1 00:00:05,720 --> 00:00:10,680 >>WELCOME TO 2 00:00:10,680 --> 00:00:12,680 THE NINTH SESSION IN THE 23rd 3 00:00:12,680 --> 00:00:15,120 YEAR IN THE COURSE OF THE NATION 4 00:00:15,120 --> 00:00:18,160 INSTITUTES OF HEALTH CALLED 5 00:00:18,160 --> 00:00:20,760 DEMYSTIFYING MEDICINE. 6 00:00:20,760 --> 00:00:28,160 I'M WIN ARIAS A SENIOR SCIENTIST 7 00:00:28,160 --> 00:00:31,280 EMERITUS AT NIH AND PLEASED TO 8 00:00:31,280 --> 00:00:32,320 BE YOUR HOST FOR THE PROGRAM 9 00:00:32,320 --> 00:00:34,000 THIS AFTERNOON. 10 00:00:34,000 --> 00:00:36,160 THIS COURSE IS A COURSE IN 11 00:00:36,160 --> 00:00:38,280 BRIDGE BUILDING. 12 00:00:38,280 --> 00:00:40,160 AS EXEMPLIFIED BY OUR LOGO WHICH 13 00:00:40,160 --> 00:00:42,480 IS THE BROOKLYN BRIDGE. 14 00:00:42,480 --> 00:00:47,120 AND THE TWO INDIVIDUALS ON THE 15 00:00:47,120 --> 00:00:50,280 CATWALK ARE EXEMPLIFIED BY OUR 16 00:00:50,280 --> 00:00:53,560 TWO SPEAKERS TODAY WHO WILL BE 17 00:00:53,560 --> 00:00:54,760 ADDRESSING ONE OF THE MAJOR 18 00:00:54,760 --> 00:00:58,680 PROBLEMS IN ALL OF MEDICINE. 19 00:00:58,680 --> 00:01:04,160 THE ABILITY TO PREDICT, DETECT, 20 00:01:04,160 --> 00:01:05,440 DIAGNOSE AND EVENTUALLY TREAT 21 00:01:05,440 --> 00:01:08,160 MEDICAL DISEASES. 22 00:01:08,160 --> 00:01:09,760 TODAY, THE SUBJECT IS CANCER. 23 00:01:09,760 --> 00:01:12,880 SO THE PURPOSE OF DEMYSTIFYING 24 00:01:12,880 --> 00:01:17,560 MEDICINE IS TO BRIDGE THE 25 00:01:17,560 --> 00:01:18,240 EXCITING DEVELOPMENTS IN BIOLOGY 26 00:01:18,240 --> 00:01:22,360 AND ENGINEERING WITH MEDICINE. 27 00:01:22,360 --> 00:01:24,880 TODAY'S PRESENTATION KINDS OF 28 00:01:24,880 --> 00:01:26,760 REMINDED ME OF SEVERAL GENERAL 29 00:01:26,760 --> 00:01:28,520 THEMES THAT GO WAY BEYOND 30 00:01:28,520 --> 00:01:31,400 ACTUALLY MEDICINE AND BEST 31 00:01:31,400 --> 00:01:33,560 REFLECTED PERHAPS IN LITERATURE. 32 00:01:33,560 --> 00:01:35,480 THERE ARE FOUR QUOTES. 33 00:01:35,480 --> 00:01:36,840 WE'RE SUCH STUFF AS DREAMS ARE 34 00:01:36,840 --> 00:01:40,680 MADE ON FROM THE TEMPEST BY 35 00:01:40,680 --> 00:01:41,000 SHAKESPEARE. 36 00:01:41,000 --> 00:01:45,840 WHO WOULD HAVE DREAMED THAT 15, 37 00:01:45,840 --> 00:01:49,320 20 OR SO YEARS AGO WE WOULD BE 38 00:01:49,320 --> 00:01:55,120 TALKING ABOUT THE TOPIC OF 39 00:01:55,120 --> 00:02:00,360 PREDICTING, DETECTING AND 40 00:02:00,360 --> 00:02:01,520 DIAGNOSING CANCER USING THE 41 00:02:01,520 --> 00:02:02,720 TECHNOLOGY THAT KEEPS FLOWING TO 42 00:02:02,720 --> 00:02:02,920 US. 43 00:02:02,920 --> 00:02:06,760 IT WAS SORT OF LIKE IT WAS IN 44 00:02:06,760 --> 00:02:10,160 THE REALM OF SCIENCE FICTION. 45 00:02:10,160 --> 00:02:10,760 THINK STAR TREK. 46 00:02:10,760 --> 00:02:12,480 THEN WE HAVE A BRAVE NEW WORLD 47 00:02:12,480 --> 00:02:14,040 WITH SUCH CREATURES IN IT AND 48 00:02:14,040 --> 00:02:19,920 THE CHALLENGES PRESENTED IB 49 00:02:19,920 --> 00:02:22,560 BRIDGING THIS INCREDIBLE SERIES 50 00:02:22,560 --> 00:02:26,080 OF ISSUES BROUGHT ABOUT AT THE 51 00:02:26,080 --> 00:02:28,840 PRESENT TIME REQUIRE INDIVIDUALS 52 00:02:28,840 --> 00:02:31,880 WHO HAVE EXPERTISE AND THAT'S 53 00:02:31,880 --> 00:02:32,600 THE REAL CHALLENGE TO DEVELOP. 54 00:02:32,600 --> 00:02:35,520 HOWEVER, NONE OF THIS IS SIMPLE. 55 00:02:35,520 --> 00:02:38,080 AND MY FAVORITE RESPONSE TO THAT 56 00:02:38,080 --> 00:02:42,640 IS FROM A QUOTE BY A WONDERFUL 57 00:02:42,640 --> 00:02:50,040 DANISH CARTOONIST GROEKS WHO 58 00:02:50,040 --> 00:02:52,120 WROTE PROBLEMS WORTH OF ATTACK 59 00:02:52,120 --> 00:02:53,880 PROVE THEIR WORTH BY STRIKING 60 00:02:53,880 --> 00:02:54,080 BACK. 61 00:02:54,080 --> 00:02:56,040 YOU'LL HEAR ABOUT THIS IN 62 00:02:56,040 --> 00:02:59,680 TODAY'S TALKS. 63 00:02:59,680 --> 00:03:01,880 THEN THERE'S THE PURPOSE OF 64 00:03:01,880 --> 00:03:03,880 DEMYSTIFYING MEDICINE AS 65 00:03:03,880 --> 00:03:06,120 EXEMPLIFIED IN A WONDERFUL 66 00:03:06,120 --> 00:03:11,040 STATEMENT BY A SWISS 67 00:03:11,040 --> 00:03:12,360 NUTRITIONIST, MUCH IS KNOWN BUT 68 00:03:12,360 --> 00:03:13,320 UNFORTUNATELY IN DIFFERENT 69 00:03:13,320 --> 00:03:13,680 HEADS. 70 00:03:13,680 --> 00:03:20,640 SO TODAY'S TOPIC IS REALLY EARLY 71 00:03:20,640 --> 00:03:24,160 CANCER AND CAN WE DETECT EARLY 72 00:03:24,160 --> 00:03:26,040 CANCER. 73 00:03:26,040 --> 00:03:31,600 TO DISCUSS THIS WE ARE FORTUNATE 74 00:03:31,600 --> 00:03:39,520 IN HAVING TWO EXPERT COLLEAGUES 75 00:03:39,520 --> 00:03:44,320 WHO REPRESENT SOMEWHAT DIFFERENT 76 00:03:44,320 --> 00:03:44,520 ASPECTS. 77 00:03:44,520 --> 00:03:47,160 THE FIRST SPEAKER IS PHILIP 78 00:03:47,160 --> 00:03:47,400 CASTLE. 79 00:03:47,400 --> 00:03:48,520 HE'S THE DIRECTOR OF THE 80 00:03:48,520 --> 00:03:51,920 DIVISION OF CANCER PREVENTION AT 81 00:03:51,920 --> 00:03:53,320 THE NATIONAL CANCER INSTITUTE AT 82 00:03:53,320 --> 00:03:55,320 THE NIH. 83 00:03:55,320 --> 00:03:58,280 HE RECEIVED HIS Ph.D. FROM 84 00:03:58,280 --> 00:04:04,840 HOPKINS IN BIO PHYSICS AND THEN 85 00:04:04,840 --> 00:04:07,320 TOOK A MIXED POST-DOCTORAL 86 00:04:07,320 --> 00:04:11,440 FELLOWSHIP AND GAINED A MASTER'S 87 00:04:11,440 --> 00:04:13,880 IN PUBLIC HEALTH BETWEEN HOPKINS 88 00:04:13,880 --> 00:04:14,880 AND THE CANCER PREVENTION 89 00:04:14,880 --> 00:04:16,120 PROGRAM HERE IN BETHESDA. 90 00:04:16,120 --> 00:04:18,200 IT WAS THE BEGINNING OF A LONG 91 00:04:18,200 --> 00:04:20,960 AND HIGHLY PRODUCTIVE CAREER AT 92 00:04:20,960 --> 00:04:27,920 THE NCI WHERE HE HAS BECOME A 93 00:04:27,920 --> 00:04:29,920 SENIOR INVESTIGATOR AND WAS IN 94 00:04:29,920 --> 00:04:31,040 2010. 95 00:04:31,040 --> 00:04:33,480 THERE WAS A BRIEF INTERLUDE FROM 96 00:04:33,480 --> 00:04:38,040 2014 WHEN HE WAS RECRUITED TO 97 00:04:38,040 --> 00:04:42,880 THE ALBERT EINSTEIN COLLEGE OF 98 00:04:42,880 --> 00:04:44,080 MEDICINE AS PROFESSOR OF 99 00:04:44,080 --> 00:04:45,480 EPIDEMIOLOGY AND POPULATION 100 00:04:45,480 --> 00:04:45,680 HEALTH. 101 00:04:45,680 --> 00:04:49,840 THEN IN 2020 RETURNED TO NIH TO 102 00:04:49,840 --> 00:04:51,480 HIS PRESENT POSITION AS DIRECTOR 103 00:04:51,480 --> 00:04:54,920 OF THE DIVISION OF CANCER 104 00:04:54,920 --> 00:04:55,920 PREVENTION. 105 00:04:55,920 --> 00:04:58,400 NOW, HE HAS AN EXCEPTIONAL 106 00:04:58,400 --> 00:05:02,080 CAREER INITIATING, CONDUCTING 107 00:05:02,080 --> 00:05:05,840 AND LEADING MAJOR, HUGE NCI 108 00:05:05,840 --> 00:05:10,560 MOLECULAR AND CLINICAL 109 00:05:10,560 --> 00:05:12,440 EPIDEMIOLOGY RESEARCH MAINLY 110 00:05:12,440 --> 00:05:14,920 INVOLVING HUMAN PAPILLOMA VIRUS 111 00:05:14,920 --> 00:05:15,920 RELATED CANCERS. 112 00:05:15,920 --> 00:05:18,480 HIS INTERESTS ARE IN EARLY 113 00:05:18,480 --> 00:05:19,400 CANCER DIAGNOSIS AND DEVELOPMENT 114 00:05:19,400 --> 00:05:23,920 OF NEW TECHNIQUES, GREENING, 115 00:05:23,920 --> 00:05:26,080 DISPARITIES IN CANCER PREVENTION 116 00:05:26,080 --> 00:05:27,920 AND EVIDENCE-BASED MEDICINE. 117 00:05:27,920 --> 00:05:33,280 HE'S RECEIVED MANY AWARDS AND IS 118 00:05:33,280 --> 00:05:36,120 HIGHLY HONORED IN THE NCI HAVING 119 00:05:36,120 --> 00:05:38,000 RECEIVED THE DISTINGUISHED 120 00:05:38,000 --> 00:05:41,320 ALUMNI AWARD AND FLEMING AWARD 121 00:05:41,320 --> 00:05:46,160 FOR GOVERNMENT SERVICE AND HAS 122 00:05:46,160 --> 00:05:47,880 BEEN A CHIEF SCIENTIFIC 123 00:05:47,880 --> 00:05:48,680 INDIVIDUAL FOR THE AMERICAN 124 00:05:48,680 --> 00:05:51,200 SOCIETY OF CLINICAL PATHOLOGY. 125 00:05:51,200 --> 00:05:55,920 AND PHILIP IS GOING TO DISCUSS 126 00:05:55,920 --> 00:05:56,840 TESTS FOR EARLY CANCER, FACT 127 00:05:56,840 --> 00:06:02,200 VERSUS OPINIONS. 128 00:06:02,200 --> 00:06:05,360 NOW, OUR SECOND SPEAKER IS 129 00:06:05,360 --> 00:06:07,640 ROBERT NUSSBAUM WHO IS ALSO VERY 130 00:06:07,640 --> 00:06:11,920 WELL KNOWN AND RESPECTED AT THE 131 00:06:11,920 --> 00:06:13,880 NATIONAL INSTITUTES OF HEALTH. 132 00:06:13,880 --> 00:06:18,640 HE IS CURRENTLY THE CHIEF 133 00:06:18,640 --> 00:06:23,320 MEDICAL OFFICER OF THE INVITIME 134 00:06:23,320 --> 00:06:26,120 COMPANY IN SUCCESS AND RECEIVED 135 00:06:26,120 --> 00:06:29,800 HIS M.D. FROM HARVARD IN APPLIED 136 00:06:29,800 --> 00:06:31,800 MATHEMATIC AND HIS UNDERGRADUATE 137 00:06:31,800 --> 00:06:34,680 DEGREE AND THEN M.D. IN THE 138 00:06:34,680 --> 00:06:38,080 HARVARD M.I.T. COMBINED PROGRAM 139 00:06:38,080 --> 00:06:43,320 FOR HEALTH SCIENCE AND 140 00:06:43,320 --> 00:06:43,760 TECHNOLOGY. 141 00:06:43,760 --> 00:06:46,640 THEN WAS IN ST. LOUIS AND THEN 142 00:06:46,640 --> 00:06:48,360 STUDIED GENETICS AT BAYLOR AND 143 00:06:48,360 --> 00:06:50,080 BE THE WAS RECRUITED TO THE 144 00:06:50,080 --> 00:06:55,080 FACULTY AT THE UNIVERSITY OF 145 00:06:55,080 --> 00:06:55,720 PENNSYLVANIA WHERE EVENTUALLY HE 146 00:06:55,720 --> 00:06:57,920 BECAME PROFESSOR OF GENETICS, 147 00:06:57,920 --> 00:07:00,800 PEDIATRICS AND MEDICINE. 148 00:07:00,800 --> 00:07:07,760 AND IN 1993 FRANCIS COLLINS WHO 149 00:07:07,760 --> 00:07:09,040 HEADED THE HUMAN GENOME 150 00:07:09,040 --> 00:07:11,920 INSTITUTE AT THE NIH RECRUITED 151 00:07:11,920 --> 00:07:15,600 DR. NUSSBAUM TO HELP LAUNCH THE 152 00:07:15,600 --> 00:07:19,920 INTRAMURAL PROGRAM OF THE NIH 153 00:07:19,920 --> 00:07:21,800 GRI. 154 00:07:21,800 --> 00:07:23,880 WHICH BOB DID WITH DISTINCTION. 155 00:07:23,880 --> 00:07:26,680 HE IDENTIFIED ALSO THE FIRST 156 00:07:26,680 --> 00:07:29,680 INHERITED FORM OF PARKINSON'S 157 00:07:29,680 --> 00:07:34,560 DISEASE INVOLVING MUTATIONS IN 158 00:07:34,560 --> 00:07:39,920 THE ALPHA-SYNUCLEIN GENE AND 159 00:07:39,920 --> 00:07:43,680 LOOKED FOR INHERITABLE DISORDERS 160 00:07:43,680 --> 00:07:46,560 OF THE LIKE OF PARKINSON'S AND 161 00:07:46,560 --> 00:07:46,800 OTHERS. 162 00:07:46,800 --> 00:07:54,240 IN 2006, HE WAS RECRUITED TO THE 163 00:07:54,240 --> 00:07:56,880 UNIVERSITY OF CALIFORNIA SAN 164 00:07:56,880 --> 00:08:04,200 FRANCISCO WHERE HE WAS THE CHIEF 165 00:08:04,200 --> 00:08:06,880 OF THE DIVISION OF HUMAN 166 00:08:06,880 --> 00:08:07,120 GENETICS. 167 00:08:07,120 --> 00:08:11,240 HE CONTINUED THE ACTIVITY IN 168 00:08:11,240 --> 00:08:14,880 2015 WHEN HE BECAME THE CHIEF 169 00:08:14,880 --> 00:08:16,760 MEDICAL OFFICER OF INVITA. 170 00:08:16,760 --> 00:08:20,840 HIS GOAL WAS TO DEVELOP, 171 00:08:20,840 --> 00:08:22,880 EVALUATE AND EVENTUALLY MARKET 172 00:08:22,880 --> 00:08:26,040 GENETIC TESTS FOR CANCER AND 173 00:08:26,040 --> 00:08:27,880 OTHER DISEASES WORLDWIDE. 174 00:08:27,880 --> 00:08:29,840 DR. NUSSBAUM HAS MANY MANY 175 00:08:29,840 --> 00:08:30,760 ACCOMPLISHMENTS AND AWARDS. 176 00:08:30,760 --> 00:08:32,160 HE'S A MEMBER OF THE NATIONAL 177 00:08:32,160 --> 00:08:36,280 ACADEMY OF MEDICINE AND WAS 178 00:08:36,280 --> 00:08:39,480 PRESIDENT OF THE AMERICAN 179 00:08:39,480 --> 00:08:40,720 SOCIETY OF HUMAN GENETICS. 180 00:08:40,720 --> 00:08:43,920 HE DESCRIBES HIMSELF AS A 181 00:08:43,920 --> 00:08:45,320 BOARD-CERTIFIED GENETICIST. 182 00:08:45,320 --> 00:08:48,040 WE KNOW HE'S AN OUTSTANDING 183 00:08:48,040 --> 00:08:51,680 TEACHER AND A LEADER IN BRIDGING 184 00:08:51,680 --> 00:08:55,920 BASIC GENETICS WITH ACCURATE 185 00:08:55,920 --> 00:08:59,200 WIDELY AVAILABLE PREDICTIVE 186 00:08:59,200 --> 00:08:59,760 DIAGNOSTIC TESTS. 187 00:08:59,760 --> 00:09:02,480 SO WE WILL BEGIN FIRST WITH 188 00:09:02,480 --> 00:09:03,880 DR. CASTLE. 189 00:09:03,880 --> 00:09:08,800 PHILIP, YOU'RE ON. 190 00:09:08,800 --> 00:09:10,040 >>THANK YOU SO VERY MUCH. 191 00:09:10,040 --> 00:09:12,720 THANK YOU FOR THE OPPORTUNITY 192 00:09:12,720 --> 00:09:15,920 AND HONOR, REALLY, TO PRESENT TO 193 00:09:15,920 --> 00:09:16,200 THIS AUDIENCE. 194 00:09:16,200 --> 00:09:18,480 TODAY WE'LL TALK ABOUT TEST FOR 195 00:09:18,480 --> 00:09:19,160 EARLY CANCER AND TALK ABOUT 196 00:09:19,160 --> 00:09:21,800 CANCER SCREENING AND NOT JUST 197 00:09:21,800 --> 00:09:25,840 FOR EARLY CANCER BUT FOR 198 00:09:25,840 --> 00:09:28,640 PRECANCER. 199 00:09:28,640 --> 00:09:32,200 >>A FEW DISCLAIMERS AND 200 00:09:32,200 --> 00:09:32,480 DISCLOSURES. 201 00:09:32,480 --> 00:09:35,000 HE'S ARE MY OPINIONS AND DON'T 202 00:09:35,000 --> 00:09:36,120 REPRESENT ANYBODY ELSE'S 203 00:09:36,120 --> 00:09:38,320 INCLUDING THE NIH, NCI AND THE 204 00:09:38,320 --> 00:09:41,160 DIVISION OF CANCER PREVENTION. 205 00:09:41,160 --> 00:09:42,520 MY COMMENTS SHOULD NOT BE TAKEN 206 00:09:42,520 --> 00:09:44,400 FOR FUNDING. 207 00:09:44,400 --> 00:09:46,200 IF I MENTION SPECIFIC PRODUCTS 208 00:09:46,200 --> 00:09:50,960 I'M NOT ENDORSING THEM. 209 00:09:50,960 --> 00:09:54,560 FOR DISCLOSURE I RECEIVED FROM 210 00:09:54,560 --> 00:10:00,360 THE FOLLOWING COMPANIES, ROCHE, 211 00:10:00,360 --> 00:10:07,640 CEPHEID, BECTON DICKINSON AND 212 00:10:07,640 --> 00:10:14,280 ARBOR VITA CORPORATION. 213 00:10:14,280 --> 00:10:16,000 WE RECOGNIZE THERE'S LIMITATIONS 214 00:10:16,000 --> 00:10:18,000 TO BOTH OBSERVATIONAL STUDIES AS 215 00:10:18,000 --> 00:10:21,760 WELL AS RANDOMIZED CONTROL 216 00:10:21,760 --> 00:10:22,440 TRIALS. 217 00:10:22,440 --> 00:10:24,400 THIS ILLUSTRATES WITH 218 00:10:24,400 --> 00:10:26,280 OBSERVATIONAL STUDIES WE CAN'T 219 00:10:26,280 --> 00:10:31,280 ALWAYS GLEAN CAUSAL 220 00:10:31,280 --> 00:10:31,920 RELATIONSHIPS BETWEEN WHAT WE 221 00:10:31,920 --> 00:10:33,720 SURVEY AND WHAT WE THINK IS 222 00:10:33,720 --> 00:10:35,600 GOING ON BUT WE CAN'T DO 223 00:10:35,600 --> 00:10:37,160 ANYTHING BY RANDOMIZED CLINICAL 224 00:10:37,160 --> 00:10:37,400 TRIALS. 