1 00:00:05,320 --> 00:00:10,160 WELCOME, EVERYBODY, TO THE ANITA 2 00:00:10,160 --> 00:00:14,760 ROBERTS LECTURE, SPONSORED BY 3 00:00:14,760 --> 00:00:16,040 THE WOMEN'S SCIENTIST ADVISER 4 00:00:16,040 --> 00:00:21,840 COMMITTEE AT THE NIH. 5 00:00:21,840 --> 00:00:25,640 I'M DORIS WU, INVESTIGATOR, THE 6 00:00:25,640 --> 00:00:26,160 MODERATOR. 7 00:00:26,160 --> 00:00:30,680 THIS EVENT IS TO HONOR DR. ANITA 8 00:00:30,680 --> 00:00:31,560 ROBERTS, BY CELEBRATING 9 00:00:31,560 --> 00:00:32,480 DISTINGUISHED WOMEN SCIENTISTS 10 00:00:32,480 --> 00:00:33,760 AT THE NIH. 11 00:00:33,760 --> 00:00:42,000 AND THIS YEAR WE ARE SHOWCASING 12 00:00:42,000 --> 00:00:43,440 THE WORK OF DR. BRIGITTE 13 00:00:43,440 --> 00:00:44,160 WIDEMANN FROM NCI. 14 00:00:44,160 --> 00:00:47,040 I WANT TO POINT OUT THERE'S A 15 00:00:47,040 --> 00:00:49,400 LIVE FEEDBACK BUTTON ON YOUR 16 00:00:49,400 --> 00:00:50,840 SCREEN THAT IF YOU HAVE 17 00:00:50,840 --> 00:00:52,880 QUESTIONS, ENTER THEM DURING THE 18 00:00:52,880 --> 00:00:56,520 SEMINAR, THE QUESTIONS WILL BE 19 00:00:56,520 --> 00:00:59,000 ADDRESSED AT THE END OF THE 20 00:00:59,000 --> 00:00:59,520 SEMINAR. 21 00:00:59,520 --> 00:01:03,680 NOW WITH THAT I WOULD LIKE TO 22 00:01:03,680 --> 00:01:08,120 INVITE YOU TO MEET OUR NEWLY 23 00:01:08,120 --> 00:01:09,720 ELECTED CHAIR, DR. MARY KEARNEY 24 00:01:09,720 --> 00:01:12,440 FROM NCI, TO SAY A FEW WORDS 25 00:01:12,440 --> 00:01:13,600 ABOUT THE WSA. 26 00:01:13,600 --> 00:01:14,680 DR. KIERNEY? 27 00:01:14,680 --> 00:01:16,920 >>THANK YOU, DR. WU. 28 00:01:16,920 --> 00:01:17,760 SO, BEFORE WE BEGIN, I'D LIKE TO 29 00:01:17,760 --> 00:01:19,920 JUST GIVE A LITTLE BIT OF 30 00:01:19,920 --> 00:01:22,840 BACKGROUND ABOUT THE NIH WOMEN 31 00:01:22,840 --> 00:01:25,320 SCIENTIST ADVISORS FOR WSA, THIS 32 00:01:25,320 --> 00:01:32,560 MEETING WAS FORMED IN RESPONSE 33 00:01:32,560 --> 00:01:33,640 TO TASK FORCE RECOMMENDATIONS IN 34 00:01:33,640 --> 00:01:35,280 1993 THAT WOMEN WERE 35 00:01:35,280 --> 00:01:36,320 UNDERREPRESENTED, THAT REMAINS 36 00:01:36,320 --> 00:01:37,640 TRUE TODAY. 37 00:01:37,640 --> 00:01:43,880 EACH INSTITUTE HAS ELECTED 38 00:01:43,880 --> 00:01:47,160 REPRESENTATIVES, REGULARLY MEET 39 00:01:47,160 --> 00:01:49,920 TO WORK TO A EQUAL STATUS, 40 00:01:49,920 --> 00:01:51,680 IDENTIFY BARRIERS AND PROMOTE 41 00:01:51,680 --> 00:01:54,240 WOMEN IN SCIENCE. 42 00:01:54,240 --> 00:01:59,360 THIS HIGHLIGHTS THE LEGACY OF AN 43 00:01:59,360 --> 00:02:00,640 OUTSTANDING SCIENTIST AND 44 00:02:00,640 --> 00:02:01,240 AMAZING ACCOMPLISHMENTS. 45 00:02:01,240 --> 00:02:05,640 A FEW WORDS ABOUT ANITA ROBERTS, 46 00:02:05,640 --> 00:02:07,400 BORN IN PITTSBURGH, ATTENDED 47 00:02:07,400 --> 00:02:09,080 OBER LAND COLLEGE, DOCTORATE 48 00:02:09,080 --> 00:02:12,760 FROM UNIVERSITY OF WISCONSIN IN 49 00:02:12,760 --> 00:02:14,080 1968 IN BIOCHEMISTRY. 50 00:02:14,080 --> 00:02:19,880 AFTER POSTDOC AT HARVARD JOINED 51 00:02:19,880 --> 00:02:22,480 NIH IN 1976, BECAME THE CHIEF OF 52 00:02:22,480 --> 00:02:25,160 THE LABORATORY OF CELL 53 00:02:25,160 --> 00:02:26,360 REGULATION AND CARCINOGENESIS IN 54 00:02:26,360 --> 00:02:26,560 1995. 55 00:02:26,560 --> 00:02:28,600 SHE IS WELL KNOWN FOR PIONEERING 56 00:02:28,600 --> 00:02:30,960 WORK ON TRANSFORMING GROWTH 57 00:02:30,960 --> 00:02:35,480 FACTOR BETA AND ITS ROLE IN 58 00:02:35,480 --> 00:02:36,120 WOUND HEALING, CARCINOGENESIS, 59 00:02:36,120 --> 00:02:37,040 AUTOIMMUNE DISEASE, PUBLISHED 60 00:02:37,040 --> 00:02:41,000 WORK HAS BEEN INCLUDED AMONG THE 61 00:02:41,000 --> 00:02:42,280 TOP 50 MOST CITED RESEARCH 62 00:02:42,280 --> 00:02:43,880 PAPERS, THE THIRD MOST CITED 63 00:02:43,880 --> 00:02:47,880 FEMALE SCIENTIST IN THE WORLD. 64 00:02:47,880 --> 00:02:51,920 DR. ROBERTS WAS RECIPIENT OF THE 65 00:02:51,920 --> 00:02:54,360 FAS EXCELLENCE AWARD FOR 66 00:02:54,360 --> 00:02:54,840 DISTINGUISHED SCIENCE. 67 00:02:54,840 --> 00:02:56,520 DR. ROBERTS WAS NOT ONLY A 68 00:02:56,520 --> 00:02:59,160 HIGHLY ACCOMPLISHED SCIENTIST 69 00:02:59,160 --> 00:03:00,400 BUT OUTSTANDING MENTOR, 70 00:03:00,400 --> 00:03:01,840 PROVIDING A WONDERFUL EXAMPLE OF 71 00:03:01,840 --> 00:03:05,120 HOW TO BALANCE FAMILY AND WORK 72 00:03:05,120 --> 00:03:07,880 LIFE AND WAS UNFAILINGLY WARM, 73 00:03:07,880 --> 00:03:08,640 CARING, ENTHUSIASTIC, 74 00:03:08,640 --> 00:03:09,240 SUPPORTIVE. 75 00:03:09,240 --> 00:03:10,720 I DIDN'T KNOW DR. ROBERTS 76 00:03:10,720 --> 00:03:11,880 PERSONALLY BUT THOSE WHO DID 77 00:03:11,880 --> 00:03:14,520 INDICATE SHE WAS NOT ONLY A 78 00:03:14,520 --> 00:03:15,280 TREMENDOUS SCIENTIST BUT A 79 00:03:15,280 --> 00:03:17,760 WONDERFUL HUMAN BEING WHO IS 80 00:03:17,760 --> 00:03:18,600 DEEPLY MISSED. 81 00:03:18,600 --> 00:03:20,080 AND IN THE END, I THINK THAT 82 00:03:20,080 --> 00:03:22,680 SAYS IT ALL, THAT'S WHY WE HONOR 83 00:03:22,680 --> 00:03:23,640 HER TODAY. 84 00:03:23,640 --> 00:03:26,520 I THANK THE PEOPLE WHO HELPED 85 00:03:26,520 --> 00:03:28,080 PUT THIS LECTURE TOGETHER, THE 86 00:03:28,080 --> 00:03:30,480 INTRAMURAL PROGRAM SPECIALIST 87 00:03:30,480 --> 00:03:34,000 WHO ORGANIZED WSA ACTIVITIES, 88 00:03:34,000 --> 00:03:36,080 DR. DORIS WU, MODERATOR, AND 89 00:03:36,080 --> 00:03:44,440 COORDINATED THIS LECTURE. 90 00:03:44,440 --> 00:03:51,080 FELICE HARPER, JOY JACKSON FARAR 91 00:03:51,080 --> 00:03:52,520 AND JONATHAN BENNETT. 92 00:03:52,520 --> 00:03:53,840 PLEASE USE THE "LIVE FEEDBACK" 93 00:03:53,840 --> 00:03:57,800 BUTTON BELOW THE SCREEN IN THE 94 00:03:57,800 --> 00:03:58,640 VIDEOCAST DESCRIPTION BOX TO 95 00:03:58,640 --> 00:04:00,800 ENTER QUESTIONS, CLICK ON THE 96 00:04:00,800 --> 00:04:03,040 ASL ICON BELOW THE FEEDBACK 97 00:04:03,040 --> 00:04:05,360 BUTTON TO VIEW SIGN LANGUAGE 98 00:04:05,360 --> 00:04:06,160 INTERPRETER DURING THE LECTURE. 99 00:04:06,160 --> 00:04:13,000 I'LL TURN IT OVER TO OUR REP, 100 00:04:13,000 --> 00:04:14,680 DR. REBECCA VOGELBY, TO 101 00:04:14,680 --> 00:04:16,840 INTRODUCE THIS YEAR'S SPEAKER. 102 00:04:16,840 --> 00:04:17,680 >>GOOD MORNING. 103 00:04:17,680 --> 00:04:19,920 I AM DELIGHTED TO INTRODUCE YOU 104 00:04:19,920 --> 00:04:23,120 TO THE SPEAKER FOR THE 2022 105 00:04:23,120 --> 00:04:30,480 ANITA B. ROBERTS LECTURE. 106 00:04:30,480 --> 00:04:32,360 DR. WIDEMANN IS A SENIOR 107 00:04:32,360 --> 00:04:33,600 INVESTIGATOR WITH NATIONAL 108 00:04:33,600 --> 00:04:37,440 CANCER INSTITUTE, CHIEF OF THE 109 00:04:37,440 --> 00:04:39,040 PEDIATRIC ONCOLOGY BRANCH. 110 00:04:39,040 --> 00:04:40,160 CAN WE MUTE? 111 00:04:40,160 --> 00:04:42,920 SHE IS A SENIOR INVESTIGATOR 112 00:04:42,920 --> 00:04:43,560 WITHIN THE NATIONAL CANCER 113 00:04:43,560 --> 00:04:45,800 INSTITUTE, CHIEF OF THE 114 00:04:45,800 --> 00:04:47,840 PEDIATRIC ONCOLOGY BRANCH, HEAD 115 00:04:47,840 --> 00:04:50,240 OF THE PHARMACOLOGY AND 116 00:04:50,240 --> 00:04:50,760 EXPERIMENTAL THERAPEUTICS 117 00:04:50,760 --> 00:04:52,520 SECTION, AND SPECIAL ADVISER TO 118 00:04:52,520 --> 00:04:55,040 THE NATIONAL CANCER INSTITUTE'S 119 00:04:55,040 --> 00:04:57,160 DIRECTOR FOR CHILDHOOD CANCER. 120 00:04:57,160 --> 00:05:01,360 DR. WIDEMANN EARNED MEDICAL 121 00:05:01,360 --> 00:05:03,240 DEGREE IN GERMANY, COMPLETED 122 00:05:03,240 --> 00:05:04,720 PEDIATRIC RESIDENCY AT THE 123 00:05:04,720 --> 00:05:07,280 UNIVERSITY CHILDREN'S HOSPITAL 124 00:05:07,280 --> 00:05:08,960 IN COLOGNE, JOINED THE NATIONAL 125 00:05:08,960 --> 00:05:10,560 CANCER INSTITUTE, ORIGINALLY AS 126 00:05:10,560 --> 00:05:13,960 PEDIATRIC HEMATOLOGY AND 127 00:05:13,960 --> 00:05:14,600 ONCOLOGY FELLOW, LATER AS 128 00:05:14,600 --> 00:05:16,080 TENURE-TRACK INVESTIGATOR. 129 00:05:16,080 --> 00:05:17,760 AFTER RECEIVING TENURE DR. 130 00:05:17,760 --> 00:05:21,400 WIDEMANN BECAME THE CHIEF OF THE 131 00:05:21,400 --> 00:05:23,120 PEDIATRIC ONCOLOGY BRANCH IN 132 00:05:23,120 --> 00:05:23,520 2016. 133 00:05:23,520 --> 00:05:25,480 IN THIS POSITION, SHE LEADS A 134 00:05:25,480 --> 00:05:27,640 GROUP OF BASIC TRANSLATIONAL AND 135 00:05:27,640 --> 00:05:29,120 CLINICAL RESEARCHERS WITH JOINT 136 00:05:29,120 --> 00:05:30,760 VISION TO IMPROVE THE SURVIVAL 137 00:05:30,760 --> 00:05:32,880 AND QUALITY OF LIFE OF CHILDREN 138 00:05:32,880 --> 00:05:38,080 AND YOUNG ADULTS WITH REFRACTORY 139 00:05:38,080 --> 00:05:40,320 OR HIGH RISK MALIGNANT TUMORS, 140 00:05:40,320 --> 00:05:41,200 RESEARCH FOCUSED ON DRUG 141 00:05:41,200 --> 00:05:42,960 DEVELOPMENT AND CLINICAL TRIALS 142 00:05:42,960 --> 00:05:44,400 FOR CHILDREN WITH REFRACTORY 143 00:05:44,400 --> 00:05:48,680 SOLID TUMORS OR GENETIC TUMOR 144 00:05:48,680 --> 00:05:59,200 PREDISPOSITION SYNDROMES, IN 145 00:05:59,960 --> 00:06:00,840 PARTICULAR NEUROFIB FIBROMATASI, 146 00:06:00,840 --> 00:06:02,120 SELUMETINIB RESULTED IN APPROVAL 147 00:06:02,120 --> 00:06:05,640 OF THERAPY FOR CHILDREN WITH 148 00:06:05,640 --> 00:06:07,360 NF1, INOPERABLE SYMPTOMATIC 149 00:06:07,360 --> 00:06:09,880 PLEXIFORM NEUROFIBROMA. 150 00:06:09,880 --> 00:06:11,280 DR. WIDEMANN CO-DIRECTS CANCER 151 00:06:11,280 --> 00:06:12,080 MOONSHOT SUPPORTED PROGRAM 152 00:06:12,080 --> 00:06:15,040 CALLED MY PEDIATRIC AND ADULT 153 00:06:15,040 --> 00:06:17,960 RARE TUMOR WORK, AIMS TO ADVANCE 154 00:06:17,960 --> 00:06:20,600 THE KNOWLEDGE OF RARE TUMORS AND 155 00:06:20,600 --> 00:06:22,440 DEVELOP THERAPIES FOR THEM. 156 00:06:22,440 --> 00:06:25,560 DR. WIDEMANN IS A MEMBER OF THE 157 00:06:25,560 --> 00:06:26,600 ASSOCIATION OF AMERICAN 158 00:06:26,600 --> 00:06:28,720 PHYSICIANS, RECIPIENT OF THE 159 00:06:28,720 --> 00:06:34,080 AMERICAN ASSOCIATION FOR CANCER 160 00:06:34,080 --> 00:06:42,120 RESEARCHERS, JOSEPH BIRCHENALL 161 00:06:42,120 --> 00:06:45,120 AWARD, HAS CONDUCTED SEVERAL 162 00:06:45,120 --> 00:06:48,480 LARGE SCALE CLINICAL TRIALS. 163 00:06:48,480 --> 00:06:51,120 HER SCIENTIFIC ACHIEVEMENTS GO 164 00:06:51,120 --> 00:06:52,240 BEYOND THESE MEASURES. 165 00:06:52,240 --> 00:06:55,480 LIKE DR. ROBERTS, DR. WIDEMANN'S 166 00:06:55,480 --> 00:06:57,040 LEGACY EXTENDS TO HER 167 00:06:57,040 --> 00:06:57,760 EXTRAORDINARY SKILLS IN 168 00:06:57,760 --> 00:07:01,120 MENTORING THE NEXT GENERATION OF 169 00:07:01,120 --> 00:07:02,080 CLINICIANS AND SCIENTISTS. 170 00:07:02,080 --> 00:07:04,440 WE REACHED OUT TO SOME OF HER 171 00:07:04,440 --> 00:07:05,440 CURRENT AND PAST MENTEES FOR 172 00:07:05,440 --> 00:07:10,680 COMMENT, I WANT TO SHARE A FEW 173 00:07:10,680 --> 00:07:12,000 WORDS PROVIDED. 174 00:07:12,000 --> 00:07:14,000 BRIGITTE IS TRULY THE EPITOME OF 175 00:07:14,000 --> 00:07:15,520 WHAT A MENTOR SHOULD BE, IT IS A 176 00:07:15,520 --> 00:07:18,960 JOB SHE TAKES VERY SERIOUSLY. 177 00:07:18,960 --> 00:07:21,760 SHE IS AN EXCEPTIONAL AND 178 00:07:21,760 --> 00:07:22,560 ACCOMPLISHED CLINICIAN 179 00:07:22,560 --> 00:07:23,680 RESEARCHER, WHAT MAKES HER 180 00:07:23,680 --> 00:07:26,080 UNIQUE IS HER ABILITY TO LEAD BY 181 00:07:26,080 --> 00:07:26,600 EXAMPLE. 182 00:07:26,600 --> 00:07:30,600 SHE IS THE PERFECT COMBINATION 183 00:07:30,600 --> 00:07:31,400 OF DIRECTION, HONESTY, 184 00:07:31,400 --> 00:07:32,640 COMPASSION, THAT ALLOWS HER 185 00:07:32,640 --> 00:07:34,920 TRAINEES TO WANT TO BECOME THE 186 00:07:34,920 --> 00:07:38,240 BEST VERSION OF THEMSELVES. 187 00:07:38,240 --> 00:07:40,240 SHE DOES NOT IMPART RULES BUT 188 00:07:40,240 --> 00:07:42,600 PROVIDES GUIDANCE AND SUPPORT. 189 00:07:42,600 --> 00:07:44,240 DESPITE HER SUCCESSES, SHE IS 190 00:07:44,240 --> 00:07:46,840 EXTREMELY HUMBLE IN HER 191 00:07:46,840 --> 00:07:50,720 INTERACTIONS WITH HER TRAINEES. 192 00:07:50,720 --> 00:07:52,720 AND SHE'S A STRONG ADVOCATE AND 193 00:07:52,720 --> 00:07:54,400 SUPPORTER OF FEMALE TRAINEES. 194 00:07:54,400 --> 00:07:57,040 SHE SEEKS DIVERSITY IN TRAINEES 195 00:07:57,040 --> 00:07:58,560 BY BACKGROUND AND OPINION, AND 196 00:07:58,560 --> 00:08:00,000 IS ABLE TO CREATE SAFE 197 00:08:00,000 --> 00:08:01,240 ENVIRONMENT WHERE TRAINEES ARE 198 00:08:01,240 --> 00:08:03,160 ABLE TO SPEAK UP WITH THEIR 199 00:08:03,160 --> 00:08:04,880 IDEAS AND CONCERNS. 200 00:08:04,880 --> 00:08:09,040 SHE CONNECTS ON A PERSONAL 201 00:08:09,040 --> 00:08:09,720 LEVEL, INDIVIDUALIZES MENTORSHIP 202 00:08:09,720 --> 00:08:12,240 BASED ON NEEDS AND GOALS OF 203 00:08:12,240 --> 00:08:14,720 EACH, ADAPTS STYLE ACCORDINGLY, 204 00:08:14,720 --> 00:08:15,920 PROVIDING CLEAR SHORT- AND 205 00:08:15,920 --> 00:08:18,480 LONG-TERM REALISTIC GOALS FOR 206 00:08:18,480 --> 00:08:19,160 THEM, ENCOURAGES COLLABORATION, 207 00:08:19,160 --> 00:08:20,800 ALWAYS MAKES SURE TO GIVE HER 208 00:08:20,800 --> 00:08:22,520 TRAINEES CREDIT FOR THEIR WORK. 209 00:08:22,520 --> 00:08:25,400 SHE PROVIDES THEM THE PLATFORM 210 00:08:25,400 --> 00:08:27,240 TO PROGRESS TO THEIR OWN CAREERS 211 00:08:27,240 --> 00:08:30,200 AND PROVIDES CAREER ADVICE WITH 212 00:08:30,200 --> 00:08:33,000 HUMILITY DESPITE HER SUCCESSES. 