODUCE 475 00:19:53,320 --> 00:19:55,000 CELL FREE DNA FROM APOT TOPIC 476 00:19:55,000 --> 00:19:55,480 CELLS. 477 00:19:55,480 --> 00:19:58,040 WE ARE ALL PRODUCING CELL FREE 478 00:19:58,040 --> 00:19:59,640 DNA AND CIRCULATING IN OUR BLOOD 479 00:19:59,640 --> 00:20:01,120 RIGHT NOW. 480 00:20:01,120 --> 00:20:04,200 IN ADULTS THE DNA IS ORIGINATING 481 00:20:04,200 --> 00:20:05,960 FROM THE BONE MARROW. 482 00:20:05,960 --> 00:20:08,640 WE SAY THAT THIS IS A FETAL 483 00:20:08,640 --> 00:20:10,480 SCREENING TEST, IT IS A 484 00:20:10,480 --> 00:20:11,440 PLACENTAL SCREENING TEST. 485 00:20:11,440 --> 00:20:15,680 SO WHEN WE DO HAVE ABNORMAL 486 00:20:15,680 --> 00:20:18,360 RESULTS IT IS REALLY GENERALLY 487 00:20:18,360 --> 00:20:20,240 ORIGINATING ON PLACENTA, IF 488 00:20:20,240 --> 00:20:21,600 FETAL IN ORIGIN. 489 00:20:21,600 --> 00:20:24,160 THE TESTING IS DONE VIA 490 00:20:24,160 --> 00:20:25,600 MASSIVELY PARALLEL SEQUENCING 491 00:20:25,600 --> 00:20:28,240 AND THAT IS PERFORMED ON A MIXED 492 00:20:28,240 --> 00:20:29,480 DNA SAMPLE. 493 00:20:29,480 --> 00:20:32,040 SO YOU ARE TAKING BLOOD, REGULAR 494 00:20:32,040 --> 00:20:34,520 PERIPHERAL BLOOD SAMPLE, AND THE 495 00:20:34,520 --> 00:20:36,360 AVERAGE SAMPLE AS YOU HEARD FROM 496 00:20:36,360 --> 00:20:39,240 DR. ANNUNZIATA IS GOING TO 497 00:20:39,240 --> 00:20:40,880 CONTAIN SOMEWHERE AROUND 10% 498 00:20:40,880 --> 00:20:44,040 FETAL PLACENTAL DNA, REMAINDER 499 00:20:44,040 --> 00:20:46,160 IS MATERNAL CELL FREE DNA AND 500 00:20:46,160 --> 00:20:47,640 YOU ARE SEQUENCING BOTH AT THE 501 00:20:47,640 --> 00:20:49,120 SAME TIME. 502 00:20:49,120 --> 00:20:51,320 THEREFORE YOU CAN'T REALLY 503 00:20:51,320 --> 00:20:54,520 DISTINGUISH BETWEEN MATERNAL DNA 504 00:20:54,520 --> 00:20:57,440 AND THE FETAL DNA UNLESS FETUS 505 00:20:57,440 --> 00:20:59,400 IS MALE, IN THAT CASE THE Y 506 00:20:59,400 --> 00:21:01,880 CHROMOSOMAL SEQUENCES ARE COMING 507 00:21:01,880 --> 00:21:03,640 FROM MALE FETUS AND ALSO 508 00:21:03,640 --> 00:21:06,280 POSSIBLE THE FETUS HAS UNIQUE 509 00:21:06,280 --> 00:21:08,840 SINGLE NUCLEOTIDE POLYMORPHISMS. 510 00:21:08,840 --> 00:21:12,360 THAT CAN BE USED TO MEASURE THE 511 00:21:12,360 --> 00:21:12,880 FETAL FRACTION. 512 00:21:12,880 --> 00:21:15,680 NEXT SLIDE. 513 00:21:15,680 --> 00:21:18,280 THERE ARE BASICALLY TWO METHODS 514 00:21:18,280 --> 00:21:20,000 OF NON-INVASIVE PRE-NATAL 515 00:21:20,000 --> 00:21:20,480 TESTING. 516 00:21:20,480 --> 00:21:23,840 ONE IS THE RANDOM GENOME WIDE 517 00:21:23,840 --> 00:21:26,640 SEQUENCING THIS IS LIGHT GOING 518 00:21:26,640 --> 00:21:27,760 -- LIKE GOING FISHING WITH A 519 00:21:27,760 --> 00:21:29,800 GIANT NET AND YOU ARE THROWING 520 00:21:29,800 --> 00:21:32,320 THE NETTED OUT AND CAPTURING 521 00:21:32,320 --> 00:21:33,040 EVERYTHING WITHIN THAT NET. 522 00:21:33,040 --> 00:21:36,120 SO THE CELL FREE DNA IN MATERNAL 523 00:21:36,120 --> 00:21:39,280 BLOOD IS RANDOMLY SAMPLED, 524 00:21:39,280 --> 00:21:42,400 SEQUENCED, MAPPED TO SPECIFIC 525 00:21:42,400 --> 00:21:44,720 CHROMOSOMES, THEN NUMBER OF TAGS 526 00:21:44,720 --> 00:21:47,920 THAT MAP TO CHROMOSOMES ARE 527 00:21:47,920 --> 00:21:50,040 COUNTED RELATIVE TO A REFERENCE 528 00:21:50,040 --> 00:21:53,720 GENOME. 529 00:21:53,720 --> 00:21:54,800 IF THERE ARE DIFFERENCES, TOO 530 00:21:54,800 --> 00:21:58,640 MUCH OF ONE CHROMOSOME OR TOO 531 00:21:58,640 --> 00:22:03,040 LITTLE THAT TRIGGERS A FLAG FOR 532 00:22:03,040 --> 00:22:03,360 ANEUPLOIDY. 533 00:22:03,360 --> 00:22:05,120 IN GENERAL THE MOST COMMON 534 00:22:05,120 --> 00:22:07,440 ITERATION OF TEST ONLY RESULTS 535 00:22:07,440 --> 00:22:10,040 FROM 13, 18, 21, X AND Y ARE 536 00:22:10,040 --> 00:22:11,600 MADE AVAILABLE ALTHOUGH THE 537 00:22:11,600 --> 00:22:14,160 TESTING IS DONE ON THE ENTIRE 538 00:22:14,160 --> 00:22:16,240 GENOME, REMAINDER OF THE RESULTS 539 00:22:16,240 --> 00:22:18,920 ARE MASKED BUT THAT MASK CAN BE 540 00:22:18,920 --> 00:22:21,640 LIFTED AS IT WAS THIS CASE. 541 00:22:21,640 --> 00:22:23,000 A DIFFERENT WAY THE TEST IS DONE 542 00:22:23,000 --> 00:22:25,200 IS USING TARGETED OR SINGLE 543 00:22:25,200 --> 00:22:28,640 NUCLEOTIDE POLYMORPHISM OR SNP 544 00:22:28,640 --> 00:22:30,760 BASED SEQUENCING. 545 00:22:30,760 --> 00:22:33,240 THAT'S LIKE FISHING WITH A 546 00:22:33,240 --> 00:22:36,320 FISHING ROD AND BLUE DOTS 547 00:22:36,320 --> 00:22:39,800 REPRESENTING BAIT AND THE BAIT 548 00:22:39,800 --> 00:22:42,000 WILL ATTRACT SPECIFIC SEQUENCES 549 00:22:42,000 --> 00:22:44,960 FROM SPECIFIC CHROMOSOMES THAT 550 00:22:44,960 --> 00:22:48,400 ARE AMPLIFIED AND SEQUENCED. 551 00:22:48,400 --> 00:22:50,640 MOTHER IN THIS CASE IS USED AS 552 00:22:50,640 --> 00:22:52,160 REFERENCE AND DIFFERENTS ARE 553 00:22:52,160 --> 00:22:55,160 CALCULATED BETWEEN MATERNAL AND 554 00:22:55,160 --> 00:22:56,840 FETAL PLACENTAL DNA SEQUENCE TO 555 00:22:56,840 --> 00:22:57,960 IDENTIFY THE PREGNANCIES THAT 556 00:22:57,960 --> 00:23:04,080 ARE AT RISK FOR ANEUPLOIDY. 557 00:23:04,080 --> 00:23:05,440 NOW, HERE IN THIS STUDY WE ARE 558 00:23:05,440 --> 00:23:08,560 INTERESTED IN THE UNUSUAL NIPT 559 00:23:08,560 --> 00:23:09,480 RESULTS. 560 00:23:09,480 --> 00:23:11,040 EITHER OF THESE METHODS, 561 00:23:11,040 --> 00:23:13,720 LABORATORIES MAY ENCOUNTER 562 00:23:13,720 --> 00:23:15,040 UNUSUAL RESULTS THAT INTERFERE 563 00:23:15,040 --> 00:23:17,520 WITH THE BIOINFORMATICS 564 00:23:17,520 --> 00:23:19,200 ALGORITHMS THAT ARE LOOKING AT 565 00:23:19,200 --> 00:23:21,440 THE RATIOS BETWEEN THE 566 00:23:21,440 --> 00:23:22,760 CHROMOSOME OF INTEREST AND THE 567 00:23:22,760 --> 00:23:24,600 REFERENCE CHROMOSOME. 568 00:23:24,600 --> 00:23:29,840 AND WHEN THERE IS THIS 569 00:23:29,840 --> 00:23:31,080 UNEXPECTED ABNORMALITY, THAT 570 00:23:31,080 --> 00:23:32,800 WILL TRIGGER A NON-REPORTABLE 571 00:23:32,800 --> 00:23:37,840 RESULT. 572 00:23:37,840 --> 00:23:40,640 IF IT IS USING THE GENOME WIDE 573 00:23:40,640 --> 00:23:43,360 TESTING THEY CAN UNMASK THE 574 00:23:43,360 --> 00:23:44,640 REMAINDER OF THE RESULTS, THIS 575 00:23:44,640 --> 00:23:46,640 WILL BE TRIGGERED BY 576 00:23:46,640 --> 00:23:47,800 NON-REPORTABLE RESULTS AND 577 00:23:47,800 --> 00:23:51,720 THEREFORE HAY WILL LOOK AT THE 578 00:23:51,720 --> 00:23:53,520 ENTIRE WHOLE GENOME SEQUENCING. 579 00:23:53,520 --> 00:23:55,840 THEY WILL OFFICIALLY SAY THERE 580 00:23:55,840 --> 00:23:57,640 IS A NON-REPORTABLE RESULT 581 00:23:57,640 --> 00:24:02,040 BECAUSE THERE IS NO STANDARD WAY 582 00:24:02,040 --> 00:24:03,520 OF COMMUNICATING RESULTS BUT 583 00:24:03,520 --> 00:24:05,840 OFTENTIMES THERE IS A VERBAL 584 00:24:05,840 --> 00:24:07,760 CONVERSATION BETWEEN LABORATORY 585 00:24:07,760 --> 00:24:10,000 AND THE CLINICIAN. 586 00:24:10,000 --> 00:24:11,640 IN THE SNP PHASE RESULTS THEY 587 00:24:11,640 --> 00:24:13,440 USUALLY SAY THERE'S ATYPICAL 588 00:24:13,440 --> 00:24:15,400 RESULT BEYOND SCOPE OF THE TEST. 589 00:24:15,400 --> 00:24:17,840 USUALLY THEY SAY A REPEAT SAMPLE 590 00:24:17,840 --> 00:24:22,600 IS NOT RECOMMENDED. 591 00:24:22,600 --> 00:24:25,040 NOW ALL THIS IS A RELATIVELY 592 00:24:25,040 --> 00:24:28,560 RECENT PROBLEM, THE VERY FIRST 593 00:24:28,560 --> 00:24:30,160 DOCUMENTATION OF THE PRESENCE OF 594 00:24:30,160 --> 00:24:32,280 PLACENTAL DNA IN MATERNAL PLASMA 595 00:24:32,280 --> 00:24:34,040 WAS ONLY IN 1997. 596 00:24:34,040 --> 00:24:37,800 IT WAS REALLY WITH THE 597 00:24:37,800 --> 00:24:39,160 DEVELOPMENT AND AVAILABILITY OF 598 00:24:39,160 --> 00:24:43,640 MASSIVELY PARALLEL SEQUENCING 599 00:24:43,640 --> 00:24:45,880 MACHINES, THAT WE COULD PERFORM 600 00:24:45,880 --> 00:24:49,560 LARGE SCALE CLINICAL STUDIES. 