225 00:10:37,400 --> 00:10:42,160 THIS IS AN ARTICLE BY A BRITISH 226 00:10:42,160 --> 00:10:51,800 MEDICAL JOURNAL ENTITLED 227 00:10:51,800 --> 00:10:53,400 PARACHUTE USE TO PREVENT DEATH 228 00:10:53,400 --> 00:10:56,400 AND MAJOR TRAUMA RELATED TO 229 00:10:56,400 --> 00:10:57,840 GRAVITATIONAL CHALLENGES 230 00:10:57,840 --> 00:11:00,440 SYSTEMIC REVIEW OF RANDOMIZED 231 00:11:00,440 --> 00:11:02,800 CONTROLLED TRIALS AND THEY FOUND 232 00:11:02,800 --> 00:11:04,360 NO CONTROL TRIALS. 233 00:11:04,360 --> 00:11:05,920 THE RANDOMIZED CONTROL TRIAL IS 234 00:11:05,920 --> 00:11:07,320 THE GOLD STANDARD. 235 00:11:07,320 --> 00:11:08,640 SOMETIMES WE CAN USE IT AND 236 00:11:08,640 --> 00:11:10,000 SOMETIMES WE CAN'T AND RECOGNIZE 237 00:11:10,000 --> 00:11:12,320 WHEN WE CAN'T, OBSERVATIONAL 238 00:11:12,320 --> 00:11:15,400 TRIALS MAY LEAD TO ERRONEOUS 239 00:11:15,400 --> 00:11:16,400 CAUSAL RELATIONSHIPS BETWEEN THE 240 00:11:16,400 --> 00:11:19,960 INTERVENTION AND THE OUTCOME. 241 00:11:19,960 --> 00:11:21,600 SO I'M GOING TO TALK A LITTLE 242 00:11:21,600 --> 00:11:22,320 BIT ABOUT SCREENING. 243 00:11:22,320 --> 00:11:24,880 I'LL REMIND YOU WHAT ARE THE 244 00:11:24,880 --> 00:11:25,920 CURRENT CANCER SCREENING 245 00:11:25,920 --> 00:11:26,280 RECOMMENDATIONS. 246 00:11:26,280 --> 00:11:31,400 I'M GOING TO ILLUSTRATE SOME OF 247 00:11:31,400 --> 00:11:33,640 THE ONE PAST SUCCESS AND FAILURE 248 00:11:33,640 --> 00:11:36,880 AND TALK ABOUT THE EMERGENCE OF 249 00:11:36,880 --> 00:11:37,520 MULTI-CANCER DETECTION WHICH I 250 00:11:37,520 --> 00:11:39,640 THINK ROBERT WILL TALK ABOUT 251 00:11:39,640 --> 00:11:41,800 AFTER ME A LITTLE BIT AND HOW DO 252 00:11:41,800 --> 00:11:43,080 WE AVOID THE PAST MISTAKE. 253 00:11:43,080 --> 00:11:46,000 I DO WANT TO TOUCH UPON CANCER 254 00:11:46,000 --> 00:11:47,360 HEALTH DISPARITIES AND SCREENING 255 00:11:47,360 --> 00:11:52,360 AND MAKE A FEW FINAL COMMENTS. 256 00:11:52,360 --> 00:11:54,200 SO WHAT IS SCREENING? 257 00:11:54,200 --> 00:11:57,160 SO THIS IS THE HEALTH.gov 258 00:11:57,160 --> 00:11:57,440 DEFINITION. 259 00:11:57,440 --> 00:11:59,000 SCREENINGS ARE MEDICAL TESTS 260 00:11:59,000 --> 00:12:00,840 DOCTORS USING TO CHECK FOR 261 00:12:00,840 --> 00:12:01,920 DISEASES AND HEALTH CONDITIONS 262 00:12:01,920 --> 00:12:02,560 BEFORE THERE'S ANY SIGNS OR 263 00:12:02,560 --> 00:12:06,440 SYMPTOMS AND THERE'S THE WEBSITE 264 00:12:06,440 --> 00:12:08,160 YOU CAN SEE YOURSELF. 265 00:12:08,160 --> 00:12:10,480 I'D LIKE TO MODIFY THIS A LITTLE 266 00:12:10,480 --> 00:12:10,680 BIT. 267 00:12:10,680 --> 00:12:12,280 I'M GOING GIVE YOU MY OWN 268 00:12:12,280 --> 00:12:13,480 DEFINITION. 269 00:12:13,480 --> 00:12:15,120 SO SCREENS ARE PROCESSES THAT 270 00:12:15,120 --> 00:12:18,240 INCLUDE MEDICAL TESTS AND 271 00:12:18,240 --> 00:12:19,400 FOLLOW-UP CARE THAT A HEALTH 272 00:12:19,400 --> 00:12:22,560 CARE PROVIDERS USE TO FIND AND 273 00:12:22,560 --> 00:12:24,080 AVERT DISEASES AND HEALTH 274 00:12:24,080 --> 00:12:25,040 CONDITIONS BEFORE THERE'S SIGNS 275 00:12:25,040 --> 00:12:26,880 OR SYSTEMS WITH THE GOAL OF 276 00:12:26,880 --> 00:12:27,840 INTERVENING TO IMPROVE HEALTH 277 00:12:27,840 --> 00:12:29,360 OUTCOMES AND QUALITY OF LIFE. 278 00:12:29,360 --> 00:12:30,480 THE IMPORTANT THING HERE IS THAT 279 00:12:30,480 --> 00:12:32,000 SCREENING IS NOT JUST A TEST. 280 00:12:32,000 --> 00:12:34,080 THAT IS PART OF IT. 281 00:12:34,080 --> 00:12:35,840 IT'S AN IMPORTANT PART. 282 00:12:35,840 --> 00:12:37,320 IT'S A RISK STRATIFIER AND 283 00:12:37,320 --> 00:12:38,920 THAT'S WHAT WE'RE TALK BECOME 284 00:12:38,920 --> 00:12:42,040 WHEN WE DO A TEST, SCREENING 285 00:12:42,040 --> 00:12:42,240 TEST. 286 00:12:42,240 --> 00:12:46,280 WE'RE SCATTEREDFYING -- 287 00:12:46,280 --> 00:12:47,680 STRATIFYING THE POPULATION AND 288 00:12:47,680 --> 00:12:48,880 PEOPLE AT HIGHER AND LOWER RISK 289 00:12:48,880 --> 00:12:52,120 AND RUNNING A TEST ALONE IS NOT 290 00:12:52,120 --> 00:12:52,320 ENOUGH. 291 00:12:52,320 --> 00:12:54,040 WE HAVE TO PROVIDE TEST FOR 292 00:12:54,040 --> 00:12:55,960 THOSE WHO SCREEN POSITIVE OR THE 293 00:12:55,960 --> 00:12:57,400 TESTING YOU'VE DONE IS 294 00:12:57,400 --> 00:12:58,280 COMPLETELY USEFUL. 295 00:12:58,280 --> 00:13:00,000 AND SCREENING AS I'LL ILLUSTRATE 296 00:13:00,000 --> 00:13:02,920 IN THE NEXT SLIDE WITH 297 00:13:02,920 --> 00:13:04,400 ARITHMETIC IS THE MOST 298 00:13:04,400 --> 00:13:06,000 CHALLENGING APPLICATION OF A 299 00:13:06,000 --> 00:13:08,280 DIAGNOSTIC WHICH IS TO USE IT IN 300 00:13:08,280 --> 00:13:10,040 A HEALTHY PERSON TO KEEP 301 00:13:10,040 --> 00:13:10,240 HEALTHY. 302 00:13:10,240 --> 00:13:12,040 MOST DIAGNOSTIC DONE IN THOSE 303 00:13:12,040 --> 00:13:14,480 WHO HAVE SOME SORT OF SYMPTOM OR 304 00:13:14,480 --> 00:13:19,440 SIGN OR SOMETHING AMISS TO MAKE 305 00:13:19,440 --> 00:13:20,680 A DIFFERENTIAL DIAGNOSIS OR 306 00:13:20,680 --> 00:13:21,600 IDENTIFY THE CAUSE OF THE 307 00:13:21,600 --> 00:13:22,120 SYMPTOM. 308 00:13:22,120 --> 00:13:26,720 AS ILLUSTRATED HERE, THIS IS AN 309 00:13:26,720 --> 00:13:28,320 EXAMPLE, A GENERAL EXAMPLE IT 310 00:13:28,320 --> 00:13:30,840 PARALLELS THE USE OF HUMAN 311 00:13:30,840 --> 00:13:33,120 PAPILLOMA VIRUS TESTING FOR 312 00:13:33,120 --> 00:13:33,760 CERVICAL CANCER. 313 00:13:33,760 --> 00:13:35,040 I'D SAY WE GO INTO A POPULATION 314 00:13:35,040 --> 00:13:39,000 WHERE THERE'S A PREVALENCE OF 315 00:13:39,000 --> 00:13:41,240 DISEASE FOR 1% AND FOR CERVICAL 316 00:13:41,240 --> 00:13:43,400 CANCER WOULD BE PRECANCER AND 317 00:13:43,400 --> 00:13:43,640 CANCER. 318 00:13:43,640 --> 00:13:46,600 LET'S SAY YOU HAVE A TEST LIKE 319 00:13:46,600 --> 00:13:49,000 HPV WHICH IS 90% SENSITIVE AND 320 00:13:49,000 --> 00:13:50,880 90% SPECIFIC WHICH IS A REALLY 321 00:13:50,880 --> 00:13:52,360 GOOD TEST. 322 00:13:52,360 --> 00:13:55,800 AND BY THE WAY, TO PUT IT IN 323 00:13:55,800 --> 00:13:59,520 PERSPECTIVE FOR THE 324 00:13:59,520 --> 00:14:00,600 GENEOLOGISTS, THAT'S AN ODDS 325 00:14:00,600 --> 00:14:01,160 RATIO OF 81. 326 00:14:01,160 --> 00:14:04,360 I DON'T KNOW ABOUT THE REST OF 327 00:14:04,360 --> 00:14:07,720 YOU BUT I'VE RARELY SEEN ODDS 328 00:14:07,720 --> 00:14:09,800 RATIOS OF 81 EXCEPT FOR A FEW 329 00:14:09,800 --> 00:14:11,600 AND MOST BIOMARKERS DON'T 330 00:14:11,600 --> 00:14:13,920 ACHIEVE THAT LEVEL OF 331 00:14:13,920 --> 00:14:14,840 ASSOCIATION. 332 00:14:14,840 --> 00:14:16,080 LET'S LOOK AT THE NUMBERS. 333 00:14:16,080 --> 00:14:19,760 LET'S TAKE THE THEORETICAL 334 00:14:19,760 --> 00:14:20,880 POPULATION OF 10,000 PEOPLE AND 335 00:14:20,880 --> 00:14:23,440 APPLY THE TEST AND 1% PREVALENCE 336 00:14:23,440 --> 00:14:24,040 OF DISEASE. 337 00:14:24,040 --> 00:14:28,360 IF THERE'S 100 CASES IN THE 338 00:14:28,360 --> 00:14:28,760 10,000. 339 00:14:28,760 --> 00:14:29,640 GUESS WHAT? 340 00:14:29,640 --> 00:14:31,000 THE POSITIVE PREDICTIVE VALUE 341 00:14:31,000 --> 00:14:34,000 FOR THAT TEST, SO THE NUMBER OF 342 00:14:34,000 --> 00:14:36,160 PEOPLE WHO TEST POSITIVE AND THE 343 00:14:36,160 --> 00:14:39,560 NUMBER OF CASES WITHIN THAT TEST 344 00:14:39,560 --> 00:14:42,160 POSITIVE POPULATION, THE RISK OR 345 00:14:42,160 --> 00:14:43,160 POSITIVE PREDICTIVE VALUE IS 346 00:14:43,160 --> 00:14:44,760 ONLY 8.3%. 347 00:14:44,760 --> 00:14:48,120 THAT MEANS 11 OUT OF 12 WHO 348 00:14:48,120 --> 00:14:50,600 TESTED POSITIVE WILL BE FALSE 349 00:14:50,600 --> 00:14:50,840 POSITIVE. 350 00:14:50,840 --> 00:14:52,440 NOW, A TEST LIKE THIS ACTUALLY 351 00:14:52,440 --> 00:14:54,480 THE REAL VALUE OF THIS OR THE 352 00:14:54,480 --> 00:14:58,440 STRENGTH OF THIS TEST IN A LOW 353 00:14:58,440 --> 00:14:59,920 PREVALENCE CIRCUMSTANCE IS THE 354 00:14:59,920 --> 00:15:01,600 NEGATIVE PREDICTIVE VALUE SHOWN 355 00:15:01,600 --> 00:15:03,960 HERE WHICH IS 99.9%. 356 00:15:03,960 --> 00:15:08,160 THAT MEANS WHEN A PERSON TESTS 357 00:15:08,160 --> 00:15:10,000 NEGATIVE YOU'LL HAVE ONLY MISSED 358 00:15:10,000 --> 00:15:11,360 ONE CASE AND THERE'LL ONLY BE 359 00:15:11,360 --> 00:15:15,240 ONE CASE IN 1,000 OUT OF THIS 360 00:15:15,240 --> 00:15:15,760 HYPOTHETICAL SITUATION. 361 00:15:15,760 --> 00:15:19,960 SO WHAT HAPPENS IF WE APPLY A 362 00:15:19,960 --> 00:15:21,280 SECOND TEST TO THE SCREEN 363 00:15:21,280 --> 00:15:22,480 POSITIVE OR GOING BACK TO THE 364 00:15:22,480 --> 00:15:24,160 EXAMPLE BEFORE LET'S SAY THEY 365 00:15:24,160 --> 00:15:25,040 HAVE A SYMPTOM? 366 00:15:25,040 --> 00:15:27,680 SO HERE WE'RE STARTING WITH A 367 00:15:27,680 --> 00:15:30,080 HIGHER PREVALENCE OF DISEASE 368 00:15:30,080 --> 00:15:34,200 8.3% AND WE JUST USE IN THIS 369 00:15:34,200 --> 00:15:44,360 CASE FOR THIS EXAMPLE ACYTOLOGY 370 00:15:44,360 --> 00:15:48,400 ACYTOLOGY -- A CYTOLOGY TEST 371 00:15:48,400 --> 00:15:52,840 AND BECAUSE IT'S ALMOST AN ORDER 372 00:15:52,840 --> 00:15:55,440 OF MAGNITUDE GREATER THE 373 00:15:55,440 --> 00:15:56,400 POSITIVE PREDICTIVE VALUE IS 374 00:15:56,400 --> 00:15:57,640 ALMOST 50%. 375 00:15:57,640 --> 00:16:01,680 SO THIS ILLUSTRATED WHEN WE CAN 376 00:16:01,680 --> 00:16:03,080 SCREEN THE GENERAL HEALTHY 377 00:16:03,080 --> 00:16:04,400 POPULATION IS BEST SERVED BY A 378 00:16:04,400 --> 00:16:06,720 RULE OUT WHICH IS WHAT WE SHOW 379 00:16:06,720 --> 00:16:07,920 ABOVE IF YOU'RE HPV NEGATIVE 380 00:16:07,920 --> 00:16:11,480 YOU'RE UNLIKELY TO HAVE DISEASE 381 00:16:11,480 --> 00:16:12,840 AND THE RULE END SHOWN AT THE 382 00:16:12,840 --> 00:16:14,880 BOTTOM WHICH IS ONCE YOU KNOW 383 00:16:14,880 --> 00:16:16,880 HAVE YOU A HIGHER RISK COHORT TO 384 00:16:16,880 --> 00:16:20,160 USE A VERY SPECIFIC TEST TO 385 00:16:20,160 --> 00:16:22,000 IDENTIFY THOSE WHO ARE BEARING 386 00:16:22,000 --> 00:16:22,280 DISEASE. 387 00:16:22,280 --> 00:16:24,400 JUST BECAUSE WE'RE NOT GOING TO 388 00:16:24,400 --> 00:16:27,040 ACT ON THE SCREEN POSITIVES WHO 389 00:16:27,040 --> 00:16:28,360 TRIAGE NEGATIVE DOESN'T MEAN 390 00:16:28,360 --> 00:16:30,240 THEY'RE COMPLETELY LOST BECAUSE 391 00:16:30,240 --> 00:16:31,720 WE ALREADY KNOW THEY'RE SCREEN 392 00:16:31,720 --> 00:16:33,280 POSITIVE AND WILL FOLLOW THEM 393 00:16:33,280 --> 00:16:34,000 MORE CLOSELY. 394 00:16:34,000 --> 00:16:35,840 THIS IS ILLUSTRATING AN 395 00:16:35,840 --> 00:16:38,320 IMPORTANT CONCEPT WHICH IS RISK 396 00:16:38,320 --> 00:16:40,360 STRATIFICATION. 397 00:16:40,360 --> 00:16:41,600 WE CAN'T DO EVERYTHING FOR 398 00:16:41,600 --> 00:16:42,000 EVERYBODY. 399 00:16:42,000 --> 00:16:44,120 WE'D LIKE TO BUT WE CAN'T, 400 00:16:44,120 --> 00:16:45,120 PRACTICALLY, SO WE HAVE TO 401 00:16:45,120 --> 00:16:46,560 DECIDE WHO'S AT THE HIGHEST RISK 402 00:16:46,560 --> 00:16:48,400 AND LOWEST RISK AND ACT 403 00:16:48,400 --> 00:16:50,160 ACCORDINGLY. 404 00:16:50,160 --> 00:16:54,200 SO REALLY WHEN YOU THINK ABOUT 405 00:16:54,200 --> 00:16:56,000 THE SCREENING CARE CONTINUUM IT 406 00:16:56,000 --> 00:16:57,320 FALLS INTO FIVE STEPS. 407 00:16:57,320 --> 00:17:00,000 SOME ARE COMBINED. 408 00:17:00,000 --> 00:17:02,240 I'LL GIVE AN EXAMPLE HERE RISK 409 00:17:02,240 --> 00:17:03,600 ASSESSMENT. 410 00:17:03,600 --> 00:17:05,040 SO WE DON'T DO ALL CANCER 411 00:17:05,040 --> 00:17:05,960 SCREENING ON EVERYBODY. 412 00:17:05,960 --> 00:17:07,880 WE OFTEN USAGE AS ONE WAY TO 413 00:17:07,880 --> 00:17:08,880 ASSESS RISK. 414 00:17:08,880 --> 00:17:10,280 WE DON'T DO CERVICAL CANCER 415 00:17:10,280 --> 00:17:11,960 SCREENING IN MEN BECAUSE THEY 416 00:17:11,960 --> 00:17:14,600 DON'T HAVE A CERVIX SO THEY'RE 417 00:17:14,600 --> 00:17:16,360 AT ZERO RISK. 418 00:17:16,360 --> 00:17:19,760 WE SHOULDN'T BE DOING CERVICAL 419 00:17:19,760 --> 00:17:24,160 CANCER SCREENING IN WOMEN WHO 420 00:17:24,160 --> 00:17:26,480 HAVE HAD A HYSTERECTOMY BECAUSE 421 00:17:26,480 --> 00:17:29,200 THEY DON'T HAVE A CERVIX AND WE 422 00:17:29,200 --> 00:17:30,640 APPLY THE SCREENING TEST AND THE 423 00:17:30,640 --> 00:17:34,600 FIRST LINE OF TEST IS TO RULE 424 00:17:34,600 --> 00:17:35,840 OUT AND TELL HEALTHY PEOPLE 425 00:17:35,840 --> 00:17:38,160 THEY'RE HEALTHY AND AMONG THE 426 00:17:38,160 --> 00:17:40,000 TEST POSITIVES WE CAN DO 427 00:17:40,000 --> 00:17:44,400 MANAGEMENT OR WHAT WE CALL 428 00:17:44,400 --> 00:17:47,960 TRIAGE TO SAY WE'LL CAN GET A 429 00:17:47,960 --> 00:17:50,440 BIOPSY FOR EXAMPLE. 430 00:17:50,440 --> 00:17:53,520 FOR THOSE WHO INDICATE 431 00:17:53,520 --> 00:17:55,560 PRECANCER, CANCER, WE MAY TREAT 432 00:17:55,560 --> 00:17:57,600 YOU FOR PRECANCER. 433 00:17:57,600 --> 00:18:00,840 SOME GETS COMBINED IF YOU THINK 434 00:18:00,840 --> 00:18:03,520 ABOUT COLONOSCOPY AND THE 435 00:18:03,520 --> 00:18:04,600 DIAGNOSIS ARE ALL PART OF ONE. 436 00:18:04,600 --> 00:18:05,880 I WANTED TO ILLUSTRATE THIS 437 00:18:05,880 --> 00:18:07,840 BECAUSE THE CHALLENGE GOING 438 00:18:07,840 --> 00:18:09,280 FORWARD FOR ANY CANCER SCREENING 439 00:18:09,280 --> 00:18:11,320 OR INTERVENTION IS HOW DO YOU 440 00:18:11,320 --> 00:18:12,720 MAXIMIZE THE BENEFITS AND 441 00:18:12,720 --> 00:18:14,520 MINIMIZE THE HARMS? 442 00:18:14,520 --> 00:18:17,160 THE REASON I'M EMPHASIZING THIS 443 00:18:17,160 --> 00:18:19,760 IS THAT MOST PEOPLE WHO COME IN 444 00:18:19,760 --> 00:18:21,040 FOR CANCER SCREENING DON'T HAVE 445 00:18:21,040 --> 00:18:22,560 CANCER. 446 00:18:22,560 --> 00:18:24,800 SO WHAT WE DO TO THEM ONLY 447 00:18:24,800 --> 00:18:25,840 CONTRIBUTES TO THE HARMS. 448 00:18:25,840 --> 00:18:28,280 SO WHEN YOU TALK ABOUT A 449 00:18:28,280 --> 00:18:29,960 POPULATION INTERVENTION IT'S 450 00:18:29,960 --> 00:18:30,760 REALLY IMPORTANT TO CONSIDER 451 00:18:30,760 --> 00:18:32,360 WHO'S GOING TO BENEFIT WHICH IS 452 00:18:32,360 --> 00:18:33,680 ONLY A SMALL TRACTION AND WHO IS 453 00:18:33,680 --> 00:18:34,600 GOING TO BE HARMED. 