213 00:08:33,000 --> 00:08:34,560 AND FINALLY, WORKING WITH DR. 214 00:08:34,560 --> 00:08:36,400 WIDEMANN HAS BEEN ONE OF THE 215 00:08:36,400 --> 00:08:38,400 MOST MEANINGFUL EXPERIENCES OF 216 00:08:38,400 --> 00:08:40,240 MY CAREER TO DATE, THROUGH HER 217 00:08:40,240 --> 00:08:42,680 EXAMPLE I LEARN NOT ONLY HOW 218 00:08:42,680 --> 00:08:43,640 CLINICAL RESEARCH TRULY SHOULD 219 00:08:43,640 --> 00:08:45,360 WORK, BUT ALSO WHAT A DIFFERENCE 220 00:08:45,360 --> 00:08:46,640 A STRONG AND SUPPORTIVE MENTOR 221 00:08:46,640 --> 00:08:49,880 CAN MAKE IN ONE'S LIFE AND 222 00:08:49,880 --> 00:08:50,360 CAREER. 223 00:08:50,360 --> 00:08:53,560 THESE EXAMPLES HELP HIGHLIGHT 224 00:08:53,560 --> 00:08:54,360 HOW DR. WIDEMANN EXEMPLIFIES 225 00:08:54,360 --> 00:08:56,280 MANY OF THE SAME QUALITIES THAT 226 00:08:56,280 --> 00:08:59,520 MADE DR. ANITA ROBERTS SUCH A 227 00:08:59,520 --> 00:09:00,240 BELOVED SCIENTIST AND MENTOR. 228 00:09:00,240 --> 00:09:03,760 IT IS A PLEASURE TO HONOR AND 229 00:09:03,760 --> 00:09:06,240 WELCOME DR. BRIGITTE WIDEMANN 230 00:09:06,240 --> 00:09:08,760 TODAY TO PRESENT THE 2022 ANITA 231 00:09:08,760 --> 00:09:11,080 B. ROBERTS LECTURE ADVANCING THE 232 00:09:11,080 --> 00:09:14,360 DEVELOPMENT OF EFFECTIVE 233 00:09:14,360 --> 00:09:16,320 THERAPIES FOR CHILDREN AND 234 00:09:16,320 --> 00:09:20,920 ADULTS WITH RARE TUMORS. 235 00:09:20,920 --> 00:09:25,120 >>THANK YOU SO MUCH FOR THIS 236 00:09:25,120 --> 00:09:26,680 TREMENDOUS HONOR. 237 00:09:26,680 --> 00:09:28,120 I'M SPEECHLESS AND I LOOK VERY 238 00:09:28,120 --> 00:09:32,520 MUCH FORWARD TO GIVING YOU A 239 00:09:32,520 --> 00:09:36,160 LECTURE TODAY, HOPEFULLY WILL DO 240 00:09:36,160 --> 00:09:37,760 DR. ANITA ROBERTS SOME JUSTICE. 241 00:09:37,760 --> 00:09:39,280 I HOPE YOU CAN HEAR ME AND YOU 242 00:09:39,280 --> 00:09:45,160 CAN SEE THE SCREEN. 243 00:09:45,160 --> 00:09:46,960 THANK YOU, WSA. 244 00:09:46,960 --> 00:09:49,200 IT'S REALLY AN EXTRAORDINARY 245 00:09:49,200 --> 00:09:51,840 EXPERIENCE FOR ME. 246 00:09:51,840 --> 00:09:53,360 I HAVE NO DISCLOSURES BUT WILL 247 00:09:53,360 --> 00:09:55,440 DESCRIBE CLINICAL TRIALS WITH 248 00:09:55,440 --> 00:09:57,000 INVESTIGATIONAL AGENTS. 249 00:09:57,000 --> 00:09:58,480 AND I HOPE THROUGHOUT THE TALK 250 00:09:58,480 --> 00:10:00,720 THAT YOU SEE THAT THE WORK OF 251 00:10:00,720 --> 00:10:02,240 MANY IN THE PEDIATRIC ONCOLOGY 252 00:10:02,240 --> 00:10:05,720 BRANCH THAT I'LL BE PRESENTING 253 00:10:05,720 --> 00:10:07,120 TODAY REALLY ADDRESSES THE CCR 254 00:10:07,120 --> 00:10:09,680 MISSION OF SOLVING IMPORTANT 255 00:10:09,680 --> 00:10:13,920 CHALLENGING AND NEGLECTED 256 00:10:13,920 --> 00:10:15,600 PROBLEMS IN CLINICAL RESEARCH. 257 00:10:15,600 --> 00:10:17,880 READING ABOUT DR. ANITA ROBERTS, 258 00:10:17,880 --> 00:10:20,520 WHO UNFORTUNATELY I NEVER MET, 259 00:10:20,520 --> 00:10:23,160 ONE THING THAT'S STRUCK WITH ME 260 00:10:23,160 --> 00:10:24,800 PARTICULARLY LAST NIGHT SHE SAID 261 00:10:24,800 --> 00:10:26,640 RESEARCH TAKES A LONG, LONG 262 00:10:26,640 --> 00:10:26,960 TIME. 263 00:10:26,960 --> 00:10:28,840 I KNOW THE PUBLIC IS ALWAYS 264 00:10:28,840 --> 00:10:30,440 LOOKING FOR A MAGIC BULLET, THEY 265 00:10:30,440 --> 00:10:32,760 WANT TO SAY THIS DOES THAT, BUT 266 00:10:32,760 --> 00:10:35,600 OUR OWN BIOLOGY IS INCREDIBLY 267 00:10:35,600 --> 00:10:37,640 COMPLEX, SO THIS DOESN'T ALWAYS 268 00:10:37,640 --> 00:10:38,840 DO THAT. 269 00:10:38,840 --> 00:10:40,240 AS BASIC SCIENTISTS WE'RE ALL 270 00:10:40,240 --> 00:10:42,040 DRIVEN BY OUR EXCITEMENT IN 271 00:10:42,040 --> 00:10:44,560 FINDING ANSWERS, WE HOPE IT ENDS 272 00:10:44,560 --> 00:10:46,360 UP AS SOMETHING THAT BECOMES 273 00:10:46,360 --> 00:10:46,720 THERAPY. 274 00:10:46,720 --> 00:10:48,160 BUT THAT DOESN'T HAPPEN UNLESS 275 00:10:48,160 --> 00:10:50,320 YOU HAVE A BASIC UNDERSTANDING 276 00:10:50,320 --> 00:10:51,440 OF THE PROCESS. 277 00:10:51,440 --> 00:10:53,960 AND THAT'S WHAT MY WORK IS ALL 278 00:10:53,960 --> 00:10:54,600 ABOUT. 279 00:10:54,600 --> 00:10:56,000 AND THIS RESONATES WITH ME SO 280 00:10:56,000 --> 00:10:58,800 MUCH, AS A CLINICAL RESEARCHER, 281 00:10:58,800 --> 00:11:02,280 WE ALSO WANT TO GET TO THERAPIES 282 00:11:02,280 --> 00:11:03,280 AND EFFECTIVE TREATMENTS BUT 283 00:11:03,280 --> 00:11:05,080 I'VE LEARNED THERE'S NO WAY OF 284 00:11:05,080 --> 00:11:07,040 CUTTING CORNERS. 285 00:11:07,040 --> 00:11:09,760 AND THIS ALSO TAKES SUBSTANTIAL 286 00:11:09,760 --> 00:11:10,120 TIME. 287 00:11:10,120 --> 00:11:13,440 I WILL GIVE AN OVERVIEW TODAY 288 00:11:13,440 --> 00:11:14,360 ABOUT PEDIATRIC CANCERS AND 289 00:11:14,360 --> 00:11:16,880 WHERE WE STAND. 290 00:11:16,880 --> 00:11:26,800 AND THEN AS REBECCA ALLUDE TO, 291 00:11:26,800 --> 00:11:28,680 I TALK ABOUT THIS SERVING AS A 292 00:11:28,680 --> 00:11:34,840 MODEL TO STUDY RARE DISEASES BY 293 00:11:34,840 --> 00:11:40,360 TALKING ABOUT OUR RAS-OPATHY 294 00:11:40,360 --> 00:11:41,840 THERAPIES, AND MYPART NETWORK, 295 00:11:41,840 --> 00:11:45,400 AND THE VISIONARY LOOK AT THE 296 00:11:45,400 --> 00:11:47,120 FUTURE WHERE WE HOPEFULLY BUILD 297 00:11:47,120 --> 00:11:48,720 A NATIONAL STRATEGY TO ADVANCE 298 00:11:48,720 --> 00:11:49,800 RARE TUMOR RESEARCH AND 299 00:11:49,800 --> 00:11:51,880 UNDERSTAND THESE TUMORS AND 300 00:11:51,880 --> 00:11:53,600 DEVELOP BETTER THERAPIES. 301 00:11:53,600 --> 00:11:55,600 ONE THING I WILL HIGHLIGHT 302 00:11:55,600 --> 00:11:57,960 THROUGH THE TALK, KEY 303 00:11:57,960 --> 00:12:00,600 REQUIREMENTS FOR SUCCESSFUL RARE 304 00:12:00,600 --> 00:12:03,280 TUMOR RESEARCH, PRESENCE OF A 305 00:12:03,280 --> 00:12:04,960 BASIC RESEARCHER, INVESTED IN 306 00:12:04,960 --> 00:12:06,840 HELPING US UNDERSTAND THE RARE 307 00:12:06,840 --> 00:12:08,800 TUMOR, PRESENCE OF THE CLINICAL 308 00:12:08,800 --> 00:12:10,480 CHAMPION, AND ALSO OF AN 309 00:12:10,480 --> 00:12:11,480 ADVOCACY CHAMPION. 310 00:12:11,480 --> 00:12:15,080 AND THEN IF YOU'RE LUCKY TO HAVE 311 00:12:15,080 --> 00:12:16,680 A PEDIATRIC PARTNERSHIP SO YOU 312 00:12:16,680 --> 00:12:18,880 CAN TREAT AND EVALUATE PATIENTS 313 00:12:18,880 --> 00:12:22,040 ACROSS THE AGES, THAT REALLY 314 00:12:22,040 --> 00:12:24,360 MAKES IT PERFECT. 315 00:12:24,360 --> 00:12:28,000 SO, PEDIATRIC CANCERS ARE MUCH 316 00:12:28,000 --> 00:12:30,400 LESS FREQUENT FOR AGES 0 TO 19, 317 00:12:30,400 --> 00:12:36,680 THEY HAVE ABOUT 17,000 NEW 318 00:12:36,680 --> 00:12:37,440 CANCER DIAGNOSES PER YEAR, 319 00:12:37,440 --> 00:12:38,760 APPROXIMATELY 2 MILLION NEW 320 00:12:38,760 --> 00:12:43,240 CANCER CASES IN THE UNITED 321 00:12:43,240 --> 00:12:43,480 STATES. 322 00:12:43,480 --> 00:12:47,680 ALL PEDIATRIC CANCERS ARE RARE 323 00:12:47,680 --> 00:12:49,760 BUT I WILL FOCUS ON THE VERY 324 00:12:49,760 --> 00:12:51,480 RARE CANCERS, DEFINED LATER. 325 00:12:51,480 --> 00:12:54,120 DESPITE RARITY OF PEDIATRIC 326 00:12:54,120 --> 00:12:56,800 CANCERS WE'VE MADE TREMENDOUS 327 00:12:56,800 --> 00:12:59,040 PROGRESS OVER THE YEARS. 328 00:12:59,040 --> 00:13:01,800 LOOKING BACK IN THE '50s AND 329 00:13:01,800 --> 00:13:03,800 '70s TO CURRENT DAY, MORTALITY 330 00:13:03,800 --> 00:13:06,680 RATE OF PEDIATRIC CANCERS HAS 331 00:13:06,680 --> 00:13:07,360 SUBSTANTIALLY DECREASED, AND 332 00:13:07,360 --> 00:13:10,080 WE'RE ACHIEVING CURES IN THE 333 00:13:10,080 --> 00:13:11,720 MAJORITY OF PEDIATRIC CANCER 334 00:13:11,720 --> 00:13:12,280 PATIENTS. 335 00:13:12,280 --> 00:13:15,880 HOWEVER, AS THE PLOT ON THE 336 00:13:15,880 --> 00:13:18,680 RIGHT SHOWS YOU, WHILE WE MADE 337 00:13:18,680 --> 00:13:22,200 TREMENDOUS STRIDES IN ACUTE 338 00:13:22,200 --> 00:13:23,920 LYMPHOPLASTIC LEUKEMIA, THERE 339 00:13:23,920 --> 00:13:27,240 ARE SOME TUMORS WHERE PROGRESS 340 00:13:27,240 --> 00:13:30,680 HAS BEEN MUCH LESS, STRIKING 341 00:13:30,680 --> 00:13:37,200 EXAMPLE IS BRAINSTEM GLIOMA, 342 00:13:37,200 --> 00:13:38,480 WITH NOT MUCH IMPROVEMENT IN 343 00:13:38,480 --> 00:13:38,760 SURVIVAL. 344 00:13:38,760 --> 00:13:42,080 HOW HAVE WE MADE PROGRESS IN 345 00:13:42,080 --> 00:13:42,680 PEDIATRIC CANCERS, THERE ARE 346 00:13:42,680 --> 00:13:44,360 MANY REASONS BUT I BELIEVE THE 347 00:13:44,360 --> 00:13:47,600 MOST IMPORTANT IS THAT WE 348 00:13:47,600 --> 00:13:49,680 COLLABORATE NATIONALLY AND 349 00:13:49,680 --> 00:13:51,760 INTERNATIONALLY TO CONDUCT 350 00:13:51,760 --> 00:13:53,880 CLINICAL TRIALS, CLINICAL TRIALS 351 00:13:53,880 --> 00:13:56,680 AVAILABLE MOST PATIENTS WILL 352 00:13:56,680 --> 00:14:02,320 INROLE, EXAMPLE SHOWN HERE FOR 353 00:14:02,320 --> 00:14:02,920 THE ACUTE LYMPHOPLASTIC 354 00:14:02,920 --> 00:14:04,280 LEUKEMIA, ST. JUDE TOTAL THERAPY 355 00:14:04,280 --> 00:14:04,600 STUDIES. 356 00:14:04,600 --> 00:14:06,960 YOU CAN SEE TREMENDOUS PROGRESS 357 00:14:06,960 --> 00:14:09,160 MADE BY CONSECUTIVE CLINICAL 358 00:14:09,160 --> 00:14:12,720 TRIALS THAT HAVE BEEN CONDUCTED 359 00:14:12,720 --> 00:14:14,840 SO FOR MANY, MANY, PEDIATRIC 360 00:14:14,840 --> 00:14:15,800 PATIENTS WE'RE ACHIEVING CURES 361 00:14:15,800 --> 00:14:16,800 TO DATE. 362 00:14:16,800 --> 00:14:19,280 I WANT TO HIGHLIGHT ONE EXAMPLE 363 00:14:19,280 --> 00:14:21,600 OF SOLID TUMOR CLINICAL TRIALS 364 00:14:21,600 --> 00:14:23,160 WHERE WE'VE SEEN TREMENDOUS 365 00:14:23,160 --> 00:14:26,120 IMPROVEMENT IN A VERY DIFFICULT 366 00:14:26,120 --> 00:14:28,560 HUMAN, HIGH RISK NEUROBLASTOMA, 367 00:14:28,560 --> 00:14:30,080 VERY AGGRESSIVELY TREATED, I'M 368 00:14:30,080 --> 00:14:32,480 SHOWING YOU HERE THE 369 00:14:32,480 --> 00:14:37,120 KAPLAN-MEIER SURVIVAL PLOT OF A 370 00:14:37,120 --> 00:14:41,560 RANDOMIZED CLINICAL TRIAL, 371 00:14:41,560 --> 00:14:46,640 IMMUNOTHERAPY WITH ANTIBODY AND 372 00:14:46,640 --> 00:14:49,080 INTERLEUKIN-2 WAS WE NEARED MANY 373 00:14:49,080 --> 00:14:50,880 YEARS AGO, AND I KNOW ANITA 374 00:14:50,880 --> 00:14:58,480 ROBERTS ALSO WORKED IN THE FIELD 375 00:14:58,480 --> 00:14:59,880 OF RETINOID METABOLISM, SHOWS 376 00:14:59,880 --> 00:15:01,560 PROGRESS FOR PATIENTS WITH 377 00:15:01,560 --> 00:15:04,080 OVERALL POOR PROGNOSIS, A RECENT 378 00:15:04,080 --> 00:15:06,000 STUDY DEMONSTRATED THAT EVEN TO 379 00:15:06,000 --> 00:15:08,200 THIS DAY THE SURVIVAL BENEFIT IS 380 00:15:08,200 --> 00:15:09,840 STILL THERE, BUT YOU CAN SEE 381 00:15:09,840 --> 00:15:12,680 THAT WE'RE FAR FROM ACHIEVING 382 00:15:12,680 --> 00:15:16,680 CURES FOR PATIENTS, FOR PATIENTS 383 00:15:16,680 --> 00:15:19,040 WITH HIGH RISK NEUROBLASTOMA. 384 00:15:19,040 --> 00:15:22,400 MY BRANCH FOCUSES ON TREATING A 385 00:15:22,400 --> 00:15:24,680 VARIETY OF TUMORS, AND LIKE MANY 386 00:15:24,680 --> 00:15:26,520 CLINICAL BRANCHES IN THE CCR, WE 387 00:15:26,520 --> 00:15:29,000 HAVE AN EFFORT ON SOLID TUMORS, 388 00:15:29,000 --> 00:15:31,040 BRAIN TUMORS, LEUKEMIAS, AND 389 00:15:31,040 --> 00:15:32,560 THEN VERY RARE TUMORS. 390 00:15:32,560 --> 00:15:35,560 I'M THRILLED THAT WE HAVE 391 00:15:35,560 --> 00:15:37,960 RESEARCHERS THAT REALLY RANGE 392 00:15:37,960 --> 00:15:39,000 FROM BASIC TO CLINICAL 393 00:15:39,000 --> 00:15:41,760 RESEARCHERS AND HAVE THE SUPPORT 394 00:15:41,760 --> 00:15:43,200 OF PSYCHOSOCIAL AND BEHAVIORAL 395 00:15:43,200 --> 00:15:48,360 RESEARCH PROGRAM WHICH IS 396 00:15:48,360 --> 00:15:49,360 OUTSTANDING, ADDRESSING RESEARCH 397 00:15:49,360 --> 00:15:53,160 THAT IS HIGH RISK AND REQUIRES 398 00:15:53,160 --> 00:15:54,040 LONG-TERM COMMITMENT. 399 00:15:54,040 --> 00:15:57,320 I WILL START BY TELLING THE NF1 400 00:15:57,320 --> 00:15:59,200 STORY, AND GIVE EXAMPLES TO 401 00:15:59,200 --> 00:16:00,480 HOPEFULLY MAKE IT MORE 402 00:16:00,480 --> 00:16:02,520 INTERESTING FOR THOSE WHO HEARD 403 00:16:02,520 --> 00:16:04,320 THIS BEFORE. 404 00:16:04,320 --> 00:16:07,000 NF1 IS A FAIRLY FREQUENT, MOST 405 00:16:07,000 --> 00:16:13,840 FREQUENT SINGLE GENE DISORDER OF 406 00:16:13,840 --> 00:16:18,720 THE NERVOUS SYSTEM, 3500 PEOPLE, 407 00:16:18,720 --> 00:16:20,560 NEUROFIBROMA IN THE NF1 GENE 408 00:16:20,560 --> 00:16:26,440 PRODUCTS FUNCTIONING A REGULATOR 409 00:16:26,440 --> 00:16:28,120 AT GTPase, PRE-SENTING RAS 410 00:16:28,120 --> 00:16:30,080 PATHWAY ACTIVATION BUT WHEN 411 00:16:30,080 --> 00:16:32,360 MUTATED THE PATHWAY IS 412 00:16:32,360 --> 00:16:33,320 ACTIVATED, PROMOTES TUMOR GROWTH 413 00:16:33,320 --> 00:16:36,040 IN THE PATIENTS AND DEVELOPMENT 414 00:16:36,040 --> 00:16:39,680 OF TUMORS WITH NF1. 415 00:16:39,680 --> 00:16:42,040 ALSO RESIDES IN DISEASE 416 00:16:42,040 --> 00:16:43,640 MANIFESTATION UNRELATED TO 417 00:16:43,640 --> 00:16:44,040 TUMORS. 418 00:16:44,040 --> 00:16:46,040 AS CLINICAL RESEARCHER AND 419 00:16:46,040 --> 00:16:50,520 WORKING IN DEVELOPMENT, WHEN 420 00:16:50,520 --> 00:16:51,760 MANY DRUGS WERE DEVELOPED, A 421 00:16:51,760 --> 00:16:54,720 GOOD DISEASE TO FOCUS ON BECAUSE 422 00:16:54,720 --> 00:16:58,040 THERE WERE NO EFFECTIVE 423 00:16:58,040 --> 00:16:58,360 TREATMENTS. 424 00:16:58,360 --> 00:17:04,280 OUR FOCUS WAS ON PLEXIFORM 425 00:17:04,280 --> 00:17:05,440 NEUROFIBROMA, THE SECOND COLUMN, 426 00:17:05,440 --> 00:17:07,680 DEVELOPED IN VERY YOUNG PATIENTS 427 00:17:07,680 --> 00:17:09,360 WHILE HISTOLOGICALLY BENIGN WE 428 00:17:09,360 --> 00:17:11,840 KNEW THEY CAN TRANSFORM TO 429 00:17:11,840 --> 00:17:16,920 HIGHLY AGGRESSIVE VERY DIFFICULT 430 00:17:16,920 --> 00:17:18,360 TO TREAT CANCERS, MALIGNANT 431 00:17:18,360 --> 00:17:19,320 PERIPHERAL NERVE SHEATH TUMORS, 432 00:17:19,320 --> 00:17:20,920 WE LEARNED THERE'S ANOTHER TUMOR 433 00:17:20,920 --> 00:17:28,560 THAT LIKELY IS A STEP IN BETWEEN 434 00:17:28,560 --> 00:17:39,080 PLEXIFORM AND NPNST, ATYPICAL 435 00:17:39,920 --> 00:17:45,040 FIBROMA. 