601 00:24:49,560 --> 00:24:50,640 THESE RESULTED IN VALIDATION 602 00:24:50,640 --> 00:24:55,480 TESTS IN 2010, 2011 SHOWING 603 00:24:55,480 --> 00:24:59,560 FIRST YOU COULD RELIABLY TEST 604 00:24:59,560 --> 00:25:00,880 TRISOMY 21, THAT LED TO THE 605 00:25:00,880 --> 00:25:02,560 FIRST COMMERCIAL AND CLINICAL 606 00:25:02,560 --> 00:25:04,760 AVAILABILITY OF THE TESTING ONLY 607 00:25:04,760 --> 00:25:06,800 A DECADE AGO. 608 00:25:06,800 --> 00:25:09,120 IT FIRST STARTED IN CHINA AND 609 00:25:09,120 --> 00:25:11,080 HONG KONG, WENT TO THE UNITED 610 00:25:11,080 --> 00:25:12,840 STATES, THEN TO EUROPE THEN TO 611 00:25:12,840 --> 00:25:16,480 THE REST OF THE WORLD. 612 00:25:16,480 --> 00:25:18,680 I LIKE TO SAY IT IS THE MOST 613 00:25:18,680 --> 00:25:22,480 SUCCESSFUL GENOMIC TEST IN 614 00:25:22,480 --> 00:25:23,360 MEDICAL HISTORY BECAUSE REALLY 615 00:25:23,360 --> 00:25:24,880 WITHIN A SHORT PERIOD OF TIME 616 00:25:24,880 --> 00:25:27,280 NOT ONLY HAVE THE TESTS BEEN 617 00:25:27,280 --> 00:25:29,960 VALIDATED BUT ALSO PAID FOR BY 618 00:25:29,960 --> 00:25:31,640 MANAGED CARE INSURANCE AND BE MY 619 00:25:31,640 --> 00:25:35,080 STATE MEDICAID PROGRAMS. 620 00:25:35,080 --> 00:25:39,720 THE SUCCESS OF SCREENING FOR 621 00:25:39,720 --> 00:25:41,360 ANEUPLOIDY LED TO EXPANSION OF 622 00:25:41,360 --> 00:25:43,240 THE MENU, WE ARE NOW SCREENING 623 00:25:43,240 --> 00:25:46,440 FOR SEX CHROMOSOME ANEUPLOIDY'S 624 00:25:46,440 --> 00:25:50,320 AS WELL AS COMMON MICRODELETIONS 625 00:25:50,320 --> 00:25:52,120 SUCH AS DELETION ON THE LONG ARM 626 00:25:52,120 --> 00:25:54,040 OF 22 ASSOCIATED WITH GEORGE 627 00:25:54,040 --> 00:25:55,200 SYNDROME. 628 00:25:55,200 --> 00:25:56,640 IN 2013 AS YOU WILL SEE IN A 629 00:25:56,640 --> 00:25:59,840 MOMENT, WE HAD THE FIRST REPORT 630 00:25:59,840 --> 00:26:03,400 OF DISCORDANT RESULT THROUGH TO 631 00:26:03,400 --> 00:26:04,440 MATERNAL MALIGNANCY. 632 00:26:04,440 --> 00:26:07,440 MORE RECENTLY SEVERAL LABORATORY 633 00:26:07,440 --> 00:26:15,000 ARE REPORTING RARE AWESOMAL 634 00:26:15,000 --> 00:26:15,720 TRISOMIES FOR RATS. 635 00:26:15,720 --> 00:26:19,120 AS I SAID, THE VERY FIRST 636 00:26:19,120 --> 00:26:20,320 IMPLEMENTATION OF THE TEST 637 00:26:20,320 --> 00:26:23,360 CLINICALLY WAS THE LATE STAGES 638 00:26:23,360 --> 00:26:26,320 OF 2011 AND TWO YEARS LATER WE 639 00:26:26,320 --> 00:26:28,560 BEGAN TO SEE ARTICLES SUCH AS 640 00:26:28,560 --> 00:26:30,640 THIS ONE, CLAIMING THAT THERE 641 00:26:30,640 --> 00:26:33,440 ARE MANY FALSE POSITIVE CASES OF 642 00:26:33,440 --> 00:26:36,520 NIPT AND MAYBE WE SHOULDN'T BE 643 00:26:36,520 --> 00:26:39,840 SO FAST TO INCORPORATE THIS TEST 644 00:26:39,840 --> 00:26:40,760 INTO CLINICAL CARE. 645 00:26:40,760 --> 00:26:43,320 NEXT SLIDE PLEASE. 646 00:26:43,320 --> 00:26:44,560 TURNS OUT THERE WASN'T ANYTHING 647 00:26:44,560 --> 00:26:46,760 WRONG WITH THE TEST, THE TEST 648 00:26:46,760 --> 00:26:48,840 WAS ACTUALLY GOING BEYOND WHAT 649 00:26:48,840 --> 00:26:52,600 IT WAS INITIALLY EXPECTED TO DO. 650 00:26:52,600 --> 00:26:56,840 IT IS SO SENSITIVE THAT IT 651 00:26:56,840 --> 00:26:58,920 DETECTS ALTERNATIVE BIOLOGICAL 652 00:26:58,920 --> 00:26:59,920 EXPLANATIONS FOR THE FALSE 653 00:26:59,920 --> 00:27:02,040 POSITIVE RESULTS. 654 00:27:02,040 --> 00:27:03,800 REALLY NOT FALSE POSITIVE JUST 655 00:27:03,800 --> 00:27:04,800 DETECTING SOMETHING OTHER THAN 656 00:27:04,800 --> 00:27:06,840 WHAT WAS EXPECTED. 657 00:27:06,840 --> 00:27:09,200 SO IF YOU ARE TALKING ABOUT THE 658 00:27:09,200 --> 00:27:12,560 FETUS AND PLACENTA, THAT 10% OF 659 00:27:12,560 --> 00:27:14,080 DNA, YOU CAN DETECT 660 00:27:14,080 --> 00:27:15,360 ABNORMALITIES THAT ARE COMBINED 661 00:27:15,360 --> 00:27:19,240 TO THE PLACENTA SUCH AS COMBINED 662 00:27:19,240 --> 00:27:25,440 PLACENTAL MOI SAKISM, YOU CAN 663 00:27:25,440 --> 00:27:26,880 DEFINE WHERE IT HAS PARTLY 664 00:27:26,880 --> 00:27:28,640 NORMAL CHROMOSOMES AN PARTLY 665 00:27:28,640 --> 00:27:29,800 ABNORMAL CHROMOSOMES. 666 00:27:29,800 --> 00:27:32,000 YOU CAN ALSO HAVE A SITUATION 667 00:27:32,000 --> 00:27:34,760 WHERE THERE WAS INITIALLY TWIN 668 00:27:34,760 --> 00:27:37,080 CONCEPTION BUT ONE TWIN HAS A 669 00:27:37,080 --> 00:27:39,720 CHROMOSOME ABNORMALITY AND THAT 670 00:27:39,720 --> 00:27:42,040 LED TO A SPONTANEOUS MISCARRIAGE 671 00:27:42,040 --> 00:27:44,920 OF THE PLACENTA MAY STILL BE 672 00:27:44,920 --> 00:27:46,120 RELEASING DNA INTO MATERNAL 673 00:27:46,120 --> 00:27:47,280 CIRCULATION SO WHAT YOU ARE 674 00:27:47,280 --> 00:27:50,360 DETECTING IN THAT CASE IS THE 675 00:27:50,360 --> 00:27:51,720 DECEASED CO-TWIN, NOT THE LIVING 676 00:27:51,720 --> 00:27:55,280 TWIN. 677 00:27:55,280 --> 00:27:55,640 MOSAICISM. 678 00:27:55,640 --> 00:27:58,040 THE MAJORITY OF DNA IN THE BLOOD 679 00:27:58,040 --> 00:27:59,000 SAMPLE FROM THE MOTHER. 680 00:27:59,000 --> 00:28:00,560 AS WE LEARNED THIS IS AN 681 00:28:00,560 --> 00:28:03,280 EXCEPTIONALLY SENSITIVE TEST FOR 682 00:28:03,280 --> 00:28:06,480 DETECTING MATERNAL VARIATION. 683 00:28:06,480 --> 00:28:08,880 THERE CAN BE EXTRA COPIES OF 684 00:28:08,880 --> 00:28:12,000 SEGMENTS OF THE CHROMOSOME OF 685 00:28:12,000 --> 00:28:13,800 INTEREST LIKE SECTION OF 686 00:28:13,800 --> 00:28:17,200 CHROMOSOME 13 THAT MAY BE BENIGN 687 00:28:17,200 --> 00:28:21,680 BUT PICKED UP AS SOMETHING HA 688 00:28:21,680 --> 00:28:23,840 TRIGGERS ABNORMAL RASH REIN 689 00:28:23,840 --> 00:28:24,360 MOTHER WITHOUT CLINICAL 690 00:28:24,360 --> 00:28:25,040 SIGNIFICANCE. 691 00:28:25,040 --> 00:28:28,560 WE ARE NOW MUCH MORE AWARE OF 692 00:28:28,560 --> 00:28:31,960 WOMEN WHO MAY HAVE MOSAICISM FOR 693 00:28:31,960 --> 00:28:34,800 TURNER SYNDROME OR FOR TRIPLE X 694 00:28:34,800 --> 00:28:37,240 SYNDROME BUT YET DOESN'T AFFECT 695 00:28:37,240 --> 00:28:38,440 FERTILITY BECAUSE BY DEFINITION 696 00:28:38,440 --> 00:28:40,120 IF THEY ARE HAVING THIS H TEST 697 00:28:40,120 --> 00:28:41,080 THEY ARE PREGNANT. 698 00:28:41,080 --> 00:28:43,640 WE ARE AWARE OF MANY WOMEN WHO 699 00:28:43,640 --> 00:28:48,440 ARE MOSAIC FOR AUTOSOMAL TRISOMY 700 00:28:48,440 --> 00:28:51,360 SUCH AS TRISOMY 8, THAT DOESN'T 701 00:28:51,360 --> 00:28:53,680 HAVE EFFECT ON THEIR FERTILITY, 702 00:28:53,680 --> 00:28:55,320 GROWTH, DEVELOPMENT OR THEIR 703 00:28:55,320 --> 00:28:58,120 INTELLIGENCE. 704 00:28:58,120 --> 00:29:01,800 TRTHERE ARE A VARIETY OF MATERNAL 705 00:29:01,800 --> 00:29:03,720 TREATMENTS AND CONDITIONS THAT 706 00:29:03,720 --> 00:29:05,520 AFFECT QUALITY OF THE CELL FREE 707 00:29:05,520 --> 00:29:09,040 DNA AND THOSE CAN TRIGGER 708 00:29:09,040 --> 00:29:10,640 ABNORMALITIES IN THE 709 00:29:10,640 --> 00:29:11,960 BIOINFORMATICS, THESE INCLUDE 710 00:29:11,960 --> 00:29:14,800 AUTOIMMUNE DISORDERS, VITAMIN B 711 00:29:14,800 --> 00:29:17,880 12 DEFICIENCY AND INTERIM COLD 712 00:29:17,880 --> 00:29:18,920 STASIS OF PREGNANCY. 713 00:29:18,920 --> 00:29:20,680 ONE INTERESTING THING WHEN YOU 714 00:29:20,680 --> 00:29:23,120 TALK ABOUT FOR EXAMPLE SEX 715 00:29:23,120 --> 00:29:25,440 CHROMOSOME ABNORMALITIES, WE ARE 716 00:29:25,440 --> 00:29:28,760 AWARE OF MANY CASES WHICH Y 717 00:29:28,760 --> 00:29:30,280 CHROMOSOMAL DNA IS DETECTED IN 718 00:29:30,280 --> 00:29:33,680 THE MOTHERS BLOOD YET FETUS 719 00:29:33,680 --> 00:29:36,640 LOOKS FEMALE ON ULTRASOUND 720 00:29:36,640 --> 00:29:37,240 EXAMINATION. 721 00:29:37,240 --> 00:29:40,320 TURNS OUT DNA BEING RELEASED IS 722 00:29:40,320 --> 00:29:41,920 ACTUALLY FROM A PRIOR SOLID 723 00:29:41,920 --> 00:29:44,000 ORGAN TRANSPLANTS SUCH AS KIDNEY 724 00:29:44,000 --> 00:29:49,240 THAT WAS DONATED BY A MALE 725 00:29:49,240 --> 00:29:49,760 DONOR. 726 00:29:49,760 --> 00:29:54,560 ALSO FIBROIDS WHICH ARE VERY 727 00:29:54,560 --> 00:29:56,840 COMMON, CAN RELEASE DNA INTO 728 00:29:56,840 --> 00:30:00,120 MATERNAL CIRCULATION VIA CAUSE 729 00:30:00,120 --> 00:30:02,040 OF FALSE POSITIVE RESULT SINCE 730 00:30:02,040 --> 00:30:04,560 YOU MOW THIS HAS DIAGNOSIS OF 731 00:30:04,560 --> 00:30:06,160 MALIGNANCY WE WILL FOCUS ON 732 00:30:06,160 --> 00:30:09,600 MALIGNANCY. 