454 00:18:34,600 --> 00:18:37,400 SO COMING BACK TO THE EXAMPLE OF 455 00:18:37,400 --> 00:18:39,920 CERVIX, THE LIFE TIME RISK OF 456 00:18:39,920 --> 00:18:41,200 CERVICAL CANCER IF WE DIDN'T DO 457 00:18:41,200 --> 00:18:43,040 ANY SCREENING OR HAVE HPV 458 00:18:43,040 --> 00:18:44,120 VACCINATION IS 2%. 459 00:18:44,120 --> 00:18:48,160 THAT MEANS ONE OUT OF 50 WOMEN 460 00:18:48,160 --> 00:18:51,040 WILL GET CERVICAL CANCER AND 49 461 00:18:51,040 --> 00:18:52,080 OUT OF 50 WOULD BE PERFECTLY 462 00:18:52,080 --> 00:18:56,920 FINE IF WE LEFT THEM ALONE. 463 00:18:56,920 --> 00:18:59,560 WE HAVE TO BE COGNITIVE OF THE 464 00:18:59,560 --> 00:19:01,040 49 WHILE WE'RE SAVING THE ONE 465 00:19:01,040 --> 00:19:02,680 WHO MAY GET CANCER. 466 00:19:02,680 --> 00:19:03,880 SO WHAT ARE THE CURRENT 467 00:19:03,880 --> 00:19:04,240 RECOMMENDATIONS? 468 00:19:04,240 --> 00:19:07,400 I PUT THIS UP TO SAY, YES, WE 469 00:19:07,400 --> 00:19:10,600 CAN DO SCREENING AND TO REMIND 470 00:19:10,600 --> 00:19:12,680 THE AUDIENCE THERE'S 471 00:19:12,680 --> 00:19:13,320 EVIDENCE-BASED SCREENING THAT 472 00:19:13,320 --> 00:19:14,080 WILL SAVE LIVES. 473 00:19:14,080 --> 00:19:17,880 THESE ARE THE U.S. PREVENTIVE 474 00:19:17,880 --> 00:19:19,040 SERVICES RECOMMENDED CANCER 475 00:19:19,040 --> 00:19:20,240 RELATED SCREENING AND BREAST 476 00:19:20,240 --> 00:19:24,120 CANCER FOR WOMEN AGE 50 TO 74 477 00:19:24,120 --> 00:19:25,120 ILLUSTRATING WE DON'T DO BREAST 478 00:19:25,120 --> 00:19:26,200 CANCER SCREENING IN EVERYBODY 479 00:19:26,200 --> 00:19:27,320 BECAUSE THE RISK IS TO LOW ON 480 00:19:27,320 --> 00:19:29,840 THE OTHER SIDE OR THE HARMS ARE 481 00:19:29,840 --> 00:19:31,040 TOO GREAT. 482 00:19:31,040 --> 00:19:34,160 SO IT'S 50 TO 74 YEARS OF AGE 483 00:19:34,160 --> 00:19:39,840 AND THAT'S BIENNIAL OR EVERY TWO 484 00:19:39,840 --> 00:19:42,720 YEARS AND CERVIX WE SCREEN FROM 485 00:19:42,720 --> 00:19:48,360 21 TO 66 AND EXIT SCREENING AT 486 00:19:48,360 --> 00:19:53,000 65 IF THERE'S NO HISTORY AND 487 00:19:53,000 --> 00:19:59,080 FROM 30 TO 65 THEY CAN GET HPV 488 00:19:59,080 --> 00:20:09,720 TESTING WITH OR WITHOUT CI 489 00:20:16,680 --> 00:20:19,600 CYTOLOGY. 490 00:20:19,600 --> 00:20:21,040 WHEN YOU HAVE MANY CHOICES YOU 491 00:20:21,040 --> 00:20:22,360 WANT TO WORK WITH YOUR PROVIDER 492 00:20:22,360 --> 00:20:26,440 TO WORK WHAT'S BEST FOR YOU BUT 493 00:20:26,440 --> 00:20:28,080 EVERYBODY BETWEEN 75 MEN AND 494 00:20:28,080 --> 00:20:32,400 WOMEN NEED THEIR COLORECTAL 495 00:20:32,400 --> 00:20:39,680 CANCER SCREENING. 496 00:20:39,680 --> 00:20:40,600 AND THERE'S THE EXACT SCIENCE 497 00:20:40,600 --> 00:20:44,360 TECHNOLOGY THAT MEASURES GENOMIC 498 00:20:44,360 --> 00:20:54,040 CHANGES IN STOOL. 499 00:20:54,040 --> 00:20:56,400 THERE'S SIGMOIDOSCOPY AND THE 500 00:20:56,400 --> 00:21:04,360 GOLD STANDARD IS COLONOSCOPY AND 501 00:21:04,360 --> 00:21:07,200 WE HAVE -- THESE ARE NOT 502 00:21:07,200 --> 00:21:10,520 DIRECTLY CANCER SCREENING BUT 503 00:21:10,520 --> 00:21:13,120 SCREENING FOR HEPATITIS B AND C 504 00:21:13,120 --> 00:21:15,440 ARE TWO MAJOR CAUSES OF LIVER 505 00:21:15,440 --> 00:21:17,240 CANCER AND SURPRISINGLY FOR 506 00:21:17,240 --> 00:21:18,240 HEPATITIS B THERE'S STILL A 507 00:21:18,240 --> 00:21:19,760 FRACTION OF PEOPLE IN THE UNITED 508 00:21:19,760 --> 00:21:22,400 STATES WHO HAVE NOT BEEN 509 00:21:22,400 --> 00:21:24,400 VACCINATED AGAINST HBV. 510 00:21:24,400 --> 00:21:26,920 SO FOR HIGH-RISK INDIVIDUALS 511 00:21:26,920 --> 00:21:29,240 THEY SHOULD BE SCREENED FOR 512 00:21:29,240 --> 00:21:32,000 HEPATITIS B AND HEPATITIS C, 18 513 00:21:32,000 --> 00:21:34,320 TO 79 YEARS ALL YOU NEED IS ONE 514 00:21:34,320 --> 00:21:36,320 ROUND OF SCREENING BUT YOU'D BE 515 00:21:36,320 --> 00:21:38,760 SURPRISED AT HOW FEW PEOPLE KNOW 516 00:21:38,760 --> 00:21:41,720 THE RECOMMENDATION AND HOW FEW 517 00:21:41,720 --> 00:21:43,480 HAVE GOTTEN HEPATITIS C VIRUS 518 00:21:43,480 --> 00:21:44,040 SCREENING. 519 00:21:44,040 --> 00:21:45,920 AND LUNG CANCER SCREENING FOR 520 00:21:45,920 --> 00:21:46,600 HEAVY SMOKERS. 521 00:21:46,600 --> 00:21:48,200 THIS IS ANOTHER PROBLEM IN THE 522 00:21:48,200 --> 00:21:49,760 UNITED STATES THAT ONLY ABOUT 5% 523 00:21:49,760 --> 00:21:55,160 TO 10% OF THE HE WILL POPULATION 524 00:21:55,160 --> 00:21:57,080 FOR LUNG CANCER SCREENING BY 525 00:21:57,080 --> 00:21:59,600 TOMOGRAPHY HAVE GOTTEN IT AND 526 00:21:59,600 --> 00:22:01,240 LUNG CANCER'S A MAJOR KILLER IN 527 00:22:01,240 --> 00:22:01,800 THE UNITED STATES. 528 00:22:01,800 --> 00:22:03,720 I CAN'T ENCOURAGE PEOPLE ENOUGH 529 00:22:03,720 --> 00:22:08,320 WHO ARE AT HIGH RISK WHO HAVE 20 530 00:22:08,320 --> 00:22:12,880 PACK YEAR SMOKING HISTORY AND 531 00:22:12,880 --> 00:22:14,600 ARE CURRENT OR QUIT IN THE LAST 532 00:22:14,600 --> 00:22:16,880 15 YEARS TO GET THEIR CANCER 533 00:22:16,880 --> 00:22:17,840 SCREENING. 534 00:22:17,840 --> 00:22:20,160 HERE'S THE CITATION AND THE 535 00:22:20,160 --> 00:22:20,600 WEBSITE TO SEE THE 536 00:22:20,600 --> 00:22:30,120 RECOMMENDATIONS. 537 00:22:30,120 --> 00:22:37,840 AND THE STUDY I LEARNED SO MUCH 538 00:22:37,840 --> 00:22:39,040 FROM AND I CONTINUE TO SEE NEW 539 00:22:39,040 --> 00:22:40,400 THINGS ALL THE TIME AND CONTINUE 540 00:22:40,400 --> 00:22:41,680 TO LEARN FROM IT. 541 00:22:41,680 --> 00:22:43,480 THE BUT THE FIRST THING TO 542 00:22:43,480 --> 00:22:45,680 RECOGNIZE IS WHY WAS THE CERVIX 543 00:22:45,680 --> 00:22:47,800 OR CERVICAL CANCER SCREENING THE 544 00:22:47,800 --> 00:22:50,160 LOW HANGING FRUIT OF CANCER 545 00:22:50,160 --> 00:22:50,480 PREVENTION? 546 00:22:50,480 --> 00:22:52,320 FIRST, IT'S A SLOW GROWING 547 00:22:52,320 --> 00:22:53,120 CANCER. 548 00:22:53,120 --> 00:22:55,160 THE TIME FROM HPV EXPOSURE TO 549 00:22:55,160 --> 00:22:56,600 CANCER IS 20 TO 25 YEARS ON 550 00:22:56,600 --> 00:22:57,600 AVERAGE. 551 00:22:57,600 --> 00:23:04,400 WE'RE LUCKY WE HAVE A SINGLE 552 00:23:04,400 --> 00:23:05,800 ET 553 00:23:05,800 --> 00:23:06,280 ET 554 00:23:06,280 --> 00:23:08,320 ET 555 00:23:08,320 --> 00:23:11,920 ET -- ETIOLOGY AND MOST WOMEN 556 00:23:11,920 --> 00:23:14,600 WILL TOLERATE GETTING A PAP 557 00:23:14,600 --> 00:23:17,480 SAMPLE WHETHER FOR CYTOLOGY OR 558 00:23:17,480 --> 00:23:19,240 HPV AND THERE'S NO ISSUE. 559 00:23:19,240 --> 00:23:25,840 THERE'S A SMALL AREA OF 560 00:23:25,840 --> 00:23:26,200 SUSCEPTIBILITY. 561 00:23:26,200 --> 00:23:30,680 THE MOST CANCERS HAPPEN IN A 562 00:23:30,680 --> 00:23:32,960 SMALL TISSUE OF SKRAUMAL TISSUE 563 00:23:32,960 --> 00:23:35,880 AND IT'S LIKELY TO BE INFECTED 564 00:23:35,880 --> 00:23:39,600 BY HPV AND BIGGER SURFACE AREA 565 00:23:39,600 --> 00:23:42,000 SO IT'S A UNIQUE BIOLOGICAL 566 00:23:42,000 --> 00:23:44,400 INTERACTION BETWEEN THE SMALL 567 00:23:44,400 --> 00:23:48,400 AREA OF SUSCEPTIBILITY AND THE 568 00:23:48,400 --> 00:23:49,440 HUMAN PAPILLOMA INFECTION. 569 00:23:49,440 --> 00:23:53,720 AND THE TEST IS NOT NECESSARILY 570 00:23:53,720 --> 00:23:56,280 GOOD BUT HELPED ELUCIDATE THE 571 00:23:56,280 --> 00:23:57,880 NATURAL HISTORY AND 572 00:23:57,880 --> 00:24:01,560 IDENTIFICATION OF THE PRECURSOR 573 00:24:01,560 --> 00:24:05,360 OF THE CIN3 THAT SERVES AS A 574 00:24:05,360 --> 00:24:06,480 SURROGATE FOR CANCER. 575 00:24:06,480 --> 00:24:07,160 WHY'S THAT IMPORTANT? 576 00:24:07,160 --> 00:24:08,640 BECAUSE IT'S ALLOWED US TO CYCLE 577 00:24:08,640 --> 00:24:10,560 THROUGH DIFFERENT INTERVENTIONS 578 00:24:10,560 --> 00:24:12,400 QUICKLY WITHOUT HAVING TO WAIT 579 00:24:12,400 --> 00:24:16,920 FOR THE ACCUMULATION OF CANCER 580 00:24:16,920 --> 00:24:18,840 WE CAN SAY IT WORKS OR DOESN'T 581 00:24:18,840 --> 00:24:22,200 WORK AND WE CAN STOP PURSUING 582 00:24:22,200 --> 00:24:23,400 THAT WITHOUT GOING TOO CANCER 583 00:24:23,400 --> 00:24:24,400 END POINT WHICH TAKES MUCH 584 00:24:24,400 --> 00:24:28,560 LONGER AND IS MUCH MORE 585 00:24:28,560 --> 00:24:33,040 EXPENSIVE. 586 00:24:33,040 --> 00:24:35,480 OVER THE LAST 25 YEARS AND 587 00:24:35,480 --> 00:24:37,280 STARTED WITH TO THE DISCOVERY OF 588 00:24:37,280 --> 00:24:44,200 HPV IN CANCERS IN THE LATE '80s 589 00:24:44,200 --> 00:24:46,680 AND THE FOUNDER GOT A NOBEL 590 00:24:46,680 --> 00:24:50,040 PRIZE LAUREATE IN 2008 AND YOU 591 00:24:50,040 --> 00:24:53,640 SEE WHAT A CYTOPATHOLOGIST HAS 592 00:24:53,640 --> 00:24:56,280 SEE AND IT'S COME TO FOUR 593 00:24:56,280 --> 00:24:56,520 STAGES. 594 00:24:56,520 --> 00:24:59,680 NORMAL INFECTED, PRECANCER AND 595 00:24:59,680 --> 00:24:59,880 CANCER. 596 00:24:59,880 --> 00:25:03,880 UP TOP YOU SEE CYTOLOGY AND IN 597 00:25:03,880 --> 00:25:12,560 THE MIDDLE YOU SEE WHAT THE 598 00:25:12,560 --> 00:25:15,720 COLPOSCOPIST SEES AND THE 599 00:25:15,720 --> 00:25:20,400 CYTOLOGY IS JUST INFECTION 600 00:25:20,400 --> 00:25:21,520 TYPICALLY WE SEE HPV INFECTION 601 00:25:21,520 --> 00:25:23,720 PEAK ABOUT FIVE YEARS AFTER THE 602 00:25:23,720 --> 00:25:26,760 AGE OF FIRST SEXUAL INITIATION. 603 00:25:26,760 --> 00:25:29,520 IN THIS COUNTRY IT'S AROUND 20, 604 00:25:29,520 --> 00:25:32,360 25 YEARS OF AGE BECAUSE THE 605 00:25:32,360 --> 00:25:34,600 MEDIAN AGE OF SEXUAL INITIATION 606 00:25:34,600 --> 00:25:38,600 IN THE UNITED STATES IS AROUND 607 00:25:38,600 --> 00:25:38,760 16. 608 00:25:38,760 --> 00:25:40,320 PRE CANCER OCCURS A FEW YEARS 609 00:25:40,320 --> 00:25:41,400 AFTER THAT WHEN WE GO IN THE 610 00:25:41,400 --> 00:25:41,960 POPULATION. 611 00:25:41,960 --> 00:25:44,360 WE TEND TO SEE A PEAK AROUND 25 612 00:25:44,360 --> 00:25:48,200 TO 30 AND CANCER IS ANOTHER 10 613 00:25:48,200 --> 00:25:50,000 TO 15 TO 20 YEARS AFTER THAT. 614 00:25:50,000 --> 00:25:52,080 FOR THE PATHOLOGISTS ON THE 615 00:25:52,080 --> 00:25:56,400 LINE, YOU OBVIOUSLY YOU CAN SEE 616 00:25:56,400 --> 00:26:04,360 VERY CLEARLY HERE THE OLD 617 00:26:04,360 --> 00:26:10,120 CYTOLOGIC CITOSYS AND SO WE'VE 618 00:26:10,120 --> 00:26:13,720 BEEN LOOKING AT HPV FOR OVER 50 619 00:26:13,720 --> 00:26:16,320 YEARS SINCE THE AMERICAN CANCER 620 00:26:16,320 --> 00:26:18,680 SOCIETY RECOMMENDED PAP SMEARS 621 00:26:18,680 --> 00:26:20,360 BACK IN THE EARLY '50s. 622 00:26:20,360 --> 00:26:25,680 NOW WE HAVE THE MEC MOLECULAR 623 00:26:25,680 --> 00:26:27,000 BASIS ONE LEADING TO VACCINATION 624 00:26:27,000 --> 00:26:28,400 AND SCREENING. 625 00:26:28,400 --> 00:26:32,400 WE MOVED FROM THE OLD STRATEGY 626 00:26:32,400 --> 00:26:40,360 FOR PREVENTION WHICH IS TO DO 627 00:26:40,360 --> 00:26:46,320 REPEATED PAP TESTS AND HIGH 628 00:26:46,320 --> 00:26:48,160 FREQUENT AND TRY TO VACCINE 629 00:26:48,160 --> 00:26:50,680 BEFORE SEXUALLY ACTIVITY AND 630 00:26:50,680 --> 00:26:52,400 APPLY A FEW HPV TESTS ON THE 631 00:26:52,400 --> 00:26:53,960 LIFE TIME DEPENDING ON THE 632 00:26:53,960 --> 00:26:55,600 RESOURCES OF THE COUNTRY TO FIND 633 00:26:55,600 --> 00:26:58,480 THE HPV INFECTIONS THAT 634 00:26:58,480 --> 00:27:00,320 DEVELOPED INTO CANCER AND PRE 635 00:27:00,320 --> 00:27:00,560 CANCER. 636 00:27:00,560 --> 00:27:04,240 THIS HAS PLAYED OUT AND I WON'T 637 00:27:04,240 --> 00:27:05,440 SHOW YOU HPV VACCINATION IT'S 638 00:27:05,440 --> 00:27:07,240 NOT PART OF THE TALK BUT WHEN WE 639 00:27:07,240 --> 00:27:10,000 LOOK AT DATA LIKE THIS A 640 00:27:10,000 --> 00:27:12,360 RANDOMIZED CONTROL TRIAL DATA 641 00:27:12,360 --> 00:27:16,360 FROM EUROPE FROM FOUR CLINICAL 642 00:27:16,360 --> 00:27:16,600 TRIALS. 643 00:27:16,600 --> 00:27:19,840 IN THE RED IS THE CYTOLOGY ARM 644 00:27:19,840 --> 00:27:24,000 AND IN THE BLUE IS THE HPV ARM. 645 00:27:24,000 --> 00:27:25,800 ON THE LEFT IS ALL WOMEN, YOU 646 00:27:25,800 --> 00:27:28,800 SEE A 50% REDUCTION IN THE 647 00:27:28,800 --> 00:27:31,480 INCIDENTS OF INVASIVE CERVICAL 648 00:27:31,480 --> 00:27:33,400 CANCER WITH ONE ROUND OF HPV 649 00:27:33,400 --> 00:27:39,440 TESTING ED COMPARED TO 650 00:27:39,440 --> 00:27:39,680 CYTOLOGY. 651 00:27:39,680 --> 00:27:41,840 ON THE WHITE SIDE YOU SEE WOMEN 652 00:27:41,840 --> 00:27:44,400 WHO TESTED NEGATIVE AND COMES 653 00:27:44,400 --> 00:27:46,600 BACK TO THE RULE OUT I SAID 654 00:27:46,600 --> 00:27:48,200 BEFORE ONCE YOU SAID THEY'RE HPV 655 00:27:48,200 --> 00:27:49,920 NEGATIVE THEIR RISK IS REALLY 656 00:27:49,920 --> 00:27:50,520 LOW. 657 00:27:50,520 --> 00:27:51,960 WHY IS THAT IMPORTANT? 658 00:27:51,960 --> 00:27:53,720 IF THEY'RE HPV NEGATIVE WE DON'T 659 00:27:53,720 --> 00:27:55,520 NEED TO SCREEN YOU EVERY ONE, 660 00:27:55,520 --> 00:27:57,320 TWO OR THREE YEARS, WE CAN 661 00:27:57,320 --> 00:27:59,680 SCREEN YOU FIVE OR MORE YEARS 662 00:27:59,680 --> 00:28:00,960 WHICH REDUCES THE HARMS. 663 00:28:00,960 --> 00:28:03,280 GOING BACK TO THE SCALE OF 664 00:28:03,280 --> 00:28:06,000 TRYING TO MAXIMIZE BENEFIT AND 665 00:28:06,000 --> 00:28:06,400 MINIMIZE HARMS. 666 00:28:06,400 --> 00:28:10,600 SCREEN THOSE PEOPLE AT RISK MORE 667 00:28:10,600 --> 00:28:12,400 HEAVILY, MORE FREQUENTLY AND 668 00:28:12,400 --> 00:28:15,440 SCREEN THOSE AT LOW RISK LESS 669 00:28:15,440 --> 00:28:16,000 FREQUENTLY. 670 00:28:16,000 --> 00:28:17,840 HERE'S THE BAD NEWS OR THE 671 00:28:17,840 --> 00:28:22,600 FAILURE WHICH IS PSA TESTING. 672 00:28:22,600 --> 00:28:28,360 SO BACK IN 1986 PSA TESTING WAS 673 00:28:28,360 --> 00:28:30,520 USED FOR MONITORING PROSTATE 674 00:28:30,520 --> 00:28:31,240 CANCER PROGRESSION. 675 00:28:31,240 --> 00:28:33,680 BY 1988 IT WAS INTRODUCED FOR 676 00:28:33,680 --> 00:28:35,160 SCREENING DESPITE THE LACK OF 677 00:28:35,160 --> 00:28:36,200 EVIDENCE. 678 00:28:36,200 --> 00:28:40,600 THE NCI IN 1990s START THE 679 00:28:40,600 --> 00:28:44,400 PROSTATE LUNG, COLORECTAL AND 680 00:28:44,400 --> 00:28:47,920 LUNG TRIAL AND THE EUROPEANS DID 681 00:28:47,920 --> 00:28:50,680 LIKEWISE AND BY 2000 THEY FOUND 682 00:28:50,680 --> 00:28:54,680 LITTLE TO NO MORTALITY REDUCTION 683 00:28:54,680 --> 00:28:56,000 AND OVERDIAGNOSIS. 