436 00:17:45,040 --> 00:17:46,080 CDK CHARACTERIZES APOPTOTIC 437 00:17:46,080 --> 00:17:46,480 TUMORS. 438 00:17:46,480 --> 00:17:51,000 I START WITH A PATIENT EXAMPLE, 439 00:17:51,000 --> 00:17:54,800 24-YEAR-OLD MALE WITH FAMILIAL 440 00:17:54,800 --> 00:17:56,560 NF1, FROM LOUISIANA, DIAGNOSED, 441 00:17:56,560 --> 00:18:01,560 A DELAY OF FOUR MONTHS WITH 442 00:18:01,560 --> 00:18:04,000 NPNST OF RIGHT THIGH AND PELVIS, 443 00:18:04,000 --> 00:18:06,400 HIS TREATMENT BACK HOME AS YOU 444 00:18:06,400 --> 00:18:11,840 CAN SEE ON THE CT SCAN, THE 445 00:18:11,840 --> 00:18:14,040 CORONAL ON THE LEFT, 446 00:18:14,040 --> 00:18:15,960 UNFORTUNATELY THIS PATIENT 447 00:18:15,960 --> 00:18:16,840 DEVELOPED PULMONARY METASTASES, 448 00:18:16,840 --> 00:18:20,840 YOU CAN SEE THE LARGE PULMONARY 449 00:18:20,840 --> 00:18:21,760 METASTASIS ON THE AXIAL CT SCAN. 450 00:18:21,760 --> 00:18:23,880 AT THAT TIME, THE PATIENT WAS 451 00:18:23,880 --> 00:18:29,560 REFERRED TO US AT THE NCI TO 452 00:18:29,560 --> 00:18:36,240 ENROLL ON OUR CHEMOTHERAPY TRIAL 453 00:18:36,240 --> 00:18:38,920 SARCO06. 454 00:18:38,920 --> 00:18:40,400 OUR THORACIC SURGEON RESECTED, 455 00:18:40,400 --> 00:18:42,720 PATIENT HAD NO RESPONSE TO 456 00:18:42,720 --> 00:18:45,120 CHEMOTHERAPY, SUBSTANTIAL 457 00:18:45,120 --> 00:18:46,800 COMPLICATIONS FROM THE 458 00:18:46,800 --> 00:18:48,080 TREATMENT. 459 00:18:48,080 --> 00:18:53,080 AFTER REMOVAL OF THE PULMONARY 460 00:18:53,080 --> 00:18:53,600 DEVELOPED RECURRENCE THAT 461 00:18:53,600 --> 00:18:55,640 PROGRESSED AS YOU CAN SEE, THE 462 00:18:55,640 --> 00:18:56,440 PATIENT DIED. 463 00:18:56,440 --> 00:19:00,520 HE DID TALK ABOUT WHAT HAPPENED 464 00:19:00,520 --> 00:19:03,080 TO MY NEPHEWS WHERE ALSO HAVE 465 00:19:03,080 --> 00:19:06,720 NF1, AND LOOKING AT THE MRI 466 00:19:06,720 --> 00:19:10,800 SCANS ON THE UPPER RIGHT, THIS 467 00:19:10,800 --> 00:19:12,640 PATIENT HAD SUBSTANTIAL 468 00:19:12,640 --> 00:19:13,920 PLEXIFORM NEUROFIBROMA BURDEN 469 00:19:13,920 --> 00:19:15,760 WITH SPINAL CORD COMPRESSION ON 470 00:19:15,760 --> 00:19:17,640 THE TOP, WITH ABDOMINAL DISEASE 471 00:19:17,640 --> 00:19:18,840 AND PELVIC DISEASE, AND TODAY WE 472 00:19:18,840 --> 00:19:22,440 WOULD KNOW THIS IS A PATIENT 473 00:19:22,440 --> 00:19:24,600 DEFINITELY AT RISK FOR 474 00:19:24,600 --> 00:19:25,680 DEVELOPING MPNST, AND I WILL 475 00:19:25,680 --> 00:19:27,320 COME BACK TO WHAT HAPPENED TO 476 00:19:27,320 --> 00:19:29,280 ONE OF HIS NEPHEWS LATER. 477 00:19:29,280 --> 00:19:32,120 OUR INITIAL FOCUS WAS TO DEVELOP 478 00:19:32,120 --> 00:19:35,280 TREATMENTS FOR THE BENIGN TUMOR 479 00:19:35,280 --> 00:19:39,600 CALLED PLEXIFORM NEUROFIBROMA. 480 00:19:39,600 --> 00:19:41,720 AS YOU CAN SEE ON THE 481 00:19:41,720 --> 00:19:43,360 PHOTOGRAPHS AND CORONAL MRI 482 00:19:43,360 --> 00:19:45,000 DEMONSTRATING LARGE TUMOR IN THE 483 00:19:45,000 --> 00:19:47,120 LEFT NECK AND ARM AND YOU CAN 484 00:19:47,120 --> 00:19:49,600 SEE IT ON THE MRI, EVERYTHING 485 00:19:49,600 --> 00:19:53,440 THAT IS BRIGHT OR WHITE IS 486 00:19:53,440 --> 00:19:56,240 PLEXIFORM NEUROFIBROMA IN THE 487 00:19:56,240 --> 00:19:57,000 NECK AND CHEST. 488 00:19:57,000 --> 00:19:59,240 THIS IS ONE EXAMPLE HOW QUICKLY 489 00:19:59,240 --> 00:20:00,920 TUMORS CAN PROGRESS, WHEN WE 490 00:20:00,920 --> 00:20:03,800 STARTED THE WORK THERE WAS 491 00:20:03,800 --> 00:20:05,600 REALLY NO EFFECTIVE MEDICAL 492 00:20:05,600 --> 00:20:07,560 THERAPY AND BARELY ANY CLINICAL 493 00:20:07,560 --> 00:20:09,080 TRIALS WERE CONDUCTED. 494 00:20:09,080 --> 00:20:11,160 SO, I DEVELOPED A NATURAL 495 00:20:11,160 --> 00:20:13,760 HISTORY STUDY OF NF1 TO 496 00:20:13,760 --> 00:20:16,920 UNDERSTAND HOW THESE TUMORS GROW 497 00:20:16,920 --> 00:20:18,360 AND CLINICAL TRIAL DESIGN, AND 498 00:20:18,360 --> 00:20:20,440 FOR THIS NATURAL HISTORY STUDY 499 00:20:20,440 --> 00:20:22,640 WE USED A THOUGHT CALLED 500 00:20:22,640 --> 00:20:26,080 BIOMETRIC MRI ANALYSIS AS I SHOW 501 00:20:26,080 --> 00:20:28,840 IN ONE PICTURE HERE, TO MEASURE 502 00:20:28,840 --> 00:20:30,080 THE TUMORS. 503 00:20:30,080 --> 00:20:33,680 A DEAR COLLEAGUE OF MINE TOLD ME 504 00:20:33,680 --> 00:20:36,080 RECENTLY, WHEN YOU STARTED THIS 505 00:20:36,080 --> 00:20:37,840 STUDY, I THOUGHT, WOW, THIS IS 506 00:20:37,840 --> 00:20:39,960 REALLY BORING, AND I HAVE TO SAY 507 00:20:39,960 --> 00:20:41,840 WHEN I STARTED THIS STUDY I 508 00:20:41,840 --> 00:20:43,600 THOUGHT, HMM, I WOULD LIKE TO 509 00:20:43,600 --> 00:20:47,640 CURE CANCER, AT LEAST TREAT 510 00:20:47,640 --> 00:20:49,680 CANCER, AND FIND EFFECTIVE 511 00:20:49,680 --> 00:20:50,000 TREATMENTS. 512 00:20:50,000 --> 00:20:56,360 I'M GLAD I LISTEN TO MY MENTOR, 513 00:20:56,360 --> 00:20:57,320 FRANK BALIS. 514 00:20:57,320 --> 00:20:59,480 ONE KEY FINDING IS SHOWN HERE ON 515 00:20:59,480 --> 00:21:00,560 THE GRAPH ON THE RIGHT SIDE 516 00:21:00,560 --> 00:21:02,840 WHERE YOU SEE THE AGE OF THE 517 00:21:02,840 --> 00:21:05,680 PATIENT AT THE INITIAL MRI, ON 518 00:21:05,680 --> 00:21:07,360 THE Y-AXIS YOU SEE PERCENT 519 00:21:07,360 --> 00:21:09,280 CHANGE IN TUMOR GROWTH PER YEAR, 520 00:21:09,280 --> 00:21:10,600 YOU CAN CLEARLY SEE THE YOUNGER 521 00:21:10,600 --> 00:21:13,480 KIDS HAVE THE MOST RAPIDLY 522 00:21:13,480 --> 00:21:15,320 GROWING TUMORS WHICH MADE US 523 00:21:15,320 --> 00:21:16,440 DETERMINED TO START DRUG 524 00:21:16,440 --> 00:21:17,800 DEVELOPMENT IN THE YOUNG 525 00:21:17,800 --> 00:21:19,840 PATIENTS WHO HOPEFULLY COULD 526 00:21:19,840 --> 00:21:21,040 BENEFIT THE MOST. 527 00:21:21,040 --> 00:21:26,000 WORK DONE BY THE TEAM ALSO 528 00:21:26,000 --> 00:21:27,600 SHOWED THAT PLEXIFORM 529 00:21:27,600 --> 00:21:28,920 NEUROFIBROMA WHEN THEY DEVELOP 530 00:21:28,920 --> 00:21:31,840 MORBIDITY IS NOT REVERSIBLE AND 531 00:21:31,840 --> 00:21:33,840 TUMORS TYPICALLY DON'T SHRINK 532 00:21:33,840 --> 00:21:35,480 SUBSTANTIALLY OVER TIME 533 00:21:35,480 --> 00:21:35,840 SPONTANEOUSLY. 534 00:21:35,840 --> 00:21:37,720 AFTER CONDUCT OF A SERIES OF 535 00:21:37,720 --> 00:21:41,480 NEGATIVE TRIALS, BY THIS I MEAN 536 00:21:41,480 --> 00:21:42,760 TRIALS THAT NEITHER SHRINK 537 00:21:42,760 --> 00:21:44,920 TUMORS NOR SLOW DOWN THE TUMOR 538 00:21:44,920 --> 00:21:47,040 GROWTH, WE CONDUCTED A STUDY 539 00:21:47,040 --> 00:21:50,760 WITH A MEK INHIBITOR RIGHT IN 540 00:21:50,760 --> 00:21:54,760 THE RAS RAF PATHWAY, SPECIFIC 541 00:21:54,760 --> 00:21:58,320 MEK INHIBITOR FOR CHILDREN WITH 542 00:21:58,320 --> 00:21:59,520 INOPERABLE SYMPTOMATIC PLEXIFORM 543 00:21:59,520 --> 00:22:00,000 NEUROFIBROMAS. 544 00:22:00,000 --> 00:22:02,200 TO OUR GREAT SURPRISE, BECAUSE 545 00:22:02,200 --> 00:22:03,320 THERE WERE NO PRE-CLINICAL DATA 546 00:22:03,320 --> 00:22:07,160 AT THAT TIME, WE SAW A TUMOR 547 00:22:07,160 --> 00:22:08,920 SHRINKAGE IN ALMOST ALL 548 00:22:08,920 --> 00:22:10,320 PATIENTS. 549 00:22:10,320 --> 00:22:13,120 BACK BARS ON THIS WATER FALL 550 00:22:13,120 --> 00:22:16,080 PLOT GO DOWN, MAXIMUM WAS 50%, 551 00:22:16,080 --> 00:22:18,440 THIS IS MODEST BUT SOMETHING WE 552 00:22:18,440 --> 00:22:21,560 HAD SIMPLY NEVER SEEN BEFORE. 553 00:22:21,560 --> 00:22:22,760 WE ALSO SAW CLINICAL IMPROVEMENT 554 00:22:22,760 --> 00:22:26,760 AS YOU CAN READILY SEE IN THIS 555 00:22:26,760 --> 00:22:29,120 PATIENT HERE, 10-YEAR-OLD, WITH 556 00:22:29,120 --> 00:22:31,920 A VERY LARGE PELVIC PLEXIFORM 557 00:22:31,920 --> 00:22:32,960 NEUROFIBROMA. 558 00:22:32,960 --> 00:22:34,640 WE STOPPED GROWTH AND SHE HAD 559 00:22:34,640 --> 00:22:37,240 LESS PAIN, IMPROVEMENT IN 560 00:22:37,240 --> 00:22:37,720 APPEARANCE. 561 00:22:37,720 --> 00:22:38,480 UNFORTUNATELY ON THIS EARLY 562 00:22:38,480 --> 00:22:41,240 PHASE STUDY IT WAS A DOSE 563 00:22:41,240 --> 00:22:43,440 FINDING STUDY, WE DID NOT 564 00:22:43,440 --> 00:22:44,240 INCORPORATE PATIENT-REPORTED 565 00:22:44,240 --> 00:22:46,440 OUTCOMES OR OTHER MEASURES OF 566 00:22:46,440 --> 00:22:48,320 CLINICAL BENEFIT WHICH IS 567 00:22:48,320 --> 00:22:50,040 REQUIRED FOR DRUG APPROVAL. 568 00:22:50,040 --> 00:22:55,720 SO WE WENT ON TO DESIGN A 569 00:22:55,720 --> 00:22:57,720 MULTI-SITE NCIC CLINICAL TRIAL, 570 00:22:57,720 --> 00:23:00,640 SELUMETINIB, WITH GOAL TO 571 00:23:00,640 --> 00:23:02,640 ACHIEVE REGISTRATION, 572 00:23:02,640 --> 00:23:03,840 POTENTIALLY, EXTREMELY 573 00:23:03,840 --> 00:23:04,400 CHALLENGING BECAUSE SHOWING 574 00:23:04,400 --> 00:23:06,600 CLINICAL BENEFIT IN TUMORS THAT 575 00:23:06,600 --> 00:23:10,920 OCCURRED ANYWHERE IN THE BODY IS 576 00:23:10,920 --> 00:23:11,640 DIFFICULT. 577 00:23:11,640 --> 00:23:12,320 HOWEVER, WE DID SUCCEED. 578 00:23:12,320 --> 00:23:13,680 FIRST AS YOU CAN SEE ON THE 579 00:23:13,680 --> 00:23:16,000 WATER FALL PLOT ON THE LEFT 580 00:23:16,000 --> 00:23:19,160 LOWER PART OF THE SLIDE, 581 00:23:19,160 --> 00:23:21,280 DEMONSTRATES AGAIN ALMOST ALL OF 582 00:23:21,280 --> 00:23:24,320 THE TUMORS HAD SOME DECREASE IN 583 00:23:24,320 --> 00:23:26,400 SIZE BY VOLUME MEASUREMENT, WE 584 00:23:26,400 --> 00:23:28,400 COULD ALSO SHOW BY FUNCTIONAL 585 00:23:28,400 --> 00:23:29,640 AND PATIENT-REPORTED OUTCOMES 586 00:23:29,640 --> 00:23:32,440 THAT PATIENTS HAD IMPROVEMENT IN 587 00:23:32,440 --> 00:23:33,640 PAIN, IMPROVEMENT IN 588 00:23:33,640 --> 00:23:36,160 DISFIGUREMENT AS YOU CAN SEE ON 589 00:23:36,160 --> 00:23:38,920 THE RIGHT, AND THEN BY 590 00:23:38,920 --> 00:23:40,240 PATIENT-REPORTED OUTCOMES THERE 591 00:23:40,240 --> 00:23:41,480 WAS SUBSTANTIAL IMPROVEMENT BOTH 592 00:23:41,480 --> 00:23:44,440 PARENT REPORTED AND CHILD 593 00:23:44,440 --> 00:23:47,480 REPORTED, AS RELATES TO SYMPTOMS 594 00:23:47,480 --> 00:23:51,880 COMING FROM THE PLEXIFORM 595 00:23:51,880 --> 00:23:55,240 NEUROFIBROMA. 596 00:23:55,240 --> 00:23:57,120 A STUDY LOOKED AT HOW DOES THE 597 00:23:57,120 --> 00:23:58,720 DRUG CHANGE THE NATURAL HISTORY 598 00:23:58,720 --> 00:24:00,920 OF DECEIT. 599 00:24:00,920 --> 00:24:02,920 AND THIS MADE ME HAPPY WE 600 00:24:02,920 --> 00:24:04,120 CONDUCTED NATURAL HISTORY STUDY 601 00:24:04,120 --> 00:24:07,160 WHERE YOU SEE IN RED PATIENTS 602 00:24:07,160 --> 00:24:10,320 THAT WERE TREATED WITH 603 00:24:10,320 --> 00:24:15,600 SELUMETINIB, THEY HAD A 604 00:24:15,600 --> 00:24:16,200 DECREASE, MODEST, PLEXIFORM 605 00:24:16,200 --> 00:24:17,920 NEUROFIBROMA, ON THE NATURAL 606 00:24:17,920 --> 00:24:21,280 HISTORY STUDY NOT RECEIVING 607 00:24:21,280 --> 00:24:21,600 SELUMETINIB. 608 00:24:21,600 --> 00:24:26,000 HERE ON THE RIGHT YOU SEE 609 00:24:26,000 --> 00:24:27,600 KAPLAN-MEIER PROGRESSION FREE 610 00:24:27,600 --> 00:24:29,720 SURVIVAL, HOW THE CURVES 611 00:24:29,720 --> 00:24:30,720 SEPARATE. 612 00:24:30,720 --> 00:24:32,680 THIS DATA WAS TAKEN TO THE FDA 613 00:24:32,680 --> 00:24:36,680 ALONG WITH CLINICAL TRIAL DATA, 614 00:24:36,680 --> 00:24:38,520 AND THEN AFTER 30 YEARS AFTER 615 00:24:38,520 --> 00:24:40,480 IDENTIFYING THE GENE AND 20 616 00:24:40,480 --> 00:24:42,960 YEARS, I WOULD SAY, AFTER 617 00:24:42,960 --> 00:24:45,720 INITIATING THE FIRST MEANINGFUL 618 00:24:45,720 --> 00:24:51,640 CLINICAL TRIALS FOR NF1 RESULTED 619 00:24:51,640 --> 00:24:53,920 IN FDA APPROVAL ARE SELUMETINIB 620 00:24:53,920 --> 00:24:55,360 FOR CHILDREN WITH NF1, VERY LONG 621 00:24:55,360 --> 00:24:56,320 TIME. 622 00:24:56,320 --> 00:24:59,080 I'M GLAD TO SAY THAT SUBSEQUENT 623 00:24:59,080 --> 00:25:01,240 DRUG APPROVALS AT LEAST FOR 624 00:25:01,240 --> 00:25:04,000 SELUMETINIB WENT MUCH QUICKER 625 00:25:04,000 --> 00:25:05,960 AND I'M PROUD OF THE TEAM. 626 00:25:05,960 --> 00:25:07,960 YOU SEE SOME TEAM MEMBERS HERE 627 00:25:07,960 --> 00:25:09,120 WHO WORKED REALLY HARD. 628 00:25:09,120 --> 00:25:11,320 THE DATA FROM THIS ONE STUDY LED 629 00:25:11,320 --> 00:25:14,200 TO APPROVAL IN MANY, MANY 630 00:25:14,200 --> 00:25:17,040 COUNTRIES, AND THIS WITHIN A 631 00:25:17,040 --> 00:25:18,000 VERY RAPID TIME STARTING IN 632 00:25:18,000 --> 00:25:18,800 2020. 633 00:25:18,800 --> 00:25:22,200 SO I THINK IT WAS VERY MUCH 634 00:25:22,200 --> 00:25:26,200 WORTH THE EFFORT. 635 00:25:26,200 --> 00:25:27,840 WE ALSO INITIATED A CLINICAL 636 00:25:27,840 --> 00:25:33,120 TRIAL FOR ADULTS WITH PLEXIFORM 637 00:25:33,120 --> 00:25:36,080 NEUROFIBROMAS, ONLY POSSIBLE 638 00:25:36,080 --> 00:25:41,120 THROUGH COLLABORATION WITH THE 639 00:25:41,120 --> 00:25:42,600 ADULT CLINIC, LET'S DO IT 640 00:25:42,600 --> 00:25:44,160 TOGETHER, SO THEY SEE THE OLDER 641 00:25:44,160 --> 00:25:47,520 PATIENTS AND WE SEE THE YOUNGER 642 00:25:47,520 --> 00:25:48,360 PATIENTS. 