733 00:30:09,600 --> 00:30:12,160 YOU DON'T EXPECT MALIGNANCY WHEN 734 00:30:12,160 --> 00:30:15,000 PREGNANT BECAUSE YOU ARE DEALING 735 00:30:15,000 --> 00:30:17,280 WITH HEALTHY RELATIVELY YOUNG 736 00:30:17,280 --> 00:30:18,360 POPULATION. 737 00:30:18,360 --> 00:30:21,080 AL HOE CANCER HAS BEEN REPORTED 738 00:30:21,080 --> 00:30:23,760 TO OCCUR IN ONE IN A THOUSAND TO 739 00:30:23,760 --> 00:30:25,840 ONE IN 2,000 PREGNANT PEOPLE. 740 00:30:25,840 --> 00:30:27,040 THE MOST COMMON TYPES OF CANCER 741 00:30:27,040 --> 00:30:28,960 TO BE EXPECTED WOULD BE THOSE 742 00:30:28,960 --> 00:30:31,800 ASSOCIATED WITH A RELATIVELY 743 00:30:31,800 --> 00:30:33,920 YOUNG AGE AND THESE INCLUDE 744 00:30:33,920 --> 00:30:36,240 BREAST CANCER, HODGKINS AND 745 00:30:36,240 --> 00:30:38,160 NON-HODGKINS LYMPHOMA, CERVICAL 746 00:30:38,160 --> 00:30:41,920 AND OVARIAN CANCER AND LEUKEMIA. 747 00:30:41,920 --> 00:30:45,320 THE REASON WHY THIS TRIGGERS A 748 00:30:45,320 --> 00:30:48,320 NON-REPORTABLE RESULT IS TUMOR 749 00:30:48,320 --> 00:30:50,640 DNA IS ALSO UNDERGOING APOPTOSIS 750 00:30:50,640 --> 00:30:54,040 AND SHEDDING CELL FREE DNA INTO 751 00:30:54,040 --> 00:30:55,000 MATERNAL CIRCULATION. 752 00:30:55,000 --> 00:30:57,280 THIS THEN CAUSES THIS 753 00:30:57,280 --> 00:30:59,120 ABNORMALITY IN THE RATIO OF TEST 754 00:30:59,120 --> 00:31:07,480 TO THE REFERENCE CHROMOSOMES. 755 00:31:07,480 --> 00:31:10,240 YOU MAY HAVE HEARD ABOUT LIQUID 756 00:31:10,240 --> 00:31:10,840 BIOPSY TEST FOR CANCER. 757 00:31:10,840 --> 00:31:13,760 THE NIPT WAS NOT DESIGNED TO 758 00:31:13,760 --> 00:31:15,960 DETECT CANCER, IT WAS DESIGNED 759 00:31:15,960 --> 00:31:20,040 TO DETECT FETAL ANEUPLOIDY SO IT 760 00:31:20,040 --> 00:31:22,040 IS REMARKABLE IT DOES IN MANY 761 00:31:22,040 --> 00:31:25,120 CASES DETECT CANCER. 762 00:31:25,120 --> 00:31:26,640 THE LIQUID BIOPSIES USE A 763 00:31:26,640 --> 00:31:28,640 VARIETY OF APPROACHES LOOKING 764 00:31:28,640 --> 00:31:30,520 FOR SPECIFIC MUTATIONS 765 00:31:30,520 --> 00:31:33,240 ASSOCIATED WITH SPECIFIC CANCER, 766 00:31:33,240 --> 00:31:35,320 OR SPECIFIC METHYLATION OF 767 00:31:35,320 --> 00:31:37,400 GENES, OR FUSION OF GENES WITH 768 00:31:37,400 --> 00:31:39,840 SOME OF THE TESTS WORK ON COPY 769 00:31:39,840 --> 00:31:43,640 NUMBER ALTERATIONS THAT DISTORT 770 00:31:43,640 --> 00:31:44,440 RATIO. 771 00:31:44,440 --> 00:31:46,080 THAT'S WAY IT IS WORKING IN THIS 772 00:31:46,080 --> 00:31:46,600 SITUATION. 773 00:31:46,600 --> 00:31:53,720 NEXT SLIDE. 774 00:31:53,720 --> 00:31:55,480 JUST AROUND THE SAME TIME THESE 775 00:31:55,480 --> 00:31:58,800 REPORTS WERE OCCURRING OF THE 776 00:31:58,800 --> 00:32:01,560 IPT TEST DOESN'T WORK, THERE'S 777 00:32:01,560 --> 00:32:03,520 SO MANY POSITIVE CASES WE BECAME 778 00:32:03,520 --> 00:32:05,480 AWARE OF THE FIRST REPORT OF 779 00:32:05,480 --> 00:32:06,720 MATERNAL MALIGNANCY IN A WOMAN 780 00:32:06,720 --> 00:32:11,640 WHO ENDED UP HAVING NIPT THREE 781 00:32:11,640 --> 00:32:13,160 TIMES AND CONSISTENTLY HAD 782 00:32:13,160 --> 00:32:16,040 MULTIPLE ANEUPLOIDY. 783 00:32:16,040 --> 00:32:20,200 AT THE TIME SHE WAS HEALTHY 784 00:32:20,200 --> 00:32:22,320 ALTHOUGH POSTPARTUM SHE 785 00:32:22,320 --> 00:32:23,680 DEVELOPED PELVIC PAIN. 786 00:32:23,680 --> 00:32:26,040 THE PATIENT IS SITTING HERE AND 787 00:32:26,040 --> 00:32:27,640 SHE ACTUALLY WENT PUBLIC WITH 788 00:32:27,640 --> 00:32:30,640 HER STORY AND GAVE AN INTERVIEW 789 00:32:30,640 --> 00:32:33,640 TO MIT TECHNOLOGY REVIEW, 790 00:32:33,640 --> 00:32:35,960 UNFORTUNATELY SHE HAS SINCE 791 00:32:35,960 --> 00:32:37,000 PASSED AWAY. 792 00:32:37,000 --> 00:32:38,640 SHE WAS PREGNANT WITH HER SON 793 00:32:38,640 --> 00:32:40,240 WHO IS ON HER LAP. 794 00:32:40,240 --> 00:32:43,880 SHE HAD AMNIOCENTESIS, HE WAS 795 00:32:43,880 --> 00:32:45,040 NORMAL. 796 00:32:45,040 --> 00:32:46,240 DIAGNOSIS WASN'T MADE UNTIL 797 00:32:46,240 --> 00:32:47,440 AFTER HER DELIVERY WHEN BECAUSE 798 00:32:47,440 --> 00:32:50,120 OF THE PELVIC PAIN SHE UNDERWENT 799 00:32:50,120 --> 00:32:52,120 A WORK UP AND WAS SHOWN TO HAVE 800 00:32:52,120 --> 00:32:53,880 WIDELY METASTATIC NEURAL 801 00:32:53,880 --> 00:32:57,240 ENDOCRINE CANCER. 802 00:32:57,240 --> 00:32:58,400 NEXT SLIDE PLEASE. 803 00:32:58,400 --> 00:33:00,160 SINCE THAT TIME THERE HAVE BEEN 804 00:33:00,160 --> 00:33:03,600 A VARIETY OF STUDIES, MOST OF 805 00:33:03,600 --> 00:33:06,160 THEM HAD BEEN REROW SPECKTIVE 806 00:33:06,160 --> 00:33:09,160 USING LARGE CLINICAL COMMERCIAL 807 00:33:09,160 --> 00:33:09,720 DATABASES. 808 00:33:09,720 --> 00:33:12,160 THE INITIAL FOCUS HAS BEEN ON 809 00:33:12,160 --> 00:33:14,800 CASES WITH MULTIPLE FALSE 810 00:33:14,800 --> 00:33:20,120 POSITIVE ANEUPLOIDYs DETECTED 811 00:33:20,120 --> 00:33:21,440 THOUGH THERE HAVE BEEN CASES OF 812 00:33:21,440 --> 00:33:23,880 CANCER WITH ONLY SINGLE 813 00:33:23,880 --> 00:33:24,920 ANEUPLOIDY. 814 00:33:24,920 --> 00:33:26,360 AS YOU CAN SEE IF YOU LOOK AT 815 00:33:26,360 --> 00:33:29,240 THE LINE THAT SAYS NUMBER OF 816 00:33:29,240 --> 00:33:32,240 CASES WITH NEOPLASTIC CONDITIONS 817 00:33:32,240 --> 00:33:34,640 CONFIRM THAT LINE ADDS UP TO 818 00:33:34,640 --> 00:33:37,280 WELL OVER 100 CASES OF 819 00:33:37,280 --> 00:33:39,840 MALIGNANCY AND A VARIETY OF THEM 820 00:33:39,840 --> 00:33:45,000 HAVE ALSO REPORTED FIBROIDS OR 821 00:33:45,000 --> 00:33:46,120 LIEL MYOMAS. 822 00:33:46,120 --> 00:33:48,520 THE MAJORITY HAVE BEEN SOLID 823 00:33:48,520 --> 00:33:49,800 TUMORS RELEASING DNA INTO THE 824 00:33:49,800 --> 00:33:54,760 CIRCULATION. 825 00:33:54,760 --> 00:33:59,200 WITH THESE OVER 100 CASES MOST 826 00:33:59,200 --> 00:34:01,040 WOMEN HAD BEEN HEALTHY 827 00:34:01,040 --> 00:34:04,880 PRE-SYMPTOMATIC HAVE NOT BEEN 828 00:34:04,880 --> 00:34:06,440 DIAGNOSED UNTIL AFTER NIPT 829 00:34:06,440 --> 00:34:06,840 RESULTS. 830 00:34:06,840 --> 00:34:08,520 THERE'S A RANGE OF TUMOR TYPES, 831 00:34:08,520 --> 00:34:11,520 I WILL SHOW YOU NEXT SLIDE. 832 00:34:11,520 --> 00:34:13,280 MAJORITY HAVE BEEN ASSOCIATED 833 00:34:13,280 --> 00:34:15,760 WITH MULTIPLE CHROMOSOME 834 00:34:15,760 --> 00:34:18,360 IMBALANCES WHICH ARE THE MOST 835 00:34:18,360 --> 00:34:20,920 SUSPICIOUS FROM MALIGNANCY. 836 00:34:20,920 --> 00:34:22,840 THE EARLIER STUDIES ESTIMATED 837 00:34:22,840 --> 00:34:26,160 WHEN YOU DID SEE MULTIPLE 838 00:34:26,160 --> 00:34:28,640 ANEUPLOIDIES THERE WAS A 20 TO 839 00:34:28,640 --> 00:34:31,280 45% RISK OF MATERNAL CANCER BUT 840 00:34:31,280 --> 00:34:33,440 MORE RECENTLY RATE OF CANCER 841 00:34:33,440 --> 00:34:35,920 DETECTION IS FELT TO BE HIGHER 842 00:34:35,920 --> 00:34:37,600 ALTHOUGH THERE HAS BEEN BIAS 843 00:34:37,600 --> 00:34:40,000 BECAUSE THESE CASES HAVE BEEN 844 00:34:40,000 --> 00:34:41,440 SELECTED FROM LARGE COMMERCIAL 845 00:34:41,440 --> 00:34:46,320 OR NATIONAL DATABASES WHERE THE 846 00:34:46,320 --> 00:34:49,480 OUTCOMES YOU HAVE ALREADY KNOWN. 847 00:34:49,480 --> 00:34:52,040 THIS IS SHOWING YOU THE 848 00:34:52,040 --> 00:34:53,840 DISTRIBUTION OF NEOPLASMS AND 849 00:34:53,840 --> 00:34:56,240 PUBLISHED REPORTS, LOOK AT THE 850 00:34:56,240 --> 00:34:58,560 UPPER RIGHT PART OF THE PIE 851 00:34:58,560 --> 00:35:00,040 CHART, THE SKY BLUE COLOR, THOSE 852 00:35:00,040 --> 00:35:03,120 ARE CASES OF LYMPHOMA. 853 00:35:03,120 --> 00:35:05,560 THE GREEN DARKER GREEN, IS 854 00:35:05,560 --> 00:35:07,640 BREAST CANCER, THOSE ARE THE 855 00:35:07,640 --> 00:35:08,040 MOST COMMON. 856 00:35:08,040 --> 00:35:10,840 THOUGH WILL IS A WIDE VARIETY OF 857 00:35:10,840 --> 00:35:12,960 CANCER TYPES INCLUDING 858 00:35:12,960 --> 00:35:17,440 COLORECTAL, MYELOMA, LIEL MYOWE 859 00:35:17,440 --> 00:35:20,960 SARCOMA, THE MALIGNANT 860 00:35:20,960 --> 00:35:24,440 TRANSMISSION FROM THE FIBROID 861 00:35:24,440 --> 00:35:25,560 GASTRIC CANCER AND I WOULD SAY 862 00:35:25,560 --> 00:35:29,440 IN OUR IDENTIFY STUDY WE HAVE 863 00:35:29,440 --> 00:35:32,080 ALREADY HAD SEVERAL VERY UNUSUAL 864 00:35:32,080 --> 00:35:33,000 CANCERS THAT HAVEN'T BEEN 865 00:35:33,000 --> 00:35:34,320 PREVIOUSLY REPORTED. 