684 00:28:56,000 --> 00:28:58,400 THERE WAS CONTAMINATION OF THE 685 00:28:58,400 --> 00:29:00,360 CONTROL ARM OVER ALL IT WAS A 686 00:29:00,360 --> 00:29:02,000 LITTLE BIT OF A MORTALITY 687 00:29:02,000 --> 00:29:08,400 REDUCTION DUE TO THE PSA BUT THE 688 00:29:08,400 --> 00:29:14,000 HARMS ASSOCIATED THAT HAS GIVEN 689 00:29:14,000 --> 00:29:15,840 POSITIVE PSA AND THEY SAID DON'T 690 00:29:15,840 --> 00:29:18,760 DO PSA SCREENING AND NOW THEY 691 00:29:18,760 --> 00:29:22,280 BROUGHT IT BACK IN 2018 TO DO IT 692 00:29:22,280 --> 00:29:23,160 IN AN INFORMED DECISION MAKE 693 00:29:23,160 --> 00:29:24,400 PROCESS WITH YOUR PROVIDER AND 694 00:29:24,400 --> 00:29:26,080 THE IDEA IS THAT THERE ARE SOME 695 00:29:26,080 --> 00:29:28,120 PEOPLE WHO ARE AT HIGHER RISK 696 00:29:28,120 --> 00:29:29,960 AND WOULD BENEFIT. 697 00:29:29,960 --> 00:29:31,320 AGAIN, THAT BENEFITS THE HARMS. 698 00:29:31,320 --> 00:29:33,040 THAT'S WHAT WE ALWAYS COME BACK 699 00:29:33,040 --> 00:29:35,400 TO WHEN WE COME BACK TO 700 00:29:35,400 --> 00:29:35,680 SCREENING. 701 00:29:35,680 --> 00:29:37,760 HOW MANY PEOPLE WILL BENEFIT AND 702 00:29:37,760 --> 00:29:38,760 HOW MANY WILL BE HARMED? 703 00:29:38,760 --> 00:29:41,200 THE SUMMARY OF THE STORY IS WHEN 704 00:29:41,200 --> 00:29:42,560 WE THINK ABOUT INTRODUCING 705 00:29:42,560 --> 00:29:43,680 SOMETHING INTO THE POPULATION, 706 00:29:43,680 --> 00:29:45,120 WE NEED TO UNDERSTAND IT. 707 00:29:45,120 --> 00:29:48,240 WE NEED TO MAXIMIZE THE BENEFITS 708 00:29:48,240 --> 00:29:50,280 TO HARMS. 709 00:29:50,280 --> 00:29:51,120 RANDOMIZED TRIALS ARE NOT 710 00:29:51,120 --> 00:29:52,840 PERFECT AS I'VE ILLUSTRATED OR 711 00:29:52,840 --> 00:29:54,800 CAN'T ALWAYS BE DONE AND THEY 712 00:29:54,800 --> 00:29:57,200 CAN BE LIMITED AND THE ANSWERS 713 00:29:57,200 --> 00:29:58,600 MAY NOT BE STRAIGHTFORWARD 714 00:29:58,600 --> 00:30:00,360 PARTICULARLY WHEN YOU THINK 715 00:30:00,360 --> 00:30:02,880 ABOUT ISSUES OF COMPLIANCE AND 716 00:30:02,880 --> 00:30:05,560 CONTAMINATION IN YOUR CONTROL 717 00:30:05,560 --> 00:30:06,680 ARM. 718 00:30:06,680 --> 00:30:08,360 YOU CAN'T SIMPLY COMPARE 719 00:30:08,360 --> 00:30:11,760 INCIDENTS OF SCREEN AND CONTROL 720 00:30:11,760 --> 00:30:12,360 ARMS. 721 00:30:12,360 --> 00:30:14,560 OUTCOMES OF SCREENING DEPEND ON 722 00:30:14,560 --> 00:30:15,760 DISEASE NATURAL HISTORY AND MUST 723 00:30:15,760 --> 00:30:17,000 UNDERSTAND IT TO SCREEN SMARTLY. 724 00:30:17,000 --> 00:30:21,040 THAT WAS ILLUSTRATED WITH THE 725 00:30:21,040 --> 00:30:23,160 CERVIX MODEL BY UNDERSTANDING 726 00:30:23,160 --> 00:30:25,440 THAT NATURAL HISTORY WE KNOW -- 727 00:30:25,440 --> 00:30:28,400 WE WANT TO VACCINE YOUNG KIDS, 728 00:30:28,400 --> 00:30:30,920 PRE TEENS BECAUSE THEY DON'T 729 00:30:30,920 --> 00:30:37,680 HAVE HVP VET -- YET AND YOUNG 730 00:30:37,680 --> 00:30:38,720 PEOPLE IT'S BETTER TO SCREEN 731 00:30:38,720 --> 00:30:40,400 THAN VACCINE BECAUSE SOME 732 00:30:40,400 --> 00:30:42,360 ALREADY HAVE HPV THAT ABOUT TO 733 00:30:42,360 --> 00:30:44,120 GO ON TO CANCER. 734 00:30:44,120 --> 00:30:45,320 OUTCOMES OF SCREENING DEPEND HOW 735 00:30:45,320 --> 00:30:46,600 YOU USE THE TEST IN PRACTICE. 736 00:30:46,600 --> 00:30:48,720 YOU CAN TURN A POSITIVE INTO A 737 00:30:48,720 --> 00:30:49,520 NEGATIVE TEST IF YOU DON'T 738 00:30:49,520 --> 00:30:50,360 SCREEN SMARTLY. 739 00:30:50,360 --> 00:30:53,680 I THINK THE PSA CAN BE REVISED. 740 00:30:53,680 --> 00:30:56,240 THE WAY IS BY USING A 741 00:30:56,240 --> 00:30:57,440 RISK-INFORMED STRATEGY WHERE YOU 742 00:30:57,440 --> 00:30:58,640 TAKE A BAYESIAN VIEW AND 743 00:30:58,640 --> 00:31:01,240 CONTINUE TO UPDATE THE RISK 744 00:31:01,240 --> 00:31:03,760 BASED ON THE INFORMATION YOU 745 00:31:03,760 --> 00:31:06,200 HAVE AND YOU DECIDE WHETHER 746 00:31:06,200 --> 00:31:10,120 TREATMENT BIOPSY AND INCREASED 747 00:31:10,120 --> 00:31:12,400 SURVEILLANCE OR ROUTINE 748 00:31:12,400 --> 00:31:16,360 SCREENING ARE APPROPRIATE. 749 00:31:16,360 --> 00:31:20,040 AND WE USE THE PSA AS A LEAD-IN 750 00:31:20,040 --> 00:31:22,560 TO MULTI-CANCER DETECTION 751 00:31:22,560 --> 00:31:24,920 BECAUSE I'M AFRAID THIS HAS A 752 00:31:24,920 --> 00:31:25,880 TREMENDOUS POTENTIAL. 753 00:31:25,880 --> 00:31:28,040 THERE'S A LOT OF HOPE BUT 754 00:31:28,040 --> 00:31:31,440 THERE'S A LOT OF HYPE AND WHAT'S 755 00:31:31,440 --> 00:31:33,520 TRUE IS WE DON'T KNOW HOW THE 756 00:31:33,520 --> 00:31:34,600 TESTS WILL WORK IN THE GENERAL 757 00:31:34,600 --> 00:31:34,880 POPULATION. 758 00:31:34,880 --> 00:31:39,560 THIS IS A GRAPHIC FROM MY 759 00:31:39,560 --> 00:31:41,640 COMMUNICATIONS TEAM WITH CANCER 760 00:31:41,640 --> 00:31:42,880 PREVENTION AND A WONDERFUL 761 00:31:42,880 --> 00:31:46,080 ILLUSTRATION THERE'S MANY 762 00:31:46,080 --> 00:31:46,800 TECHNOLOGIES EMERGING WE DON'T 763 00:31:46,800 --> 00:31:51,720 KNOW HOW WELL THEY WORK AND THIS 764 00:31:51,720 --> 00:31:54,240 IS A SUBSET AND THERE'S PROBABLY 765 00:31:54,240 --> 00:31:55,440 DOUBLE THE NUMBER BEING 766 00:31:55,440 --> 00:31:56,280 DEVELOPED AND SOME WHICH WE 767 00:31:56,280 --> 00:31:58,600 DON'T KNOW AND PROBABLY ANOTHER 768 00:31:58,600 --> 00:32:00,880 20 TO 50 ACADEMIC CENTERS 769 00:32:00,880 --> 00:32:02,120 DEVELOPING A TEST. 770 00:32:02,120 --> 00:32:03,440 THIS IS A WHOLE NEW FIELD. 771 00:32:03,440 --> 00:32:04,640 WE'VE NEVER SEEN ANYTHING LIKE 772 00:32:04,640 --> 00:32:07,000 IT AND THE CARTOON ON THE RIGHT 773 00:32:07,000 --> 00:32:13,160 SAYS I THINK I'D LIKE TO HAVE AN 774 00:32:13,160 --> 00:32:15,920 MCED TEST, DOC, BUT I DON'T KNOW 775 00:32:15,920 --> 00:32:18,520 WHICH ONE AND RIGHT NOW WE DON'T 776 00:32:18,520 --> 00:32:23,200 HAVE ADVICE FOR ANYONE. 777 00:32:23,200 --> 00:32:24,800 BACKGROUND IN ASSAY. 778 00:32:24,800 --> 00:32:25,680 EACH MEASURES DIFFERENT 779 00:32:25,680 --> 00:32:26,840 MOLECULAR PROFILES IN BLOOD FOR 780 00:32:26,840 --> 00:32:27,760 DIFFERENT SET OF CANCERS. 781 00:32:27,760 --> 00:32:30,360 A POSITIVE RESULT IS A SIGNAL 782 00:32:30,360 --> 00:32:32,400 FOR CANCER BUT NOT DIAGNOSED 783 00:32:32,400 --> 00:32:32,760 CANCER. 784 00:32:32,760 --> 00:32:35,360 SOME TESTS SUGGEST TISSUE OF 785 00:32:35,360 --> 00:32:40,360 ORIGIN, SOME TESTS REQUIRE 786 00:32:40,360 --> 00:32:41,440 EXTENSIVE IMAGING. 787 00:32:41,440 --> 00:32:42,560 THEY'RE UNDER DEVELOPMENT SO 788 00:32:42,560 --> 00:32:43,720 GETTING THEM LOCKED DOWN AND 789 00:32:43,720 --> 00:32:44,640 KNOWING HOW THEY PERFORM IS A 790 00:32:44,640 --> 00:32:48,280 MOVING TARGET. 791 00:32:48,280 --> 00:32:49,960 THIS IS A SUBSET OF A SUBSET I 792 00:32:49,960 --> 00:32:52,840 SHOWED YOU AND YOU CAN SEE THE 793 00:32:52,840 --> 00:32:54,880 COMPLEXITY OF THE FIELD. 794 00:32:54,880 --> 00:32:58,320 I LISTED HERE A HANDFUL OF THESE 795 00:32:58,320 --> 00:32:59,600 THAT ARE DIFFERENT COMPANIES, 796 00:32:59,600 --> 00:33:02,200 DIFFERENT NAMES, DIFFERENT 797 00:33:02,200 --> 00:33:02,520 TECHNOLOGIES. 798 00:33:02,520 --> 00:33:07,320 EVERYTHING FROM CFDNA ROBERT 799 00:33:07,320 --> 00:33:14,880 WILL BE TALKING ABOUT TO 800 00:33:14,880 --> 00:33:15,480 PRAGMA 801 00:33:15,480 --> 00:33:16,280 PRAGMATTOMICS AND WHICH ONE IS 802 00:33:16,280 --> 00:33:17,520 BEST FOR YOU? 803 00:33:17,520 --> 00:33:19,720 I DON'T KNOW WHICH IS BEST FOR 804 00:33:19,720 --> 00:33:23,120 ME BUT SAY A BRCA PATIENT WOULD 805 00:33:23,120 --> 00:33:24,440 PROBABLY WANT FOR PANCREAS, 806 00:33:24,440 --> 00:33:28,400 BREAST AND OVARIES. 807 00:33:28,400 --> 00:33:30,680 I THINK IT'S EXCITING FOR 808 00:33:30,680 --> 00:33:32,360 CANCERS FOR WHICH WE DON'T HAVE 809 00:33:32,360 --> 00:33:35,480 TESTS LIKE PANCREAS AND OVARY 810 00:33:35,480 --> 00:33:39,040 WHICH ARE LETHAL CANCERS BUT 811 00:33:39,040 --> 00:33:40,600 HAVE NO DATA TO SHOW THEY YET 812 00:33:40,600 --> 00:33:43,000 WORK I'LL TALK ABOUT IN THE NEXT 813 00:33:43,000 --> 00:33:43,440 SLIDE. 814 00:33:43,440 --> 00:33:46,920 IT'S UNKNOWN IF A SYMPTOMATIC 815 00:33:46,920 --> 00:33:48,400 PEOPLE WITH CANCER WITH ASSAYS 816 00:33:48,400 --> 00:33:49,800 WILL RESULT IN MORTALITY 817 00:33:49,800 --> 00:33:50,800 REDUCTION OF CANCER. 818 00:33:50,800 --> 00:33:55,400 THE WHOLE POINT OF SCREENING, IS 819 00:33:55,400 --> 00:33:58,720 TO REDUCE MORTALITY. 820 00:33:58,720 --> 00:34:00,880 FOR MANY OF THESE WE HAVE NO 821 00:34:00,880 --> 00:34:01,240 DATA. 822 00:34:01,240 --> 00:34:03,880 ALL THEY'VE SHOWN IS WE CAN 823 00:34:03,880 --> 00:34:05,960 DETECT CANCER. 824 00:34:05,960 --> 00:34:07,440 CAN WE SAVE LIVES? 825 00:34:07,440 --> 00:34:09,280 THAT'S THE KEY ISSUES. 826 00:34:09,280 --> 00:34:10,760 THERE'S POTENTIAL HARMS 827 00:34:10,760 --> 00:34:12,840 ASSOCIATED WITH THE ASSAYS. 828 00:34:12,840 --> 00:34:14,560 HOW MANY DIAGNOSTIC TESTS ARE 829 00:34:14,560 --> 00:34:17,960 NEEDED TO MAKE THE CANCER 830 00:34:17,960 --> 00:34:18,320 DIAGNOSIS? 831 00:34:18,320 --> 00:34:19,600 WHAT HAPPENS FOLLOWING A 832 00:34:19,600 --> 00:34:21,440 POSITIVE MCED TEST IF YOU DON'T 833 00:34:21,440 --> 00:34:23,400 FIND A CANCER, HOW MANY INVASIVE 834 00:34:23,400 --> 00:34:25,680 PROCEDURES AND WHAT WILL BE THE 835 00:34:25,680 --> 00:34:26,680 HARMS AND COMPLICATIONS 836 00:34:26,680 --> 00:34:29,240 ASSOCIATED WITH THE PROCEDURES? 837 00:34:29,240 --> 00:34:32,360 WILL PEOPLE STOP GETTING THE 838 00:34:32,360 --> 00:34:33,280 STANDARD OF CARE SCREENING? 839 00:34:33,280 --> 00:34:38,120 NAY GET -- IF THEY GET A 840 00:34:38,120 --> 00:34:39,960 NEGATIVE AND WILL IT LEAD TO 841 00:34:39,960 --> 00:34:42,000 OVER DIAGNOSIS OF UNKNOWN 842 00:34:42,000 --> 00:34:42,360 CANCERS? 843 00:34:42,360 --> 00:34:45,800 WE HAVE STOOD UP A MULTI-PRONGED 844 00:34:45,800 --> 00:34:47,680 RESEARCH PROGRAM. 845 00:34:47,680 --> 00:34:49,520 A MULTI-LEVEL RESEARCH PROGRAM 846 00:34:49,520 --> 00:34:52,840 AT THE NCI TO STUDY THESE FROM 847 00:34:52,840 --> 00:34:54,840 BASIC SCIENCE TO CLINICAL 848 00:34:54,840 --> 00:34:55,080 TRIALS. 849 00:34:55,080 --> 00:34:57,320 OF COURSE IF ANY OF THESE WORK 850 00:34:57,320 --> 00:34:58,320 BECAUSE WITH A LITTLE KNOW ABOUT 851 00:34:58,320 --> 00:35:00,840 MORE ABOUT THE NATURAL HISTORY 852 00:35:00,840 --> 00:35:02,720 WE'LL BE ABLE TO MAKE BETTER 853 00:35:02,720 --> 00:35:04,040 MCED TESTS AND WILL PROBABLY 854 00:35:04,040 --> 00:35:07,640 SPUR THE DEVELOPMENT OF NEW 855 00:35:07,640 --> 00:35:08,640 THERAPIES BECAUSE WE'LL SEE 856 00:35:08,640 --> 00:35:10,640 CANCERS AT A MOLECULAR STAGE 857 00:35:10,640 --> 00:35:15,240 WE'VE NEVER SEEN BEFORE. 858 00:35:15,240 --> 00:35:19,520 THIS IS A CARTOON OF THE TRIAL 859 00:35:19,520 --> 00:35:23,440 WE'RE PROPOSING COMPARING MCEDs 860 00:35:23,440 --> 00:35:29,280 VERSUS DIFFERENT ARMS AND THEY 861 00:35:29,280 --> 00:35:31,200 DETECT DIFFERENT TISSUES FOR 862 00:35:31,200 --> 00:35:34,120 CANCER AND SO THEY'RE NOT REALLY 863 00:35:34,120 --> 00:35:34,600 DIRECTLY COMPARABLE. 864 00:35:34,600 --> 00:35:37,080 ONLY DIRECTLY COMPARABLE TO THE 865 00:35:37,080 --> 00:35:40,360 STANDARD OF CARE ARM FOR MANY 866 00:35:40,360 --> 00:35:40,960 CANCERS THERE'S NO SCREENING 867 00:35:40,960 --> 00:35:42,680 TEST. 868 00:35:42,680 --> 00:35:43,640 AND MORTALITY WILL BE THE 869 00:35:43,640 --> 00:35:47,280 PRIMARY OUTCOME. 870 00:35:47,280 --> 00:35:48,760 THAT'S UNEQUIVOCAL. 871 00:35:48,760 --> 00:35:52,200 YOU CAN'T ARGUE IF YOU REDUCE 872 00:35:52,200 --> 00:35:54,080 MORTALITY RELATED TO THESE 873 00:35:54,080 --> 00:35:54,400 CANCERS. 874 00:35:54,400 --> 00:35:55,480 NOBODY CAN ARGUE WHETHER OR NOT 875 00:35:55,480 --> 00:35:56,400 THOSE WERE THE RIGHT CANCERS TO 876 00:35:56,400 --> 00:35:58,400 FIND. 877 00:35:58,400 --> 00:36:03,360 SO I WANT TO TALK ABOUT CANCER 878 00:36:03,360 --> 00:36:05,320 HEALTH DISPARITIES AND I'LL COME 879 00:36:05,320 --> 00:36:09,480 BACK TO HPV AND CERVICAL CANCER. 880 00:36:09,480 --> 00:36:11,080 YOU SEE MORTALITY RATES FOR THE 881 00:36:11,080 --> 00:36:12,120 WORLD AND THE TREMENDOUS 882 00:36:12,120 --> 00:36:14,080 DISPARITIES ACROSS THE WORLD. 883 00:36:14,080 --> 00:36:16,360 IT'S REALLY AN ORDER OF 884 00:36:16,360 --> 00:36:18,640 MAGNITUDE DIFFERENCE BETWEEN THE 885 00:36:18,640 --> 00:36:21,680 RATES IN AFRICA AND IN THE 886 00:36:21,680 --> 00:36:24,200 WESTERN WORLD ILLUSTRATED IN THE 887 00:36:24,200 --> 00:36:26,760 UNITED STATES IN THE LIGHT PINK 888 00:36:26,760 --> 00:36:28,920 FOR RED VERSUS THE DARK RED IN 889 00:36:28,920 --> 00:36:29,440 AFRICA. 890 00:36:29,440 --> 00:36:31,320 WE HAVE IMPORTANT HEALTH 891 00:36:31,320 --> 00:36:32,360 DISPARITIES HERE IN THE UNITED 892 00:36:32,360 --> 00:36:32,600 STATES. 893 00:36:32,600 --> 00:36:35,280 YOU CAN SEE THAT IN THE SOUTHERN 894 00:36:35,280 --> 00:36:37,080 STATES PARTICULARLY AROUND THE 895 00:36:37,080 --> 00:36:39,080 MISSISSIPPI DELTA AND THE STATE 896 00:36:39,080 --> 00:36:40,400 OF MISSISSIPPI THEY HAVE MUCH 897 00:36:40,400 --> 00:36:42,800 HIGHER RATES THAN YOU WOULD SEE 898 00:36:42,800 --> 00:36:45,880 IN OTHER PARTS OF THE COUNTRY. 899 00:36:45,880 --> 00:36:51,400 SO DESPITE OUR ADVANCES IN 900 00:36:51,400 --> 00:36:52,360 UNIVER 901 00:36:52,360 --> 00:36:57,200 UNDERSTANDING CERVICAL KAECANCE 902 00:36:57,200 --> 00:36:59,400 AND TARGETING HUMAN PAPILLOMA 903 00:36:59,400 --> 00:37:03,360 STRATEGY THERE'S THE HAVEs AND 904 00:37:03,360 --> 00:37:03,840 HAVE-NOTs. 905 00:37:03,840 --> 00:37:04,640 ONE WAY TO INCREASE SCREENING IN 906 00:37:04,640 --> 00:37:08,240 THE POPULATIONS IS TO USE 907 00:37:08,240 --> 00:37:08,640 SELF-COLLECTION. 