643 00:25:48,360 --> 00:25:51,360 THIS STUDY RECENTLY COMPLETED 644 00:25:51,360 --> 00:25:52,600 ENROLLMENT, 33 PATIENTS, THIS IS 645 00:25:52,600 --> 00:25:56,480 PRELIMINARY DATA BUT WE ALSO SAW 646 00:25:56,480 --> 00:25:58,760 RESPONSES WITH 63% RESPONSE RATE 647 00:25:58,760 --> 00:26:01,000 IN PATIENTS, AND VERY 648 00:26:01,000 --> 00:26:02,200 IMPORTANTLY ON THIS STUDY WHICH 649 00:26:02,200 --> 00:26:03,720 IS SOMETHING WE CANNOT DO IN 650 00:26:03,720 --> 00:26:08,560 CHILDREN EASILY, WE WERE ABLE TO 651 00:26:08,560 --> 00:26:09,640 OBTAIN SERIAL BIOPSIES 652 00:26:09,640 --> 00:26:12,280 PRE-TREATMENT, ABLE TO SHOW THAT 653 00:26:12,280 --> 00:26:18,760 INDEED BLOCKING THE TARGETS AND 654 00:26:18,760 --> 00:26:20,480 BY DECREASING PHOSPHO-ERK, MANY 655 00:26:20,480 --> 00:26:21,560 ADDITIONAL COMING FORWARD, 656 00:26:21,560 --> 00:26:23,480 WONDERFUL FOR US IN THE CCR TO 657 00:26:23,480 --> 00:26:28,440 HAVE THIS ABILITY TO COLLABORATE 658 00:26:28,440 --> 00:26:29,040 WITH OUR ADULT PARTNERS. 659 00:26:29,040 --> 00:26:31,440 I WANT TO HIGHLIGHT WHAT WE'VE 660 00:26:31,440 --> 00:26:32,360 NOT ACCOMPLISHED. 661 00:26:32,360 --> 00:26:33,800 TWO KEY ASPECTS THAT I WANT TO 662 00:26:33,800 --> 00:26:34,880 HIGHLIGHT ON THIS SLIDE, THIS 663 00:26:34,880 --> 00:26:36,600 WAS A PATIENT I MET FIRST WHEN 664 00:26:36,600 --> 00:26:41,280 HE WAS 5 YEARS OLD. 665 00:26:41,280 --> 00:26:42,040 TUMOR VOLUME WAS ABOUT 800 CC AT 666 00:26:42,040 --> 00:26:45,480 THAT TIME. 667 00:26:45,480 --> 00:26:46,720 HE PARTICIPATED IN MULTIPLE OF 668 00:26:46,720 --> 00:26:49,480 MY TRIALS WITH NO IMPACT, 669 00:26:49,480 --> 00:26:55,360 TREATED WITH SELUMETINIB, 670 00:26:55,360 --> 00:27:01,000 DEVELOPED A TOXICITY, EJECTION 671 00:27:01,000 --> 00:27:01,360 REFRACTION. 672 00:27:01,360 --> 00:27:03,240 WE RESTARTED, TUMOR BEGAN TO 673 00:27:03,240 --> 00:27:03,440 SHRINK. 674 00:27:03,440 --> 00:27:04,840 THE PATIENT IS STILL ON TRIAL 675 00:27:04,840 --> 00:27:06,680 AFTER MANY YEARS. 676 00:27:06,680 --> 00:27:09,320 BUT YOU SEE WE NEED TO GIVE 677 00:27:09,320 --> 00:27:10,000 SELUMETINIB CONTINUOUSLY FOR 678 00:27:10,000 --> 00:27:12,720 VERY LONG TIME, IF WE WANT TO 679 00:27:12,720 --> 00:27:14,400 HAVE SUSTAINED EFFECT. 680 00:27:14,400 --> 00:27:15,840 AND ALSO THIS PATIENT WHILE WE 681 00:27:15,840 --> 00:27:20,080 STOPPED THE TUMOR GROWTH DID NOT 682 00:27:20,080 --> 00:27:20,880 ACTUALLY EXPERIENCE CLINICAL 683 00:27:20,880 --> 00:27:21,400 BENEFIT. 684 00:27:21,400 --> 00:27:23,800 SO WHAT CAN WE DO TO CHANGE THIS 685 00:27:23,800 --> 00:27:25,480 AND TO POTENTIALLY MAXIMIZE THE 686 00:27:25,480 --> 00:27:30,920 BENEFIT THAT ONE CAN GET FROM A 687 00:27:30,920 --> 00:27:32,160 DRUG LIKE SELUMETINIB? 688 00:27:32,160 --> 00:27:34,120 OUR TEAM HAS DEVELOPED VERY 689 00:27:34,120 --> 00:27:35,880 INTERESTING AND INNOVATIVE STUDY 690 00:27:35,880 --> 00:27:42,040 WHERE WE AIM TO GIVE CHILDREN 691 00:27:42,040 --> 00:27:43,560 WHO ARE ASYMPTOMATIC, LOOK AT 692 00:27:43,560 --> 00:27:46,560 THE BABY WHERE FACIAL TUMOR IS 693 00:27:46,560 --> 00:27:47,760 BARELY VISIBLE, COMPARISON TO 694 00:27:47,760 --> 00:27:50,520 WHEN SHE'S 3 YEARS OLD. 695 00:27:50,520 --> 00:27:51,800 AND WE WILL START TREATING AND 696 00:27:51,800 --> 00:27:56,600 THIS WILL BE A RANDOMIZED STUDY, 697 00:27:56,600 --> 00:27:58,840 CHILDREN WITH ASYMPTOMATIC 698 00:27:58,840 --> 00:28:02,000 PLEXIFORM NEUROFIBROMAS IN 699 00:28:02,000 --> 00:28:05,240 CRITICAL LOCATIONS, EITHER WITH 700 00:28:05,240 --> 00:28:07,360 SELUMETINIB OR OBSERVATION TO 701 00:28:07,360 --> 00:28:12,840 SEE IF WE CAN PREVENT 702 00:28:12,840 --> 00:28:17,320 DEVELOPMENT OF DISFIGURING 703 00:28:17,320 --> 00:28:20,920 PAINFUL TUMORS AND SUSTAIN 704 00:28:20,920 --> 00:28:22,800 RESPONSES, PART OF A NEW EFFORT 705 00:28:22,800 --> 00:28:25,960 IN THE NCI, WHERE WE NOW HAVE 706 00:28:25,960 --> 00:28:28,840 NCI PREVENTION CLINIC AND OTHER 707 00:28:28,840 --> 00:28:32,080 CLINICAL TRIALS ACROSS THE CCR 708 00:28:32,080 --> 00:28:33,760 CONTRIBUTING TO THIS EFFORT. 709 00:28:33,760 --> 00:28:36,240 BASIC RESEARCHERS, I WANT TO 710 00:28:36,240 --> 00:28:38,680 HIGHLIGHT WE NOW ALSO HAVE 711 00:28:38,680 --> 00:28:42,360 GENETIC MOUSE MODELS OF NF 712 00:28:42,360 --> 00:28:45,080 NEUROFIBROMAS THAT PREDICTED FOR 713 00:28:45,080 --> 00:28:48,520 THE BENEFIT OF SELUMETINIB, DR. 714 00:28:48,520 --> 00:28:50,640 NANCY RATNER IN CINCINNATI AND 715 00:28:50,640 --> 00:28:53,320 DR. WAYNE CLAPPEN IN INDIANA 716 00:28:53,320 --> 00:28:56,000 HAVE MODELS THAT HAVE 717 00:28:56,000 --> 00:28:57,120 DEMONSTRATED BENEFIT OF MEK 718 00:28:57,120 --> 00:28:59,680 INHIBITORS COMPARED TO OTHER 719 00:28:59,680 --> 00:29:01,480 AGENTS, WE NOW HAVE VALIDATED 720 00:29:01,480 --> 00:29:03,640 MOUSE MODELS SO FUTURE CLINICAL 721 00:29:03,640 --> 00:29:05,360 TRIALS CAN BE MUCH MORE INFORMED 722 00:29:05,360 --> 00:29:07,720 THAN OUR EARLY CLINICAL TRIALS 723 00:29:07,720 --> 00:29:08,160 WERE. 724 00:29:08,160 --> 00:29:11,360 COMING BACK TO THE PATIENT WITH 725 00:29:11,360 --> 00:29:14,320 MPNST WHO UNFORTUNATELY DIED 726 00:29:14,320 --> 00:29:16,120 FROM HIS DISEASE, WHERE WOULD WE 727 00:29:16,120 --> 00:29:19,760 BE TODAY? 728 00:29:19,760 --> 00:29:22,120 AND UNFORTUNATELY COMPARED TO 20 729 00:29:22,120 --> 00:29:24,400 YEARS AGO DOES NOT HAVE BETTER 730 00:29:24,400 --> 00:29:26,360 TREATMENT OPTIONS. 731 00:29:26,360 --> 00:29:28,160 THE ONLY EFFECTIVE TREATMENT IS 732 00:29:28,160 --> 00:29:29,680 COMPLETE SURGICAL RESECTION 733 00:29:29,680 --> 00:29:33,040 WHICH FREQUENTLY IS NOT FEASIBLE 734 00:29:33,040 --> 00:29:37,760 AND THE CLINICAL TRIALS WITH 735 00:29:37,760 --> 00:29:39,280 TARGETED THERAPIES ALL 736 00:29:39,280 --> 00:29:40,000 UNSUCCESSFUL, THE 737 00:29:40,000 --> 00:29:41,400 PROGRESSION-FREE SURVIVAL WAS 738 00:29:41,400 --> 00:29:44,240 VERY SHORT AND RESPONSES WERE 739 00:29:44,240 --> 00:29:46,200 NOT DEMONSTRATED. 740 00:29:46,200 --> 00:29:51,320 WE HAVE TRIAL REPORTED AT THE 741 00:29:51,320 --> 00:29:52,200 CONNECTIVE TISSUE AND ONCOLOGY 742 00:29:52,200 --> 00:29:55,040 SOCIETY IN A FEW WEEKS WITH A 743 00:29:55,040 --> 00:30:01,080 HINT OF ACTIVITY CONNECTING 744 00:30:01,080 --> 00:30:01,680 WITH mTOR INHIBITOR, 745 00:30:01,680 --> 00:30:03,440 DEFINITELY NOT A HOME RUN. 746 00:30:03,440 --> 00:30:05,120 I WANTED TO BRIEFLY HIGHLIGHT A 747 00:30:05,120 --> 00:30:11,080 CLINICAL TRIAL THAT WILL START 748 00:30:11,080 --> 00:30:13,160 COMBINING MEK INHIBITOR AND 749 00:30:13,160 --> 00:30:17,520 PD-L1 INHIBITOR BASED ON 750 00:30:17,520 --> 00:30:19,240 EXCITING DATA WITH SIGNIFICANT 751 00:30:19,240 --> 00:30:21,440 SHRINKAGE ONLY WHEN ALL THREE 752 00:30:21,440 --> 00:30:23,440 AGENTS ARE COMBINED, TAKEN TO 753 00:30:23,440 --> 00:30:25,200 THE CLINIC SOON, AND I HOPE WE 754 00:30:25,200 --> 00:30:27,840 WILL MAKE PROGRESS FOR 755 00:30:27,840 --> 00:30:29,120 ESTABLISHED MPNST SOMETIME IN 756 00:30:29,120 --> 00:30:30,040 THE NEAR FUTURE. 757 00:30:30,040 --> 00:30:32,400 WHAT DO WE HAVE UNTIL THEN? 758 00:30:32,400 --> 00:30:35,400 I WOULD SAY WE'VE MADE 759 00:30:35,400 --> 00:30:36,240 SUBSTANTIAL PROGRESS, 760 00:30:36,240 --> 00:30:37,440 POTENTIALLY DEVELOPING STRATEGY 761 00:30:37,440 --> 00:30:47,920 TO PREVENT THE DEVELOPMENT 762 00:30:48,880 --> 00:30:51,080 OFMPNST, IN PATIENTS, TEAM 763 00:30:51,080 --> 00:30:52,640 IDENTIFIED MODULAR LESIONS WITH 764 00:30:52,640 --> 00:30:56,400 THE RED ARROWS DEVELOPED OVER 765 00:30:56,400 --> 00:30:57,160 TIME, BACKGROUND PLEXIFORM 766 00:30:57,160 --> 00:30:58,440 NEUROFIBROMA THAT MAY NOT 767 00:30:58,440 --> 00:31:02,520 ACTUALLY CHANGE. 768 00:31:02,520 --> 00:31:05,840 WE CALL THESE LESIONS DISTINCT 769 00:31:05,840 --> 00:31:08,040 MODULAR LESIONS, THEY HAVE A 770 00:31:08,040 --> 00:31:09,920 DIFFERENT GROWTH PATTERN 771 00:31:09,920 --> 00:31:11,640 COMPARED TO THE PLEXIFORM 772 00:31:11,640 --> 00:31:13,800 NEUROFIBROMAS, THEIR GROWTH IS 773 00:31:13,800 --> 00:31:14,720 INDEPENDENT OF AGE, AND 774 00:31:14,720 --> 00:31:18,440 SOMETIMES EXCEEDS THE GROWTH OF 775 00:31:18,440 --> 00:31:20,880 PLEXIFORM NEUROFIBROMAS IN TECH 776 00:31:20,880 --> 00:31:22,360 IN ADULTS, IN A WONDERFUL 777 00:31:22,360 --> 00:31:28,520 CONFERENCE, RESPOND -- 778 00:31:28,520 --> 00:31:33,280 SPONSORED BY THE TUMOR 779 00:31:33,280 --> 00:31:36,240 FOUNDATION, INCLUDING OUR 780 00:31:36,240 --> 00:31:43,440 PATHOLOGISTS HERE, IDENTIFIED 781 00:31:43,440 --> 00:31:44,280 ATYPICAL NEUROFIBROMA, 782 00:31:44,280 --> 00:31:45,880 BORDERLINE TUMORS THAT ARE NOT 783 00:31:45,880 --> 00:31:48,800 MALIGNANT BUT ARE AT RISK OF 784 00:31:48,800 --> 00:31:49,840 TRANSFORMING TO MALIGNANT 785 00:31:49,840 --> 00:31:50,120 TUMORS. 786 00:31:50,120 --> 00:31:53,520 SO, WITH THIS WE ESTABLISHED A 787 00:31:53,520 --> 00:31:55,760 HYPOTHESIS THAT MOST MPNST MAY 788 00:31:55,760 --> 00:31:59,240 ARISE FROM THE ATYPICAL 789 00:31:59,240 --> 00:32:02,760 NEUROFIBROMA PRECURSOR, NOT FROM 790 00:32:02,760 --> 00:32:03,280 PLEXIFORM NEUROFIBROMAS, 791 00:32:03,280 --> 00:32:06,480 OFFERING THE OPPORTUNITY FOR 792 00:32:06,480 --> 00:32:07,920 MARGINAL RESECTIONS OF ATYPICAL 793 00:32:07,920 --> 00:32:08,960 NEUROFIBROMAS, MEANING RESECTION 794 00:32:08,960 --> 00:32:12,080 THAT DOES NOT HAVE TO BE WITH 795 00:32:12,080 --> 00:32:15,640 BROAD NEGATIVE MARGINS AND MUCH 796 00:32:15,640 --> 00:32:19,720 LESS MORBID, AND A NEUROSURGEON 797 00:32:19,720 --> 00:32:22,000 FROM NINDS PERFORMED SURGERIES 798 00:32:22,000 --> 00:32:25,800 ON MORE THAN 40 PATIENTS, VERY 799 00:32:25,800 --> 00:32:26,240 SUCCESSFULLY. 800 00:32:26,240 --> 00:32:29,000 WE OF YOU SEE HIS THEORY HERE 801 00:32:29,000 --> 00:32:31,800 THAT THESE NODULES THAT EXPAND 802 00:32:31,800 --> 00:32:34,760 ATYPICAL NEUROFIBROMAS CAN BE 803 00:32:34,760 --> 00:32:36,960 EXCISED WITHOUT ACTUALLY 804 00:32:36,960 --> 00:32:38,040 SEVERING THE NERVE AND PATIENTS 805 00:32:38,040 --> 00:32:41,920 FOR THE MOST PART REMAIN TO HAVE 806 00:32:41,920 --> 00:32:44,040 COMPLETELY NORMAL FUNCTION. 807 00:32:44,040 --> 00:32:45,000 ALSO VERY EXCITED, I'LL TALK 808 00:32:45,000 --> 00:32:49,200 ABOUT THIS IN A MOMENT, WORK 809 00:32:49,200 --> 00:32:52,200 FROM TAYLOR SUNDBY AND JACK 810 00:32:52,200 --> 00:32:55,040 SHERN, WHO DEVELOPED SERIAL 811 00:32:55,040 --> 00:32:58,280 DETECTION OF CELL-FREE DNA AS 812 00:32:58,280 --> 00:32:59,640 MARKER FOR MALIGNANT 813 00:32:59,640 --> 00:33:03,160 TRANSFORMATION, COLLABORATING 814 00:33:03,160 --> 00:33:05,720 WITH THE SAME TEAM, ZHANG, TO 815 00:33:05,720 --> 00:33:12,200 STUDY THIS BETTER IN AND ANDRE A 816 00:33:12,200 --> 00:33:14,920 GROSS DEVELOPED INHIBITOR FOR 817 00:33:14,920 --> 00:33:16,560 ATYPICAL NEUROFIBROMAS, WE CAN 818 00:33:16,560 --> 00:33:17,640 TREAT THESE TUMORS. 819 00:33:17,640 --> 00:33:20,280 AGAIN, WE HAVE BASIC SCIENCE 820 00:33:20,280 --> 00:33:22,120 COLLABORATORS NOW HAVE 821 00:33:22,120 --> 00:33:24,040 ESTABLISHED MODELS THAT ACTUALLY 822 00:33:24,040 --> 00:33:25,120 SHOW MALIGNANT TRANSFORMATION 823 00:33:25,120 --> 00:33:31,200 FROM PLEXI FORMS. 824 00:33:31,200 --> 00:33:35,960 THIS IS A FIGURE FROM TAYLOR'S 825 00:33:35,960 --> 00:33:39,040 PAPER THAT IN COLLABORATION WITH 826 00:33:39,040 --> 00:33:40,840 WASHINGTON UNIVERSITY, BLOOD 827 00:33:40,840 --> 00:33:50,240 SAMPLES FROM HEALTHY VOLUNTEERS, 828 00:33:50,240 --> 00:33:51,160 PLEXYFORM NEUROFIBROMAS AND 829 00:33:51,160 --> 00:33:53,480 MPNST, COPY-NUMBER VARIATION TO 830 00:33:53,480 --> 00:33:58,520 SEPARATE AND DISTINGUISH FROM 831 00:33:58,520 --> 00:34:02,920 PLEXYFORM NEUROFIBROMA, BASED ON 832 00:34:02,920 --> 00:34:04,800 ANECDOTAL, WE CAN MONITOR 833 00:34:04,800 --> 00:34:07,280 RESISTANCE AND RESPONSE 834 00:34:07,280 --> 00:34:10,160 POTENTIALLY ON CLINICAL TRIALS. 835 00:34:10,160 --> 00:34:12,720 COMING BACK TO MY PATIENT, THIS 836 00:34:12,720 --> 00:34:17,480 IS CELL BODY MRI SERIES OF HIS 837 00:34:17,480 --> 00:34:20,920 NEPHEW, FOLLOWED FOR A NUMBER OF 838 00:34:20,920 --> 00:34:21,360 YEARS. 839 00:34:21,360 --> 00:34:23,880 CORONAL MRIs, AND THE 840 00:34:23,880 --> 00:34:25,680 STRUCTURE OF THE SCIATIC NERVES, 841 00:34:25,680 --> 00:34:29,360 THIS IS WHAT YOU SEE THROUGHOUT 842 00:34:29,360 --> 00:34:30,440 HIS BODY, TUMOR BURDEN. 843 00:34:30,440 --> 00:34:34,800 IF YOU FOCUS NEXT TO HIS LEFT 844 00:34:34,800 --> 00:34:36,120 KIDNEY, THERE'S A PERIPHERAL 845 00:34:36,120 --> 00:34:39,240 TUMOR AT AGE 15 AND 18, AND AGE 846 00:34:39,240 --> 00:34:40,640 21 ENLARGING. 847 00:34:40,640 --> 00:34:43,360 YOU SEE THE SAME ON AXIAL SCANS 848 00:34:43,360 --> 00:34:45,200 ON LOWER PANEL. 849 00:34:45,200 --> 00:34:47,320 WHEN WE DO SOMETHING WE CALLED 850 00:34:47,320 --> 00:34:50,080 DIFFUSION WEIGHTED IMAGING ON 851 00:34:50,080 --> 00:34:52,280 MRI, WE GET A COEFFICIENT, IF 852 00:34:52,280 --> 00:34:54,960 IT'S LESS THAN 1 IT MEANS 853 00:34:54,960 --> 00:34:57,280 DIFFUSION RESTRICTION AND THIS 854 00:34:57,280 --> 00:34:59,800 IS CONCERNING, POTENTIAL 855 00:34:59,800 --> 00:35:02,520 DEVELOPMENT OF MPNST. 856 00:35:02,520 --> 00:35:05,320 ON FDG-PET SCANNING WE SAW THERE 857 00:35:05,320 --> 00:35:08,120 WAS SUBSTANTIAL UPTAKE IN THIS 858 00:35:08,120 --> 00:35:10,120 TUMOR. 