866 00:35:34,320 --> 00:35:35,600 APPROXIMATELY ONE IN FIVE 867 00:35:35,600 --> 00:35:37,360 MATERNAL FETAL MEDICINE 868 00:35:37,360 --> 00:35:38,640 SPECIALISTS HAVE ESTIMATED THAT 869 00:35:38,640 --> 00:35:41,760 THEY HAVE HAD AT LEAST ONE CASE 870 00:35:41,760 --> 00:35:47,640 OF CANCER IN THEIR PRACTICE. 871 00:35:47,640 --> 00:35:49,720 THIS IS WHAT A REPORT COULD LOOK 872 00:35:49,720 --> 00:35:50,600 LIQUEUR YOU SAW ACTUAL PATIENTS 873 00:35:50,600 --> 00:35:52,400 REPORT, IN BIG LETTERS YOU SEE 874 00:35:52,400 --> 00:35:56,760 IT IS NOT REPORTABLE, DOESN'T 875 00:35:56,760 --> 00:36:01,440 REALLY EXPLAIN MORE THAN THAT. 876 00:36:01,440 --> 00:36:03,480 A DIFFERENT TEST RESULT MIGHT 877 00:36:03,480 --> 00:36:06,680 SAY TYPICAL FINDING AND LIKELY A 878 00:36:06,680 --> 00:36:08,960 MATERNAL ORIGIN. 879 00:36:08,960 --> 00:36:10,200 IT IS INTERESTING NOT ALL 880 00:36:10,200 --> 00:36:12,040 REPORTS SAY THE SAME THING OR 881 00:36:12,040 --> 00:36:13,880 EVEN INDICATE THAT THIS COULD BE 882 00:36:13,880 --> 00:36:15,560 A MATERNAL CONDITION. 883 00:36:15,560 --> 00:36:18,200 BUT THEY DO SAY REPEAT CELL FREE 884 00:36:18,200 --> 00:36:20,000 DNA TESTING IS NOT RECOMMENDED 885 00:36:20,000 --> 00:36:24,440 THOUGH THEY DO RECOMMEND GENETIC 886 00:36:24,440 --> 00:36:26,520 COUNSELING, CONSULTATION WITH 887 00:36:26,520 --> 00:36:28,680 MATERNAL FETAL SPECIALIST, AND 888 00:36:28,680 --> 00:36:31,960 MATERNAL FETAL EVALUATIONS. 889 00:36:31,960 --> 00:36:33,800 GENETIC COUNSELING IS 890 00:36:33,800 --> 00:36:35,600 RECOMMENDED UNFORTUNATELY THERE 891 00:36:35,600 --> 00:36:39,880 AREN'T ENOUGH COUNSELORS TO GO 892 00:36:39,880 --> 00:36:42,000 AROUND FOR ALL THE ABNORMAL NIPT 893 00:36:42,000 --> 00:36:45,640 CASES BUT I WANTED TO MENTION A 894 00:36:45,640 --> 00:36:49,440 STUDY DONE BY MEGHAN JILES IN 895 00:36:49,440 --> 00:36:52,160 THE PICTURE HERE DID A SURVEY OF 896 00:36:52,160 --> 00:36:54,720 OVER 300 GENETIC COUNSELORS, A 897 00:36:54,720 --> 00:36:57,680 MAJORITY WERE AWARE THAT NIPT 898 00:36:57,680 --> 00:36:58,840 COULD DISCLOSE RESULTSES 899 00:36:58,840 --> 00:37:00,280 SUGGESTING OF MATERNAL CANCER 900 00:37:00,280 --> 00:37:01,920 THOUGH THE -- MOST DID NOT 901 00:37:01,920 --> 00:37:02,960 MENTION DURING PRE-TEST 902 00:37:02,960 --> 00:37:05,760 COUNSELING. 903 00:37:05,760 --> 00:37:08,520 HOWEVER, 77% SAID THEY WOULD 904 00:37:08,520 --> 00:37:09,640 DISCLOSE THESE RESULTS DURING 905 00:37:09,640 --> 00:37:11,080 POST TEST COUNSELING. 906 00:37:11,080 --> 00:37:12,440 AND THE MANAGEMENT 907 00:37:12,440 --> 00:37:13,320 RECOMMENDATIONS WERE HIGH LIE 908 00:37:13,320 --> 00:37:18,640 VARIABLE. 909 00:37:18,640 --> 00:37:20,840 THERE WERE MIXED FEELINGS ABOUT 910 00:37:20,840 --> 00:37:22,720 THE BENEFITS VERSUS THE HARM, 911 00:37:22,720 --> 00:37:26,040 HOWEVER THEY ALMOST ALL SAID 912 00:37:26,040 --> 00:37:27,040 INSTITUTIONAL OR NATIONAL 913 00:37:27,040 --> 00:37:28,520 GUIDELINES WERE NEEDED TO INFORM 914 00:37:28,520 --> 00:37:33,160 PATIENT MANAGEMENT. 915 00:37:33,160 --> 00:37:36,040 IN THE UNITED STATES THERE'S 916 00:37:36,040 --> 00:37:39,120 REALLY ONLY ONE PUBLICATION THAT 917 00:37:39,120 --> 00:37:43,000 SUGGESTS A WAY TO MANAGE THESE 918 00:37:43,000 --> 00:37:45,040 PATIENTS. 919 00:37:45,040 --> 00:37:48,080 NOTICE IT DOES SAY MAGNETIC 920 00:37:48,080 --> 00:37:49,640 RESONANCE IMAGE BUT PART OF THE 921 00:37:49,640 --> 00:37:53,280 PROBLEM IS SO MANY STUDIES ARE 922 00:37:53,280 --> 00:37:56,240 NOT COVERED BY INSURANCE BECAUSE 923 00:37:56,240 --> 00:37:58,400 LACK OF PROSPECTIVE EVIDENCE TO 924 00:37:58,400 --> 00:38:00,960 GUIDE MANAGEMENT. 925 00:38:00,960 --> 00:38:03,720 THIS IS SUGGESTED MANAGEMENT BY 926 00:38:03,720 --> 00:38:07,600 GROUP IN NORTH CAROLINA BUT IT 927 00:38:07,600 --> 00:38:12,240 IS NOT BASED ON EVIDENCE SO WE 928 00:38:12,240 --> 00:38:18,960 FELT THE NEED FOR EVIDENCE. 929 00:38:18,960 --> 00:38:20,080 THESE ARE SOME OF THE CHALLENGES 930 00:38:20,080 --> 00:38:23,000 WE FACE NOT ONLY GETTING THE 931 00:38:23,000 --> 00:38:26,840 STUDY GOING BUT EVEN ONGOING 932 00:38:26,840 --> 00:38:28,480 STUDY YOU WILL HEAR ABOUT IN A 933 00:38:28,480 --> 00:38:29,000 MOMENT. 934 00:38:29,000 --> 00:38:30,560 IF YOU LOOK IN THE UPPER LEFT 935 00:38:30,560 --> 00:38:32,560 PART OF THE PIE, MANY DIFFERENT 936 00:38:32,560 --> 00:38:34,080 LABORATORIES ARE OFFERING NIPT 937 00:38:34,080 --> 00:38:37,280 IN THE UNITED STATES. 938 00:38:37,280 --> 00:38:39,280 AND EACH ONE ANALYZES AND 939 00:38:39,280 --> 00:38:43,280 REPORTS THE RESULTS DIFFERENTLY. 940 00:38:43,280 --> 00:38:45,040 WE HAD DIFFICULTY WITH 941 00:38:45,040 --> 00:38:46,960 CLINICIANS, NOT EVERYBODY AGREES 942 00:38:46,960 --> 00:38:48,160 THESE RESULTS SHOULD BE 943 00:38:48,160 --> 00:38:48,800 DISCLOSED. 944 00:38:48,800 --> 00:38:53,360 IN FACT SPECIALISTS PRE-NATAL 945 00:38:53,360 --> 00:38:55,040 DIAGNOSTIC SPECIALIST DEBATED 946 00:38:55,040 --> 00:38:56,480 THIS LEVELLY, I MODERATED THE 947 00:38:56,480 --> 00:38:58,880 DEBATE BACK IN 201, AND THERE 948 00:38:58,880 --> 00:39:01,960 WAS A SIGNIFICANT AMOUNT OF 949 00:39:01,960 --> 00:39:03,560 DISAGREEMENT WHETHER OR NOT THE 950 00:39:03,560 --> 00:39:04,520 RESULTS SHOULD BE DISCLOSED 951 00:39:04,520 --> 00:39:07,640 BECAUSE THE TEST WAS NOT 952 00:39:07,640 --> 00:39:09,840 DESIGNED THE O DETECT 953 00:39:09,840 --> 00:39:10,240 MALIGNANCY. 954 00:39:10,240 --> 00:39:12,000 NO EVIDENCE BASED GUIDELINES. 955 00:39:12,000 --> 00:39:14,160 WHEN WE HAVE TRIED TO REFER SOME 956 00:39:14,160 --> 00:39:16,320 OF THESE WOMEN TO ONCOLOGISTS, 957 00:39:16,320 --> 00:39:19,520 MANY ONCOLOGISTS ARE UNAWARE 958 00:39:19,520 --> 00:39:21,520 MATERNAL CANCER CAN BE DETECTED 959 00:39:21,520 --> 00:39:23,760 BY PRE-NATAL SCREENING. 960 00:39:23,760 --> 00:39:27,280 I HAVE ALREADY MENTIONED THAT 961 00:39:27,280 --> 00:39:29,040 INSURANCE COMPANIES ARE UNLIKELY 962 00:39:29,040 --> 00:39:30,680 TO COVER COSTS OF MATERNAL 963 00:39:30,680 --> 00:39:32,240 EVALUATION PARTICULARLY IN 964 00:39:32,240 --> 00:39:33,480 HEALTHY PREGNANT WOMAN WITHOUT 965 00:39:33,480 --> 00:39:34,720 SYMPTOMS. 966 00:39:34,720 --> 00:39:37,280 LASTLY, THE PATIENTS ARE OFTEN 967 00:39:37,280 --> 00:39:39,400 REASSURED BY LACK OF SYMPTOMS, 968 00:39:39,400 --> 00:39:42,440 THEY DECLINE EVALUATION OR THEY 969 00:39:42,440 --> 00:39:46,120 COULD HAVE A PARTIAL WORK UP 970 00:39:46,120 --> 00:39:48,400 SUCH AS CHEST X-RAY AND IF HA IS 971 00:39:48,400 --> 00:39:50,400 NORMAL THEY MAY BE FALSELY 972 00:39:50,400 --> 00:39:50,920 REASSURED. 973 00:39:50,920 --> 00:39:52,040 WE ARE TRYING TO DEAL WITH SOME 974 00:39:52,040 --> 00:39:55,840 OF THESE CHALLENGES. 975 00:39:55,840 --> 00:39:57,240 SO ED I'M GOING TO HAND THE 976 00:39:57,240 --> 00:39:59,240 VIRTUAL MICROPHONE OVER TO AMY 977 00:39:59,240 --> 00:40:01,080 TURRIFF WHO WILL DESCRIBE THE 978 00:40:01,080 --> 00:40:03,280 IDENTIFY STUDY THAT IS BEING 979 00:40:03,280 --> 00:40:04,160 PERFORMED AT THE CLINICAL 980 00:40:04,160 --> 00:40:04,720 CENTER. 981 00:40:04,720 --> 00:40:05,360 THANK YOU. 982 00:40:05,360 --> 00:40:07,440 >> THANKS, SO MUCH. 983 00:40:07,440 --> 00:40:10,320 SO THE IDENTIFY STUDY IS A 984 00:40:10,320 --> 00:40:11,800 COLLABORATION AMONG NATIONAL 985 00:40:11,800 --> 00:40:13,440 HUMAN GENOME RESEARCH INSTITUTE 986 00:40:13,440 --> 00:40:15,840 AND NATIONAL CANCER INSTITUTE. 987 00:40:15,840 --> 00:40:18,040 WE WORK VERY CLOSE WITH THE 988 00:40:18,040 --> 00:40:19,720 CLINICAL CENTERS DEPARTMENT OF 989 00:40:19,720 --> 00:40:23,560 RADIOLOGY AND DEPARTMENT OF 990 00:40:23,560 --> 00:40:25,040 BIOETHICS. 991 00:40:25,040 --> 00:40:26,760 WE ARE ENROLLING PEOPLE WHO ARE 992 00:40:26,760 --> 00:40:29,080 18 YEARS AND OLDER WHO HAVE 993 00:40:29,080 --> 00:40:30,760 RECEIVED ABNORMAL OR 994 00:40:30,760 --> 00:40:32,440 NON-REPORTABLE NIPT RESULTS 995 00:40:32,440 --> 00:40:33,560 DURING PREGNANCY. 