908 00:37:08,640 --> 00:37:11,880 THOUGH WOMEN WILL UNDER GO 909 00:37:11,880 --> 00:37:14,360 PELVIC EXAMS, NOT ALL WOMEN WILL 910 00:37:14,360 --> 00:37:16,360 AND IT REQUIRES OBVIOUSLY TRAVEL 911 00:37:16,360 --> 00:37:17,800 AND APPOINTMENT AND THINGS LIKE 912 00:37:17,800 --> 00:37:18,080 THAT. 913 00:37:18,080 --> 00:37:19,960 IT'S A REAL CHALLENGE FOR MANY 914 00:37:19,960 --> 00:37:21,600 WOMEN TO UNDER GO CERVICAL 915 00:37:21,600 --> 00:37:24,680 CANCER SCREENING AND WHAT WE 916 00:37:24,680 --> 00:37:29,200 FOUND IS DNA APPLICATION A PCR 917 00:37:29,200 --> 00:37:31,280 TEST TO OFFER SELF-COLLECTION TO 918 00:37:31,280 --> 00:37:34,080 WOMEN AND ACHIEVE THE SAME 919 00:37:34,080 --> 00:37:38,240 CLINICAL PERFORMANCE AS IF THE 920 00:37:38,240 --> 00:37:46,520 PROVIDER WAS PROVIDING A PELVIC 921 00:37:46,520 --> 00:37:49,520 EXAM AND GETTING A BIOPSY FROM A 922 00:37:49,520 --> 00:37:52,360 CERVIX AND WOMEN PREFER IT AND 923 00:37:52,360 --> 00:37:54,760 WHEN YOU PROVIDE THE 924 00:37:54,760 --> 00:37:56,040 SELF-COLLECTION KIT YOU CAN 925 00:37:56,040 --> 00:37:57,720 INCREASE PARTICIPATION IN 926 00:37:57,720 --> 00:37:59,440 ABSOLUTE NUMBERS BY ALMOST 40%. 927 00:37:59,440 --> 00:38:04,360 THE OTHER METRIC IS BY DOING SO 928 00:38:04,360 --> 00:38:05,760 YOU INCREASE THE NUMBERS OF 929 00:38:05,760 --> 00:38:07,600 PRECANCERS YOU FIND IN THE 930 00:38:07,600 --> 00:38:07,920 POPULATION. 931 00:38:07,920 --> 00:38:09,640 FOR EVERY 1,000 WOMEN SCREENED 932 00:38:09,640 --> 00:38:15,040 YOU FIND ALMOST 2.5 MORE 933 00:38:15,040 --> 00:38:16,640 PRECANCERS COMPARED TO OFFERING 934 00:38:16,640 --> 00:38:20,080 A PROVIDER-COLLECTED SAMPLE TO 935 00:38:20,080 --> 00:38:23,920 POPULATIONS THAT DON'T PAR 936 00:38:23,920 --> 00:38:24,480 PARTICIPATE IN SCREENING. 937 00:38:24,480 --> 00:38:32,320 THE NCI IS WORKING WITH THE FDA 938 00:38:32,320 --> 00:38:34,520 TO GET SELF-COLLECTION TESTING 939 00:38:34,520 --> 00:38:36,360 APPROVED AND CAN REACH UNDER 940 00:38:36,360 --> 00:38:37,240 SERVED POPULATIONS THROUGH A 941 00:38:37,240 --> 00:38:38,400 VARIETY OF METHODS. 942 00:38:38,400 --> 00:38:40,160 THEY MAY NOT WANT TO COME TO THE 943 00:38:40,160 --> 00:38:40,400 CLINIC. 944 00:38:40,400 --> 00:38:44,400 THEY MAY WANT TO GO TO CVS OR 945 00:38:44,400 --> 00:38:46,560 ANOTHER PHARMACY AND GET THEIR 946 00:38:46,560 --> 00:38:48,360 SELF-COLLECTION KIT, DO IT IN 947 00:38:48,360 --> 00:38:52,000 THE COMFORT OF THEIR HOME 948 00:38:52,000 --> 00:38:53,680 WITHOUT A PELVIC EXAM AND HAVE 949 00:38:53,680 --> 00:38:57,200 IT TESTED AND IF IT'S POSITIVE 950 00:38:57,200 --> 00:38:58,640 BRING THEM TO THE CLINIC FOR THE 951 00:38:58,640 --> 00:39:00,360 REST OF THE CARE. 952 00:39:00,360 --> 00:39:02,880 I WANT TO HIGHLIGHT PLACES LIKE 953 00:39:02,880 --> 00:39:04,360 THE MISSISSIPPI DELTA ARE NOT 954 00:39:04,360 --> 00:39:07,560 THE ONLY DISEASES THEY HAVE A 955 00:39:07,560 --> 00:39:08,360 DISPROPORTIONATE BURDEN. 956 00:39:08,360 --> 00:39:11,160 HERE COLORECTAL CANCER, BREAST, 957 00:39:11,160 --> 00:39:13,640 LUNG, NOT SO MUCH LUNG BUT YOU 958 00:39:13,640 --> 00:39:16,400 CAN SEE SLIGHTLY LIGHTER AND 959 00:39:16,400 --> 00:39:17,240 PROSTATE CANCER THEY EXPERIENCE 960 00:39:17,240 --> 00:39:19,720 A HIGHER BURDEN THAN MANY OTHER 961 00:39:19,720 --> 00:39:20,440 PLACES IN THE COUNTRY. 962 00:39:20,440 --> 00:39:22,640 SO WE REALLY HAVE TO THINK ABOUT 963 00:39:22,640 --> 00:39:24,440 NOT JUST CERVICAL CANCER BUT HOW 964 00:39:24,440 --> 00:39:26,720 WE PROVIDE A PACKAGE OF CARE TO 965 00:39:26,720 --> 00:39:28,360 THESE POPULATIONS WHO ARE IN 966 00:39:28,360 --> 00:39:30,720 NEED. 967 00:39:30,720 --> 00:39:33,640 SO MY FINAL COMMENTS, NATURAL 968 00:39:33,640 --> 00:39:36,280 HISTORY INFORMS, PERIOD. 969 00:39:36,280 --> 00:39:37,680 BUT NATURAL HISTORY INFORMS 970 00:39:37,680 --> 00:39:39,160 INTERVENTIONS AND HOW BEST TO 971 00:39:39,160 --> 00:39:40,200 USE THEM. 972 00:39:40,200 --> 00:39:42,600 HAVING A GOOD SURROGATE ALLOWS 973 00:39:42,600 --> 00:39:44,720 RAPID CYCLING THROUGH 974 00:39:44,720 --> 00:39:45,040 INTERVENTIONS. 975 00:39:45,040 --> 00:39:49,680 INTERVENTION AND SCREENING 976 00:39:49,680 --> 00:39:50,840 MODALITIES CAN CAUSE HARMS LIKE 977 00:39:50,840 --> 00:39:53,880 THE INTRODUCTION OF PSA AND 978 00:39:53,880 --> 00:39:55,280 LESSER INTERVENTION PATH LEADS 979 00:39:55,280 --> 00:39:56,880 IT A BETTER ONE. 980 00:39:56,880 --> 00:39:58,600 PREDICATE TESTS ARE FOR 981 00:39:58,600 --> 00:39:59,840 UNDERSTANDING THE NATURAL 982 00:39:59,840 --> 00:40:00,080 HISTORY. 983 00:40:00,080 --> 00:40:01,840 IN MY OPINION SCREENING WORKS 984 00:40:01,840 --> 00:40:03,520 BEST AS A TWO-STEP PROCESS, RULE 985 00:40:03,520 --> 00:40:05,080 OUT AND RULE IN AND RULE OUT 986 00:40:05,080 --> 00:40:07,120 DISEASE IN THE HEALTHY WHICH SAY 987 00:40:07,120 --> 00:40:09,160 BENEFIT NOBODY TALKS ABOUT AND 988 00:40:09,160 --> 00:40:10,480 CREATING AN ENRICHED POPULATION 989 00:40:10,480 --> 00:40:14,920 FOR THE RULE-IN TEST. 990 00:40:14,920 --> 00:40:15,480 HIGHER PREVALENCE LEADS TO 991 00:40:15,480 --> 00:40:18,360 BETTER PREDICTIVE VALUES. 992 00:40:18,360 --> 00:40:19,760 IMPLEMENTING BEST PRACTICES YOU 993 00:40:19,760 --> 00:40:20,880 SAW IN MISSISSIPPI NOT EVERYBODY 994 00:40:20,880 --> 00:40:23,440 GETS THE SAME BENEFITS. 995 00:40:23,440 --> 00:40:24,240 IMPLEMENTING BEST PRACTICE IS 996 00:40:24,240 --> 00:40:26,440 DIFFICULT AND SLOW EVEN WHEN THE 997 00:40:26,440 --> 00:40:30,480 SCIENCE AND EVIDENCE IS ROBUST. 998 00:40:30,480 --> 00:40:31,520 ESPECIALLY IN DISORGANIZED 999 00:40:31,520 --> 00:40:32,280 HEALTH CARE SYSTEMS LIKE WE HAVE 1000 00:40:32,280 --> 00:40:32,880 IN THE UNITED STATES. 1001 00:40:32,880 --> 00:40:34,640 THE DEVELOPMENT OF INTRODUCTION 1002 00:40:34,640 --> 00:40:36,440 AND NEW TECHNOLOGIES HAS 1003 00:40:36,440 --> 00:40:39,080 HISTORICALLY EXACERBATED RATHER 1004 00:40:39,080 --> 00:40:39,920 THAN MITIGATED HEALTH 1005 00:40:39,920 --> 00:40:40,360 DISPARITIES. 1006 00:40:40,360 --> 00:40:42,120 WE NEED TO DO BETTER. 1007 00:40:42,120 --> 00:40:45,160 AND MY FINAL POINT IS PREVENTION 1008 00:40:45,160 --> 00:40:50,440 SCREENING WILL BE KEY TO 1009 00:40:50,440 --> 00:40:52,400 REDUCING CANCER MORTALITY IN 15 1010 00:40:52,400 --> 00:40:56,360 TO 25 YEARS AND INCREASING 1011 00:40:56,360 --> 00:40:58,640 UPTAKE OF EVIDENCE-BASED 1012 00:40:58,640 --> 00:41:00,400 PREVENTION AND SCREENING 1013 00:41:00,400 --> 00:41:01,400 PRACTICES IN UNDER SERVED 1014 00:41:01,400 --> 00:41:04,360 POPULATION AND LOOKING AT THE 1015 00:41:04,360 --> 00:41:07,080 MOST LETHAL CANCERS SUCH AS 1016 00:41:07,080 --> 00:41:08,280 PANCREAS AND OVARY. 1017 00:41:08,280 --> 00:41:08,760 THANK YOU VERY MUCH. 1018 00:41:08,760 --> 00:41:12,240 I'LL LET YOU ENJOY THE TWO 1019 00:41:12,240 --> 00:41:12,520 CARTOONS. 1020 00:41:12,520 --> 00:41:14,440 ON THE LEFT IT SAID I'LL HAVE AN 1021 00:41:14,440 --> 00:41:17,560 OUNCE OF PREVENTION AND MANY ARE 1022 00:41:17,560 --> 00:41:18,680 AWARE OF THAT SAYING. 1023 00:41:18,680 --> 00:41:20,720 AND SAYING WHAT COULD WE ACHIEVE 1024 00:41:20,720 --> 00:41:24,400 WITH A POUND OF PREVENTION? 1025 00:41:24,400 --> 00:41:26,840 ON THE RIGHT, THERE'S AN '80s 1026 00:41:26,840 --> 00:41:30,200 BAND CALLED THE CURE AND THE 1027 00:41:30,200 --> 00:41:32,080 CARTOON SAYS APPARENTLY THE 1028 00:41:32,080 --> 00:41:35,080 PREVENTION IS BETTER THAN THE 1029 00:41:35,080 --> 00:41:35,280 CURE. 1030 00:41:35,280 --> 00:41:38,440 I'LL TURN IT OVER TO ROBERT TO 1031 00:41:38,440 --> 00:41:40,720 BRING US HOME. 1032 00:41:40,720 --> 00:41:42,640 >>HELLO, EVERYONE. 1033 00:41:42,640 --> 00:41:44,000 THANK YOU FOR JOINING US TODAY. 1034 00:41:44,000 --> 00:41:46,720 IT'S A GREAT HONOR TO BE ABLE TO 1035 00:41:46,720 --> 00:41:48,800 PARTICIPATE IN THE DEMYSTIFYING 1036 00:41:48,800 --> 00:41:49,440 MEDICINE SERIES. 1037 00:41:49,440 --> 00:41:52,880 THESE ARE MY OWN OPINIONS, NOT 1038 00:41:52,880 --> 00:41:56,640 NECESSARILY THOSE OF MY 1039 00:41:56,640 --> 00:41:58,800 EMPLOYER, THE INVITA CORPORATION 1040 00:41:58,800 --> 00:42:01,400 AND I'M AN EMPLOYEE AND SERVED 1041 00:42:01,400 --> 00:42:06,400 AS A CONSULTANT FOR PFIZER AND 1042 00:42:06,400 --> 00:42:07,640 GENOME MEDICAL. 1043 00:42:07,640 --> 00:42:09,840 AND I LIKE THE SCREENINGS. 1044 00:42:09,840 --> 00:42:13,280 THEY'RE MEDICAL TESTS DOCTORS 1045 00:42:13,280 --> 00:42:14,920 USE TO LOOK FOR HEALTH DISEASES 1046 00:42:14,920 --> 00:42:15,880 BEFORE THERE'S SIGNS AND 1047 00:42:15,880 --> 00:42:17,200 SYMPTOMS AND IT'S NOT JUST A 1048 00:42:17,200 --> 00:42:19,600 TEST BUT THE PROVISION OF CARE. 1049 00:42:19,600 --> 00:42:22,520 AND EMPHASIZE AS WITH THE 1050 00:42:22,520 --> 00:42:23,320 NEWBORN SCREENING IT'S NOT JUST 1051 00:42:23,320 --> 00:42:26,000 A TEST, IT'S A PROGRAM THAT NOT 1052 00:42:26,000 --> 00:42:29,560 ONLY PROVIDES THE TEST BUT THE 1053 00:42:29,560 --> 00:42:31,200 FOLLOW-UP NECESSARY. 1054 00:42:31,200 --> 00:42:33,120 FOR THE PURPOSE OF THIS 1055 00:42:33,120 --> 00:42:33,880 DEMYSTIFYING MEDICINE TALK I'D 1056 00:42:33,880 --> 00:42:35,640 LIKE TO EXPAND THE DEFINITION TO 1057 00:42:35,640 --> 00:42:37,560 INCLUDE NOT ONLY TESTING DESIGN 1058 00:42:37,560 --> 00:42:39,640 TO LOOK FOR CANCER IN 1059 00:42:39,640 --> 00:42:42,520 ASYMPTOMATIC HEALTHY INDIVIDUALS 1060 00:42:42,520 --> 00:42:43,520 IN THE POPULATION BUT ALSO 1061 00:42:43,520 --> 00:42:45,720 MONITOR NEW PATIENTS FOR 1062 00:42:45,720 --> 00:42:51,600 RESPONSE OR RELAPSE FOLLOWING 1063 00:42:51,600 --> 00:42:54,480 INTENT TO CURE THERAPY. 1064 00:42:54,480 --> 00:42:58,680 CFDNA AND CIRCULATED TUMOR DNA. 1065 00:42:58,680 --> 00:43:01,360 WHAT WAS DISCOVERED NOW A COUPLE 1066 00:43:01,360 --> 00:43:05,000 DECADES AGO A FASCINATING AND 1067 00:43:05,000 --> 00:43:08,240 INTERESTING OBSERVATION WAS THAT 1068 00:43:08,240 --> 00:43:09,960 PLASMA CONTAINED CELL-FREE DNA. 1069 00:43:09,960 --> 00:43:13,440 THE FRAGMENT DERIVED MAINLY FROM 1070 00:43:13,440 --> 00:43:15,800 DYING WHITE BLOOD CELLS. 1071 00:43:15,800 --> 00:43:19,480 BUT WITHIN THE CELL-FREE DNA 1072 00:43:19,480 --> 00:43:21,280 COMPARTMENT IN PATIENTS WITH 1073 00:43:21,280 --> 00:43:26,320 CANCER THERE'S CIRCULATING TUMOR 1074 00:43:26,320 --> 00:43:29,520 DNA FRAGMENTS SHED FROM THE 1075 00:43:29,520 --> 00:43:31,360 TUMOR AND MIXED WITH THE 1076 00:43:31,360 --> 00:43:35,000 CELL-FREE DNA. 1077 00:43:35,000 --> 00:43:41,080 THE LEVELS OF CT DNA CAN DIFFER 1078 00:43:41,080 --> 00:43:42,520 FROM HOW MUCH CANCER IS IN THE 1079 00:43:42,520 --> 00:43:45,160 BODY AND WHAT SITES THE PRIMARY 1080 00:43:45,160 --> 00:43:47,040 AND MANY METASTATIC SITES AND 1081 00:43:47,040 --> 00:43:49,520 THERE'S PROBABLY OTHER ASPECTS 1082 00:43:49,520 --> 00:43:51,080 OF TUMOR BIOLOGY THAT GOVERN 1083 00:43:51,080 --> 00:43:55,880 WHAT THE LEVEL OF CT DNA WOULD 1084 00:43:55,880 --> 00:43:56,240 BE. 1085 00:43:56,240 --> 00:43:59,600 HERE'S A COUPLE EXAMPLES OF THE 1086 00:43:59,600 --> 00:44:02,320 AMOUNT OF CT DNA SHED. 1087 00:44:02,320 --> 00:44:05,240 BLADDER IS ONE THAT PRODUCES 1088 00:44:05,240 --> 00:44:09,360 QUITE A BIT OF CT DNA AND 1089 00:44:09,360 --> 00:44:13,600 COLORECTAL AND PANCREATIC AND 1090 00:44:13,600 --> 00:44:13,960 OVARIAN. 1091 00:44:13,960 --> 00:44:20,400 THESE ARE EXAMPLES PHIL 1092 00:44:20,400 --> 00:44:21,760 MENTIONED, GASTROESOPHAGEAL MAY 1093 00:44:21,760 --> 00:44:24,120 BE DIFFICULT TO DETECT IN 1094 00:44:24,120 --> 00:44:27,000 CERTAIN KINDS OF GASTRIC CANCER 1095 00:44:27,000 --> 00:44:30,680 BUT THEY DO SHED DETECTABLE 1096 00:44:30,680 --> 00:44:34,320 AMOUNTS OF CT DNA AND BREAST AND 1097 00:44:34,320 --> 00:44:37,840 MELANOMA AND HEAD AND NECK, 1098 00:44:37,840 --> 00:44:40,200 ETCETERA, DOWN TO GLIOMA TUMOR 1099 00:44:40,200 --> 00:44:42,880 THAT HAS THE FREQUENCY OF CASES 1100 00:44:42,880 --> 00:44:44,320 THAT HAVE DETECTABLE CT DNA IS 1101 00:44:44,320 --> 00:44:47,040 SMALL BUT WE THINK IT HAS TO DO 1102 00:44:47,040 --> 00:44:50,320 WITH THE BLOOD BRAIN BARRIER BUT 1103 00:44:50,320 --> 00:44:51,640 THERE MAY BE OTHER REASONS WITH 1104 00:44:51,640 --> 00:44:55,640 THE BIOLOGY OF GLIOMA THAT 1105 00:44:55,640 --> 00:44:57,520 INTERFERES. 1106 00:44:57,520 --> 00:45:06,720 THYROID IS A HIGHLY WELL 1107 00:45:06,720 --> 00:45:07,600 VASCULARIZED TISSUE. 1108 00:45:07,600 --> 00:45:09,800 YOU CAN SEE IT'S NOT ALWAYS 1109 00:45:09,800 --> 00:45:12,800 OBVIOUS WHICH CANCERS ARE GOING 1110 00:45:12,800 --> 00:45:16,760 TO BE FREQUENTLY DEMONSTRATING 1111 00:45:16,760 --> 00:45:17,400 DETECTABLE CT DNA AND WHICH ARE 1112 00:45:17,400 --> 00:45:21,320 NOT. 1113 00:45:21,320 --> 00:45:22,160 THERE ARE SOME CONFOUNDING 1114 00:45:22,160 --> 00:45:24,680 FACTORS TO KEEP IN MIND WHEN 1115 00:45:24,680 --> 00:45:26,440 MEASURES CT DNA. 1116 00:45:26,440 --> 00:45:28,600 IN PREGNANCY, A COUPLE YEARS AGO 1117 00:45:28,600 --> 00:45:31,640 WE HEARD A TALK FROM DR. BIANCHI 1118 00:45:31,640 --> 00:45:34,160 THE INSTITUTE DIRECTOR OF THE 1119 00:45:34,160 --> 00:45:35,400 NATIONAL INSTITUTE OF CHILD 1120 00:45:35,400 --> 00:45:39,880 HEALTH WHO TALKED ABOUT THE USE 1121 00:45:39,880 --> 00:45:43,120 OF FETAL CELL FREE DNA IN THE 1122 00:45:43,120 --> 00:45:44,400 MATERNAL PLASMA AND PREGNANCY 1123 00:45:44,400 --> 00:45:45,880 WILL BE A CONFOUNDING FACTOR IF 1124 00:45:45,880 --> 00:45:52,160 WHAT YOU'RE LOOKING FOR IS CT 1125 00:45:52,160 --> 00:45:54,800 DNA. 1126 00:45:54,800 --> 00:45:56,240 ACTIVE MALIGNANCIES AND IF YOU 1127 00:45:56,240 --> 00:45:57,840 HAD A BLOOD TRANSFUSION IN THE 1128 00:45:57,840 --> 00:46:01,240 LAST TWO WEEKS THERE'LL BE CELL 1129 00:46:01,240 --> 00:46:04,760 FREE DNA DERIVED FROM THE 1130 00:46:04,760 --> 00:46:06,320 TRANSFUSED BLOOD WHICH CAN 1131 00:46:06,320 --> 00:46:11,680 INTERFERE AND OBSCURE, CONFOUND 1132 00:46:11,680 --> 00:46:12,280 YOUR ABILITY TO DETECT IN THE 1133 00:46:12,280 --> 00:46:16,840 INDIVIDUAL. 