859 00:35:10,120 --> 00:35:12,080 AFTER OBTAINING A BIOPSY THIS 860 00:35:12,080 --> 00:35:17,200 LESION WAS REMOVED AND IT WAS 861 00:35:17,200 --> 00:35:19,200 INDEED AN ATYPICAL NEUROFIBROMA 862 00:35:19,200 --> 00:35:22,560 NEOPLASM OF UNCERTAIN POTENTIAL, 863 00:35:22,560 --> 00:35:23,640 REMOVED TWO LESIONS IN THE 864 00:35:23,640 --> 00:35:25,280 PATIENT OVER THE YEAR, AND I 865 00:35:25,280 --> 00:35:27,840 HOPE THAT MY CONCLUSION THAT WE 866 00:35:27,840 --> 00:35:29,920 MAY HAVE PREVENTED AN MPNST IN 867 00:35:29,920 --> 00:35:31,040 THIS PATIENT IS CORRECT. 868 00:35:31,040 --> 00:35:32,800 I WOULD LIKE TO SHOW THIS IS 869 00:35:32,800 --> 00:35:35,240 TRICKY THOUGH. 870 00:35:35,240 --> 00:35:37,320 THIS IS A 33-YEAR-OLD FEMALE, 871 00:35:37,320 --> 00:35:39,520 ALSO WITH FAMILIAL NF1, WHO WE 872 00:35:39,520 --> 00:35:41,040 FOLLOWED FOR MANY YEARS, AT THE 873 00:35:41,040 --> 00:35:49,120 NIH, WHO ALSO HAS A HISTORY OF 874 00:35:49,120 --> 00:35:52,200 PRIOR MPNST, YOU CAN SEE CLEARLY 875 00:35:52,200 --> 00:35:53,680 INCREASING PERIPHERAL TUMOR NEXT 876 00:35:53,680 --> 00:35:55,520 TO THE LEFT SCAPULAR. 877 00:35:55,520 --> 00:36:02,480 LOWER PANEL YOU CAN SEE INCREASE 878 00:36:02,480 --> 00:36:04,480 IN SUV MAX TO 15.9, PRESENT AT 879 00:36:04,480 --> 00:36:07,200 THE MOST RECENT EVALUATION, THAT 880 00:36:07,200 --> 00:36:14,120 IS DEFINITELY CONCERNING FOR AN 881 00:36:14,120 --> 00:36:15,080 MPNST, WAS THE COEFFICIENT LESS 882 00:36:15,080 --> 00:36:16,520 THAN 1. 883 00:36:16,520 --> 00:36:21,760 WE OBTAINED A BIOPSY OF THE 884 00:36:21,760 --> 00:36:23,640 LESION, ATYPICAL, PROCEEDED WITH 885 00:36:23,640 --> 00:36:25,800 SURGERY WITH MARGINAL RESECTION. 886 00:36:25,800 --> 00:36:29,720 HOWEVER, THIS TUMOR ACTUALLY WAS 887 00:36:29,720 --> 00:36:31,160 HIGH GRADE MPNST. 888 00:36:31,160 --> 00:36:32,440 WE'RE FORTUNATE WE CAN 889 00:36:32,440 --> 00:36:34,880 COLLABORATE WITH JACK'S LAB AND 890 00:36:34,880 --> 00:36:38,000 WITH JOANNE WITH HIGHLY TALENTED 891 00:36:38,000 --> 00:36:41,480 POSTDOC IN HIS GROUP, SO THEY 892 00:36:41,480 --> 00:36:43,480 PERFORMED SINGLE CELL SEQUENCING 893 00:36:43,480 --> 00:36:46,320 ON OUR NF1 TUMORS, AND SHOWN 894 00:36:46,320 --> 00:36:49,680 HERE IS THE DIAGNOSTIC BIOPSY 895 00:36:49,680 --> 00:36:54,480 WHICH FOR US WAS AN ANNUBP, AND 896 00:36:54,480 --> 00:36:57,040 A FEW WEEKS AGO MPNTS. 897 00:36:57,040 --> 00:36:58,920 USING SINGLE CELL ANALYSIS YOU 898 00:36:58,920 --> 00:37:00,000 CAN SEE HERE ALL THE CELL TYPES 899 00:37:00,000 --> 00:37:03,440 THEY SAW IN BOTH OF THESE 900 00:37:03,440 --> 00:37:05,320 TUMORS, MALIGNANT TUMORS, CELLS, 901 00:37:05,320 --> 00:37:08,600 VARIETY OF OTHER CELLS. 902 00:37:08,600 --> 00:37:13,080 BY USING SOMETHING THAT'S CALLED 903 00:37:13,080 --> 00:37:15,000 INFERCNV LOOKED AT THE CELLS 904 00:37:15,000 --> 00:37:16,200 LIKELY MALIGNANT CELLS TO 905 00:37:16,200 --> 00:37:18,160 IDENTIFY WHAT EXACTLY THE 906 00:37:18,160 --> 00:37:21,080 MALIGNANT CELLS ARE, AND 907 00:37:21,080 --> 00:37:25,960 IDENTIFIED EVERY ROLE OF CELL, 908 00:37:25,960 --> 00:37:28,080 CHROMOSOMES ON TOP. 909 00:37:28,080 --> 00:37:30,800 CHANGE IN 17, PRESENT IN THE 910 00:37:30,800 --> 00:37:31,840 MALIGNANT CELLS IN PARTICULAR 911 00:37:31,840 --> 00:37:34,480 PATIENT, THERE WERE MANY, MANY 912 00:37:34,480 --> 00:37:35,400 MALIGNANT CELLS. 913 00:37:35,400 --> 00:37:37,480 WHAT WAS REALLY INTERESTING WAS 914 00:37:37,480 --> 00:37:39,480 WHEN THEY SEPARATED AND LOOKED 915 00:37:39,480 --> 00:37:43,280 AT THE INITIAL SAMPLE UNDER THE 916 00:37:43,280 --> 00:37:45,280 MICROSCOPE THAT LOOKED LIKE AN 917 00:37:45,280 --> 00:37:47,480 ANODE, AND THE RESECTION WERE 918 00:37:47,480 --> 00:37:48,560 VERY SIMILAR. 919 00:37:48,560 --> 00:37:50,160 AND I BELIEVE THIS IS 920 00:37:50,160 --> 00:37:51,440 POTENTIALLY SOMETHING THAT CAN 921 00:37:51,440 --> 00:37:53,680 TEACH US FOR FUTURE PATIENTS 922 00:37:53,680 --> 00:37:56,160 BECAUSE CLEARLY KNOWING THAT 923 00:37:56,160 --> 00:37:58,760 THIS WAS AN MPNST PRIOR TO 924 00:37:58,760 --> 00:38:00,680 RESECTION WOULD HAVE IMPACTED ON 925 00:38:00,680 --> 00:38:04,920 THE SURGICAL MANAGEMENT OF THIS 926 00:38:04,920 --> 00:38:06,240 PATIENT. 927 00:38:06,240 --> 00:38:09,000 JOANNE AND JACK AND TEAM ARE 928 00:38:09,000 --> 00:38:13,440 ESTABLISHING A SINGLE CELL 929 00:38:13,440 --> 00:38:17,000 ATLAS, 55 SPECIMENS, 25 930 00:38:17,000 --> 00:38:18,160 PLEXIFORMS, I THINK THIS WILL BE 931 00:38:18,160 --> 00:38:20,600 VERY IMPORTANT FOR US TO 932 00:38:20,600 --> 00:38:22,800 UNDERSTAND MORE ABOUT THE CLONAL 933 00:38:22,800 --> 00:38:26,040 EVOLUTION OF TUMORS, AND 934 00:38:26,040 --> 00:38:29,120 HOPEFULLY ALSO IDENTIFY 935 00:38:29,120 --> 00:38:30,960 POTENTIAL OPPORTUNITIES FOR 936 00:38:30,960 --> 00:38:31,520 TREATMENT. 937 00:38:31,520 --> 00:38:32,720 THIS SHOWS THE DISCOVERY THEN 938 00:38:32,720 --> 00:38:35,200 SUBSEQUENTLY BY LOOKING AT THE 939 00:38:35,200 --> 00:38:37,480 DIFFERENT TUMORS, WHAT CELL 940 00:38:37,480 --> 00:38:41,800 TYPES THEY ARE, 34 CLUSTERS, 7 941 00:38:41,800 --> 00:38:43,640 MAJOR CELL TYPES, HAVE BEEN ABLE 942 00:38:43,640 --> 00:38:44,960 TO SEPARATE THESE DIFFERENT 943 00:38:44,960 --> 00:38:48,840 CLUSTERS SO THAT WE CAN SEPARATE 944 00:38:48,840 --> 00:38:55,080 OUT THE PLEXIFORMS, ATYPICALS, 945 00:38:55,080 --> 00:38:59,880 CHANGES WITH EXPANSION OF THE 946 00:38:59,880 --> 00:39:01,160 MALIGNANT CELLS AND MPNST, 947 00:39:01,160 --> 00:39:02,320 CHANGES IN IMMUNE COMPARTMENT 948 00:39:02,320 --> 00:39:04,000 MAY HELP US IN THE DEVELOPMENT 949 00:39:04,000 --> 00:39:08,760 OF MORE TARGETED TREATMENT 950 00:39:08,760 --> 00:39:09,840 APPROACHES. 951 00:39:09,840 --> 00:39:15,200 WE HAVE DEVELOPED A IN A NATURAL 952 00:39:15,200 --> 00:39:17,160 HISTORY STUDY, TARGETING HIGH 953 00:39:17,160 --> 00:39:18,080 RISK MALIGNANT TRANSFORMATION, 954 00:39:18,080 --> 00:39:21,440 THEY WILLING UNDERGO 955 00:39:21,440 --> 00:39:24,400 STANDARDIZEDs MEDICAL AND 956 00:39:24,400 --> 00:39:26,040 CLINICAL EVALUATION, IMAGING, 957 00:39:26,040 --> 00:39:29,640 SERIAL BLOOD SAMPLES, MANAGEMENT 958 00:39:29,640 --> 00:39:30,600 USING AN ALGORITHM, 959 00:39:30,600 --> 00:39:32,560 PROSPECTIVELY AND IN A 960 00:39:32,560 --> 00:39:34,000 STANDARDIZED FASHION. 961 00:39:34,000 --> 00:39:35,720 DEPENDING ON WHETHER THERE'S 962 00:39:35,720 --> 00:39:38,720 CONCERN FOR MPNST FOR AN 963 00:39:38,720 --> 00:39:40,240 ATYPICAL NEUROFIBROMA, NO 964 00:39:40,240 --> 00:39:41,760 CERTAIN MANAGEMENT WILL DIFFER, 965 00:39:41,760 --> 00:39:47,040 I HOPE THIS STUDY WILL GET US TO 966 00:39:47,040 --> 00:39:48,000 SOLVE THE BETTER DIAGNOSIS AND 967 00:39:48,000 --> 00:39:49,000 TREATMENT FOR PATIENTS WITH 968 00:39:49,000 --> 00:39:50,520 THESE TUMORS. 969 00:39:50,520 --> 00:39:52,640 GOING BACK TO THE BORING NATURAL 970 00:39:52,640 --> 00:39:54,640 HISTORY STUDY I ALSO LOOKED WHAT 971 00:39:54,640 --> 00:39:56,040 HAVE WE ACCOMPLISHED OVER THE 972 00:39:56,040 --> 00:40:02,520 YEARS, AND SHOWN HERE ARE 973 00:40:02,520 --> 00:40:03,760 MANUSCRIPTS THAT MADE 974 00:40:03,760 --> 00:40:05,160 SUBSTANTIAL ADVANCES IN BASIC 975 00:40:05,160 --> 00:40:06,320 SCIENCE. 976 00:40:06,320 --> 00:40:08,240 WE NOW DO HAVE AN ASSAY FOR CELL 977 00:40:08,240 --> 00:40:11,320 FREE DNA WHICH WILL HELP US WITH 978 00:40:11,320 --> 00:40:19,480 PATIENTS ON THIS STUDY. 979 00:40:19,480 --> 00:40:23,560 WE'VE CHARACTERIZED GROWTH OF 980 00:40:23,560 --> 00:40:23,920 TUMORS. 981 00:40:23,920 --> 00:40:28,640 RESECTION IS A STRATEGY TO 982 00:40:28,640 --> 00:40:29,840 PREVENT MPNST, WE'VE LEARNED 983 00:40:29,840 --> 00:40:30,880 ABOUT SOCIAL AND EMOTIONAL 984 00:40:30,880 --> 00:40:34,720 FUNCTION, PAIN AND PAIN 985 00:40:34,720 --> 00:40:37,080 INTERFERENCE, AND WE'VE RECEIVED 986 00:40:37,080 --> 00:40:39,520 REGULATORY APPROVAL AT THE SAME 987 00:40:39,520 --> 00:40:42,760 TIME AS WE PUBLISHED THE PAPER 988 00:40:42,760 --> 00:40:47,480 ABOUT THIS STUDY. 989 00:40:47,480 --> 00:40:49,120 IN ADDITION, THE NATURAL HISTORY 990 00:40:49,120 --> 00:40:50,520 STUDY SERVES AS THE MOM FOR 991 00:40:50,520 --> 00:40:51,920 SOMETHING ALONG THOSE LINES FOR 992 00:40:51,920 --> 00:40:56,440 THE NEW EFFORT DIRECTED BY DCEG, 993 00:40:56,440 --> 00:40:56,960 NCCR INVESTIGATORS WITH 994 00:40:56,960 --> 00:41:03,200 ENGAGEMENT OF THE RAS INITIATIVE 995 00:41:03,200 --> 00:41:05,000 AND ADVOCACY GROUPS, ADVANCING 996 00:41:05,000 --> 00:41:06,400 RASOPATHY THERAPIES, A WONDERFUL 997 00:41:06,400 --> 00:41:11,440 EFFORT FROM THE GET-GO INCLUDES 998 00:41:11,440 --> 00:41:16,200 PRE-CLINICAL WORK, DEVELOPMENT 999 00:41:16,200 --> 00:41:18,880 OF RASOPATHY CLINIC, AND A 1000 00:41:18,880 --> 00:41:22,640 PUBLIC HEALTH GENOMICS APPROACH 1001 00:41:22,640 --> 00:41:25,560 DIRECTED BY DOUG STEWART. 1002 00:41:25,560 --> 00:41:28,360 THERE WILL BE MORE COMING. 1003 00:41:28,360 --> 00:41:30,280 THE IN THE HISTORY STUDIES 1004 00:41:30,280 --> 00:41:31,040 INFORM THE RARE RESEARCH TUMORS 1005 00:41:31,040 --> 00:41:33,040 I TALK ABOUT NOW. 1006 00:41:33,040 --> 00:41:34,560 WE MENTIONED THAT EVERY 1007 00:41:34,560 --> 00:41:35,720 PEDIATRIC CANCER IS RARE. 1008 00:41:35,720 --> 00:41:37,520 THE FOCUS OF THE REMAINDER OF 1009 00:41:37,520 --> 00:41:41,800 THE TALK ABOUT BE ON VERY RARE 1010 00:41:41,800 --> 00:41:43,880 PEDIATRIC CANCERS, LESS THAN 2 1011 00:41:43,880 --> 00:41:45,640 MILLION CASES PER YEAR, 1012 00:41:45,640 --> 00:41:48,840 APPROXIMATELY 11% OF ALL 1013 00:41:48,840 --> 00:41:49,320 PEDIATRIC CANCERS. 1014 00:41:49,320 --> 00:41:53,000 TREMENDOUS CHALLENGES COME FROM 1015 00:41:53,000 --> 00:41:54,160 THIS INCLUDING ESTABLISHING 1016 00:41:54,160 --> 00:41:54,640 DIAGNOSIS, INCOMPLETE 1017 00:41:54,640 --> 00:41:56,840 UNDERSTANDING OF THE NATURAL 1018 00:41:56,840 --> 00:41:58,400 HISTORY STUDY, NO STANDARD CARE, 1019 00:41:58,400 --> 00:42:00,400 NO CLINICAL TRIALS FOR MANY OF 1020 00:42:00,400 --> 00:42:02,960 THESE TUMORS, LACK OF 1021 00:42:02,960 --> 00:42:05,040 PRE-CLINICAL MODELS, AND 1022 00:42:05,040 --> 00:42:06,480 DIFFICULTY CONDUCTING 1023 00:42:06,480 --> 00:42:09,320 PRE-CLINICAL STUDIES. 1024 00:42:09,320 --> 00:42:10,560 CHRISTINA VIVELO FROM MYPART 1025 00:42:10,560 --> 00:42:13,600 TEAM LOOKED AT RARE TUMOR 1026 00:42:13,600 --> 00:42:14,240 RESEARCH PUBLICATIONS, IT'S 1027 00:42:14,240 --> 00:42:16,600 CLEAR A HUGE INTEREST HAS 1028 00:42:16,600 --> 00:42:20,280 INCREASED OVER THE LAST YEARS, 1029 00:42:20,280 --> 00:42:23,120 THAT ALSO MANY PROGRAMS, PUBLIC 1030 00:42:23,120 --> 00:42:24,440 AND PRIVATE, AND ADVOCACY THAT 1031 00:42:24,440 --> 00:42:26,080 STUDY RARE TUMORS WHICH LEADS ME 1032 00:42:26,080 --> 00:42:27,520 TO BELIEVE THERE ALREADY 1033 00:42:27,520 --> 00:42:28,720 TREMENDOUS PROGRESS. 1034 00:42:28,720 --> 00:42:29,560 HOWEVER, THE PROGRAMS DON'T 1035 00:42:29,560 --> 00:42:32,520 REALLY TALK TO EACH OTHER THAT 1036 00:42:32,520 --> 00:42:32,920 MUCH. 1037 00:42:32,920 --> 00:42:34,760 BEFORE I TALK ABOUT MY PART, I 1038 00:42:34,760 --> 00:42:37,880 WANT TO BRIEFLY MENTION THE FDA 1039 00:42:37,880 --> 00:42:39,520 REALLY IS A PARTNER FOR RARE 1040 00:42:39,520 --> 00:42:40,760 TUMOR RESEARCH, THEY UNDERSTAND 1041 00:42:40,760 --> 00:42:43,520 HOW DIFFICULT IT IS TO DO THIS. 1042 00:42:43,520 --> 00:42:44,880 AND HAVE IMPLEMENTED A FEW 1043 00:42:44,880 --> 00:42:47,400 STRATEGIES TO HELP US. 1044 00:42:47,400 --> 00:42:51,720 ONE IS FDA RECOMMENDS INCLUSION 1045 00:42:51,720 --> 00:42:52,880 OF CHILDREN IN ADULT EARLY 1046 00:42:52,880 --> 00:42:56,200 CLINICAL TRIALS, IF IT IS TARGET 1047 00:42:56,200 --> 00:42:56,840 APPROPRIATE. 1048 00:42:56,840 --> 00:43:00,800 THE FDA ALSO HAS THE RACE ACT 1049 00:43:00,800 --> 00:43:06,120 WHICH REQUIRES TO CONDUCT 1050 00:43:06,120 --> 00:43:07,480 CLINICAL TRIALS IN MOLECULAR 1051 00:43:07,480 --> 00:43:09,240 AGENTS ARE RELEVANT TO PEDIATRIC 1052 00:43:09,240 --> 00:43:11,840 CANCERS AND FINALLY THE FDA HAS 1053 00:43:11,840 --> 00:43:13,040 DEVELOPED DRAFT GUIDANCE FOR THE 1054 00:43:13,040 --> 00:43:16,880 DEVELOPMENT OF NATURAL HISTORY 1055 00:43:16,880 --> 00:43:17,880 STUDIES, NATURAL HISTORY STUDIES 1056 00:43:17,880 --> 00:43:20,840 CAN SERVE AS CONTROL GROUP FOR 1057 00:43:20,840 --> 00:43:23,560 THE POTENTIAL DRUG APPROVAL 1058 00:43:23,560 --> 00:43:24,520 WITHOUT HAVING TO CONDUCT 1059 00:43:24,520 --> 00:43:26,080 RANDOMIZED CLINICAL TRIAL. 1060 00:43:26,080 --> 00:43:27,120 AND BASED ON THIS, THERE HAVE 1061 00:43:27,120 --> 00:43:31,040 BEEN A NUMBER OF FDA APPROVALS 1062 00:43:31,040 --> 00:43:32,360 FOR VERY RARE TUMORS, AND THIS 1063 00:43:32,360 --> 00:43:35,600 IS REALLY WONDERFUL FOR ME TO 1064 00:43:35,600 --> 00:43:39,160 SEE THE BEST EXAMPLE IS AN 1065 00:43:39,160 --> 00:43:45,560 INHIBITOR APPROVED FOR VERY 1066 00:43:45,560 --> 00:43:47,440 YOUNG PEDIATRIC AND ADULT 1067 00:43:47,440 --> 00:43:48,840 PATIENTS PROVIDING THERE ARE 1068 00:43:48,840 --> 00:43:51,840 Trk FUSIONS. 1069 00:43:51,840 --> 00:43:54,160 I'M FOCUS ON THE CANCER MOONSHOT 1070 00:43:54,160 --> 00:43:56,640 SUPPORTED PROGRAM, ESTABLISHED 1071 00:43:56,640 --> 00:43:58,360 AND CO-DEVELOPED INITIALLY BY 1072 00:43:58,360 --> 00:43:59,600 COLLEEN RILEY AS BASIC SCIENTIST 1073 00:43:59,600 --> 00:44:01,880 AND MYSELF, BUT IT IS A HUGE 1074 00:44:01,880 --> 00:44:04,360 TEAM WORKING ON THIS, FOCUSING 1075 00:44:04,360 --> 00:44:06,560 ON CHILDREN AND ADOLESCENTS AND 1076 00:44:06,560 --> 00:44:07,600 YOUNG ADULTS. 