996 00:40:33,560 --> 00:40:35,440 WITH FOLLOW-UP EVALUATION THAT 997 00:40:35,440 --> 00:40:37,880 SHOWS EITHER NORMAL APPEARING 998 00:40:37,880 --> 00:40:40,000 FETUS ON ULTRASOUND EXAMINATION 999 00:40:40,000 --> 00:40:42,280 OR NORMAL FETAL OR NEONATAL 1000 00:40:42,280 --> 00:40:43,320 CHROMOSOMES ON DIAGNOSTIC 1001 00:40:43,320 --> 00:40:46,080 TESTING. 1002 00:40:46,080 --> 00:40:47,520 WE CAN ENROLL PEOPLE WHILE 1003 00:40:47,520 --> 00:40:50,160 PREGNANT OR UP TO TWO YEARS 1004 00:40:50,160 --> 00:40:50,600 POSTPARTUM. 1005 00:40:50,600 --> 00:40:52,920 NEXT SLIDE. 1006 00:40:52,920 --> 00:40:54,480 ALL PARTICIPANTS COME TO NIH 1007 00:40:54,480 --> 00:40:57,360 CLINICAL CENTER FOR THEIR 1008 00:40:57,360 --> 00:41:00,240 EVALUATION NO COST FOR 1009 00:41:00,240 --> 00:41:00,920 PARTICIPATION WITHIN THE UNITED 1010 00:41:00,920 --> 00:41:02,440 STATES WE CAN ENROLL 1011 00:41:02,440 --> 00:41:03,600 INTERNATIONAL PARTICIPANTS, THEY 1012 00:41:03,600 --> 00:41:04,880 JUST MUST TRAVEL TO U.S. PORT OF 1013 00:41:04,880 --> 00:41:09,800 ENTRY. 1014 00:41:09,800 --> 00:41:12,240 THERE ARE SEVERAL OBJECTIVES FOR 1015 00:41:12,240 --> 00:41:14,040 THE IDENTIFY STUDY. 1016 00:41:14,040 --> 00:41:16,440 OUR PRIMARY OBJECTIVE IS TO 1017 00:41:16,440 --> 00:41:18,440 COLLECT PROSPECTIVE EVIDENCE TO 1018 00:41:18,440 --> 00:41:21,240 DETERMINE BEST APPROACH FOR 1019 00:41:21,240 --> 00:41:24,960 DIAGNOSTIC WORK UP OF PREGNANT 1020 00:41:24,960 --> 00:41:27,080 WOMEN WHO RECEIVED DISCORDANT 1021 00:41:27,080 --> 00:41:28,400 NIPT RESULTS O TO GENERATE 1022 00:41:28,400 --> 00:41:30,040 EVIDENCE NEEDED TO INFORM 1023 00:41:30,040 --> 00:41:31,000 PROFESSIONAL GUIDELINES. 1024 00:41:31,000 --> 00:41:33,240 WE ALSO WANT TO IDENTIFY DNA 1025 00:41:33,240 --> 00:41:35,200 SEQUENCING PATTERNS OR OTHER 1026 00:41:35,200 --> 00:41:36,440 BIOMARKERS THAT CORRELATE WITH 1027 00:41:36,440 --> 00:41:39,480 THE PRESENCE OF MALIGNANCY, AS 1028 00:41:39,480 --> 00:41:41,680 DR. BIANCHI MENTIONED 1029 00:41:41,680 --> 00:41:43,120 DIFFERENTIAL IS WIDE FOR THESE 1030 00:41:43,120 --> 00:41:46,120 CASES, WE KNOW IT IS NOT ALWAYS 1031 00:41:46,120 --> 00:41:47,560 GOING TO BE CANCER SO WE ARE 1032 00:41:47,560 --> 00:41:49,320 LOOKING TO -- THERE'S OTHER 1033 00:41:49,320 --> 00:41:50,440 INFORMATION THAT WE CAN USE 1034 00:41:50,440 --> 00:41:51,760 MOVING FORWARDS. 1035 00:41:51,760 --> 00:41:53,840 TO HELP PRIORITIZE THOSE CASES 1036 00:41:53,840 --> 00:41:58,240 LIKELY TO BE MA LEG NAN. 1037 00:41:58,240 --> 00:42:00,360 WE WANT TO EVALUATE RISK AND 1038 00:42:00,360 --> 00:42:03,120 BENEFITS OF DISCLOSING NIPT 1039 00:42:03,120 --> 00:42:05,960 RESULTS SUGGESTED OF MATERNAL MA 1040 00:42:05,960 --> 00:42:06,640 KLIGERMAN SHY AND OFFERING A 1041 00:42:06,640 --> 00:42:07,320 CLINICAL WORK UP DURING 1042 00:42:07,320 --> 00:42:08,920 PREGNANCY. 1043 00:42:08,920 --> 00:42:11,480 AND AS MENTIONED NIPT IS WORKING 1044 00:42:11,480 --> 00:42:13,720 AS A TYPE OF LIQUID BIOPSY 1045 00:42:13,720 --> 00:42:16,000 THOUGH IT WASN'T DESIGNED TO DO 1046 00:42:16,000 --> 00:42:19,440 SO SO THE FINDINGS FROM THE 1047 00:42:19,440 --> 00:42:21,000 STUDY CONTINUE TO CONTRIBUTE TO 1048 00:42:21,000 --> 00:42:27,720 BROADER AREA OF RESEARCH. 1049 00:42:27,720 --> 00:42:28,680 SO THIS SLIDE PROVIDES 1050 00:42:28,680 --> 00:42:30,600 INFORMATION WHAT TO EXPECT FROM 1051 00:42:30,600 --> 00:42:30,960 PARTICIPATION. 1052 00:42:30,960 --> 00:42:32,720 WHAT I WANT TO POINT OUT HERE IS 1053 00:42:32,720 --> 00:42:36,480 WE ARE COLLECTING LONGITUDINAL 1054 00:42:36,480 --> 00:42:38,440 PSYCHOLOGICAL IMPACT DATA FOR 1055 00:42:38,440 --> 00:42:41,640 PARTICIPANTS BY ASKING THEM TO 1056 00:42:41,640 --> 00:42:43,360 BRIEF SURVEY ENGAGE IN PHONE 1057 00:42:43,360 --> 00:42:44,520 INTERVIEWS WITH US. 1058 00:42:44,520 --> 00:42:47,960 PART OF THE CONCERNS THAT HAVE 1059 00:42:47,960 --> 00:42:50,240 BEEN RAISED AMONG MEDICAL 1060 00:42:50,240 --> 00:42:51,040 SCIENTIFIC COMMUNITY IS WHETHER 1061 00:42:51,040 --> 00:42:52,640 WE ARE CAUSING PSYCHOLOGICAL 1062 00:42:52,640 --> 00:42:55,240 HARM BY DISCLOSING THESE 1063 00:42:55,240 --> 00:42:56,480 UNEXPECTED SECONDARY FINDINGS 1064 00:42:56,480 --> 00:43:00,960 FROM NIPT. 1065 00:43:00,960 --> 00:43:04,240 SO WE DESIGNED THOSE INTERVIEWS 1066 00:43:04,240 --> 00:43:06,960 AND VARIES TO USE VOICES OF OUR 1067 00:43:06,960 --> 00:43:07,800 PARTICIPANTS, TO CENT TO THAT 1068 00:43:07,800 --> 00:43:08,840 ONGOING DIALOGUE. 1069 00:43:08,840 --> 00:43:14,040 -- CONTRIBUTE TO THAT DIALOGUE. 1070 00:43:14,040 --> 00:43:15,680 ONCE AT THE NIH CLINICAL CENTER 1071 00:43:15,680 --> 00:43:18,760 THEY UNDERGO A VARIETY OF 1072 00:43:18,760 --> 00:43:20,760 EVALUATIONS FOR MALIGNANCY 1073 00:43:20,760 --> 00:43:22,200 INCLUDING BLOOD WORK, FETAL 1074 00:43:22,200 --> 00:43:26,040 BLOOD TEST, FULL BODY MRI, 1075 00:43:26,040 --> 00:43:29,240 HISTORY AND PHYSICAL WITH 1076 00:43:29,240 --> 00:43:30,480 MEDICAL ONCOLOGIST. 1077 00:43:30,480 --> 00:43:32,120 WE CAN COMPLETE THE ENTIRE 1078 00:43:32,120 --> 00:43:33,880 EVALUATION IN A DAY AND 1079 00:43:33,880 --> 00:43:35,160 EVERYTHING IS SAFE TO DO DURING 1080 00:43:35,160 --> 00:43:37,040 PREGNANCY. 1081 00:43:37,040 --> 00:43:40,640 NEXT SLIDE PLEASE. 1082 00:43:40,640 --> 00:43:41,000 ALL RESULTS ARE SHARED WITH THE 1083 00:43:41,000 --> 00:43:43,480 PATIENT. 1084 00:43:43,480 --> 00:43:44,080 WHEN THE CLINICAL EVALUATION IS 1085 00:43:44,080 --> 00:43:47,040 ABNORMAL AND MALIGNANCY IS 1086 00:43:47,040 --> 00:43:50,440 SUSPECTED, FOLLOWING INITIAL 1087 00:43:50,440 --> 00:43:51,720 CONVERSATION WITH NIH ONCOLOGIST 1088 00:43:51,720 --> 00:43:53,560 WE WORK WITH PARTICIPANTS LOCAL 1089 00:43:53,560 --> 00:43:55,280 TEAM, USUALLY PRE-NATAL CARE 1090 00:43:55,280 --> 00:43:56,800 TEAM, TO IDENTIFY THE 1091 00:43:56,800 --> 00:43:59,800 APPROPRIATE PROVIDER FOR BIOPSY 1092 00:43:59,800 --> 00:44:00,680 AND TREATMENT IN THE 1093 00:44:00,680 --> 00:44:02,120 PARTICIPANTS HOMETOWN. 1094 00:44:02,120 --> 00:44:03,720 WHEN CLINICAL EVALUATION IS 1095 00:44:03,720 --> 00:44:05,120 NORMAL, WE DO STILL HAVE TO 1096 00:44:05,120 --> 00:44:07,040 FIGURE OUT WHAT WAS THE 1097 00:44:07,040 --> 00:44:09,760 BIOLOGICAL EXPLANATION FOR THAT 1098 00:44:09,760 --> 00:44:11,680 NON-REPORTABLE NIPT RESULT. 1099 00:44:11,680 --> 00:44:14,360 SO WHEN POSSIBLE WE DO EVALUATE 1100 00:44:14,360 --> 00:44:16,560 PLACENTA TO SEE IF ABNORMALITIES 1101 00:44:16,560 --> 00:44:20,880 DETECTED BY NIPT ARE COMBINED TO 1102 00:44:20,880 --> 00:44:23,320 PLACENTA AND IF EXPLANATION WE 1103 00:44:23,320 --> 00:44:24,680 ESTABLISH A PLAN FOR CLINICAL 1104 00:44:24,680 --> 00:44:28,520 FOLLOW-UP EVALUATION OF THE 1105 00:44:28,520 --> 00:44:29,840 PARTICIPANT WE ARE AWARE OF A 1106 00:44:29,840 --> 00:44:32,520 HANDFUL OF CASES NOW WHERE 1107 00:44:32,520 --> 00:44:34,880 PREGNANT WOMAN RECEIVED ABNORMAL 1108 00:44:34,880 --> 00:44:36,040 NIPT RESULT IN INITIAL 1109 00:44:36,040 --> 00:44:37,400 PREGNANCY, AND THEN THE SAME 1110 00:44:37,400 --> 00:44:39,720 HAPPENED A COUPLE OF YEARS LATER 1111 00:44:39,720 --> 00:44:42,600 WHEN SHE BECAME PREGNANT AGAIN 1112 00:44:42,600 --> 00:44:44,440 AND MANY CASES THE PERSON WENT 1113 00:44:44,440 --> 00:44:47,360 ON TO ULTIMATELY BE DIAGNOSED 1114 00:44:47,360 --> 00:44:48,520 WITH MALIGNANCY SO IT IS 1115 00:44:48,520 --> 00:44:50,080 IMPORTANT FOR US TO COLLECT 1116 00:44:50,080 --> 00:44:51,640 FOLLOW-UP ON ALL OUR 1117 00:44:51,640 --> 00:44:53,400 PARTICIPANTS, NOT ONLY WHEN 1118 00:44:53,400 --> 00:44:55,360 CANCER HAS BEEN DETECTED BUT 1119 00:44:55,360 --> 00:45:00,160 ESPECIALLY WHEN IT HAS NOT. 1120 00:45:00,160 --> 00:45:00,720 NEXT SLIDE PLEASE. 