1134 00:46:16,840 --> 00:46:18,080 ANOTHER DEFINITION CALLED 1135 00:46:18,080 --> 00:46:18,760 MINIMAL RESIDUAL DISEASE. 1136 00:46:18,760 --> 00:46:21,160 THE PRESENCE OF RESIDUAL TUMOR 1137 00:46:21,160 --> 00:46:22,360 CELLS FOLLOWING THERAPY THAT 1138 00:46:22,360 --> 00:46:25,200 CANNOT BE DETECTED BY STANDARD 1139 00:46:25,200 --> 00:46:27,000 IMAGING STUDIES OR OTHER ROUTINE 1140 00:46:27,000 --> 00:46:27,240 METHODS. 1141 00:46:27,240 --> 00:46:29,920 THIS IS ONE OF THE AREAS WHERE 1142 00:46:29,920 --> 00:46:33,640 CT DNA WILL COME INTO ITS OWN. 1143 00:46:33,640 --> 00:46:35,600 THE DETECTING CT DNA IS EVIDENCE 1144 00:46:35,600 --> 00:46:38,760 OF MINIMAL RESIDUAL DISEASE AND 1145 00:46:38,760 --> 00:46:42,800 MRD IS FREQUENTLY CALLED 1146 00:46:42,800 --> 00:46:44,360 MOLECULAR RESIDUAL DISEASE OR 1147 00:46:44,360 --> 00:46:45,160 MEASURABLE RATHER THAN MINIMAL 1148 00:46:45,160 --> 00:46:47,600 BECAUSE IT WILL BE DETECTABLE BY 1149 00:46:47,600 --> 00:46:48,600 MOLECULAR METHODS. 1150 00:46:48,600 --> 00:46:50,720 AND A LOT OF TRADITIONAL METHODS 1151 00:46:50,720 --> 00:46:53,040 LIKE IMAGING OR PATHOLOGICAL 1152 00:46:53,040 --> 00:46:55,520 FEATURES OR BLOOD MARKERS HAVE A 1153 00:46:55,520 --> 00:46:57,240 PROBLEM PREDICTING RISK OF 1154 00:46:57,240 --> 00:47:00,520 RELAPSE OR DETECTING TUMOR 1155 00:47:00,520 --> 00:47:03,880 GROWTH OR MRD UNTIL AFTER THEY 1156 00:47:03,880 --> 00:47:09,840 HAVE ALREADY METASTASIZED. 1157 00:47:09,840 --> 00:47:12,760 THE ISSUE IS WHETHER CT DNA 1158 00:47:12,760 --> 00:47:15,600 OFFERS INCREASED SENSITIVITY AND 1159 00:47:15,600 --> 00:47:17,600 IS THAT AN ADVANTAGE? 1160 00:47:17,600 --> 00:47:22,320 SO THIS IS AN EXAMPLE OF A TIME 1161 00:47:22,320 --> 00:47:24,880 COURSE OF WHAT HAPPENS TO CT DNA 1162 00:47:24,880 --> 00:47:27,640 BASED ON DISEASE BURDEN AND THE 1163 00:47:27,640 --> 00:47:30,840 PASSAGE OF TIME FROM THE 1164 00:47:30,840 --> 00:47:31,240 DIAGNOSIS. 1165 00:47:31,240 --> 00:47:39,640 YOU BEGIN WITH SAY A TUMOR THAT 1166 00:47:39,640 --> 00:47:43,240 HAS AND THIS IS OVER SIMPLIFIED 1167 00:47:43,240 --> 00:47:45,600 BUT THE IDEA IS TO DEMONSTRATE 1168 00:47:45,600 --> 00:47:47,280 YOU HAVE A VARIANT, MUTATION 1, 1169 00:47:47,280 --> 00:47:50,480 THEY CALL IT, A MARKER FOR THE 1170 00:47:50,480 --> 00:47:53,360 CANCER DISTINCT FROM A MARKER 1171 00:47:53,360 --> 00:47:55,320 PRESENT IN THE PATIENT'S OWN 1172 00:47:55,320 --> 00:47:57,240 GERM LINE DNA. 1173 00:47:57,240 --> 00:48:04,600 IT IS A DISTINGUISHING FEATURE 1174 00:48:04,600 --> 00:48:07,600 AND THE AMOUNT OF CT DNA 1175 00:48:07,600 --> 00:48:08,560 CONTAINING THIS MUTATION 1176 00:48:08,560 --> 00:48:10,520 INCREASES OVER TIME AND AT SOME 1177 00:48:10,520 --> 00:48:14,840 POINT THERE'S BE AN INTENT TO 1178 00:48:14,840 --> 00:48:15,640 CURE SURGICAL INTERVENTION SHOWN 1179 00:48:15,640 --> 00:48:18,480 BY THE ARROW AND THE AMOUNT OF 1180 00:48:18,480 --> 00:48:20,920 CT DNA DROPS VERY QUICKLY 1181 00:48:20,920 --> 00:48:22,560 BECAUSE YOU'VE REMOVED THE VAST 1182 00:48:22,560 --> 00:48:23,880 MAJORITY OF THE TUMOR. 1183 00:48:23,880 --> 00:48:26,640 BUT IF IT HASN'T ALL BEEN 1184 00:48:26,640 --> 00:48:29,400 REMOVED OR BEEN A METASTASIS 1185 00:48:29,400 --> 00:48:35,080 THAT WAS NOT REMOVED, OVER 1186 00:48:35,080 --> 00:48:35,720 MUTATION NUMBER ONE IT WILL 1187 00:48:35,720 --> 00:48:37,360 INCREASE AND WILL START TO 1188 00:48:37,360 --> 00:48:39,320 INCREASE AND ON TOP OF IT, 1189 00:48:39,320 --> 00:48:40,200 THERE'S GOING TO BE CLONAL 1190 00:48:40,200 --> 00:48:42,320 EVOLUTION OF THE CANCER. 1191 00:48:42,320 --> 00:48:45,000 SO THAT ANOTHER MUTATION, 1192 00:48:45,000 --> 00:48:46,960 MUTATION NUMBER 2 MAY START 1193 00:48:46,960 --> 00:48:48,320 RISING IN ITS LEVELS. 1194 00:48:48,320 --> 00:48:51,600 AND FURTHER ON DOWN THERE MAY BE 1195 00:48:51,600 --> 00:48:53,120 ADDITIONAL MUTATIONS REQUIRED BY 1196 00:48:53,120 --> 00:48:56,400 THE CANCER AS IT EVOLVES AND 1197 00:48:56,400 --> 00:48:57,200 DEVELOPS. 1198 00:48:57,200 --> 00:49:00,400 SO YOU END UP WITH HIGHER LEVELS 1199 00:49:00,400 --> 00:49:03,600 OF CT DNA WITH MULTIPLE 1200 00:49:03,600 --> 00:49:07,600 MUTATIONS PRESENT OVER TIME. 1201 00:49:07,600 --> 00:49:11,320 NOW, ONE OF THE USES FOR CT DNA? 1202 00:49:11,320 --> 00:49:13,320 THERE'S A COUPLE OF 1203 00:49:13,320 --> 00:49:13,640 POSSIBILITIES. 1204 00:49:13,640 --> 00:49:19,240 ONE SETTING IS TO SCREEN FOR 1205 00:49:19,240 --> 00:49:19,440 CANCER. 1206 00:49:19,440 --> 00:49:21,360 AND PHIL TOUCHED ON THIS AND I 1207 00:49:21,360 --> 00:49:26,000 THINK GAVE A CLEAR EXPLANATION 1208 00:49:26,000 --> 00:49:29,240 FOR HOW DIFFICULT IT IS TO USE 1209 00:49:29,240 --> 00:49:34,640 CT DNA TO SCREEN DE NOVO FOR 1210 00:49:34,640 --> 00:49:35,600 UNDETECTED CANCER IN A SETTING 1211 00:49:35,600 --> 00:49:36,520 OF A POPULATION. 1212 00:49:36,520 --> 00:49:39,240 IT COMES DOWN TO A KEY CONCEPT I 1213 00:49:39,240 --> 00:49:40,640 HOPE EVERYONE UNDERSTANDS OR BY 1214 00:49:40,640 --> 00:49:43,240 THE END OF THE SESSION FULLY 1215 00:49:43,240 --> 00:49:45,880 UNDERSTANDS AND THAT IS THE 1216 00:49:45,880 --> 00:49:50,120 DIFFERENCE BETWEEN FALSE 1217 00:49:50,120 --> 00:49:54,840 POSITIVE RATE OR SPECIFICITY OF 1218 00:49:54,840 --> 00:49:56,720 A TEST DOES NOT GIVE YOU A FIXED 1219 00:49:56,720 --> 00:50:00,120 PREDICTIVE VALUE OF THAT TEST. 1220 00:50:00,120 --> 00:50:01,360 IT DEPENDS ON THE PREVALENCE OF 1221 00:50:01,360 --> 00:50:04,280 THE DISORDER YOU'RE TRYING TO 1222 00:50:04,280 --> 00:50:04,960 DETECT IN THE POPULATION. 1223 00:50:04,960 --> 00:50:08,000 SO A GIVEN TEST WITH A GIVEN 1224 00:50:08,000 --> 00:50:08,920 SENSITIVITY AND GIVEN 1225 00:50:08,920 --> 00:50:09,880 SPECIFICITY WILL HAVE A 1226 00:50:09,880 --> 00:50:11,560 DIFFERENT POSITIVE PREDICTIVE 1227 00:50:11,560 --> 00:50:13,480 VALUE AND NEGATIVE PREDICTIVE 1228 00:50:13,480 --> 00:50:14,920 VALUE DEPENDING ON THE 1229 00:50:14,920 --> 00:50:15,200 PREVALENCE. 1230 00:50:15,200 --> 00:50:17,280 SO THE SETTING IN WHICH YOU'RE 1231 00:50:17,280 --> 00:50:21,880 TRYING TO APPLY ONE OF THESE 1232 00:50:21,880 --> 00:50:25,000 TESTS MATTERS A LOT. 1233 00:50:25,000 --> 00:50:27,880 SO SCREENING FOR CANCER, YOU CAN 1234 00:50:27,880 --> 00:50:31,520 LOOK FOR SINCE YOU ACTUALLY 1235 00:50:31,520 --> 00:50:33,520 DON'T KNOW WHAT SPECIFIC 1236 00:50:33,520 --> 00:50:36,560 VARIANCE OR CHANGES MIGHT BE 1237 00:50:36,560 --> 00:50:39,520 PRESENT IN A CANCER, YOU HAVEN'T 1238 00:50:39,520 --> 00:50:41,120 BIOPSIED OR REMOVED A PIECE OR 1239 00:50:41,120 --> 00:50:42,720 BEEN ABLE TO LOOK AT IT. 1240 00:50:42,720 --> 00:50:44,920 YOU GENERALLY TRY TO DEVELOP 1241 00:50:44,920 --> 00:50:47,920 SOME KIND OF A PANEL THAT 1242 00:50:47,920 --> 00:50:48,960 CONTAINS MOST THE COMMON 1243 00:50:48,960 --> 00:50:50,240 VARIANTS FOUND IN CANCER. 1244 00:50:50,240 --> 00:50:52,320 THE WELL KNOWN DRIVER MUTATIONS 1245 00:50:52,320 --> 00:50:57,080 FOUND IN THE CANCERS AND TRY TO 1246 00:50:57,080 --> 00:50:59,640 DETECT THEM IN AN INDIVIDUAL. 1247 00:50:59,640 --> 00:51:02,240 THEN YOU HAVE SAY A CANCER 1248 00:51:02,240 --> 00:51:04,280 DEVELOPS AND YOU DO A SURGICAL 1249 00:51:04,280 --> 00:51:06,440 INTERVENTION AND NOW YOU 1250 00:51:06,440 --> 00:51:10,800 ACTUALLY HAVE TISSUE. 1251 00:51:10,800 --> 00:51:12,120 SO YOU CAN SEQUENCE THAT TISSUE 1252 00:51:12,120 --> 00:51:13,560 AND AT THAT POINT ASK THE 1253 00:51:13,560 --> 00:51:16,080 QUESTION, FOLLOWING SURGICAL 1254 00:51:16,080 --> 00:51:19,040 INTERVENTION, WHAT'S THE RISK OF 1255 00:51:19,040 --> 00:51:19,360 RELAPSE? 1256 00:51:19,360 --> 00:51:23,600 CAN WE USE CT DNA TO DETECT 1257 00:51:23,600 --> 00:51:25,800 MINIMAL RESIDUAL DISEASE OR 1258 00:51:25,800 --> 00:51:26,360 MOLECULAR RESIDUAL DISEASE 1259 00:51:26,360 --> 00:51:27,480 FOLLOWING THE SURGICAL 1260 00:51:27,480 --> 00:51:30,560 INTERVENTION AND IF SO, IS THAT 1261 00:51:30,560 --> 00:51:32,240 PREDICTIVE OF THE POSSIBILITY 1262 00:51:32,240 --> 00:51:33,880 THAT THIS CANCER WILL ACTUALLY 1263 00:51:33,880 --> 00:51:35,600 RECUR? 1264 00:51:35,600 --> 00:51:39,600 IF IT DOES RECUR, WILL CT DNA 1265 00:51:39,600 --> 00:51:43,280 GIVE YOU AN EARLIER DETECTION OF 1266 00:51:43,280 --> 00:51:45,040 THAT RECURRENCE BEFORE ANY OTHER 1267 00:51:45,040 --> 00:51:48,240 IMAGING OR OTHER SORTS OF 1268 00:51:48,240 --> 00:51:50,440 MARKERS SO YOU HAVE GREATER LEAD 1269 00:51:50,440 --> 00:51:53,760 TIME TO BE ABLE TO DETECT IT? 1270 00:51:53,760 --> 00:51:56,960 AND THEN FINALLY YOU THEN 1271 00:51:56,960 --> 00:52:04,840 INSTITUTE SAY KEEM -- 1272 00:52:04,840 --> 00:52:09,520 CHEMOTHERAPY CAN YOU FOLLOW THE 1273 00:52:09,520 --> 00:52:11,080 PROGRESSION USING CT DNA HOW 1274 00:52:11,080 --> 00:52:13,320 WELL IS THE CANCER RESPONDING TO 1275 00:52:13,320 --> 00:52:16,360 THE THERAPY YOU INSTITUTED? 1276 00:52:16,360 --> 00:52:19,600 SO THERE'S SCREENING, THERE'S 1277 00:52:19,600 --> 00:52:21,440 PROGNOSIS FOLLOWING INTENT TO 1278 00:52:21,440 --> 00:52:23,120 CURE SURGICAL INTERVENTION. 1279 00:52:23,120 --> 00:52:24,760 THERE'S DETECTING A REOCCURRENCE 1280 00:52:24,760 --> 00:52:27,600 IF A REOCCURRENCE DOES OCCUR AND 1281 00:52:27,600 --> 00:52:28,560 THERAPY RESPONSE. 1282 00:52:28,560 --> 00:52:31,600 OF COURSE, DEPENDING ON HOW YOU 1283 00:52:31,600 --> 00:52:35,360 DO THE CT DNA IF YOU'RE ACTUALLY 1284 00:52:35,360 --> 00:52:39,640 LOOKING FOR DRIVER MUTATIONS OR 1285 00:52:39,640 --> 00:52:41,520 OTHER TARGETS FOR TREATMENT OR 1286 00:52:41,520 --> 00:52:45,680 OTHER MARKERS FOR TREATMENT SUCH 1287 00:52:45,680 --> 00:52:48,880 AS SAY A TUMOR MORE LIKELY TO 1288 00:52:48,880 --> 00:52:50,480 RESPOND TO THE CHECKPOINT 1289 00:52:50,480 --> 00:52:52,720 THERAPY BECAUSE OF A HIGHER 1290 00:52:52,720 --> 00:52:54,320 TUMOR MUTATION BURDEN THEN YOU 1291 00:52:54,320 --> 00:52:57,480 ALSO HAVE THAT AS A FIFTH 1292 00:52:57,480 --> 00:53:04,640 PURPOSE, A FIFTH USE OF CT DNA. 1293 00:53:04,640 --> 00:53:07,200 THAT'S OUTLINED IN THE BULLET 1294 00:53:07,200 --> 00:53:10,200 POINT ON THE LEFT. 1295 00:53:10,200 --> 00:53:11,320 ONE OF THE BIG PROBLEMS RIGHT 1296 00:53:11,320 --> 00:53:13,240 NOW IS WE DON'T NO WHICH 1297 00:53:13,240 --> 00:53:15,000 PATIENTS HAVE BEEN CURED POST 1298 00:53:15,000 --> 00:53:15,280 THERAPY. 1299 00:53:15,280 --> 00:53:16,680 SURGERY CURES A PORTION OF 1300 00:53:16,680 --> 00:53:18,640 PATIENTS BUT HARD TO KNOW WHO'S 1301 00:53:18,640 --> 00:53:19,600 BEEN CURED. 1302 00:53:19,600 --> 00:53:25,520 MOST GO ON ADJUVANT THERAPY 1303 00:53:25,520 --> 00:53:26,920 THOUGH WE RECOGNIZE PROBABLY 1304 00:53:26,920 --> 00:53:29,720 DON'T NEED TO GO ON ADJUVANT 1305 00:53:29,720 --> 00:53:31,520 THERAPY AFTER SURGERY SO IT'D BE 1306 00:53:31,520 --> 00:53:33,480 GREAT TO HAVE A TOOL TO 1307 00:53:33,480 --> 00:53:34,400 DETERMINE WHO NEEDS TO BE 1308 00:53:34,400 --> 00:53:35,960 EXPOSED TO THE COMPLICATIONS AND 1309 00:53:35,960 --> 00:53:38,320 PROBLEMS OF ADJUVANT THERAPY AND 1310 00:53:38,320 --> 00:53:39,600 WHO DOESN'T. 1311 00:53:39,600 --> 00:53:42,720 SOME PATIENTS CAN BENEFIT FROM 1312 00:53:42,720 --> 00:53:43,600 ADJUVANT THERAPY. 1313 00:53:43,600 --> 00:53:44,520 WHO NEEDS IT? 1314 00:53:44,520 --> 00:53:47,160 AND WOULD PATIENTS DECLINE 1315 00:53:47,160 --> 00:53:48,520 ADJUVANT THERAPY NOT KNOWING 1316 00:53:48,520 --> 00:53:51,600 THEY'RE AT HIGHER RISK. 1317 00:53:51,600 --> 00:53:55,600 CAN CT DNA PROVIDE INSIGHT INTO 1318 00:53:55,600 --> 00:53:58,360 A BETTER CHOICE OF WHO NEEDS TO 1319 00:53:58,360 --> 00:54:01,920 GO POST SURGERY ON ADJUVANT 1320 00:54:01,920 --> 00:54:03,960 THERAPY AND SOME PATIENTS CANNOT 1321 00:54:03,960 --> 00:54:06,080 BE CURED BY THERAPY AND ADJUVANT 1322 00:54:06,080 --> 00:54:08,720 THERAPY SO WHO IS STILL AT HIGH 1323 00:54:08,720 --> 00:54:10,160 RISK AFTER SUCH TREATMENT AND 1324 00:54:10,160 --> 00:54:12,320 CAN WE FOLLOW THEM PERHAPS ALTER 1325 00:54:12,320 --> 00:54:15,600 THEIR THERAPY IF THERE'S 1326 00:54:15,600 --> 00:54:18,000 EVIDENCE THAT THEY ARE RECURRING 1327 00:54:18,000 --> 00:54:20,440 AND ARE RELAPSING AND THE 1328 00:54:20,440 --> 00:54:21,840 CURRENT REGIMENT IS NOT HOLDING 1329 00:54:21,840 --> 00:54:23,600 THEIR CANCER IN CHECK. 1330 00:54:23,600 --> 00:54:27,480 CAN WE FIND THAT EARLIER AT A 1331 00:54:27,480 --> 00:54:29,800 TIME WHEN PERHAPS IT MAY BE 1332 00:54:29,800 --> 00:54:31,000 EASIER TO TREAT? 1333 00:54:31,000 --> 00:54:35,160 AS I'LL TALK ABOUT LATER, THERE 1334 00:54:35,160 --> 00:54:37,480 ARE STILL MANY QUESTIONS AROUND 1335 00:54:37,480 --> 00:54:39,480 THE USE OF CT DNA IN THESE 1336 00:54:39,480 --> 00:54:43,880 VARIOUS SETTINGS THAT NEED TO BE 1337 00:54:43,880 --> 00:54:44,920 ADDRESSED. 1338 00:54:44,920 --> 00:54:47,440 SO HOW DO WE DETECT RELAPSE 1339 00:54:47,440 --> 00:54:47,720 CURRENTLY? 1340 00:54:47,720 --> 00:54:49,200 ONCE A TUMOR IS LARGE ENOUGH TO 1341 00:54:49,200 --> 00:54:51,240 BE DETECTED ON IMAGING. 1342 00:54:51,240 --> 00:54:56,240 AT THIS POINT THE TUMOR MAY HAVE 1343 00:54:56,240 --> 00:54:56,600 METASTASIZED. 1344 00:54:56,600 --> 00:54:58,840 THE CONCERN IS WE HAVE FOUND IT 1345 00:54:58,840 --> 00:55:03,520 TOO LATE AND TUMOR MARKERS, CEA 1346 00:55:03,520 --> 00:55:08,440 ARE SURROGATES FOR DISEASE. 1347 00:55:08,440 --> 00:55:11,640 THIS IS CEA THEY FREQUENTLY 1348 00:55:11,640 --> 00:55:17,440 DON'T CORRELATE WITH A TUMOR 1349 00:55:17,440 --> 00:55:19,520 VOLUME AND NOT THE BEST WAY TO 1350 00:55:19,520 --> 00:55:21,880 ASSESS THE STATUS OF THE PATIENT 1351 00:55:21,880 --> 00:55:27,320 UNDERGOING A RELAPSE. 