1077 00:44:07,600 --> 00:44:10,520 NCI DEFINITION IS LESS OR EQUAL 1078 00:44:10,520 --> 00:44:12,440 30 YEARS OLD WITH TUMORS THAT 1079 00:44:12,440 --> 00:44:17,200 ARE DIFFICULT TO TREAT AND VERY 1080 00:44:17,200 --> 00:44:17,400 RARE. 1081 00:44:17,400 --> 00:44:21,040 AND WE -- I GIVE YOU THE -- WE 1082 00:44:21,040 --> 00:44:23,040 ARE DOING STUDY, PART OF MY PART 1083 00:44:23,040 --> 00:44:26,600 IS TO DEVELOP NATURAL HISTORY 1084 00:44:26,600 --> 00:44:32,200 STUDY CO-LED BY MARY FRANCES AND 1085 00:44:32,200 --> 00:44:35,480 HEIDI, ADULT ONCOLOGIST, MARY 1086 00:44:35,480 --> 00:44:38,240 FRANCES IS PEDIATRIC ONCOLOGIST. 1087 00:44:38,240 --> 00:44:40,480 THIS INCLUDES STANDARDIZED 1088 00:44:40,480 --> 00:44:41,960 LONGITUDINAL RETROSPECTIVE AND 1089 00:44:41,960 --> 00:44:42,480 PROSPECTIVE EVALUATIONS 1090 00:44:42,480 --> 00:44:45,720 INCLUDING MEDICAL AND FAMILY 1091 00:44:45,720 --> 00:44:50,480 HISTORY, PATIENT-REPORTED 1092 00:44:50,480 --> 00:44:53,400 OUTCOMES, CLINICAL EVALUATION, 1093 00:44:53,400 --> 00:44:54,720 EXTENSIVE DATA EXTRACTION, 1094 00:44:54,720 --> 00:44:56,680 PATIENTS WITH RARE SOLID TUMORS 1095 00:44:56,680 --> 00:44:58,720 OR BIOLOGICAL RELATIVES ARE 1096 00:44:58,720 --> 00:44:59,480 ELIGIBLE. 1097 00:44:59,480 --> 00:45:02,960 WE PROVIDE TREATMENT 1098 00:45:02,960 --> 00:45:05,440 RECOMMENDATIONS IN COLLABORATION 1099 00:45:05,440 --> 00:45:07,600 WITH PATHOLOGY AT NCI, CONDUCT 1100 00:45:07,600 --> 00:45:08,680 PROFILING, HAVE GENETIC 1101 00:45:08,680 --> 00:45:12,360 COUNSELING, AND WE ARE 1102 00:45:12,360 --> 00:45:13,960 DEVELOPING ANNOTATED BIOSPECIMEN 1103 00:45:13,960 --> 00:45:14,240 REPOSITORY. 1104 00:45:14,240 --> 00:45:15,400 SHOWN HERE IS WHAT HAPPENINGS 1105 00:45:15,400 --> 00:45:17,920 WITH THE SAMPLES WE GET, FOR THE 1106 00:45:17,920 --> 00:45:21,120 MOST PART ARE PARAFFIN EMBEDDED 1107 00:45:21,120 --> 00:45:26,160 SLIDES, IN COLLABORATION WITH 1108 00:45:26,160 --> 00:45:33,280 LAB OF PATHOLOGY WE PERFORM TSO 1109 00:45:33,280 --> 00:45:36,480 500 PANEL SEQUENCING, CLINICALLY 1110 00:45:36,480 --> 00:45:38,520 APPROVED FOR EXOME SEQUENCING 1111 00:45:38,520 --> 00:45:40,040 AND RNA SEQUENCING, AND THEN WE 1112 00:45:40,040 --> 00:45:42,760 DO A NUMBER OF ANALYSES FOR 1113 00:45:42,760 --> 00:45:45,920 RESEARCH SUCH AS METHYLATION 1114 00:45:45,920 --> 00:45:48,240 ARRAYS, AND WHOLE GENOME 1115 00:45:48,240 --> 00:45:49,080 SEQUENCING. 1116 00:45:49,080 --> 00:45:51,360 IN ADDITION WE DO BLOOD 1117 00:45:51,360 --> 00:45:52,560 BIOMARKERS, POTENTIAL BIOMARKERS 1118 00:45:52,560 --> 00:45:54,080 IN THESE PATIENTS. 1119 00:45:54,080 --> 00:45:56,000 IN COLLABORATION WITH MULTIPLE 1120 00:45:56,000 --> 00:46:00,720 INVESTIGATORS IN THE CCR WE'RE 1121 00:46:00,720 --> 00:46:03,000 CONDUCTING IMMUNE CELLS AND HAVE 1122 00:46:03,000 --> 00:46:04,480 ESTABLISHED A LYMPHOCYTE PANEL 1123 00:46:04,480 --> 00:46:07,080 AND MYELOID PANEL AND SAMPLES 1124 00:46:07,080 --> 00:46:10,720 NOW, A NUMBER OF PATIENTS, WAY 1125 00:46:10,720 --> 00:46:13,560 MORE THAN 100 PATIENTS, WOULD 1126 00:46:13,560 --> 00:46:14,640 SUPPORT BY THE NCI CANCER DATA 1127 00:46:14,640 --> 00:46:19,200 KNISH INITIATIVE, EXPANDING THE 1128 00:46:19,200 --> 00:46:21,480 EFFORT TO INCLUDE MANY OTHER 1129 00:46:21,480 --> 00:46:24,000 TUMORS TO ESTABLISH IN 1130 00:46:24,000 --> 00:46:26,040 COLLABORATION WITH MULTIPLE 1131 00:46:26,040 --> 00:46:28,280 BRANCHES IN THE CCR, AND 1132 00:46:28,280 --> 00:46:29,920 PEDIATRIC SINGLE CELL TUMOR 1133 00:46:29,920 --> 00:46:30,800 ATLAS. 1134 00:46:30,800 --> 00:46:33,720 AND I'M SHOWING YOU NOW WHERE WE 1135 00:46:33,720 --> 00:46:35,920 ARE WITH ENROLLMENT ON THE 1136 00:46:35,920 --> 00:46:38,120 BIPART STUDY, STARTING IN 2019 1137 00:46:38,120 --> 00:46:40,640 WE HAVE ENROLLED 451 1138 00:46:40,640 --> 00:46:41,680 PARTICIPANTS, WE HAVE A 1139 00:46:41,680 --> 00:46:42,480 WONDERFUL SUPPORTIVE TEAM. 1140 00:46:42,480 --> 00:46:46,320 YOU SEE SOME OF THE FACES ON THE 1141 00:46:46,320 --> 00:46:48,520 RIGHT UPPER CORNER. 1142 00:46:48,520 --> 00:46:50,960 BOTH PEDIATRIC AND ADULT 1143 00:46:50,960 --> 00:46:51,960 PATIENTS, FROM SIX CONTINENTS, 1144 00:46:51,960 --> 00:46:55,160 AND 46 STATES IN THE UNITED 1145 00:46:55,160 --> 00:46:55,360 STATES. 1146 00:46:55,360 --> 00:46:57,720 HERE YOU SEE THE TYPES OF TUMORS 1147 00:46:57,720 --> 00:47:00,080 THAT WE HAVE ENROLLED. 1148 00:47:00,080 --> 00:47:08,640 YOU CAN CLEARLY SEE 1149 00:47:08,640 --> 00:47:16,080 NEUROENDOCRINE TUMORS, 1150 00:47:16,080 --> 00:47:17,720 INTESTINAL STROMAL TUMORS, 1151 00:47:17,720 --> 00:47:18,920 ADRENOCORTICOID CARCINOMA, AND 1152 00:47:18,920 --> 00:47:20,360 NUMBERS WHERE WE CAN REALLY 1153 00:47:20,360 --> 00:47:21,480 LEARN FROM. 1154 00:47:21,480 --> 00:47:23,440 WE HAVE MANY ADDITIONAL TUMORS 1155 00:47:23,440 --> 00:47:24,800 WHERE WE HAVE SMALLER NUMBERS, 1156 00:47:24,800 --> 00:47:26,160 AND THAT'S SOMETHING I WILL 1157 00:47:26,160 --> 00:47:28,680 ADDRESS LATER, WHERE WE NEED 1158 00:47:28,680 --> 00:47:31,240 MORE NUMBERS TO IMPROVE OUR 1159 00:47:31,240 --> 00:47:34,000 LEARNING FOR THESE SPECIFIC 1160 00:47:34,000 --> 00:47:34,720 TUMORS. 1161 00:47:34,720 --> 00:47:36,280 COLLEEN RILEY IS CURRENTLY 1162 00:47:36,280 --> 00:47:37,640 ANALYZING THE SAMPLES WE HAVE 1163 00:47:37,640 --> 00:47:38,720 RECEIVED FROM THE TUMORS. 1164 00:47:38,720 --> 00:47:43,000 AND AS I SAID, THIS IS FOR THE 1165 00:47:43,000 --> 00:47:44,240 MOST PART PARAFFIN-EMBEDDED 1166 00:47:44,240 --> 00:47:46,600 TISSUE, OUT OF I THINK 160-SOME 1167 00:47:46,600 --> 00:47:48,280 PATIENTS WHERE WE GOT TISSUE 1168 00:47:48,280 --> 00:47:51,000 FROM THE FIRST 200 PATIENTS 1169 00:47:51,000 --> 00:47:53,360 ONLY, WE SUCCEEDED WITH TSO OR 1170 00:47:53,360 --> 00:47:55,240 LAB OF PATHOLOGY SUCCEEDED WITH 1171 00:47:55,240 --> 00:47:56,840 TSO IN 125 OF THEM. 1172 00:47:56,840 --> 00:47:58,760 WE CAN SEE HERE IT'S NOT ONLY 1173 00:47:58,760 --> 00:48:01,280 AGE OF THE SAMPLE BUT OTHER 1174 00:48:01,280 --> 00:48:03,920 FACTORS THAT IMPACT ON WHETHER 1175 00:48:03,920 --> 00:48:05,600 WE ARE SUCCESSFUL TO GET PANEL 1176 00:48:05,600 --> 00:48:09,280 SEQUENCING DONE. 1177 00:48:09,280 --> 00:48:11,640 HERE WE SEE IN WORK DONE, 1178 00:48:11,640 --> 00:48:15,360 RESULTS OF PANEL SEQUENCING FOR 1179 00:48:15,360 --> 00:48:18,880 PATIENTS WITH ACC, 26 PATIENTS, 1180 00:48:18,880 --> 00:48:21,120 WE HAVE THE SAME VARIANT IN MORE 1181 00:48:21,120 --> 00:48:21,600 THAN THREE PATIENTS. 1182 00:48:21,600 --> 00:48:26,880 FOR EXAMPLE YOU CAN SEE FOR ACC, 1183 00:48:26,880 --> 00:48:30,840 TP A 53 WAS MOST FREQUENTLY 1184 00:48:30,840 --> 00:48:31,040 SEEN. 1185 00:48:31,040 --> 00:48:32,280 WHERE WE HAD 23 PATIENTS WITH 1186 00:48:32,280 --> 00:48:37,480 MORE THAN THERE, GIVEN WE SEE 1187 00:48:37,480 --> 00:48:39,400 SDH DEFICIENCY, AND FOR PATIENTS 1188 00:48:39,400 --> 00:48:40,720 WITH MEDULLARY THYROID CARCINOMA 1189 00:48:40,720 --> 00:48:44,480 FOR THE PATIENTS THAT WE SEE IT 1190 00:48:44,480 --> 00:48:46,720 IS RET WE MOST FREQUENTLY SEE 1191 00:48:46,720 --> 00:48:48,520 AND FOR CORDOMA, THE LEAST, 1192 00:48:48,520 --> 00:48:53,160 PATIENTS WITH POORLY 1193 00:48:53,160 --> 00:48:54,640 DIFFERENTIAL THE CORDOMA, YOU 1194 00:48:54,640 --> 00:48:56,320 CAN ALSO SEE ACTIONABILITY AND 1195 00:48:56,320 --> 00:48:59,320 WHETHER THESE ARE PATHOGENIC OR 1196 00:48:59,320 --> 00:49:00,520 LIKELY PATHOGENIC VARIANTS WE 1197 00:49:00,520 --> 00:49:01,720 SEE, FOR EXAMPLE IF YOU LOOK AT 1198 00:49:01,720 --> 00:49:04,480 THE PLOT ON THE RIGHT, LOWER 1199 00:49:04,480 --> 00:49:06,960 HAND, TO BE EXPECTED MEDULLARY 1200 00:49:06,960 --> 00:49:09,080 THYROID CARCINOMA, AT THE MOST 1201 00:49:09,080 --> 00:49:11,800 ACTIONABLE MUTATIONS WITH RET 1202 00:49:11,800 --> 00:49:14,200 WHERE WE HAVE EFFECTIVE MEDICAL 1203 00:49:14,200 --> 00:49:15,600 THERAPY, EXPANDING THIS TO 1204 00:49:15,600 --> 00:49:17,840 ANALYZE ALL OF THE DATA, 1205 00:49:17,840 --> 00:49:19,440 HOPEFULLY WILL RESULT IN A 1206 00:49:19,440 --> 00:49:21,720 PUBLICATION SOON. 1207 00:49:21,720 --> 00:49:23,600 WE'RE COLLECTING MANY, MANY 1208 00:49:23,600 --> 00:49:25,280 DATA, CLINICAL DATA, IMAGING 1209 00:49:25,280 --> 00:49:27,880 DATA, PATHOLOGY DATA, AND I'VE 1210 00:49:27,880 --> 00:49:31,960 BEEN VERY FORTUNATE TO WORK WITH 1211 00:49:31,960 --> 00:49:33,880 NIDA, NIH INTEGRATED DATA 1212 00:49:33,880 --> 00:49:34,920 ANALYSIS PLATFORM, TO REALLY 1213 00:49:34,920 --> 00:49:38,480 MAKE SENSE OF THE DATA, THIS HAS 1214 00:49:38,480 --> 00:49:39,840 BEEN WONDERFUL OPPORTUNITY FOR 1215 00:49:39,840 --> 00:49:42,760 US TO BRING DATA FROM MULTIPLE 1216 00:49:42,760 --> 00:49:43,560 SOURCES TOGETHER. 1217 00:49:43,560 --> 00:49:45,760 HOW DO WE GET THE RESULTS TO OUR 1218 00:49:45,760 --> 00:49:47,600 PATIENTS THAT ARE THE MOST 1219 00:49:47,600 --> 00:49:50,000 IMPORTANT PATIENTS GET RESULTS 1220 00:49:50,000 --> 00:49:52,720 INCLUDING THE TSO 500 PANEL 1221 00:49:52,720 --> 00:49:55,240 SEQUENCING, FROM THE NIH 1222 00:49:55,240 --> 00:49:56,240 CLINICAL CENTER PORTAL, 1223 00:49:56,240 --> 00:49:57,320 COMMUNICATE TREATMENT WITH 1224 00:49:57,320 --> 00:49:59,560 RECOMMENDATIONS WITH THE 1225 00:49:59,560 --> 00:50:01,280 PATIENTS DIRECTLY, AND HAVE 1226 00:50:01,280 --> 00:50:04,680 WEEKLY DISCUSSIONS WITH OUR 1227 00:50:04,680 --> 00:50:06,680 GENETIC COUNSELOR, LAB OF 1228 00:50:06,680 --> 00:50:07,360 PATHOLOGY, CLINICIANS, REVIEW 1229 00:50:07,360 --> 00:50:09,320 PATHOLOGY OF THE PATIENTS AND 1230 00:50:09,320 --> 00:50:11,360 THEN MAKE OUR RECOMMENDATIONS. 1231 00:50:11,360 --> 00:50:15,760 WE HAVE NEWSLETTER, SOCIAL 1232 00:50:15,760 --> 00:50:17,680 MEDIA, AND PUBLICATIONS TO SHARE 1233 00:50:17,680 --> 00:50:22,000 DATA AND SUMMARIES OF 1234 00:50:22,000 --> 00:50:22,320 PUBLICATIONS. 1235 00:50:22,320 --> 00:50:25,560 COMMUNICATION IS A HUGE EFFORT, 1236 00:50:25,560 --> 00:50:26,840 DIRECTED BY CHRISTINA, AS YOU 1237 00:50:26,840 --> 00:50:29,440 CAN SEE HERE WE HAVE MADE 1238 00:50:29,440 --> 00:50:30,760 SUBSTANTIAL EFFORT OF SPREADING 1239 00:50:30,760 --> 00:50:34,880 THE NEWS ABOUT MY PART, MANY 1240 00:50:34,880 --> 00:50:39,480 SUBSCRIBERS VISIT FOR 1241 00:50:39,480 --> 00:50:42,400 INFORMATION MOSTLY ABOUT RARE 1242 00:50:42,400 --> 00:50:42,640 TUMORS. 1243 00:50:42,640 --> 00:50:44,920 ADVOCACY IS CRITICAL TO WORKING 1244 00:50:44,920 --> 00:50:50,400 IN RARE TUMORS, AND ABBY 1245 00:50:50,400 --> 00:50:53,560 SANDLER DIRECTS THIS EFFORT, 1246 00:50:53,560 --> 00:50:54,320 FOUNDATIONS STUDY RARE TUMORS, 1247 00:50:54,320 --> 00:50:56,960 AND I WOULD LIKE TO HIGHLIGHT 1248 00:50:56,960 --> 00:51:06,520 EFFORT IN PEDIATRIC CORDOMA, 1249 00:51:06,520 --> 00:51:10,400 SPEARHEADED BY MARY FRANCES. 1250 00:51:10,400 --> 00:51:18,840 CHORDOMA IS A RARE SARCOMA, 1251 00:51:18,840 --> 00:51:20,920 ORIGINATES IN THREE LOCATIONS, 1252 00:51:20,920 --> 00:51:22,040 APPROXIMATELY 325 CASES NEW IN 1253 00:51:22,040 --> 00:51:25,120 THE UNITED STATES PER YEAR BUT 1254 00:51:25,120 --> 00:51:28,600 APPROXIMATELY ONLY 30 OR SO 1255 00:51:28,600 --> 00:51:30,400 PEDIATRIC CHORDOMAS. 1256 00:51:30,400 --> 00:51:33,760 THESE TUMORS ARE TYPICALLY 1257 00:51:33,760 --> 00:51:44,280 POSITIVE FOR BRAKEORI, TYPICALLY 1258 00:51:58,680 --> 00:51:59,840 SMARCB1 DEFICIENT. 1259 00:51:59,840 --> 00:52:04,560 ON THE RIGHT LOWER PANEL, A PET 1260 00:52:04,560 --> 00:52:10,520 SCAN WITH SUBSTANTIAL UPTICK AT 1261 00:52:10,520 --> 00:52:16,720 BASELINE, SUBSTANTIAL 1262 00:52:16,720 --> 00:52:17,880 IMPROVEMENT AFTER FOUR CYCLES. 1263 00:52:17,880 --> 00:52:20,720 CHORDOMA GAVE US THE BACKGROUND 1264 00:52:20,720 --> 00:52:23,480 WE HAVE, BASIC SCIENCE 1265 00:52:23,480 --> 00:52:25,960 CHAMPIONS, AND WE ESTABLISHED A 1266 00:52:25,960 --> 00:52:27,120 PARTNERSHIP WITH CHORDOMA 1267 00:52:27,120 --> 00:52:28,960 FOUNDATION, DEVELOPED OUR 1268 00:52:28,960 --> 00:52:32,000 NATURAL HISTORY STUDY, HAD THE 1269 00:52:32,000 --> 00:52:33,240 FIRST PEDIATRIC CHORDOMA CLINIC, 1270 00:52:33,240 --> 00:52:37,480 WHERE WE BRING EXPERTS FROM THE 1271 00:52:37,480 --> 00:52:38,640 OUTSIDE TO THE NIH CLINICAL 1272 00:52:38,640 --> 00:52:40,240 CENTER WITH PATIENTS, AND THE 1273 00:52:40,240 --> 00:52:43,840 PATIENTS ARE SEEN AND GET 1274 00:52:43,840 --> 00:52:44,440 INDIVIDUALIZED RECOMMENDATIONS, 1275 00:52:44,440 --> 00:52:46,760 REALLY TREMENDOUS EXPERIENCE FOR 1276 00:52:46,760 --> 00:52:49,200 THE PATIENTS, SUBSEQUENTLY WE 1277 00:52:49,200 --> 00:52:50,400 HAVE ENGAGED IN PARTICIPATING IN 1278 00:52:50,400 --> 00:52:53,040 THE BOSTON TUMOR BOARD FOR THESE 1279 00:52:53,040 --> 00:52:55,480 PATIENTS, IT'S HAPPENING ON AN 1280 00:52:55,480 --> 00:52:57,120 EVERY-OTHER-WEEK BASIS. 