1121 00:45:00,720 --> 00:45:02,320 WHAT WAS A LITTLE BIT DIFFERENT 1122 00:45:02,320 --> 00:45:04,760 ABOUT THE CASE THAT WE PRESENTED 1123 00:45:04,760 --> 00:45:07,960 HERE TODAY IS THAT THIS 1124 00:45:07,960 --> 00:45:10,400 PARTICIPANT WAS ULTIMATELY 1125 00:45:10,400 --> 00:45:11,640 DIAGNOSED AND BEGAN CANCER 1126 00:45:11,640 --> 00:45:13,080 TREATMENT AFTER SHE DELIVERED 1127 00:45:13,080 --> 00:45:16,960 HER BABY. 1128 00:45:16,960 --> 00:45:18,320 IN MOST CASES WITH THE 1129 00:45:18,320 --> 00:45:19,720 PARTICIPANTS IN IDENTIFY STUDY 1130 00:45:19,720 --> 00:45:21,680 BEING DIAGNOSED WITH CANCER, IT 1131 00:45:21,680 --> 00:45:22,400 IS HAPPENING WHILE THEY ARE 1132 00:45:22,400 --> 00:45:25,360 PREGNANT. 1133 00:45:25,360 --> 00:45:26,520 AND THEY ARE BEGINNING TREATMENT 1134 00:45:26,520 --> 00:45:26,920 WHILE PREGNANT. 1135 00:45:26,920 --> 00:45:31,400 SO STUDIES HAVE SHOWN MANY 1136 00:45:31,400 --> 00:45:32,000 CANCER TREATMENT CAN BE GIVEN 1137 00:45:32,000 --> 00:45:34,720 SAFELY DURING PREGNANCY AND IN 1138 00:45:34,720 --> 00:45:38,160 MOST CASES PREGNANT WOMEN SHOULD 1139 00:45:38,160 --> 00:45:40,040 BE ASSESS AND TREATED IN A MANE 1140 00:45:40,040 --> 00:45:41,720 EQUIVALENT TO NON-PREGNANT 1141 00:45:41,720 --> 00:45:42,920 PEOPLE SO PREGNANCY IS NOT A 1142 00:45:42,920 --> 00:45:43,800 REASON TO DELAY EVALUATION OR 1143 00:45:43,800 --> 00:45:51,720 TREATMENT. 1144 00:45:51,720 --> 00:45:53,920 CANCER IS A RARE INCREASINGLY 1145 00:45:53,920 --> 00:45:55,160 EXPLANATION FOR NON-REPORTABLE 1146 00:45:55,160 --> 00:45:57,440 OR DISCORDANT NIPT RESULTS. 1147 00:45:57,440 --> 00:46:01,720 THOSE WITH MULTIPLE ANEUPLOIDIES 1148 00:46:01,720 --> 00:46:03,200 ARE MOST SO SPIES SHUTS, IT IS 1149 00:46:03,200 --> 00:46:05,000 NOT ALWAYS GOING TO BE CANCER, 1150 00:46:05,000 --> 00:46:08,640 FIBROIDS OR OTHER BETUMORS CAN 1151 00:46:08,640 --> 00:46:11,080 BE DETECTED BY NIPT BUT YOU 1152 00:46:11,080 --> 00:46:12,760 CAN'T EXCLUDE MALIGNANCY WITHOUT 1153 00:46:12,760 --> 00:46:13,640 HAVING DONE THE APPROPRIATE 1154 00:46:13,640 --> 00:46:17,640 EVALUATION. 1155 00:46:17,640 --> 00:46:19,080 ADDITIONAL EVIDENCE IS NEEDED TO 1156 00:46:19,080 --> 00:46:20,200 DETERMINE MANAGEMENT 1157 00:46:20,200 --> 00:46:21,640 RECOMMENDATIONS AND WHETHER 1158 00:46:21,640 --> 00:46:24,080 EARLY DETECTION OF OKAY CULT 1159 00:46:24,080 --> 00:46:25,640 MALIGNANCIES IMPROVES OUTCOMES. 1160 00:46:25,640 --> 00:46:27,200 PLEASE REFER CASES TO THE NIH 1161 00:46:27,200 --> 00:46:33,520 IDENTIFY STUDY. 1162 00:46:33,520 --> 00:46:35,520 SO WE WANT TO ACKNOWLEDGE 1163 00:46:35,520 --> 00:46:37,800 EVERYONE WHO IS INVOLVED IN THIS 1164 00:46:37,800 --> 00:46:38,200 STUDY. 1165 00:46:38,200 --> 00:46:40,320 THANK YOU ALL FOR YOUR 1166 00:46:40,320 --> 00:46:41,480 ATTENTION, WE WOULD BE HAPPY TO 1167 00:46:41,480 --> 00:46:46,080 TAKE ANY QUESTIONS. 1168 00:46:46,080 --> 00:46:47,560 >> THANK YOU TO ALL THE 1169 00:46:47,560 --> 00:46:50,880 PRESENTERS FOR THAT FASCINATING 1170 00:46:50,880 --> 00:46:51,240 STUDY. 1171 00:46:51,240 --> 00:46:54,880 WE ACTUALLY DO HAVE TWO 1172 00:46:54,880 --> 00:46:56,640 QUESTIONS FROM VIDEOCAST LIVE 1173 00:46:56,640 --> 00:46:57,440 FEEDBACK BUTTON. 1174 00:46:57,440 --> 00:47:00,600 I WANT TO REMIND ALL VIEWERS 1175 00:47:00,600 --> 00:47:04,680 THAT THEY CAN SUBMIT COMMENTS OR 1176 00:47:04,680 --> 00:47:05,720 QUESTIONS USING THE LIVE 1177 00:47:05,720 --> 00:47:07,280 FEEDBACK BUTTON ON THE VIDEOCAST 1178 00:47:07,280 --> 00:47:07,800 SCREEN. 1179 00:47:07,800 --> 00:47:09,200 THE FIRST QUESTION IS FROM 1180 00:47:09,200 --> 00:47:14,000 RACHEL JOHNSON, I'M GUESSING DR. 1181 00:47:14,000 --> 00:47:16,720 BIANCHI WHICH SEQUENCING FOR 1182 00:47:16,720 --> 00:47:24,200 NIPT TESTING IS LESS EXPENSIVE? 1183 00:47:24,200 --> 00:47:26,920 >> SO SOME OF THAT DEPENDS 1184 00:47:26,920 --> 00:47:29,560 WHETHER YOU ARE PAYING OUT OF 1185 00:47:29,560 --> 00:47:31,920 POCKET OR NOT. 1186 00:47:31,920 --> 00:47:34,040 IN GENERAL TARGETED SEQUENCING 1187 00:47:34,040 --> 00:47:37,360 IS LESS EXPENSIVE. 1188 00:47:37,360 --> 00:47:40,880 BUT IF YOU ARE IN A HIGH RISK 1189 00:47:40,880 --> 00:47:42,760 CATEGORY YOUR INSURANCE MAY BE 1190 00:47:42,760 --> 00:47:45,680 PAYING FOR IT AS I MENTIONED 1191 00:47:45,680 --> 00:47:48,520 THERE ARE MANY STATE MEDICAID 1192 00:47:48,520 --> 00:47:52,160 PROGRAMS THAT WILL PAY, MEDICAID 1193 00:47:52,160 --> 00:47:57,040 COVERS 50% PREGNANCIES 1194 00:47:57,040 --> 00:47:58,280 NATIONALLY SO THE STATE YOU LIVE 1195 00:47:58,280 --> 00:48:01,120 IN MAKES A DIFFERENCE SOSA WILL 1196 00:48:01,120 --> 00:48:02,800 COVER TESTING FOR HIGH RISK 1197 00:48:02,800 --> 00:48:07,200 PREGNANT PEOPLE WHO ARE ON 1198 00:48:07,200 --> 00:48:08,960 MEDICATE, IT IS A COMPLICATED 1199 00:48:08,960 --> 00:48:10,720 ISSUE, MANY PAYING OUT OF POCKET 1200 00:48:10,720 --> 00:48:12,560 ARE LOOKING FOR FETAL SEX. 1201 00:48:12,560 --> 00:48:14,720 I THINK IT IS FAIR TO SAY THE 1202 00:48:14,720 --> 00:48:19,040 WHOLE GENOME SEQUENCING APPROACH 1203 00:48:19,040 --> 00:48:19,960 IS MORE EXSPENDTIVE THAN THE 1204 00:48:19,960 --> 00:48:23,000 OTHERS. 1205 00:48:23,000 --> 00:48:25,680 SECOND QUESTION FROM RACHEL 1206 00:48:25,680 --> 00:48:27,040 JOHNSTON. 1207 00:48:27,040 --> 00:48:28,720 HOW ARE YOU RECRUITING WOMEN WHO 1208 00:48:28,720 --> 00:48:31,040 ARE RECEIVING ABNORMAL OR 1209 00:48:31,040 --> 00:48:33,320 NON-REPORTABLE NIPT TEST, HOW DO 1210 00:48:33,320 --> 00:48:37,000 YOU GET CONTACTING INFORMATION? 1211 00:48:37,000 --> 00:48:39,000 ARE THEY BEING REFERRED? 1212 00:48:39,000 --> 00:48:40,920 I GUESS THAT IS THE GIST ANOTHER 1213 00:48:40,920 --> 00:48:41,200 QUESTION. 1214 00:48:41,200 --> 00:48:42,800 >> I WILL SAY COUPLE OF THINGS 1215 00:48:42,800 --> 00:48:48,360 THEN HAND TO AMY FIRST POINT OF 1216 00:48:48,360 --> 00:48:48,600 CONTACT. 1217 00:48:48,600 --> 00:48:50,120 WE ARE DOING OUTREACH SPEAKING 1218 00:48:50,120 --> 00:48:55,040 ABOUT THE PROJECT AT 1219 00:48:55,040 --> 00:48:56,080 PROFESSIONAL SOCIETY MEETINGS 1220 00:48:56,080 --> 00:49:01,040 AND AT CME COURSES, GIVEN OTHER 1221 00:49:01,040 --> 00:49:03,440 GRAND ROUNDS. 1222 00:49:03,440 --> 00:49:05,080 SO WE HOPE PEOPLE ARE WARE OF IT 1223 00:49:05,080 --> 00:49:06,920 AND USING GENETIC COUNSELING 1224 00:49:06,920 --> 00:49:09,920 LIST SERVE TO ADVERTISE THE 1225 00:49:09,920 --> 00:49:15,120 STUDY OTHERWISE IT IS PRETTY 1226 00:49:15,120 --> 00:49:17,320 MUCH WORD OF MOUTH, THEN WE 1227 00:49:17,320 --> 00:49:19,120 RECOMMEND THEY CONTACT AMY SO 1228 00:49:19,120 --> 00:49:20,120 MAYBE AMY YOU CAN DESCRIBE WHAT 1229 00:49:20,120 --> 00:49:23,880 HAPPENS AFTER THAT. 1230 00:49:23,880 --> 00:49:25,440 >> SURE. 1231 00:49:25,440 --> 00:49:26,120 MOST RELATES COME THROUGH A 1232 00:49:26,120 --> 00:49:28,000 GENETIC COUNSELOR OR THE 1233 00:49:28,000 --> 00:49:29,600 PATIENT'S PRE-NATAL PROVIDER 1234 00:49:29,600 --> 00:49:32,040 WHETHER MATERNAL FETAL MEDICINE 1235 00:49:32,040 --> 00:49:35,200 SPECIALIST, MIDWIFE, OB, THE 1236 00:49:35,200 --> 00:49:37,560 PERSON WHO'S THIS NON-REPORTABLE 1237 00:49:37,560 --> 00:49:41,600 RESULT LANDED ON THEIR DESK. 1238 00:49:41,600 --> 00:49:42,760 THERE ARE COMMERCIAL 1239 00:49:42,760 --> 00:49:43,520 LABORATORIES HERE IN THE UNITED 1240 00:49:43,520 --> 00:49:44,920 STATES OFFERED NIPT. 1241 00:49:44,920 --> 00:49:46,320 ALL OF THEM ARE AWARE THAT WE 1242 00:49:46,320 --> 00:49:49,320 ARE DOING THIS STUDY. 1243 00:49:49,320 --> 00:49:51,080 USUALLY THERE IS A LOT OF 1244 00:49:51,080 --> 00:49:52,520 CONVERSATION THAT HAPPENS 1245 00:49:52,520 --> 00:49:55,440 BETWEEN NIPT LABORATORY, AND THE 1246 00:49:55,440 --> 00:49:56,680 ORDER AND CLINICIAN WHEN THESE 1247 00:49:56,680 --> 00:50:01,120 CASES COME UP. 1248 00:50:01,120 --> 00:50:02,960 MOST PROVIDERS HAVEN'T SEEN THIS 1249 00:50:02,960 --> 00:50:04,600 BEFORE, THIS MIGHT BE THE FIRST 1250 00:50:04,600 --> 00:50:07,120 TIME THEY HAVE RECEIVED THIS 1251 00:50:07,120 --> 00:50:08,520 NON-REPORTABLE RESULT. 1252 00:50:08,520 --> 00:50:13,520 SO THE LABS TRY TO OFFER SOME 1253 00:50:13,520 --> 00:50:14,640 GUIDANCE TO WHAT SHOULD BE 1254 00:50:14,640 --> 00:50:16,960 CONSIDERED AND WHAT MIGHT BE 1255 00:50:16,960 --> 00:50:20,280 APPROPRIATE FOLLOW-UP FOR THE 1256 00:50:20,280 --> 00:50:20,720 PATIENT. 