1352 00:55:27,320 --> 00:55:30,240 SO WHAT CT DNA INVOLVES IS THE 1353 00:55:30,240 --> 00:55:32,040 LOOKING AT VARIANTS. 1354 00:55:32,040 --> 00:55:35,920 LOOKING AT VARIANTS IN THE TUMOR 1355 00:55:35,920 --> 00:55:38,320 THAT ARE NOT PRESENT IN THE 1356 00:55:38,320 --> 00:55:41,120 NORMAL DNA AND THEREFORE YOU CAN 1357 00:55:41,120 --> 00:55:44,640 IDENTIFY THE SUBSET, THE 1358 00:55:44,640 --> 00:55:47,240 FRACTION OF TOTAL CELL-FREE DNA 1359 00:55:47,240 --> 00:55:50,160 THAT IS DERIVED FROM THE TUMOR, 1360 00:55:50,160 --> 00:55:51,160 CT DNA. 1361 00:55:51,160 --> 00:55:54,000 AND THE SENSITIVITY OF SUCH 1362 00:55:54,000 --> 00:55:55,600 VARIANT-BASED TEST IS TO FIND BY 1363 00:55:55,600 --> 00:55:57,240 ITS ABILITY TO DETECT A 1364 00:55:57,240 --> 00:56:00,000 PARTICULAR VARIANT OR SET OF 1365 00:56:00,000 --> 00:56:01,640 VARIANTS EVEN WHEN PRESENT AT 1366 00:56:01,640 --> 00:56:04,240 VERY LOW AMOUNTS. 1367 00:56:04,240 --> 00:56:09,880 THERE ARE SOME CT DNAs THAT CAN 1368 00:56:09,880 --> 00:56:14,240 DETECT THE PRESENCE OF A 1369 00:56:14,240 --> 00:56:18,680 CIRCULATING TUMOR DNA DOWN TO 1370 00:56:18,680 --> 00:56:21,400 LEVELS AS LOW AS .08% OF THE 1371 00:56:21,400 --> 00:56:22,360 TOTAL ALLELE FREQUENCY. 1372 00:56:22,360 --> 00:56:30,760 THEY CAN BE VERY SENSITIVE. 1373 00:56:30,760 --> 00:56:33,880 AND CT DNA SURVEILLANCE CAN 1374 00:56:33,880 --> 00:56:36,800 DETECT RELAPSE AND POSITIVITY 1375 00:56:36,800 --> 00:56:39,040 CAN CAPTURE THE MAJORITY OF 1376 00:56:39,040 --> 00:56:41,160 RELAPSE EVENTS AHEAD OF STANDARD 1377 00:56:41,160 --> 00:56:42,880 CARE METHODS POTENTIALLY -- I 1378 00:56:42,880 --> 00:56:45,920 WANT TO STRESS, POTENTIALLY, 1379 00:56:45,920 --> 00:56:47,920 ALLOWING FOR EARLIER 1380 00:56:47,920 --> 00:56:48,280 INTERVENTION. 1381 00:56:48,280 --> 00:56:51,040 CT DNA MAY BE UNDETECTABLE 1382 00:56:51,040 --> 00:56:55,560 SHORTLY AFTER SURGERY OR SHORTLY 1383 00:56:55,560 --> 00:56:58,480 AFTER THERAPY AND LONGITUDINAL 1384 00:56:58,480 --> 00:56:59,440 TESTS INCREASES THE SENSITIVITY 1385 00:56:59,440 --> 00:57:02,800 OF THE ABILITY TO DETECT MINIMAL 1386 00:57:02,800 --> 00:57:03,880 RESIDUAL DISEASE AND THE FACT 1387 00:57:03,880 --> 00:57:07,640 THE TUMOR IS AT RISK FOR 1388 00:57:07,640 --> 00:57:09,600 RELAPSING. 1389 00:57:09,600 --> 00:57:10,840 CT DNA ALSO CAN BE A MEASURE OF 1390 00:57:10,840 --> 00:57:13,480 THERAPY RESPONSE. 1391 00:57:13,480 --> 00:57:16,360 THE ABSENCE OF CT DNA DURING 1392 00:57:16,360 --> 00:57:19,880 THERAPY COULD BE INDICATIVE TO 1393 00:57:19,880 --> 00:57:21,920 RESPONSE TO THERAPY IF IT HAS 1394 00:57:21,920 --> 00:57:23,600 PREVIOUSLY BEEN DETECTED. 1395 00:57:23,600 --> 00:57:25,760 IT WAS THERE BEFORE AND NOW HAD 1396 00:57:25,760 --> 00:57:26,960 THE PATIENT GO THROUGH THERAPY 1397 00:57:26,960 --> 00:57:29,840 AND IT'S NO LONGER THERE. 1398 00:57:29,840 --> 00:57:32,800 BUT CT DNA DYNAMICS ARE A 1399 00:57:32,800 --> 00:57:34,600 GROWING FIELD AND THERE NEEDS TO 1400 00:57:34,600 --> 00:57:39,160 BE A LOT MORE RESEARCH DONE TO 1401 00:57:39,160 --> 00:57:41,040 DOCUMENT AND UTILIZE CT DNA 1402 00:57:41,040 --> 00:57:42,640 TRAJECTORIES TO KNOW WHAT THEY 1403 00:57:42,640 --> 00:57:43,960 MEAN DURING AND FOLLOWING CANCER 1404 00:57:43,960 --> 00:57:46,160 TREATMENT. 1405 00:57:46,160 --> 00:57:47,960 THERE ARE SITUATIONS WHERE YOU 1406 00:57:47,960 --> 00:57:51,840 CAN EASILY IMAGINE THE CT DNA IS 1407 00:57:51,840 --> 00:57:55,520 NOT DETECTED BECAUSE IT'S 1408 00:57:55,520 --> 00:57:57,520 ACTUALLY LOOKING FOR VARIANTS 1409 00:57:57,520 --> 00:57:59,600 THAT PERHAPS ARE NO LONGER 1410 00:57:59,600 --> 00:58:02,320 PRESENT IN LARGE AMOUNTS IN THE 1411 00:58:02,320 --> 00:58:03,600 CANCER AND THERE MAY BE OTHER 1412 00:58:03,600 --> 00:58:06,800 VARIANTS THAT ARE NOT BEING USED 1413 00:58:06,800 --> 00:58:09,880 TO DETECT THE CT DNA WHICH NOW 1414 00:58:09,880 --> 00:58:13,600 ARE STARTING TO DEVELOP THESE 1415 00:58:13,600 --> 00:58:15,600 ADDITIONAL MUTATIONAL BURDENS 1416 00:58:15,600 --> 00:58:17,680 THAT'S OCCURRING SO THEREFORE 1417 00:58:17,680 --> 00:58:20,680 YOU ARE NOT LOOKING AT THE 1418 00:58:20,680 --> 00:58:21,800 VARIANTS MOST REPRESENTATIVE OF 1419 00:58:21,800 --> 00:58:25,960 THE CANCER AT ITS CURRENT STATE. 1420 00:58:25,960 --> 00:58:29,520 SO HERE'S A SUMMARY. 1421 00:58:29,520 --> 00:58:39,320 WITHIN CELL FREE DNA IN PATIENTS 1422 00:58:39,320 --> 00:58:41,080 WITH CANCER HAVE CT DNA CELLS 1423 00:58:41,080 --> 00:58:43,600 THAT SHED AND THERE ARE METHODS 1424 00:58:43,600 --> 00:58:48,640 THAT WILL DETECT MAGNITUDES LESS 1425 00:58:48,640 --> 00:58:50,000 AND CAN HELP INFORM RISK 1426 00:58:50,000 --> 00:58:51,600 STRATIFICATION FOR PATIENTS. 1427 00:58:51,600 --> 00:58:54,360 MANY STUDIES HAVE SHOWN CT DNA 1428 00:58:54,360 --> 00:58:56,200 DETECTION IS PROGNOSTIC FOR HOW 1429 00:58:56,200 --> 00:58:59,600 LIKELY A PERSON'S CANCER WILL 1430 00:58:59,600 --> 00:59:02,280 RECUR FOLLOWING INTENT TO CURE 1431 00:59:02,280 --> 00:59:02,800 THERAPY. 1432 00:59:02,800 --> 00:59:03,360 SURVEILLANCE. 1433 00:59:03,360 --> 00:59:05,720 THERE ARE MANY STUDIES THAT SHOW 1434 00:59:05,720 --> 00:59:09,000 CT DNA DETECTS RELAPSE AHEAD OF 1435 00:59:09,000 --> 00:59:10,640 STANDARD OF CARE METHODS 1436 00:59:10,640 --> 00:59:12,320 POTENTIALLY, ONCE AGAIN, 1437 00:59:12,320 --> 00:59:16,600 POTENTIALLY, ALLOWING FOR 1438 00:59:16,600 --> 00:59:17,240 EARLIER INTERVENTION AND IT 1439 00:59:17,240 --> 00:59:18,520 NEEDS TO BE PROVEN AND THERAPY 1440 00:59:18,520 --> 00:59:19,440 RESPONSE. 1441 00:59:19,440 --> 00:59:22,240 THE ABSENCE OF CT DNA DETECTED 1442 00:59:22,240 --> 00:59:23,600 DURING THERAPY MAY BE INDICATIVE 1443 00:59:23,600 --> 00:59:27,600 OF RESPONSE TO THERAPY IN A MORE 1444 00:59:27,600 --> 00:59:30,320 SENSITIVE WAY THAN SOME OF THE 1445 00:59:30,320 --> 00:59:31,600 STANDARD TOOLS USED FOR 1446 00:59:31,600 --> 00:59:35,600 MEASURING RESPONSE. 1447 00:59:35,600 --> 00:59:38,200 HERE'S AN EXAMPLE OF CT DNA USED 1448 00:59:38,200 --> 00:59:42,400 FOR RISK STRATIFICATION. 1449 00:59:42,400 --> 00:59:45,400 THIS IS AN AMALGAMATION ACROSS 1450 00:59:45,400 --> 00:59:48,760 MANY STUDIES THAT WAS SUMMARIZED 1451 00:59:48,760 --> 00:59:50,080 IN THE PAPER ACROSS 20 STUDIES, 1452 00:59:50,080 --> 00:59:57,800 PATIENTS DETECTED TO HAVE CT DNA 1453 00:59:57,800 --> 00:59:59,520 FOLLOWING CURATIVE SURGERY WERE 1454 00:59:59,520 --> 01:00:01,000 AT A HIGHER RISK OF RELAPSE THAN 1455 01:00:01,000 --> 01:00:03,160 THOSE NOT DETECTED TO HAVE CT 1456 01:00:03,160 --> 01:00:03,600 DNA. 1457 01:00:03,600 --> 01:00:05,880 IN THE GRAPH YOU CAN SEE IS 1458 01:00:05,880 --> 01:00:09,760 FREEDOM FROM PROGRESSION AS A 1459 01:00:09,760 --> 01:00:11,640 PERCENTAGE AND THE YELLOW LINE 1460 01:00:11,640 --> 01:00:14,720 ARE THE PATIENTS WHO HAD CT DNA 1461 01:00:14,720 --> 01:00:15,600 FOLLOWING SURGERY AND THE BLUE 1462 01:00:15,600 --> 01:00:18,640 LINE ARE PATIENTS WHO DID NOT 1463 01:00:18,640 --> 01:00:21,880 HAVE CT DNA DURING SURGERY -- 1464 01:00:21,880 --> 01:00:23,080 AFTER SURGERY. 1465 01:00:23,080 --> 01:00:25,280 YOU CAN SEE THE VERY SIGNIFICANT 1466 01:00:25,280 --> 01:00:30,040 DIFFERENCE IN THE FREEDOM FROM 1467 01:00:30,040 --> 01:00:31,280 PROGRESSION INDICATING FOLLOWING 1468 01:00:31,280 --> 01:00:35,600 SURGERY IN THE STUDIES THE CT 1469 01:00:35,600 --> 01:00:37,480 DNA WAS STRONGLY PROGNOSTIC FOR 1470 01:00:37,480 --> 01:00:39,720 WHO IS LIKELY TO RELAPSE AND WHO 1471 01:00:39,720 --> 01:00:40,520 IS NOT. 1472 01:00:40,520 --> 01:00:44,840 I THINK IT'S INTERESTING TO SEE 1473 01:00:44,840 --> 01:00:47,600 THAT 20% OF THE PATIENTS WHO DID 1474 01:00:47,600 --> 01:00:54,120 NOT HAVE CT DNA DETECTED STILL 1475 01:00:54,120 --> 01:00:54,560 PROGRESSED. 1476 01:00:54,560 --> 01:00:57,600 IT WAS 80%. 1477 01:00:57,600 --> 01:01:00,560 BUT FAR FEWER THAN THE ONES WHO 1478 01:01:00,560 --> 01:01:01,680 HAD DETECTABLE CT DNA FOUR TO 1479 01:01:01,680 --> 01:01:07,000 SIX WEEKS AFTER SURGERY. 1480 01:01:07,000 --> 01:01:09,680 SO THERE'S A NUMBER OF DIFFERENT 1481 01:01:09,680 --> 01:01:11,560 TEST TYPES USED FOR A CT DNA. 1482 01:01:11,560 --> 01:01:13,360 THEY FULL TO TWO MAIN 1483 01:01:13,360 --> 01:01:13,680 CATEGORIES. 1484 01:01:13,680 --> 01:01:16,560 ONE IS WHAT ARE CALLED TUMOR 1485 01:01:16,560 --> 01:01:17,000 AGNOSTIC. 1486 01:01:17,000 --> 01:01:23,600 THESE ARE ASSAYS DESIGN TO FIND 1487 01:01:23,600 --> 01:01:25,600 COMMON ALTERATION IB CANCER AND 1488 01:01:25,600 --> 01:01:27,560 SET ON A PRE SET VARIANT PANEL. 1489 01:01:27,560 --> 01:01:28,800 THEY'RE LESS SENSITIVE BECAUSE 1490 01:01:28,800 --> 01:01:32,880 THEY'RE NOT REALLY TAILORED TO 1491 01:01:32,880 --> 01:01:34,560 THE SPECIFIC CANCER THE PATIENT 1492 01:01:34,560 --> 01:01:37,240 HAS BUT DON'T REQUIRE TUMOR 1493 01:01:37,240 --> 01:01:37,520 SEQUENCE. 1494 01:01:37,520 --> 01:01:39,600 SO THESE ASSAYS ARE DESIGN TO 1495 01:01:39,600 --> 01:01:44,160 FIND COMMON ALTERATIONS IN 1496 01:01:44,160 --> 01:01:44,400 CANCER. 1497 01:01:44,400 --> 01:01:45,920 THE OTHER IS TUMOR INFORMED. 1498 01:01:45,920 --> 01:01:51,600 YOU HAVE TO HAVE AT LEAST SOME 1499 01:01:51,600 --> 01:01:52,960 DNA REPRESENTATIVE OF THE 1500 01:01:52,960 --> 01:01:54,960 PATIENT'S TUMOR AND USE IT TO 1501 01:01:54,960 --> 01:01:55,800 IDENTIFY VARIANTS. 1502 01:01:55,800 --> 01:01:57,000 THERE ARE DIFFERENT ASSAYS -- I 1503 01:01:57,000 --> 01:01:59,440 DON'T WANT TO GO INTO ALL THE 1504 01:01:59,440 --> 01:02:04,760 DETAILS BUT GENERALLY INVOLVE 1505 01:02:04,760 --> 01:02:08,800 MULTIPLE VARIANTS THAT INCREASE 1506 01:02:08,800 --> 01:02:11,640 THE SENSITIVITY AND SPECIFICITY 1507 01:02:11,640 --> 01:02:15,600 AND CHARACTERISTIC OF THE 1508 01:02:15,600 --> 01:02:18,360 TUMOR'S DNA AND NOT THE 1509 01:02:18,360 --> 01:02:21,920 PATIENT'S OWN GERM LINE DNA AND 1510 01:02:21,920 --> 01:02:23,280 HAVE HIGHER SPECIFICITY BUT 1511 01:02:23,280 --> 01:02:24,480 REQUIRE UP FRONT TUMOR 1512 01:02:24,480 --> 01:02:24,760 SEQUENCING. 1513 01:02:24,760 --> 01:02:26,880 IN BOTH CASES THEY CAN BE USED 1514 01:02:26,880 --> 01:02:30,720 TO DETECT AND MONITOR 1515 01:02:30,720 --> 01:02:31,000 ALTERATIONS. 1516 01:02:31,000 --> 01:02:33,000 EACH HAS CERTAIN PROS AND CONS 1517 01:02:33,000 --> 01:02:34,720 IN TERMS OF HAVING TO HAVE A 1518 01:02:34,720 --> 01:02:42,040 PIECE OF TUMOR VERSUS A BETTER 1519 01:02:42,040 --> 01:02:43,600 SPECIFICITY FOR THE 1520 01:02:43,600 --> 01:02:46,920 TUMOR-INFORMED TYPE OF TEST. 1521 01:02:46,920 --> 01:02:49,600 FOR THE TUMOR-INFORMED, THE 1522 01:02:49,600 --> 01:02:51,080 ALTERATIONS COULD BE THE DRIVING 1523 01:02:51,080 --> 01:02:56,880 MUTATIONS THAT CAN THEN SERVE AS 1524 01:02:56,880 --> 01:02:59,000 THERAPEUTIC TARGETS OR TUMOR, 1525 01:02:59,000 --> 01:03:00,960 PASSENGER MUTATIONS CHOSEN TO 1526 01:03:00,960 --> 01:03:03,600 IMPROVE THE SENSITIVITY OF THE 1527 01:03:03,600 --> 01:03:03,920 TEST. 1528 01:03:03,920 --> 01:03:07,600 THERE ARE CERTAIN FORMS OF CT 1529 01:03:07,600 --> 01:03:13,600 DNA TESTING THAT ARE DESIGN TO 1530 01:03:13,600 --> 01:03:14,960 IMPROVE SENSITIVITY AND NOT 1531 01:03:14,960 --> 01:03:18,440 NECESSARILY THE DRIVER 1532 01:03:18,440 --> 01:03:18,720 MUTATIONS. 1533 01:03:18,720 --> 01:03:22,320 THEY WOULD NOT SERVE AS A 1534 01:03:22,320 --> 01:03:24,280 THERAPY SELECTION ASSAY BUT 1535 01:03:24,280 --> 01:03:27,600 SERVE AS A VERY SENSITIVE 1536 01:03:27,600 --> 01:03:32,960 MONITORING TEST FOR THE CANCER. 1537 01:03:32,960 --> 01:03:35,600 CT DNA DETECTION CAN BE IMPROVED 1538 01:03:35,600 --> 01:03:39,600 BY TARGETING MANY VARIANTS IN 1539 01:03:39,600 --> 01:03:41,920 THE TUMOR AS YOU INCREASE THE 1540 01:03:41,920 --> 01:03:44,320 NUMBER OF VARIANTS YOU CAN LOOK 1541 01:03:44,320 --> 01:03:46,880 AT WITH THE TUMOR-INFORMED PANEL 1542 01:03:46,880 --> 01:03:49,760 YOU CAN DETECT THESE AT A LOWER 1543 01:03:49,760 --> 01:03:52,680 LEVEL THAN TUMOR AGNOSTIC PANEL 1544 01:03:52,680 --> 01:03:54,640 WHICH REQUIRES MORE PRE SET 1545 01:03:54,640 --> 01:03:57,920 VARIANTS TO BE PRESENT FOR YOU 1546 01:03:57,920 --> 01:04:03,320 TO BE ABLE TO DETECT. 1547 01:04:03,320 --> 01:04:04,520 YOU ALSO NEED A LOT OF 1548 01:04:04,520 --> 01:04:06,400 SPECIFICITY. 1549 01:04:06,400 --> 01:04:08,720 THIS IS THE POINT THAT PHIL MADE 1550 01:04:08,720 --> 01:04:09,360 WELL. 1551 01:04:09,360 --> 01:04:12,840 ON LEFT IS THE GRAPH OF THE 1552 01:04:12,840 --> 01:04:14,640 AFFECT OF SPECIFICITY ON FALSE 1553 01:04:14,640 --> 01:04:16,200 POSITIVE RATES DURING 1554 01:04:16,200 --> 01:04:16,520 MONITORING. 1555 01:04:16,520 --> 01:04:18,160 SO HERE'S THE FALSE POSITIVE 1556 01:04:18,160 --> 01:04:24,200 RATE THE Y AXIS AROUND ON THE X 1557 01:04:24,200 --> 01:04:26,680 AXIS IS HOW MANY TIME POINTS OF 1558 01:04:26,680 --> 01:04:32,600 CT DNA OR MRD DETECTION YOU ARE 1559 01:04:32,600 --> 01:04:32,920 DOING? 1560 01:04:32,920 --> 01:04:34,960 YOU CAN SEE THE FALSE POSITIVE 1561 01:04:34,960 --> 01:04:37,200 RATE GOES UP QUITE A BIT WHEN 1562 01:04:37,200 --> 01:04:39,600 YOUR SPECIFICITY IS 97% BUT AS 1563 01:04:39,600 --> 01:04:47,600 IT INCREASES TO 99% OR 99. 9% 1564 01:04:47,600 --> 01:04:50,200 YOU ELIMINATE THE FALSE POSITIVE 1565 01:04:50,200 --> 01:04:53,440 RATE BY HAVING HIGH SPECIFICITY. 1566 01:04:53,440 --> 01:04:55,240 EVEN SO JUST WANT TO REMIND YOU 1567 01:04:55,240 --> 01:04:57,680 APPLYING A TEST WITH HIGH 1568 01:04:57,680 --> 01:04:59,120 SPECIFICITY TO A POPULATION THAT 1569 01:04:59,120 --> 01:05:01,920 HAS A VERY LOW PREVALENCE OF THE 1570 01:05:01,920 --> 01:05:05,960 DISEASE YOU'RE SCREENING FOR 1571 01:05:05,960 --> 01:05:07,600 STILL GENERATES A POSITIVE 1572 01:05:07,600 --> 01:05:10,880 PREDICTIVE VALUE LESS THAN 100% 1573 01:05:10,880 --> 01:05:13,600 AND WILL STILL FLAG PEOPLE WHO 1574 01:05:13,600 --> 01:05:16,000 ARE FALSE POSITIVES FOR THAT 1575 01:05:16,000 --> 01:05:21,800 TEST DESPITE HIGH SPECIFICITY. 