1281 00:52:57,120 --> 00:52:59,480 AND WE ARE PROUD TO SAY THAT WE 1282 00:52:59,480 --> 00:53:02,200 ALSO HAVE ENROLLED MANY, MANY 1283 00:53:02,200 --> 00:53:05,000 PEDIATRIC PATIENTS SUBSEQUENTLY 1284 00:53:05,000 --> 00:53:09,640 ON OUR PEDIATRIC ARM OF THE 1285 00:53:09,640 --> 00:53:13,200 MYPART STUDY, MARY FRANCES AND 1286 00:53:13,200 --> 00:53:15,680 LINY JOHN ARE LEADING, MEDIAN 1287 00:53:15,680 --> 00:53:18,080 AGE IS 34 YEARS, THIS IS YOUNGER 1288 00:53:18,080 --> 00:53:20,680 THAN THE MEDIAN AGE OF CHORDOMA 1289 00:53:20,680 --> 00:53:22,720 ALL OVER, AND IN THE UNITED 1290 00:53:22,720 --> 00:53:25,320 STATES, AND WE HAVE ENROLLED 1291 00:53:25,320 --> 00:53:33,560 SOME PATIENTS WITH POORLY 1292 00:53:33,560 --> 00:53:35,280 DIFFERENTIATED SMARCB1, SOME ARE 1293 00:53:35,280 --> 00:53:37,200 INTERNATIONAL PATIENTS AND THEY 1294 00:53:37,200 --> 00:53:39,800 CAN PARTICIPATE REMOTELY IN 1295 00:53:39,800 --> 00:53:42,320 CLINICS, WE JUST HAD OUR VIRTUAL 1296 00:53:42,320 --> 00:53:44,800 CHORDOMA CLINIC FOR FIVE 1297 00:53:44,800 --> 00:53:46,960 PATIENTS, FOR ANOTHER FIVE THAT 1298 00:53:46,960 --> 00:53:49,240 ATTENDED IN PERSON, 12 EXTERNAL 1299 00:53:49,240 --> 00:53:50,280 CLINICIANS THAT ALL 1300 00:53:50,280 --> 00:53:51,320 PARTICIPATED, VIRTUALLY, BUT 1301 00:53:51,320 --> 00:53:53,560 IT'S BEEN A TREMENDOUS 1302 00:53:53,560 --> 00:53:55,160 EXPERIENCE TO SEE HOW PATIENTS 1303 00:53:55,160 --> 00:53:57,360 CAN GET THEIR KEY QUESTIONS 1304 00:53:57,360 --> 00:53:59,560 ADDRESSED BY EXPERTS THAT DON'T 1305 00:53:59,560 --> 00:54:01,560 EXIST IN JUST ONE CENTER. 1306 00:54:01,560 --> 00:54:03,320 THEY REALLY COME FROM ACROSS THE 1307 00:54:03,320 --> 00:54:03,640 COUNTRY. 1308 00:54:03,640 --> 00:54:07,000 IF YOU CAN BRING THOSE TOGETHER 1309 00:54:07,000 --> 00:54:09,560 PATIENTS REALLY CAN BENEFIT 1310 00:54:09,560 --> 00:54:14,880 SUBSTANTIALLY FROM THIS. 1311 00:54:14,880 --> 00:54:20,480 IN COLLABORATION, WE ARE ALSO 1312 00:54:20,480 --> 00:54:21,240 ESTABLISHING MODELS OF MANY 1313 00:54:21,240 --> 00:54:24,640 TUMORS AS LONG AS PATIENTS HAVE 1314 00:54:24,640 --> 00:54:29,080 SURGERY AND ONE EXAMPLE IS SHOWN 1315 00:54:29,080 --> 00:54:30,760 HERE OF CHORDOMA PDX, THE LAB IS 1316 00:54:30,760 --> 00:54:32,080 WORKING WITH US IN THE LAB TO 1317 00:54:32,080 --> 00:54:34,680 SEE HOW WE CAN UNDERSTAND 1318 00:54:34,680 --> 00:54:36,200 CHORDOMA BETTER AND POTENTIALLY 1319 00:54:36,200 --> 00:54:37,880 DEVELOP TREATMENTS. 1320 00:54:37,880 --> 00:54:39,520 I MENTIONED THAT CHORDOMA, 1321 00:54:39,520 --> 00:54:42,040 PEDIATRIC CHORDOMA, CAN BE 1322 00:54:42,040 --> 00:54:46,640 RESPONSIVE TO IMMUNOTHERAPY, AND 1323 00:54:46,640 --> 00:54:48,800 MARY FRANCES AND OTHERS ARE 1324 00:54:48,800 --> 00:54:59,280 CONDUCTING PHASE 2 TRIAL OF PD-1 1325 00:54:59,280 --> 00:55:02,880 INHIBITOR FOR SMARCB1 TUMORS, 1326 00:55:02,880 --> 00:55:06,840 MULTI-SITE NIH OF 1327 00:55:06,840 --> 00:55:08,320 NCI-COORDINATED CLINICAL TRIALS 1328 00:55:08,320 --> 00:55:09,920 FOR SMARCB1 TUMORS. 1329 00:55:09,920 --> 00:55:12,840 RARE COHORTS FROM FULLY 1330 00:55:12,840 --> 00:55:14,960 DIFFERENTIATED CHORDOMA, 1331 00:55:14,960 --> 00:55:23,000 MEDULLARY CARCINOMA, MALIGNANT 1332 00:55:23,000 --> 00:55:24,480 TUMOR, ATYPICALLY TERATOID 1333 00:55:24,480 --> 00:55:28,000 TUMORS AND OTHERS TO SEE IF OUR 1334 00:55:28,000 --> 00:55:29,440 OUTREACH TO THE CHORDOMA 1335 00:55:29,440 --> 00:55:31,880 FOUNDATION AND PARTNERSHIPS WILL 1336 00:55:31,880 --> 00:55:35,760 HELP GET ENROLLMENT ON THE TRIAL 1337 00:55:35,760 --> 00:55:37,200 IN EFFICIENT MANNER. 1338 00:55:37,200 --> 00:55:38,800 I WOULD ALSO HIGHLIGHT WORK THAT 1339 00:55:38,800 --> 00:55:44,160 IS ENTIRELY NOT MY WORK BUT OF 1340 00:55:44,160 --> 00:55:45,760 OUR COLLABORATORS, AND 1341 00:55:45,760 --> 00:55:48,800 SUBSTANTIAL EFFORT IN CHORDOMA 1342 00:55:48,800 --> 00:55:59,320 WITH DEVELOPMENT OF VACCINES, 1343 00:55:59,920 --> 00:56:02,360 BRACHYURY VACCINES, ONE PATIENT 1344 00:56:02,360 --> 00:56:06,120 ON THE RIGHT, THE PHOTOGRAPHY 1345 00:56:06,120 --> 00:56:10,000 AND IMAGERY AND VOLUMETRIC 1346 00:56:10,000 --> 00:56:14,760 ANALYSIS, SHOWED DRAMATIC 1347 00:56:14,760 --> 00:56:22,520 RESPONSE TO BRACHYURY VACCINE, 1348 00:56:22,520 --> 00:56:29,840 DEVELOPED CYTOKINE RELEASE 1349 00:56:29,840 --> 00:56:33,320 SYNDROME, WE'RE GRATEFUL FOR 1350 00:56:33,320 --> 00:56:34,440 COLLABORATION WITH THOSE WHO 1351 00:56:34,440 --> 00:56:35,200 HELPED US UNDERSTAND THESE 1352 00:56:35,200 --> 00:56:38,800 TUMORS AND WOULD LIKE TO GIVE A 1353 00:56:38,800 --> 00:56:41,760 SHOUT OUT TO A NEW PROGRAM IN 1354 00:56:41,760 --> 00:56:43,320 THE CENTER FOR IMMUNO-ONCOLOGY, 1355 00:56:43,320 --> 00:56:46,520 THIS REALLY WILL PROVIDE A BASIS 1356 00:56:46,520 --> 00:56:48,720 FOR VERY COMPREHENSIVE PROGRAM 1357 00:56:48,720 --> 00:56:51,560 IN PEDIATRIC AND ADULT PATIENTS 1358 00:56:51,560 --> 00:56:52,480 WITH CHORDOMA. 1359 00:56:52,480 --> 00:56:54,480 THE LAST TWO SLIDES I THINK, 1360 00:56:54,480 --> 00:56:56,120 THREE SLIDES, I HAVE HIGHLIGHTED 1361 00:56:56,120 --> 00:56:58,040 THIS EFFORT, AGAIN GOING BACK TO 1362 00:56:58,040 --> 00:57:00,680 THE NEED TO DEVELOP TRIALS FOR 1363 00:57:00,680 --> 00:57:02,200 PEDIATRIC AND ADULT PATIENTS, 1364 00:57:02,200 --> 00:57:04,960 WHEN THERE IS THE SCIENTIFIC 1365 00:57:04,960 --> 00:57:07,320 RATIONALE, VERY GRATEFUL FOR THE 1366 00:57:07,320 --> 00:57:08,880 DEVELOPMENT OF THERAPEUTICS 1367 00:57:08,880 --> 00:57:13,160 CLINIC WITH ALICE CHEN, 1368 00:57:13,160 --> 00:57:16,480 GERALDINE AND JIM DOROSHOW, WE 1369 00:57:16,480 --> 00:57:18,280 WILL TREAT YOUNGER PATIENTS ON 1370 00:57:18,280 --> 00:57:20,280 ADULT CLINICAL TRIALS AND ADULT 1371 00:57:20,280 --> 00:57:22,240 TEAM WILL TREAT OLDER PATIENTS 1372 00:57:22,240 --> 00:57:24,200 ON STUDIES THAT ORIGINATE FROM 1373 00:57:24,200 --> 00:57:25,240 THE PEDIATRIC ONCOLOGY BRANCH. 1374 00:57:25,240 --> 00:57:26,800 I WANT TO GIVE ONE EXAMPLE. 1375 00:57:26,800 --> 00:57:32,840 THIS IS THE LAST EXAMPLE I'LL 1376 00:57:32,840 --> 00:57:38,160 GIVE FOR TODAY, A PD-L1 1377 00:57:38,160 --> 00:57:40,200 INHIBITOR, ADULT CLINICAL TRIAL 1378 00:57:40,200 --> 00:57:46,200 RUN BY ALICE CHEN AND GERALDINE 1379 00:57:46,200 --> 00:57:51,120 O'SULLIVAN, IT'S A RARE SARCOMA 1380 00:57:51,120 --> 00:57:56,520 CHARACTERIZED BY A GENE, A TUMOR 1381 00:57:56,520 --> 00:57:57,320 GROWS SLOWLY, UNRELENTLESSLY, 1382 00:57:57,320 --> 00:57:57,920 UNRESPONSIVE TO CHEMOTHERAPY. 1383 00:57:57,920 --> 00:58:01,040 IN THE CLINICAL TRIAL THAT WAS 1384 00:58:01,040 --> 00:58:04,040 CONDUCTED, AN OBJECTIVE RESPONSE 1385 00:58:04,040 --> 00:58:07,680 RATE OF 37%, IN PATIENTS WITH 1386 00:58:07,680 --> 00:58:08,320 ALVEOLAR SOFT PART SARCOMA, 1387 00:58:08,320 --> 00:58:09,600 PEDIATRIC BRANCH IS THE ONLY 1388 00:58:09,600 --> 00:58:12,240 SITE WHERE WE CAN ENROLL 1389 00:58:12,240 --> 00:58:14,040 PATIENTS TWO YEARS TO TWELVE 1390 00:58:14,040 --> 00:58:16,640 YEARS OF AGE, OTHER SITES CAN 1391 00:58:16,640 --> 00:58:18,840 ENROLL ADOLESCENTS AND YOUNG 1392 00:58:18,840 --> 00:58:19,720 ADULTS. 1393 00:58:19,720 --> 00:58:21,880 BASED ON THE RESPONSE THE FDA 1394 00:58:21,880 --> 00:58:23,000 GRANTED BREAKTHROUGH THERAPY 1395 00:58:23,000 --> 00:58:24,000 DESIGNATION, I'M SHOWING EXAMPLE 1396 00:58:24,000 --> 00:58:29,720 OF ONE OF THE PEDIATRIC PATIENTS 1397 00:58:29,720 --> 00:58:32,800 ENROLLED, VERY SUBSTANTIAL 1398 00:58:32,800 --> 00:58:33,960 PULMONARY METASTASIS AT 1399 00:58:33,960 --> 00:58:35,480 ENROLLMENT, PATIENTS ON CYCLE 1400 00:58:35,480 --> 00:58:37,120 NUMBER 60, NEAR RESOLUTION OF 1401 00:58:37,120 --> 00:58:40,000 THE DISEASE AND COLLABORATOR ON 1402 00:58:40,000 --> 00:58:42,800 THIS STUDY IS JOHN GLOD, OUR 1403 00:58:42,800 --> 00:58:44,320 CLINICAL DIRECTOR IN THE POB. 1404 00:58:44,320 --> 00:58:46,400 I HOPE I HAVE SHOWN YOU WHAT 1405 00:58:46,400 --> 00:58:49,400 WE'VE LEARNED FROM THE MYPART 1406 00:58:49,400 --> 00:58:51,240 EXPERIENCE, THAT ADVOCACY IS 1407 00:58:51,240 --> 00:58:54,200 CRITICAL AS WELL AS BASIC AND 1408 00:58:54,200 --> 00:58:56,520 CLINICAL TUMOR EXPERTISE. 1409 00:58:56,520 --> 00:58:58,560 WE NEED CHAMPIONS FOR THESE 1410 00:58:58,560 --> 00:58:58,920 DISEASES. 1411 00:58:58,920 --> 00:59:00,120 RARE TUMOR CLINICS PROVIDE 1412 00:59:00,120 --> 00:59:02,920 UNIQUE INSIGHT WE COULD NOT GET 1413 00:59:02,920 --> 00:59:05,160 FROM SEEING INDIVIDUAL PATIENTS 1414 00:59:05,160 --> 00:59:08,360 AT MULTIPLE DIFFERENT SITES. 1415 00:59:08,360 --> 00:59:11,840 BUILDING COHORTS IS RESOURCE AND 1416 00:59:11,840 --> 00:59:13,040 TIME INTENSIVE, AS DR. ROBERTS 1417 00:59:13,040 --> 00:59:14,120 SAID, IT TAKES A LONG TIME. 1418 00:59:14,120 --> 00:59:15,760 I THINK WE HAVE TO FOCUS ON 1419 00:59:15,760 --> 00:59:19,280 SELECT TUMOR TYPES TO MAKE THE 1420 00:59:19,280 --> 00:59:20,480 MOST PROGRESS. 1421 00:59:20,480 --> 00:59:22,480 IN ORDER TO MAKE PROGRESS IN 1422 00:59:22,480 --> 00:59:24,920 MULTIPLE RARE TUMORS AT THE SAME 1423 00:59:24,920 --> 00:59:28,560 TIME I BELIEVE WE NEED TO HAVE 1424 00:59:28,560 --> 00:59:30,160 EFFECTIVE PARTNERSHIPS WITH 1425 00:59:30,160 --> 00:59:32,520 MULTIPLE OTHER PARTICIPATING 1426 00:59:32,520 --> 00:59:37,520 SITES AND THE NCI CANCER DATA 1427 00:59:37,520 --> 00:59:38,400 INITIATIVE, ESTABLISHED IN 2019, 1428 00:59:38,400 --> 00:59:40,920 SUBSTANTIAL FUNDING FOR TEN 1429 00:59:40,920 --> 00:59:42,920 YEARS TO DEVELOP DATA ECOSYSTEM 1430 00:59:42,920 --> 00:59:46,600 AND TO LEARN OPT MIAMI FROM 1431 00:59:46,600 --> 00:59:48,160 EVERY CHILD WITH CANCER AND 1432 00:59:48,160 --> 00:59:51,920 BRINGING DATE -- DATA FROM 1433 00:59:51,920 --> 01:00:01,440 MULTIPLES SOURCES PROVIDE THE 1434 01:00:01,440 --> 01:00:02,840 OPPORTUNITY TO COME TRUE. 1435 01:00:02,840 --> 01:00:07,400 THIS BUILDS UPON ONE EFFORT IN 1436 01:00:07,400 --> 01:00:09,360 THE CCDI, MOLECULAR 1437 01:00:09,360 --> 01:00:11,040 CHARACTERIZATION INITIATIVE, 1438 01:00:11,040 --> 01:00:15,640 WHICH IS CO-CHAIRED BY JACK AND 1439 01:00:15,640 --> 01:00:20,800 KATIE AND MALCOLM. 1440 01:00:20,800 --> 01:00:23,400 CHILDREN IN PROJECT EVERY CHILD 1441 01:00:23,400 --> 01:00:25,480 ARE ABLE TO RECEIVE 1442 01:00:25,480 --> 01:00:26,040 STATE-OF-THE-ART MOLECULAR 1443 01:00:26,040 --> 01:00:29,080 DIAGNOSIS AT THE TIME OF 1444 01:00:29,080 --> 01:00:30,240 DIAGNOSIS. 1445 01:00:30,240 --> 01:00:32,040 RESULTS OF THE SEQUENCING ARE 1446 01:00:32,040 --> 01:00:33,640 RETURNED WITHIN 21 DAYS. 1447 01:00:33,640 --> 01:00:39,680 THIS IS CURRENTLY OPEN FOR NEWLY 1448 01:00:39,680 --> 01:00:41,560 DIAGNOSED CNS AND RARE TUMORS, A 1449 01:00:41,560 --> 01:00:47,240 NEED FOR RELAPSE TUMORS 1450 01:00:47,240 --> 01:00:48,920 UNDERSTANDING TO GET ENHANCED 1451 01:00:48,920 --> 01:00:50,600 CLINICAL ANNOTATION BUT IF WE 1452 01:00:50,600 --> 01:00:53,360 CAN BUILD ON THIS AND EXTEND TO 1453 01:00:53,360 --> 01:00:54,440 TRUE NATIONAL EFFORT FOR RARE 1454 01:00:54,440 --> 01:00:56,800 TUMORS I THINK WE CAN MAKE 1455 01:00:56,800 --> 01:00:58,840 PROGRESS MUCH MORE QUICKLY, I DO 1456 01:00:58,840 --> 01:01:00,640 WANT TO HIGHLIGHT THERE WILL BE 1457 01:01:00,640 --> 01:01:02,880 VIRTUAL WORKSHOP ON THIS TOPIC 1458 01:01:02,880 --> 01:01:06,240 ON NOVEMBER 18, BY THE CCDI, AND 1459 01:01:06,240 --> 01:01:08,600 I HOPE YOU CAN PARTICIPATE. 1460 01:01:08,600 --> 01:01:09,880 WE LOOK FORWARD TO COLLABORATING 1461 01:01:09,880 --> 01:01:14,200 WITH AS MANY BASIC AND CLINICAL 1462 01:01:14,200 --> 01:01:15,360 RESEARCHERS AS POSSIBLE. 1463 01:01:15,360 --> 01:01:17,960 I WOULD LIKE TO THANK THE WSA 1464 01:01:17,960 --> 01:01:21,320 AGAIN FOR THIS TREMENDOUS HONOR. 1465 01:01:21,320 --> 01:01:31,800 I THANK OUR PATIENTS FAMILIES, 1466 01:01:33,320 --> 01:01:35,520 ADVOCATES, CCR, DCEG, AND I 1467 01:01:35,520 --> 01:01:37,040 PRESENTED WORK OF MANY AND IF I 1468 01:01:37,040 --> 01:01:38,640 FAILED TO ACKNOWLEDGE PLEASE 1469 01:01:38,640 --> 01:01:40,080 FORGIVE ME. 1470 01:01:40,080 --> 01:01:40,560 FINALLY OBVIOUSLY MOST 1471 01:01:40,560 --> 01:01:42,800 IMPORTANT, I WANT TO THANK ALL 1472 01:01:42,800 --> 01:01:44,640 THE PATIENTS THAT CONTRIBUTED TO 1473 01:01:44,640 --> 01:01:45,120 THIS EFFORT. 1474 01:01:45,120 --> 01:01:50,400 THANK YOU SO MUCH. 1475 01:01:50,400 --> 01:01:52,840 >>THANK YOU, DR. WIDEMANN, FOR 1476 01:01:52,840 --> 01:01:55,520 THE COMPREHENSIVE TALK. 1477 01:01:55,520 --> 01:01:57,000 IT TAKES -- PEOPLE SAY IT TAKES 1478 01:01:57,000 --> 01:02:02,520 A VILLAGE TO RAISE A CHILD. 1479 01:02:02,520 --> 01:02:04,440 IT TAKES COMMUNITIES TOO, TO 1480 01:02:04,440 --> 01:02:05,760 SOLVE THIS CANCER ISSUE, RARE 1481 01:02:05,760 --> 01:02:06,640 TUMOR ISSUE. 1482 01:02:06,640 --> 01:02:08,760 SO THERE'S A COUPLE QUESTIONS IN 1483 01:02:08,760 --> 01:02:09,280 THE CHAT. 1484 01:02:09,280 --> 01:02:13,000 AND ONE OF THEM CAME FROM MARY, 1485 01:02:13,000 --> 01:02:15,840 WHO ASKED THAT MUTATIONS THAT 1486 01:02:15,840 --> 01:02:17,920 CAUSE RARE TUMORS TYPICALLY 1487 01:02:17,920 --> 01:02:21,320 INHERITED OR ARE THEY 1488 01:02:21,320 --> 01:02:21,600 STOCHASTIC? 1489 01:02:21,600 --> 01:02:25,360 >>YEAH, SO ALL IN ALL, FOR 1490 01:02:25,360 --> 01:02:28,280 PEDIATRIC CANCERS, WE HAVE NOW 1491 01:02:28,280 --> 01:02:33,800 DATA THAT INDICATES ABOUT 12% 1492 01:02:33,800 --> 01:02:34,280 HAVE GENETIC GERMLINE 1493 01:02:34,280 --> 01:02:35,120 PREDISPOSITION, SOMETHING WE DID 1494 01:02:35,120 --> 01:02:39,200 NOT KNOW PRIOR TO THE SEQUENCING 1495 01:02:39,200 --> 01:02:39,800 EFFORTS. 