1257 00:50:20,720 --> 00:50:23,440 BECAUSE WE HAVE THIS ONGOING 1258 00:50:23,440 --> 00:50:25,120 STUDY I THINK SOMETIMES 1259 00:50:25,120 --> 00:50:26,440 COMMERCIAL LABORATORIES DO 1260 00:50:26,440 --> 00:50:28,080 ACTUALLY MAKE SURE THAT THIS 1261 00:50:28,080 --> 00:50:29,880 ORDERING CLINICIAN IS AWARE THAT 1262 00:50:29,880 --> 00:50:31,400 THIS WOULD BE AN OPTION TO 1263 00:50:31,400 --> 00:50:36,520 CONSIDER FOR THE PARTICIPANTS OR 1264 00:50:36,520 --> 00:50:37,520 PATIENT. 1265 00:50:37,520 --> 00:50:40,360 >> THANK YOU. 1266 00:50:40,360 --> 00:50:43,680 THE NEXT QUESTION IS FROM 1267 00:50:43,680 --> 00:50:44,200 PATRICIA WILLIAMS. 1268 00:50:44,200 --> 00:50:46,640 REGARDING MRI HOW LONG DOES 1269 00:50:46,640 --> 00:50:48,520 WHOLE BODY MRI TAKE TO PERFORM 1270 00:50:48,520 --> 00:50:49,680 AND IS IT DONE SINGLE SESSION? 1271 00:50:49,680 --> 00:50:51,360 AND IS THERE A SPECIFIC TYPE OF 1272 00:50:51,360 --> 00:50:53,240 MRI MACHINE THAT IS PREFERRED 1273 00:50:53,240 --> 00:50:54,520 FOR PREGNANT WOMEN OR IS THIS 1274 00:50:54,520 --> 00:50:59,040 JUST A ROUTINE MRI? 1275 00:50:59,040 --> 00:51:04,200 >> WHAT WE DO AT NIH IS NOT A 1276 00:51:04,200 --> 00:51:05,360 ROUTINE MRI YOU CAN GET 1277 00:51:05,360 --> 00:51:08,440 ANYWHERE. 1278 00:51:08,440 --> 00:51:10,880 THE WAY WE DO IT, THE WAY IT'S 1279 00:51:10,880 --> 00:51:16,120 DONE, WE USE A POWER MAGNET AS I 1280 00:51:16,120 --> 00:51:21,160 MENTIONED BECAUSE WE WANT TO BE 1281 00:51:21,160 --> 00:51:22,520 EXTREMELY SAFE WITH THE FETUS. 1282 00:51:22,520 --> 00:51:25,920 WE USE A 1.5 TIER SCANNER. 1283 00:51:25,920 --> 00:51:27,320 THIS IS -- EVERYTHING IS DONE IN 1284 00:51:27,320 --> 00:51:27,840 ONE SESSION. 1285 00:51:27,840 --> 00:51:31,760 SO DEPENDING ON WHAT IS 1286 00:51:31,760 --> 00:51:33,440 PROTOCOL, WHAT PROTOCOL WE ARE 1287 00:51:33,440 --> 00:51:37,320 DOING STUDY FOR, THIS IS NOT THE 1288 00:51:37,320 --> 00:51:40,920 ONLY TIME WE USE WHOLE BODY MRI. 1289 00:51:40,920 --> 00:51:42,760 SOMETIMES WE HAVE TO GIVE 1290 00:51:42,760 --> 00:51:44,360 CONTRAST, SOMETIMES IN OTHER 1291 00:51:44,360 --> 00:51:47,840 PROTOCOLS NOT IDENTIFY STUDY, 1292 00:51:47,840 --> 00:51:51,120 WHOLE BODY MRI MAY TAKE LONGER. 1293 00:51:51,120 --> 00:51:54,280 FOR IDENTIFY STUDY PARTICIPANTS 1294 00:51:54,280 --> 00:51:56,600 IT USUALLY TAKES 45 MINUTES TO 1295 00:51:56,600 --> 00:52:00,320 AN HOUR TO BE IN THE SCANNER. 1296 00:52:00,320 --> 00:52:03,720 >> MAY I ADD, WE HAVE HAD THE 1297 00:52:03,720 --> 00:52:05,400 SITUATION SINCE STUDY STARTED 1298 00:52:05,400 --> 00:52:07,720 PRIOR TO BEGINNING OF THE 1299 00:52:07,720 --> 00:52:09,280 PANDEMIC, WE HAD SEVERAL 1300 00:52:09,280 --> 00:52:11,840 PARTICIPANTS WHO WANTED TO COME 1301 00:52:11,840 --> 00:52:12,840 BUT WERE UNARABLE TO TRAVEL 1302 00:52:12,840 --> 00:52:14,560 EITHER BECAUSE THEY COULDN'T 1303 00:52:14,560 --> 00:52:15,680 CROSS THE CANADIAN BORDER OR 1304 00:52:15,680 --> 00:52:16,880 DIDN'T WANT TO FLY ACROSS THE 1305 00:52:16,880 --> 00:52:18,840 COUNTRY. 1306 00:52:18,840 --> 00:52:21,120 SO THEY DID HAVE MRI BUT THEY 1307 00:52:21,120 --> 00:52:23,160 COULDN'T HAVE A WHOLE BODY MRI. 1308 00:52:23,160 --> 00:52:27,440 SO THEY ENDED UP HAVING MULTIPLE 1309 00:52:27,440 --> 00:52:29,320 MRIs, SOMETIMES ON DIFFERENT 1310 00:52:29,320 --> 00:52:30,680 DAYS JUST TO COVER THE ENTIRE 1311 00:52:30,680 --> 00:52:31,160 BODY. 1312 00:52:31,160 --> 00:52:32,640 THAT IS ONE OF THE GREAT 1313 00:52:32,640 --> 00:52:34,360 ADVANTAGES OF THIS STUDY, IS IT 1314 00:52:34,360 --> 00:52:36,720 CAN ALL BE DONE AT ONCE IN A 1315 00:52:36,720 --> 00:52:37,720 RELATIVELY LIMITED PERIOD OF 1316 00:52:37,720 --> 00:52:41,320 TIME. 1317 00:52:41,320 --> 00:52:46,600 IT DOESN'T COST ANYTHING WHICH 1318 00:52:46,600 --> 00:52:47,920 IS A MAIN EVENT. 1319 00:52:47,920 --> 00:52:51,480 >> ANOTHER QUESTION FROM -- IS 1320 00:52:51,480 --> 00:52:53,920 THERE ANY WORK UNDERWAY TO 1321 00:52:53,920 --> 00:52:56,880 ORIGINAL NIPT SEQUENCING RESULTS 1322 00:52:56,880 --> 00:52:58,760 TO REFINE ASSESSMENT OF MOST 1323 00:52:58,760 --> 00:53:01,120 LIKELY CAUSE OF THE PERTURBATION 1324 00:53:01,120 --> 00:53:03,200 THAT IS TO SAY WHETHER MATERNAL 1325 00:53:03,200 --> 00:53:07,360 VERSUS FETAL, FIBROMAS OR VERSUS 1326 00:53:07,360 --> 00:53:08,440 MALIGNANCIES. 1327 00:53:08,440 --> 00:53:11,920 RELATED QUESTION TO THAT, IS 1328 00:53:11,920 --> 00:53:15,400 COULD THERE BE A FUTURE FINITE 1329 00:53:15,400 --> 00:53:17,920 ASSAY AS ROUTINE CANCER 1330 00:53:17,920 --> 00:53:18,400 SCREENING IN THE GENERAL 1331 00:53:18,400 --> 00:53:30,120 POPULATION? 1332 00:53:30,120 --> 00:53:32,960 PART OF OUR STUDY IS TO USE NOT 1333 00:53:32,960 --> 00:53:34,120 ONLY THE GENOME SEQUENCING BUT 1334 00:53:34,120 --> 00:53:36,880 TO LOOK FOR DEEPLY FOR EXAMPLE 1335 00:53:36,880 --> 00:53:41,400 IN TISSUE OF ORIGIN AND ALSO 1336 00:53:41,400 --> 00:53:43,720 LOOKING AT OTHER WAYS THAT 1337 00:53:43,720 --> 00:53:46,160 TISSUE OF ORIGIN CAN BE DETECTED 1338 00:53:46,160 --> 00:53:49,920 IN SAMPLES SUCH AS METHYLATION 1339 00:53:49,920 --> 00:53:51,600 USING RESEARCH BLOOD SAMPLES. 1340 00:53:51,600 --> 00:53:53,160 NOT EVERYBODY WILL HAVE ACCESS 1341 00:53:53,160 --> 00:53:57,320 TO AN MRI SO IT WOULD BE GREAT 1342 00:53:57,320 --> 00:54:01,640 IF ULTIMATELY YOU COULD AT LEAST 1343 00:54:01,640 --> 00:54:03,520 DETERMINE SOMEONE IS MUCH MORE 1344 00:54:03,520 --> 00:54:06,320 LIKELY TO HAVE CANCER WHEN 1345 00:54:06,320 --> 00:54:07,480 SIMPLY A BLOOD TEST. 1346 00:54:07,480 --> 00:54:09,320 WE WILL HAVE ALL SEQUENCES 1347 00:54:09,320 --> 00:54:11,000 AVAILABLE, WE HAVE THE RESEARCH 1348 00:54:11,000 --> 00:54:14,120 DATA AVAILABLE TO DO DEEPER 1349 00:54:14,120 --> 00:54:15,400 DIVES AND DEEPER ANALYSIS. 1350 00:54:15,400 --> 00:54:17,520 THAT IS ON THE ORIGINAL WHOLE 1351 00:54:17,520 --> 00:54:18,480 GENOME SEQUENCE. 1352 00:54:18,480 --> 00:54:22,720 I DON'T THINK WE MENTION THAT 1353 00:54:22,720 --> 00:54:24,600 EACH OF THE PARTICIPANTS WILL 1354 00:54:24,600 --> 00:54:28,240 HAVE HAD INITIAL NIPT BY ONE OF 1355 00:54:28,240 --> 00:54:29,600 SEVERAL COMPANIES. 1356 00:54:29,600 --> 00:54:31,520 ONCE THEY ENTER THE STUDY WE 1357 00:54:31,520 --> 00:54:34,600 REPEAT THE NIPT USING A SINGLE 1358 00:54:34,600 --> 00:54:35,480 LABORATORY. 1359 00:54:35,480 --> 00:54:38,080 SO WE CAN COMPARE EVERYONE'S 1360 00:54:38,080 --> 00:54:41,800 RESULTS TO THE OTHER 1361 00:54:41,800 --> 00:54:42,720 PARTICIPANTS. 1362 00:54:42,720 --> 00:54:44,120 QUESTION OF WHETHER YOU WOULD 1363 00:54:44,120 --> 00:54:49,840 USE NIPT APPROACH, THE WAY THE 1364 00:54:49,840 --> 00:54:50,960 BIOINFORMATICS ALGORITHMS ARE 1365 00:54:50,960 --> 00:54:55,440 BEING USED TO DETECT 1366 00:54:55,440 --> 00:54:58,680 ABNORMALITIES IN RATIOS, THERE 1367 00:54:58,680 --> 00:55:00,280 ARE GROUPS DOING THAT, WHETHER 1368 00:55:00,280 --> 00:55:03,160 OR NOT THAT'S THE MOST COST 1369 00:55:03,160 --> 00:55:05,120 EFFECTIVE AND EFFICIENT AND 1370 00:55:05,120 --> 00:55:06,440 ACCURATE WAY OF SCREENING FOR 1371 00:55:06,440 --> 00:55:10,520 CANCER I CAN'T ANSWER THAT BUT 1372 00:55:10,520 --> 00:55:13,920 CERTAINLY THE CONNECTION SAY 1373 00:55:13,920 --> 00:55:18,000 BETWEEN ALUMINA SEQUENCING 1374 00:55:18,000 --> 00:55:20,040 APPROACH AND THE GRAIL APPROACH 1375 00:55:20,040 --> 00:55:22,080 WHICH IS NOW SUPPOSED TO BE 1376 00:55:22,080 --> 00:55:24,520 TAKEN OVER BY ALUMINA, THAT 1377 00:55:24,520 --> 00:55:25,840 THERE IS THAT CONNECTION THERE 1378 00:55:25,840 --> 00:55:28,240 SO THEY ARE AWARE OF THE FACT 1379 00:55:28,240 --> 00:55:31,040 THAT THE INITIAL ANEUPLOIDY 1380 00:55:31,040 --> 00:55:33,360 SCREENING APPROACH MIGHT ALSO BE 1381 00:55:33,360 --> 00:55:34,840 USED IN A CANCER CONTEXT. 1382 00:55:34,840 --> 00:55:37,800 BUT AGAIN, THAT MAY NOT BE THE 1383 00:55:37,800 --> 00:55:40,080 CHEAPEST WAY TO DO SCREENING. 