1496 01:02:39,800 --> 01:02:41,440 BUT IT'S ACTUALLY A SUBSTANTIAL 1497 01:02:41,440 --> 01:02:43,640 NUMBER, AND I BELIEVE THIS WOULD 1498 01:02:43,640 --> 01:02:45,040 BE AN EXCELLENT COHORT, FOR 1499 01:02:45,040 --> 01:02:50,040 EXAMPLE, IF WE CAN IDENTIFY THE 1500 01:02:50,040 --> 01:02:51,280 COHORT, THROUGH MOLECULAR 1501 01:02:51,280 --> 01:02:52,320 CHARACTERIZATION INITIATIVE TO 1502 01:02:52,320 --> 01:02:53,520 FOLLOW PROSPECTIVELY AS ONE OF 1503 01:02:53,520 --> 01:02:56,120 THE COHORTS BECAUSE THESE 1504 01:02:56,120 --> 01:03:00,720 PATIENTS ARE AT INCREASED RISK 1505 01:03:00,720 --> 01:03:02,160 TO DEVELOP TUMORS, SOME OF WHICH 1506 01:03:02,160 --> 01:03:05,120 ARE VERY RARE. 1507 01:03:05,120 --> 01:03:05,480 >>OKAY. 1508 01:03:05,480 --> 01:03:11,840 SO, ANOTHER QUESTION IS VERY 1509 01:03:11,840 --> 01:03:13,240 IMPRESSIVE WORK, HOW WAS 1510 01:03:13,240 --> 01:03:14,760 SELUMETINIB SELECTED FOR THE 1511 01:03:14,760 --> 01:03:18,560 STUDIES AND SIDE EFFECTS IN 1512 01:03:18,560 --> 01:03:19,280 CHILDREN. 1513 01:03:19,280 --> 01:03:22,400 >>YEAH, A GREAT QUESTION. 1514 01:03:22,400 --> 01:03:23,120 SELECTION WAS VERY PRAGMATICAL, 1515 01:03:23,120 --> 01:03:26,320 WHAT I COULD GET ACCESS TO. 1516 01:03:26,320 --> 01:03:27,640 AS THE AUDIENCE LIKELY KNOW, 1517 01:03:27,640 --> 01:03:30,520 THERE ARE MANY MEK INHIBITORS 1518 01:03:30,520 --> 01:03:33,560 THAT WERE ALL DEVELOPED AT THE 1519 01:03:33,560 --> 01:03:33,840 SAME TIME. 1520 01:03:33,840 --> 01:03:35,480 IT WAS IMPOSSIBLE WHEN I WAS 1521 01:03:35,480 --> 01:03:37,560 TRYING TO CONDUCT THE STUDY TO 1522 01:03:37,560 --> 01:03:39,360 GET ANY DRUG COMPANY TO SAY YES, 1523 01:03:39,360 --> 01:03:42,200 YOU CAN DO THIS STUDY. 1524 01:03:42,200 --> 01:03:43,200 EVERYBODY SAID I'M TOO 1525 01:03:43,200 --> 01:03:44,800 CONCERNED, THIS IS A YOUNG 1526 01:03:44,800 --> 01:03:47,560 PATIENT POPULATION, THEY DON'T 1527 01:03:47,560 --> 01:03:49,800 HAVE CANCER, SO THESE WERE THE 1528 01:03:49,800 --> 01:03:51,640 LIMITATIONS FROM THE COMPANIES. 1529 01:03:51,640 --> 01:03:54,360 I HAVE TO REALLY THANK NCIC 1530 01:03:54,360 --> 01:03:56,480 BECAUSE THEY SAID, WE'LL LET YOU 1531 01:03:56,480 --> 01:04:03,120 DO THIS STUDY, AND SO I GOT THE 1532 01:04:03,120 --> 01:04:05,760 DRUG FROM CTEP AFTER TRYING AND 1533 01:04:05,760 --> 01:04:08,560 CTEP HAD SELUMETINIB AS THE 1534 01:04:08,560 --> 01:04:08,920 AGENT. 1535 01:04:08,920 --> 01:04:10,560 IN HINDSIGHT I WAS HAPPY, IT HAS 1536 01:04:10,560 --> 01:04:12,240 A VERY SHORT HALF-LIFE SO WHEN A 1537 01:04:12,240 --> 01:04:13,960 PATIENT DEVELOPS A SIDE EFFECT 1538 01:04:13,960 --> 01:04:15,080 IT REVERSES MORE QUICKLY THAN 1539 01:04:15,080 --> 01:04:19,560 SOME OF THE OTHER MEK 1540 01:04:19,560 --> 01:04:19,840 INHIBITORS. 1541 01:04:19,840 --> 01:04:22,040 >>SEEMS LIKE IT'S REALLY 1542 01:04:22,040 --> 01:04:23,280 WORKING WELL, EVEN THOUGH NOT 1543 01:04:23,280 --> 01:04:23,560 COMPLETE. 1544 01:04:23,560 --> 01:04:25,160 >>THAT IS CORRECT. 1545 01:04:25,160 --> 01:04:26,160 >>YEAH, YEAH, AMAZING. 1546 01:04:26,160 --> 01:04:29,640 SO I HAVE A COUPLE OF GENERAL 1547 01:04:29,640 --> 01:04:30,480 QUESTIONS. 1548 01:04:30,480 --> 01:04:34,120 ONE IS, IT SEEMS LIKE -- IS 1549 01:04:34,120 --> 01:04:36,840 THERE ANY SPATIAL PREFERENCE FOR 1550 01:04:36,840 --> 01:04:39,120 THE TUMOR ARISING FOR THE 1551 01:04:39,120 --> 01:04:40,960 NEUROBLASTOMA, IS THERE 1552 01:04:40,960 --> 01:04:42,280 LOCATIONAL PREFERENCE? 1553 01:04:42,280 --> 01:04:42,520 >>YES. 1554 01:04:42,520 --> 01:04:47,800 >>IT SEEMED LIKE A LOT OF HEAD 1555 01:04:47,800 --> 01:04:50,880 AND NECK REGION. 1556 01:04:50,880 --> 01:04:52,880 >>SO, NEUROFIBROMAS OR 1557 01:04:52,880 --> 01:04:53,840 NEUROBLASTOMAS. 1558 01:04:53,840 --> 01:04:54,120 >>NF1. 1559 01:04:54,120 --> 01:04:57,720 >>YEAH, SO THAT'S A GREAT 1560 01:04:57,720 --> 01:05:00,080 QUESTION. 1561 01:05:00,080 --> 01:05:04,560 I WOULD SAY THEY ARISE ANYWHERE, 1562 01:05:04,560 --> 01:05:05,000 PERIPHERAL NERVE. 1563 01:05:05,000 --> 01:05:07,240 I THINK TRUNK IS ONE OF THE MOST 1564 01:05:07,240 --> 01:05:08,960 FREQUENT LOCATIONS THAT WE HAVE. 1565 01:05:08,960 --> 01:05:09,960 >>OKAY. 1566 01:05:09,960 --> 01:05:12,400 >>MANY OF THE PATIENTS HAVE 1567 01:05:12,400 --> 01:05:13,160 MULTIPLE BODY PARTS INVOLVED, 1568 01:05:13,160 --> 01:05:14,640 THIS IS SOMETHING WE'VE LEARNED 1569 01:05:14,640 --> 01:05:17,840 FROM WHOLE BODY MRI THAT WE USE. 1570 01:05:17,840 --> 01:05:20,680 AND THAT I NEED TO ACTUALLY LOOK 1571 01:05:20,680 --> 01:05:23,480 BACK AND GIVE YOU THE 1572 01:05:23,480 --> 01:05:23,800 PROPORTIONS. 1573 01:05:23,800 --> 01:05:26,160 WE HAVE SEEN THEM EVERYWHERE, 1574 01:05:26,160 --> 01:05:29,320 THERE'S DEFINITELY NOTHING THAT 1575 01:05:29,320 --> 01:05:30,520 IS STRIKING COMMON, CERVICAL 1576 01:05:30,520 --> 01:05:34,120 AREA AND PELVIC AREA IS MORE 1577 01:05:34,120 --> 01:05:35,200 FREQUENT THAN THORACIC, ONE 1578 01:05:35,200 --> 01:05:36,320 THING I CAN SAY. 1579 01:05:36,320 --> 01:05:38,320 >>IT SEEMED LIKE LOOKING AT THE 1580 01:05:38,320 --> 01:05:39,160 IMAGES. 1581 01:05:39,160 --> 01:05:39,440 >>YEAH. 1582 01:05:39,440 --> 01:05:43,640 >>SEEMED LIKE A LOT OF THEM 1583 01:05:43,640 --> 01:05:45,640 WERE HIGHER UP. 1584 01:05:45,640 --> 01:05:47,080 THIS OTHER QUESTION I HAVE IS 1585 01:05:47,080 --> 01:05:51,560 KIND OF -- SO FROM YOUR SINGLE 1586 01:05:51,560 --> 01:05:54,600 CELL DATA, IT SEEMED LIKE IF I'M 1587 01:05:54,600 --> 01:05:57,440 CORRECT THAT THERE'S A LOT OF 1588 01:05:57,440 --> 01:06:07,760 SIMILARITY IN THE PROFILE 1589 01:06:07,760 --> 01:06:10,520 BETWEEN STAGES. 1590 01:06:10,520 --> 01:06:12,800 >>I THINK MOST SIMILARITY IS -- 1591 01:06:12,800 --> 01:06:17,280 JACK CAN SPEAK BEST TO THIS, 1592 01:06:17,280 --> 01:06:20,360 BETWEEN PLEXIFORMS AND ATYPICAL 1593 01:06:20,360 --> 01:06:21,560 NEUROFIBROMAS THEY ARE VERY 1594 01:06:21,560 --> 01:06:23,840 SIMILAR, THIS IS SOMETHING THEY 1595 01:06:23,840 --> 01:06:25,800 ARE TEASING APART. 1596 01:06:25,800 --> 01:06:29,000 THE PLEXYFORMS THAT ARE BENIGN, 1597 01:06:29,000 --> 01:06:32,080 ATYPICALS THAT ARE ATYPICAL 1598 01:06:32,080 --> 01:06:33,880 UNDER THE MICROSCOPE AND THEN 1599 01:06:33,880 --> 01:06:37,240 ATYPICAL TUMORS THAT WE'RE MOST 1600 01:06:37,240 --> 01:06:37,960 CONCERNED ABOUT MALIGNANT 1601 01:06:37,960 --> 01:06:41,680 TRANSFORMATION TRYING TO 1602 01:06:41,680 --> 01:06:43,720 UNDERSTAND DIFFERENCES BUT THE 1603 01:06:43,720 --> 01:06:44,600 MPNSTs ARE DISTINCT. 1604 01:06:44,600 --> 01:06:46,120 >>I SEE. 1605 01:06:46,120 --> 01:06:51,600 SO THE T IS LIKE TRYING TO FIND 1606 01:06:51,600 --> 01:06:54,400 THE MOLECULAR LINK THAT MAKES IT 1607 01:06:54,400 --> 01:06:56,640 JUMP TO BE THE MALIGNANT -- 1608 01:06:56,640 --> 01:06:59,800 >>YES, AND THE ONE LINK WE HAVE 1609 01:06:59,800 --> 01:07:08,080 IS THIS CDKN TO A LOSS, NOT 1610 01:07:08,080 --> 01:07:10,840 PRESENT IN PLEXFORMS, ALSO 1611 01:07:10,840 --> 01:07:11,840 PRESENT IN MPNST. 1612 01:07:11,840 --> 01:07:15,880 >>A QUESTION FROM MARY AGAIN. 1613 01:07:15,880 --> 01:07:18,480 HOW COMBINATION THERAPIES HAVE 1614 01:07:18,480 --> 01:07:21,320 BEEN USED THAT TARGET DIFFERENT 1615 01:07:21,320 --> 01:07:26,240 GENE BROADS, IF SO DOES 1616 01:07:26,240 --> 01:07:27,720 COMBINATION THERAPY REDUCE OR DO 1617 01:07:27,720 --> 01:07:28,080 YOU NOT SEE -- 1618 01:07:28,080 --> 01:07:30,200 >>THANK YOU FOR THE QUESTION. 1619 01:07:30,200 --> 01:07:32,440 WE'RE EXPLORING AND WILL SOON 1620 01:07:32,440 --> 01:07:36,040 OPEN WITH THE NF CLINICAL TRIALS 1621 01:07:36,040 --> 01:07:37,320 CONSORTIUM, FIRST TRIAL 1622 01:07:37,320 --> 01:07:41,320 COMBINING TWO THERAPIES FOR 1623 01:07:41,320 --> 01:07:42,840 BENIGN PLEXIFORM NEUROFIBROMAS, 1624 01:07:42,840 --> 01:07:48,440 WILL BE A COMBINATION OF KINASE 1625 01:07:48,440 --> 01:07:50,680 INHIBITOR, CABOZANTANIB AND 1626 01:07:50,680 --> 01:07:52,720 SELUMETINIB, FOR MPNST 100% I 1627 01:07:52,720 --> 01:07:54,560 THINK WE'LL NEED COMBINATORIAL 1628 01:07:54,560 --> 01:07:55,560 TREATMENT TO EVEN GET TO THE 1629 01:07:55,560 --> 01:07:57,960 POINT WHERE WE SEE WE CAN SHRINK 1630 01:07:57,960 --> 01:07:59,800 THE TUMORS AND BENEFIT PATIENTS 1631 01:07:59,800 --> 01:08:04,560 WHICH WE'VE NOT BEEN ABLE TO DO 1632 01:08:04,560 --> 01:08:05,360 DATE. 1633 01:08:05,360 --> 01:08:07,840 >>A QUESTION FROM THE AUDIENCE, 1634 01:08:07,840 --> 01:08:10,080 THANK YOU FOR COMPREHENSIVE 1635 01:08:10,080 --> 01:08:12,440 REPORT OF ALL THE TREMENDOUS 1636 01:08:12,440 --> 01:08:15,040 EFFORTS WITHIN THE POB FOR 1637 01:08:15,040 --> 01:08:16,280 PEDIATRIC RARE TUMORS. 1638 01:08:16,280 --> 01:08:17,880 HATS OFF TO YOU. 1639 01:08:17,880 --> 01:08:20,720 I'M SURE YOU GET ANY NUMBER OF 1640 01:08:20,720 --> 01:08:22,720 REQUESTS TO COLLABORATE WITH 1641 01:08:22,720 --> 01:08:25,960 INDUSTRY TO FILL UNMET NEEDS YOU 1642 01:08:25,960 --> 01:08:26,440 MENTIONED. 1643 01:08:26,440 --> 01:08:28,400 BUT IT WOULD HELP TO KNOW HOW WE 1644 01:08:28,400 --> 01:08:32,320 COULD GET INVOLVED BY CONNECTING 1645 01:08:32,320 --> 01:08:34,880 EFFECTIVELY WITH INTERESTING 1646 01:08:34,880 --> 01:08:35,560 RESEARCHERS EXTRAMURALLY. 1647 01:08:35,560 --> 01:08:39,520 >>YEAH, SO WE ACTUALLY 1648 01:08:39,520 --> 01:08:40,160 COLLABORATE EXTENSIVELY, REALLY 1649 01:08:40,160 --> 01:08:42,280 EXTENSIVELY, POB IS ONE OF THE 1650 01:08:42,280 --> 01:08:43,240 MOST COLLABORATIVE BRANCHES, 1651 01:08:43,240 --> 01:08:46,240 THAT DOESN'T ONLY APPLY TO MY 1652 01:08:46,240 --> 01:08:48,440 WORK OR MYPART WORK BUT LEUKEMIA 1653 01:08:48,440 --> 01:08:50,080 SECTION AND EVERYBODY ELSE. 1654 01:08:50,080 --> 01:08:52,240 WE DO THINK EXTRAMURAL 1655 01:08:52,240 --> 01:08:55,080 PARTNERSHIPS ARE CRITICAL, SOME 1656 01:08:55,080 --> 01:08:57,200 MECHANISMS HOW THEY ACTUALLY 1657 01:08:57,200 --> 01:08:58,360 SUPPORT THROUGH NIH UO1 GRANTS, 1658 01:08:58,360 --> 01:09:00,120 FOR EXAMPLE, WHERE WE CAN HAVE 1659 01:09:00,120 --> 01:09:03,840 AN EXTRAMURAL P.I. AND 1660 01:09:03,840 --> 01:09:06,840 INTRAMURAL P.I., BUT WE NEED 1661 01:09:06,840 --> 01:09:07,560 EXTRAMURAL COLLABORATORS, EVEN 1662 01:09:07,560 --> 01:09:09,720 THOUGH WE HAVE SUBSTANTIAL 1663 01:09:09,720 --> 01:09:11,400 EXPERTISE IN INTRAMURAL AND NCI 1664 01:09:11,400 --> 01:09:15,600 THERE'S SO MUCH EXTRAMURAL 1665 01:09:15,600 --> 01:09:17,840 INVESTIGATORS CONTRIBUTE AND 1666 01:09:17,840 --> 01:09:19,600 THERE ARE MECHANISMS AND I THINK 1667 01:09:19,600 --> 01:09:21,800 WE CAN COLLABORATE EVEN IF NO 1668 01:09:21,800 --> 01:09:23,080 FUNDS ARE EXCHANGED, IT'S 1669 01:09:23,080 --> 01:09:23,640 CRITICAL. 1670 01:09:23,640 --> 01:09:25,960 FOR THE RARE TUMOR WORK WE NEED 1671 01:09:25,960 --> 01:09:26,680 THE EXTRAMURAL CLINICIANS TOO 1672 01:09:26,680 --> 01:09:29,640 BECAUSE WE DON'T HAVE ALL OF THE 1673 01:09:29,640 --> 01:09:31,280 CLINICAL EXPERTISE FOR THAT RARE 1674 01:09:31,280 --> 01:09:32,520 TEAMS, THAT'S WHAT WE BRING WHEN 1675 01:09:32,520 --> 01:09:37,560 WE HAVE THE RARE TUMOR CLINICS. 1676 01:09:37,560 --> 01:09:40,520 >>SO, ANOTHER QUESTION IS, IS 1677 01:09:40,520 --> 01:09:43,760 THERE ANY IMMUNE CELL 1678 01:09:43,760 --> 01:09:47,000 INFILTRATION IN THE NF1 TUMORS. 1679 01:09:47,000 --> 01:09:47,480 >>REPEAT. 1680 01:09:47,480 --> 01:09:50,040 >>IS THERE ANY IMMUNE CELL 1681 01:09:50,040 --> 01:09:51,800 INFILTRATION? 1682 01:09:51,800 --> 01:09:52,880 >>YEAH, SO THERE'S 1683 01:09:52,880 --> 01:09:54,800 SUBSTANTIALLY, THESE TUMORS ARE 1684 01:09:54,800 --> 01:09:56,200 ACTUALLY KNOWN TO HAVE MAST 1685 01:09:56,200 --> 01:09:59,280 CELLS AND MYELOID CELLS, I 1686 01:09:59,280 --> 01:10:00,760 BELIEVE THIS IS SOMETHING TRIED 1687 01:10:00,760 --> 01:10:06,600 TO BE TARGETED WITH THERAPIES, 1688 01:10:06,600 --> 01:10:16,520 ROSY DID A STUDY, AND THE CLAPP 1689 01:10:16,520 --> 01:10:19,080 STUDY DID A STUDY, 1690 01:10:19,080 --> 01:10:19,920 MICROENVIRONMENT, AS A SINGLE 1691 01:10:19,920 --> 01:10:23,720 AGENT I THINK IT HAS NOT BEEN 1692 01:10:23,720 --> 01:10:26,520 SUCCESSFUL ON LIMITED SUCCESS I 1693 01:10:26,520 --> 01:10:27,400 WOULD SAY, COMBINATORIAL 1694 01:10:27,400 --> 01:10:29,640 STRATEGIES HAVE NOT BEEN 1695 01:10:29,640 --> 01:10:30,120 EXPLORED. 1696 01:10:30,120 --> 01:10:31,720 >>OKAY. 1697 01:10:31,720 --> 01:10:33,520 SO THAT'S ALL THE QUESTIONS I 1698 01:10:33,520 --> 01:10:37,400 SEE ON THE CHAT SO FAR. 1699 01:10:37,400 --> 01:10:39,840 AND ARE THERE ANY OTHER 1700 01:10:39,840 --> 01:10:44,320 QUESTIONS FROM THE PANEL? 1701 01:10:44,320 --> 01:10:46,000 WELL, IF NOT, I'D LIKE TO TAKE 1702 01:10:46,000 --> 01:10:48,320 THE OPPORTUNITY TO THANK YOU 1703 01:10:48,320 --> 01:10:50,360 AGAIN, DR. WIDEMANN, FOR THE 1704 01:10:50,360 --> 01:10:51,840 WONDERFUL LECTURE AND 1705 01:10:51,840 --> 01:10:52,520 CONGRATULATIONS ON THE AWARD. 1706 01:10:52,520 --> 01:10:54,120 >>THANK YOU SO MUCH. 1707 01:10:54,120 --> 01:10:56,320 I APPRECIATE THE QUESTIONS AND 1708 01:10:56,320 --> 01:10:59,640 THE AUDIENCE AND VERY MUCH THE 1709 01:10:59,640 --> 01:11:00,400 NOMINATION. 1710 01:11:00,400 --> 01:11:01,520 >>THANK YOU. 1711 01:11:01,520 --> 01:11:02,360 BYE. 1712 01:11:02,360 --> 01:11:03,040 >>BYE. 1713 01:11:03,040 --> 00:00:00,000 >>THAT CLOSES THE SESSION.