1384 00:55:40,080 --> 00:55:42,400 THE LIQUID BIOPSY APPROACH IS 1385 00:55:42,400 --> 00:55:45,600 REALLY BEING RECOMMENDED AS 1386 00:55:45,600 --> 00:55:47,240 SCREEN FOR EVERYBODY WHO MIGHT 1387 00:55:47,240 --> 00:55:49,360 BE AT RISK FOR CANCER SO IT IS 1388 00:55:49,360 --> 00:55:51,280 PART OF YOUR ANNUAL PHYSICAL YOU 1389 00:55:51,280 --> 00:55:53,160 COULD HAVE A BLOOD TEST INSTEAD 1390 00:55:53,160 --> 00:55:57,880 OF A COLONOSCOPY FOR EXAMPLE. 1391 00:55:57,880 --> 00:55:59,320 >> THIS IS KIND OF A FOLLOW-UP 1392 00:55:59,320 --> 00:56:00,160 ON THAT. 1393 00:56:00,160 --> 00:56:02,120 FOR THE INSTANCES OF POSITIVE 1394 00:56:02,120 --> 00:56:04,120 NIPT THAT YOU KNOW OF, WHAT 1395 00:56:04,120 --> 00:56:06,520 PROPORTION OF THESE CASES HAVE 1396 00:56:06,520 --> 00:56:09,480 NEGATIVE MRI OR PET FINDINGS AND 1397 00:56:09,480 --> 00:56:11,520 DOES THIS DIFFER DEPENDENT ON 1398 00:56:11,520 --> 00:56:13,120 MALIGNANCY ORIGIN OR TYPE? 1399 00:56:13,120 --> 00:56:15,440 I GUESS THIS IS ONE OF THE 1400 00:56:15,440 --> 00:56:16,440 QUESTIONS YOUR STUDY WILL BE 1401 00:56:16,440 --> 00:56:16,720 ANSWERING. 1402 00:56:16,720 --> 00:56:17,400 >> YEAH. 1403 00:56:17,400 --> 00:56:19,320 I DON'T THINK WE ARE READY TO 1404 00:56:19,320 --> 00:56:21,880 DISCLOSE OUR RESULTS OTHER THAN 1405 00:56:21,880 --> 00:56:23,720 TO SAY EVEN FROM THE VERY 1406 00:56:23,720 --> 00:56:26,920 BEGINNING WHEN OUR VERY FIRST 1407 00:56:26,920 --> 00:56:28,400 PARTICIPANT WAS SHOWN THAT 1408 00:56:28,400 --> 00:56:30,200 CANCER, WE ARE DETECTING CANCER 1409 00:56:30,200 --> 00:56:35,080 AT A VERY HIGH RATE. 1410 00:56:35,080 --> 00:56:38,200 WHAT IS SURPRISING THOUGH IS THE 1411 00:56:38,200 --> 00:56:40,400 WIDE VARIETY OF CANCERS AND 1412 00:56:40,400 --> 00:56:42,720 CANCERS THAT EVEN PATHOLOGISTS 1413 00:56:42,720 --> 00:56:44,960 DON'T AGREE ON THE UNDERLYING 1414 00:56:44,960 --> 00:56:45,920 DIAGNOSIS. 1415 00:56:45,920 --> 00:56:46,720 WHEN THEY HAVE THE CANCER IN 1416 00:56:46,720 --> 00:56:47,680 FRONT OF THEM UNDER THE 1417 00:56:47,680 --> 00:56:52,120 MICROSCOPE. 1418 00:56:52,120 --> 00:56:54,320 AGAIN, I WANT TO EMPHASIZE THAT 1419 00:56:54,320 --> 00:56:56,320 OUR STUDIES ARE PROSPECTIVE SO 1420 00:56:56,320 --> 00:56:58,080 WE ARE TAKING A REAL LIKE 1421 00:56:58,080 --> 00:57:00,080 APPROACH, WHAT DO YOU DO IN THIS 1422 00:57:00,080 --> 00:57:04,120 SITUATION AND THEN HAVING EACH 1423 00:57:04,120 --> 00:57:06,800 PARTICIPANT UNDERGO THE SAME 1424 00:57:06,800 --> 00:57:09,680 PROTOCOL SO WE CAN EFFECTIVELY 1425 00:57:09,680 --> 00:57:10,920 GIVE ACCURATE ESTIMATE OF WHAT 1426 00:57:10,920 --> 00:57:12,680 IS THE RISK. 1427 00:57:12,680 --> 00:57:16,160 TAKING ALL WOMEN AND NOT BIASING 1428 00:57:16,160 --> 00:57:19,800 IT WITH SOME SORT OF 1429 00:57:19,800 --> 00:57:20,400 RETROSPECTIVE KNOWLEDGE. 1430 00:57:20,400 --> 00:57:22,200 I WOULD SAY THAT AT LEAST OF THE 1431 00:57:22,200 --> 00:57:23,640 WOMEN WHO HAVE COME TO THE 1432 00:57:23,640 --> 00:57:25,400 CLINICAL CENTER, THERE IS A VERY 1433 00:57:25,400 --> 00:57:27,720 HIGH RISK OF CANCER. 1434 00:57:27,720 --> 00:57:29,520 >> SO THIS QUESTION ACTUALLY 1435 00:57:29,520 --> 00:57:31,200 JUST TOUCHES ON WHAT YOU JUST 1436 00:57:31,200 --> 00:57:32,480 SAID, DR. BIANCHI. 1437 00:57:32,480 --> 00:57:34,760 IT SAYS DR. BIANCHI MENTIONED A 1438 00:57:34,760 --> 00:57:36,320 BIAS MAY EXIST IN THE POSITIVITY 1439 00:57:36,320 --> 00:57:39,600 RATE OF CANCER DETECTED DRAWING 1440 00:57:39,600 --> 00:57:40,640 FROM AVAILABLE DATA SETS. 1441 00:57:40,640 --> 00:57:42,160 CAN YOU EXPAND ON POTENTIAL 1442 00:57:42,160 --> 00:57:42,600 BIAS? 1443 00:57:42,600 --> 00:57:43,160 THANK YOU. 1444 00:57:43,160 --> 00:57:46,680 >> YES. 1445 00:57:46,680 --> 00:57:50,720 SO AGAIN, MUCH OF THE LITERATURE 1446 00:57:50,720 --> 00:57:52,960 COMES FROM THE NATIONAL 1447 00:57:52,960 --> 00:57:54,520 DATABASES OR THESE CLINICAL 1448 00:57:54,520 --> 00:57:57,080 TESTING LABORATORY DATABASES. 1449 00:57:57,080 --> 00:58:00,120 WHERE AT LEAST IN THE NATIONAL 1450 00:58:00,120 --> 00:58:02,760 REPORTS COMING FROM BELGIUM 1451 00:58:02,760 --> 00:58:05,960 AUSTRALIA AND NETHERLANDS, THEY 1452 00:58:05,960 --> 00:58:07,440 -- WHAT THEY ARE DOING THERE IS 1453 00:58:07,440 --> 00:58:09,320 THEY KNOW THE WOMAN HAS CANCER 1454 00:58:09,320 --> 00:58:11,000 AND THEN THEY ARE GOING BACK TO 1455 00:58:11,000 --> 00:58:14,760 LOOK AT WHAT DID THE 1456 00:58:14,760 --> 00:58:16,560 BIOINFORMATICS RESULTS SHOW AND 1457 00:58:16,560 --> 00:58:19,520 NOW THAT THEY KNOW WHAT IT COULD 1458 00:58:19,520 --> 00:58:21,680 LOOK LIKE THEY ARE ABLE TO DO A 1459 00:58:21,680 --> 00:58:24,720 BETTER JOB PREDICTING 1460 00:58:24,720 --> 00:58:25,440 PROSPECTIVELY WHO MIGHT HAVE 1461 00:58:25,440 --> 00:58:27,200 CANCER BUT THE LITERATURE WE 1462 00:58:27,200 --> 00:58:29,880 SHOWED IN THOSE SLIDES INCLUDING 1463 00:58:29,880 --> 00:58:32,920 OUR OWN REPORT FROM TUFTS BACK 1464 00:58:32,920 --> 00:58:36,720 IN 2015, WERE BIASED WITH 1465 00:58:36,720 --> 00:58:37,400 KNOWLEDGE THESE WOMEN DID HAVE 1466 00:58:37,400 --> 00:58:39,480 CANCER. 1467 00:58:39,480 --> 00:58:42,240 I SHOULD ALSO SAY THERE ARE MANY 1468 00:58:42,240 --> 00:58:45,120 GROUPS IN EUROPE THAT ARE USING 1469 00:58:45,120 --> 00:58:48,400 FREELY AVAILABLE SOFTWARE THAT 1470 00:58:48,400 --> 00:58:51,120 AUTOMATICALLY DISPLAYS ALL 1471 00:58:51,120 --> 00:58:51,880 CHROMOSOMES. 1472 00:58:51,880 --> 00:58:52,920 ONE OF THE DIFFICULTIES MANY THE 1473 00:58:52,920 --> 00:58:54,800 UNITED STATES IS THAT EACH 1474 00:58:54,800 --> 00:58:56,560 COMMERCIAL LABORATORY USES A 1475 00:58:56,560 --> 00:58:59,120 DIFFERENT BIOINFORMATICS 1476 00:58:59,120 --> 00:58:59,520 APPROACH. 1477 00:58:59,520 --> 00:59:01,640 SO THEY INTERPRET THE RESULTS 1478 00:59:01,640 --> 00:59:02,680 DIFFERENTLY, THEY MASK THE 1479 00:59:02,680 --> 00:59:05,120 RESULTS DIFFERENTLY, AND YOU ARE 1480 00:59:05,120 --> 00:59:07,720 NOT OPENING UP A WHOLE GENOME 1481 00:59:07,720 --> 00:59:09,880 SEQUENCING RESULTS TO SEE WHAT 1482 00:59:09,880 --> 00:59:12,600 IS GOING ON WITH SOME OF THE 1483 00:59:12,600 --> 00:59:13,800 LABORATORIES IN EUROPE THESE 1484 00:59:13,800 --> 00:59:15,920 NATIONAL LABORATORIES THEY SEE 1485 00:59:15,920 --> 00:59:19,600 RIGHT AWAY IF THERE ARE 1486 00:59:19,600 --> 00:59:21,360 ABNORMALITIES IN MULTIPLE 1487 00:59:21,360 --> 00:59:21,760 CHROMOSOMES. 1488 00:59:21,760 --> 00:59:23,240 WE SHOULD POINT OUT THAT WHEN 1489 00:59:23,240 --> 00:59:27,200 YOU GET A RESULT OF MONOSOMY FOR 1490 00:59:27,200 --> 00:59:30,840 CHROMOSOME 1 AND TRISOMY FOR 1491 00:59:30,840 --> 00:59:31,880 CHROMOSOME 2 AS WE HAD IN THIS 1492 00:59:31,880 --> 00:59:33,320 CASE THAT'S NOT CONSISTENT WITH 1493 00:59:33,320 --> 00:59:34,800 NORMAL FETAL DEVELOPMENT. 1494 00:59:34,800 --> 00:59:37,960 AND WHEN THIS WOMAN PRESENTED 1495 00:59:37,960 --> 00:59:40,200 EVEN LATE -- EARLY SECOND 1496 00:59:40,200 --> 00:59:42,000 TRIMESTER, THE FETUS WAS 1497 00:59:42,000 --> 00:59:45,520 DEVELOPING NORMALLY AT THAT 1498 00:59:45,520 --> 00:59:46,520 POINT, SO U YOU DO HAVE THIS 1499 00:59:46,520 --> 00:59:48,240 DISCREPANCY THERE THAT WE NOW 1500 00:59:48,240 --> 00:59:49,320 HAVE A MUCH HIGHER CONCERN THAT 1501 00:59:49,320 --> 00:59:51,800 IT IS COMING FROM THE MOTHER, 1502 00:59:51,800 --> 00:59:53,040 THOUGH IT COULD BE -- YOU CAN 1503 00:59:53,040 --> 00:59:58,880 GET MULTIPLE ANEUPLOIDIES WITH 1504 00:59:58,880 --> 00:59:59,880 CONFINED MOW SAFE HARBORRISM. 1505 00:59:59,880 --> 01:00:00,520 >> OKAY. 1506 01:00:00,520 --> 01:00:03,200 I WILL JUST REPEAT WITH WHAT WAS 1507 01:00:03,200 --> 01:00:05,640 SAID, BOTH MYSELF AND FROM ONE 1508 01:00:05,640 --> 01:00:06,600 OF THE COMMENTATORS. 1509 01:00:06,600 --> 01:00:09,520 THANK YOU FOR THIS INTERESTING 1510 01:00:09,520 --> 01:00:10,120 INFORMATIVE PRESENTATION. 1511 01:00:10,120 --> 01:00:11,720 IT WAS REALLY A DELIGHT HAVING 1512 01:00:11,720 --> 01:00:12,000 YOU ALL PRESENT TODAY. 1513 01:00:12,000 --> 01:01:59,760 >> THANK YOU FOR HAVING US.