1576 01:05:21,800 --> 01:05:25,640 WHICH IS WHY A LOT OF WHAT I'VE 1577 01:05:25,640 --> 01:05:26,640 BEEN TALKING ABOUT TODAY ARE 1578 01:05:26,640 --> 01:05:28,040 PEOPLE AT HIGH RISK OF RELAPSE 1579 01:05:28,040 --> 01:05:31,640 OF THEIR CANCER OR MINIMAL 1580 01:05:31,640 --> 01:05:33,280 RESIDUAL DISEASE FOLLOWING 1581 01:05:33,280 --> 01:05:33,480 THERAPY. 1582 01:05:33,480 --> 01:05:34,680 I'VE NOT BEEN TALKING ABOUT WHAT 1583 01:05:34,680 --> 01:05:36,280 HAPPENS WHEN YOU TAKE ONE OF 1584 01:05:36,280 --> 01:05:39,600 THESE STEPS AND APPLY IT TIE 1585 01:05:39,600 --> 01:05:44,280 POPULATION WHERE 1% OR LESS OF 1586 01:05:44,280 --> 01:05:45,960 PEOPLE IN THAT POPULATION HAVE A 1587 01:05:45,960 --> 01:05:47,080 CANCER YOU'LL DETECT. 1588 01:05:47,080 --> 01:05:50,160 WHAT ARE SOME LIMITATIONS? 1589 01:05:50,160 --> 01:05:53,360 WHAT ARE REASONS A CT DNA OR 1590 01:05:53,360 --> 01:05:58,000 MRNA MAY BE DETECTED? 1591 01:05:58,000 --> 01:06:01,040 NO RESIDUAL TUMOR CELLS WHICH 1592 01:06:01,040 --> 01:06:04,000 REMAIN, THAT IS GOOD OR IT MAY 1593 01:06:04,000 --> 01:06:09,240 BE A POOR SHEDDER. 1594 01:06:09,240 --> 01:06:11,440 DIFFERENT TYPES HAVE DIFFERENT 1595 01:06:11,440 --> 01:06:14,320 AMOUNTS AND IT MAY BE BELOW THE 1596 01:06:14,320 --> 01:06:15,400 DETECTION AND SOME HAVE MORE 1597 01:06:15,400 --> 01:06:19,360 SENSITIVITY THAN OTHERS AND THE 1598 01:06:19,360 --> 01:06:21,960 TUMOR-INFORMED ASSAY IS 1599 01:06:21,960 --> 01:06:23,600 CALIBRATED TO A SPECIFIC 1600 01:06:23,600 --> 01:06:24,680 MOLECULAR SIGNATURE AND 1601 01:06:24,680 --> 01:06:27,040 THEREFORE MAY NOT DETECT A NEW 1602 01:06:27,040 --> 01:06:28,800 CANCER WITH A DIFFERENT SET OF 1603 01:06:28,800 --> 01:06:31,920 MARKERS THAT AFFECTS THE 1604 01:06:31,920 --> 01:06:32,880 PATIENT. 1605 01:06:32,880 --> 01:06:35,600 THESE ARE ALL THINGS TO KEEP IN 1606 01:06:35,600 --> 01:06:35,800 MIND. 1607 01:06:35,800 --> 01:06:39,280 THE CT DNA PARTICULARLY THE 1608 01:06:39,280 --> 01:06:41,480 TUMOR-INFORMED DNA AND ALL THESE 1609 01:06:41,480 --> 01:06:46,800 TESTS WHETHER TUMOR-INFORMED OR 1610 01:06:46,800 --> 01:06:52,520 NOT ARE CUSTOMIZED TO PARTICULAR 1611 01:06:52,520 --> 01:06:53,120 CANCERS EITHER BY CHOOSING 1612 01:06:53,120 --> 01:06:54,760 PARTICULAR DRIVER MUTATIONS OR 1613 01:06:54,760 --> 01:06:55,880 DERIVING THEM FROM SEQUENCING OF 1614 01:06:55,880 --> 01:06:57,960 THE PATIENT'S OWN TUMOR. 1615 01:06:57,960 --> 01:07:02,880 AND THEY ARE NOT SOME SORT OF 1616 01:07:02,880 --> 01:07:03,240 TOTAL SOLUTION. 1617 01:07:03,240 --> 01:07:12,560 ALL CANCER'S DETECTABLE. 1618 01:07:12,560 --> 01:07:15,160 THEY DO NOT OPERATE THAT WAY AND 1619 01:07:15,160 --> 01:07:18,720 WE HAD TRACER X WITH PEOPLE WITH 1620 01:07:18,720 --> 01:07:21,360 TUMOR STAGE NON-CELL LUNG CANCER 1621 01:07:21,360 --> 01:07:23,600 AND A CT DNA TEST CUSTOMIZED TO 1622 01:07:23,600 --> 01:07:25,760 EACH PATIENT WITH TIME POINTS 1623 01:07:25,760 --> 01:07:27,360 AND THEN THE PATIENTS WERE 1624 01:07:27,360 --> 01:07:29,200 FOLLOWED WITH STANDARD OF CARE 1625 01:07:29,200 --> 01:07:35,160 IMAGING, ETCETERA, THOUGH IT 1626 01:07:35,160 --> 01:07:36,400 VARIED FROM SITES FROM WHICH THE 1627 01:07:36,400 --> 01:07:38,440 STUDY WAS DONE. 1628 01:07:38,440 --> 01:07:41,040 IT'S A NINE-YEAR PROSPECTIVE 1629 01:07:41,040 --> 01:07:46,280 STUDY TO FIND THE CLONAL 1630 01:07:46,280 --> 01:07:56,800 EVOLUTION OF EARLY STAGE NON 1631 01:07:57,440 --> 01:08:01,800 -SMALL LUNG CANCER AND THE 1632 01:08:01,800 --> 01:08:04,960 INITIAL FINDINGS ARE CT DNA 1633 01:08:04,960 --> 01:08:07,040 DETECTED BEFORE RELAPSE IN 37 1634 01:08:07,040 --> 01:08:08,760 OUT OF 45 CLINICAL RELAPSING 1635 01:08:08,760 --> 01:08:12,240 PATIENTS WITH A MEDIAN LEAD TIME 1636 01:08:12,240 --> 01:08:14,800 BEFORE CLINICAL EVIDENCE FOR 1637 01:08:14,800 --> 01:08:16,400 RELAPSE OF 151 DAYS. 1638 01:08:16,400 --> 01:08:20,680 NO CT DNA WAS DETECTED IN 190 1639 01:08:20,680 --> 01:08:24,840 OUT OF 199 PLASMA SAMPLES IN THE 1640 01:08:24,840 --> 01:08:27,600 23 PATIENT WHO'S DIDN'T RELAPSE 1641 01:08:27,600 --> 01:08:29,000 AND REINFORCES THE POINT PHIL 1642 01:08:29,000 --> 01:08:32,280 MADE WHICH IS NEGATIVE SCREENING 1643 01:08:32,280 --> 01:08:34,120 TESTS ARE VERY POWERFUL PIECES 1644 01:08:34,120 --> 01:08:41,320 OF INFORMATION. 1645 01:08:41,320 --> 01:08:42,680 IT COULD BE HAVE ALL IN PREDICT 1646 01:08:42,680 --> 01:08:44,360 OFFICER HIGH VALUES AND HAVING 1647 01:08:44,360 --> 01:08:48,560 NO CT DNA DETECTED IN 10 OUT OF 1648 01:08:48,560 --> 01:08:51,560 10 PATIENTS WITH SECOND PRIMARY 1649 01:08:51,560 --> 01:08:54,720 TUMORS AND REFLECTING THE TEST 1650 01:08:54,720 --> 01:08:56,160 IS SPECIFIC TO THE PRIMARY 1651 01:08:56,160 --> 01:08:56,360 TUMOR. 1652 01:08:56,360 --> 01:08:58,000 THAT'S IMPORTANT TO KEEP IN 1653 01:08:58,000 --> 01:08:59,000 MIND. 1654 01:08:59,000 --> 01:09:00,400 THERE'S ALSO OTHER LANDMARK 1655 01:09:00,400 --> 01:09:06,200 DATA, THE PRESENCE OF CT DNA 1656 01:09:06,200 --> 01:09:09,080 MOST CURATIVE IN PATIENTS WITH 1657 01:09:09,080 --> 01:09:09,800 METASTATIC COLORECTAL CANCER AND 1658 01:09:09,800 --> 01:09:12,360 THE CT DNA PREDICTED RISK OF 1659 01:09:12,360 --> 01:09:16,000 RELAPSE IN PATIENTS WITH EARLY 1660 01:09:16,000 --> 01:09:18,240 STAGE DISEASE, LONGITUDINAL 1661 01:09:18,240 --> 01:09:20,240 MONITORING AND SENSITIVE AND THE 1662 01:09:20,240 --> 01:09:22,000 LEAD TIME ACROSSIES VARIED WITH 1663 01:09:22,000 --> 01:09:24,840 MOST IT WAS A MEDIAN OF SIX 1664 01:09:24,840 --> 01:09:26,080 MONTHS OR GREATER LEAD TIME 1665 01:09:26,080 --> 01:09:29,680 COMPARED TO STANDARD OF CARE. 1666 01:09:29,680 --> 01:09:37,160 I THINK THE CT DNA WORKS FOR 1667 01:09:37,160 --> 01:09:38,080 FINDING RELAPSES EARLIER AND IT 1668 01:09:38,080 --> 01:09:43,160 BEGS THE QUESTION, DOES THAT 1669 01:09:43,160 --> 01:09:43,560 IMPROVE OUTCOMES? 1670 01:09:43,560 --> 01:09:44,080 THAT STILL NEEDS TO BE 1671 01:09:44,080 --> 01:09:50,560 DETERMINED. 1672 01:09:50,560 --> 01:09:57,240 THIS WAS CT DNA DETECTION MOST 1673 01:09:57,240 --> 01:10:06,000 INITIAL TRANS URETHRA DETECTION 1674 01:10:06,000 --> 01:10:08,040 AND ON THE LEFT IS PROBABILITY 1675 01:10:08,040 --> 01:10:10,120 OF DISEASE-FREE SURVIVAL. 1676 01:10:10,120 --> 01:10:14,320 ON THE TOP TWO, RED AND BLUE IS 1677 01:10:14,320 --> 01:10:16,760 THE CT DNA NEGATIVE. 1678 01:10:16,760 --> 01:10:20,120 AND IN THE BOTTOM IS THE CT DNA 1679 01:10:20,120 --> 01:10:20,400 POSITIVE. 1680 01:10:20,400 --> 01:10:21,280 THE DIFFERENCE BETWEEN THE TWO 1681 01:10:21,280 --> 01:10:26,440 LINES WERE THE PATIENTS WHO 1682 01:10:26,440 --> 01:10:27,560 RECEIVED ADJUVANT THERAPY. 1683 01:10:27,560 --> 01:10:29,560 YOU CAN SEE THE PATIENTS WHO 1684 01:10:29,560 --> 01:10:31,600 WERE CT DNA POSITIVE POST 1685 01:10:31,600 --> 01:10:36,080 SURGERY RECEIVED GREATER BENEFIT 1686 01:10:36,080 --> 01:10:38,440 FROM THE ADJUVANT THERAPY THAN 1687 01:10:38,440 --> 01:10:41,560 PATIENTS WHO WERE CT DNA 1688 01:10:41,560 --> 01:10:42,080 NEGATIVE. 1689 01:10:42,080 --> 01:10:44,520 THE PROBABILITY OF DISEASE 1690 01:10:44,520 --> 01:10:46,560 SURVIVAL WAS MUCH GREATER IF THE 1691 01:10:46,560 --> 01:10:51,600 CT DNA WAS NEGATIVE AND THE 1692 01:10:51,600 --> 01:10:54,040 PATIENTS REALLY DIDN'T SHOW 1693 01:10:54,040 --> 01:10:55,840 SIGNIFICANT RESPONSE TO ADJUVANT 1694 01:10:55,840 --> 01:10:59,240 THERAPY COMPARED TO THOSE WHO 1695 01:10:59,240 --> 01:11:00,640 RECEIVED THE ONE LOWER POSITIVE 1696 01:11:00,640 --> 01:11:02,840 AND ON THE RIGHT IS SIMILAR 1697 01:11:02,840 --> 01:11:05,680 EXCEPT THE PROS PROBABILITY OF 1698 01:11:05,680 --> 01:11:08,880 OVER ALL SURVIVAL. 1699 01:11:08,880 --> 01:11:11,640 AND SAME THING, CT DNA POSITIVE 1700 01:11:11,640 --> 01:11:17,720 HAD WORSE SURVIVAL AND A 1701 01:11:17,720 --> 01:11:18,640 POSITIVE RESPONSE COMPARED TO 1702 01:11:18,640 --> 01:11:22,520 THE CT DNA NEGATIVE PATIENTS IN 1703 01:11:22,520 --> 01:11:24,280 THE TOP TWO CURVES. 1704 01:11:24,280 --> 01:11:26,280 SO THERE'S KEY REMAINING 1705 01:11:26,280 --> 01:11:29,400 QUESTIONS AMONG OTHERS. 1706 01:11:29,400 --> 01:11:30,720 ONE IS CAN CT DNA BECOME 1707 01:11:30,720 --> 01:11:32,160 SPECIFIC ENOUGH TO ALLOW 1708 01:11:32,160 --> 01:11:33,480 DETECTION IN THE GENERAL 1709 01:11:33,480 --> 01:11:33,800 POPULATION? 1710 01:11:33,800 --> 01:11:35,240 I THINK PHIL MADE THE POINT AND 1711 01:11:35,240 --> 01:11:36,600 I'VE TRIED TO HAMMER IT HOME 1712 01:11:36,600 --> 01:11:38,640 BECAUSE I THINK IT'S A KEY POINT 1713 01:11:38,640 --> 01:11:42,360 TO MAKE HERE AND THAT IS YOU 1714 01:11:42,360 --> 01:11:45,080 NEED AN AMAZINGLY SPECIFIC TEST 1715 01:11:45,080 --> 01:11:47,080 IF YOU'RE GOING TO APPLY IT TO A 1716 01:11:47,080 --> 01:11:49,520 POPULATION WHERE THE PREVALENCE 1717 01:11:49,520 --> 01:11:49,800 IS LOW. 1718 01:11:49,800 --> 01:11:51,840 AND IF YOU END UP WITH A FALSE 1719 01:11:51,840 --> 01:11:54,360 POSITIVE YOU NOW HAVE CREATED A 1720 01:11:54,360 --> 01:12:02,400 GROUP OF PEOPLE IN WHOM IT'S GO 1721 01:12:02,400 --> 01:12:07,400 BE TO BE HARD TO FIND A POSITIVE 1722 01:12:07,400 --> 01:12:11,640 A LOT OF THEM ARE FALSE 1723 01:12:11,640 --> 01:12:12,240 POSITIVES AND VERY WORRIED 1724 01:12:12,240 --> 01:12:14,560 INDIVIDUALS WHEN IT WAS A FALSE 1725 01:12:14,560 --> 01:12:14,840 POSITIVE. 1726 01:12:14,840 --> 01:12:15,880 THIS IS OPEN FOR FURTHER 1727 01:12:15,880 --> 01:12:18,800 DEVELOPMENT. 1728 01:12:18,800 --> 01:12:20,400 HOWE ABOUT HIGH RISK PEOPLE? 1729 01:12:20,400 --> 01:12:22,560 HOW ABOUT THE PEOPLE WHO ARE 1730 01:12:22,560 --> 01:12:27,400 POSITIVE FOR BRCA1 AND 2 1731 01:12:27,400 --> 01:12:30,760 PATHOGENIC VARIANTS OR FOR ATM 1732 01:12:30,760 --> 01:12:33,680 PATHOGENIC VARIANTS WITH 1733 01:12:33,680 --> 01:12:35,400 PANCREATIC AND OVARIAN CANCERS. 1734 01:12:35,400 --> 01:12:37,800 THEY'RE HARD CANCERS TO LOOK 1735 01:12:37,800 --> 01:12:38,440 FOR. 1736 01:12:38,440 --> 01:12:39,760 THEY'RE PRIOR PROBABILITY IS NOT 1737 01:12:39,760 --> 01:12:42,360 THE SAME AS THE GENERAL 1738 01:12:42,360 --> 01:12:42,640 POPULATION. 1739 01:12:42,640 --> 01:12:44,640 THEY'RE AT GREATER RISK SO A 1740 01:12:44,640 --> 01:12:47,200 TEST WITH A GIVEN SPECIFICITY 1741 01:12:47,200 --> 01:12:51,080 WILL HAVE A HY POSITIVE 1742 01:12:51,080 --> 01:12:52,040 PREDICTIVE VALUE THAN IN THE 1743 01:12:52,040 --> 01:12:53,040 GENERAL POPULATION. 1744 01:12:53,040 --> 01:12:57,480 MIGHT WE HAVE A ROLE TO PLI IN 1745 01:12:57,480 --> 01:13:01,600 THOSE S PATIENTS? 1746 01:13:01,600 --> 01:13:03,640 IS VARIANT CT DNA THE BEST WAY 1747 01:13:03,640 --> 01:13:05,400 TO SCREEN OR AS DEVELOPED BY A 1748 01:13:05,400 --> 01:13:10,000 NUMBER OF INVESTIGATORS, 1749 01:13:10,000 --> 01:13:11,600 METHYLATION SIGNATURES ON THE CT 1750 01:13:11,600 --> 01:13:13,560 DNA FRAGMENTS? 1751 01:13:13,560 --> 01:13:17,680 WOULD THEY ADD TO THE 1752 01:13:17,680 --> 01:13:19,280 SPECIFICITY AND MIGHT I HELP 1753 01:13:19,280 --> 01:13:21,480 IDENTIFY THE TISSUE OF ORGAN? 1754 01:13:21,480 --> 01:13:23,600 THAT'S ONE THING BEING LOOKED 1755 01:13:23,600 --> 01:13:24,800 AT. 1756 01:13:24,800 --> 01:13:27,200 JUST THE PRESENCE OF CT DNA 1757 01:13:27,200 --> 01:13:29,320 THERE'LL GOING TO BE MORE 1758 01:13:29,320 --> 01:13:33,200 DEVELOPMENT LOOKING AT DNA AND 1759 01:13:33,200 --> 01:13:33,520 METHYLATION. 1760 01:13:33,520 --> 01:13:34,720 BIG QUESTION, DOES EARLIER 1761 01:13:34,720 --> 01:13:35,600 DETECTION OF RELAPSE IMPROVE 1762 01:13:35,600 --> 01:13:39,600 SURVIVAL S&P -- SURVIVAL? 1763 01:13:39,600 --> 01:13:42,600 I THINK THE CT DNA IN MANY 1764 01:13:42,600 --> 01:13:46,040 SITUATIONS IS CLEARLY 1765 01:13:46,040 --> 01:13:49,600 OUTPERFORMING CLINICAL RELAPSE 1766 01:13:49,600 --> 01:13:50,600 DOES IT MAKE A DIFFERENCE? 1767 01:13:50,600 --> 01:13:59,400 THAT NEEDS TO BE PROVEN. 1768 01:13:59,400 --> 01:14:02,120 WILL CT DNA BE EFFECTIVE IN THE 1769 01:14:02,120 --> 01:14:03,600 SHARED DECISION MAKING BETWEEN 1770 01:14:03,600 --> 01:14:06,480 THE ONCOLOGIST AND PATIENT. 1771 01:14:06,480 --> 01:14:11,640 SAY I'M NOT SURE IF POST SURGERY 1772 01:14:11,640 --> 01:14:13,760 THE PATIENT WILL ASK THE 1773 01:14:13,760 --> 01:14:14,760 SURGEON, DOC, DID YOU GET IT 1774 01:14:14,760 --> 01:14:17,560 ALL? 1775 01:14:17,560 --> 01:14:19,400 THE SURGEON IS LEFT WITH THE 1776 01:14:19,400 --> 01:14:22,000 SITUATION WHERE, I THINK I GOT 1777 01:14:22,000 --> 01:14:23,600 IT ALL. 1778 01:14:23,600 --> 01:14:25,360 I DON'T SEE EVIDENCE BUT MAYBE 1779 01:14:25,360 --> 01:14:29,160 JUST TO BE ON THE SAFE SIDE WE 1780 01:14:29,160 --> 01:14:31,400 SHOULD USE ADJUVANT CHEMOTHERAPY 1781 01:14:31,400 --> 01:14:34,720 BECAUSE I CAN'T BE SURE AND THE 1782 01:14:34,720 --> 01:14:37,920 CHANCE OF REOCCURRENCE IS 1783 01:14:37,920 --> 01:14:39,600 SIGNIFICANT IN THE CANCER. 1784 01:14:39,600 --> 01:14:41,680 WILL CT DNA BE ACCEPTED AND 1785 01:14:41,680 --> 01:14:45,560 PROVEN TO ALLOW PEOPLE WHO DON'T 1786 01:14:45,560 --> 01:14:47,800 NEED ADJUVANT CHEMOTHERAPY TO 1787 01:14:47,800 --> 01:14:52,600 SKIP IT AND THE PEOPLE WHO NEED 1788 01:14:52,600 --> 01:14:55,080 IT TO FEEL CONFIDENT, YES, THIS 1789 01:14:55,080 --> 01:14:56,120 IS THE RIGHT NEXT STEP. 1790 01:14:56,120 --> 01:14:58,000 FINALLY WE HAVE TO TALK ABOUT 1791 01:14:58,000 --> 01:14:59,920 THE COST OF CT DNA MONITORING? 1792 01:14:59,920 --> 01:15:02,680 IS IT JUSTIFIED JUST BY THE 1793 01:15:02,680 --> 01:15:06,680 IMPROVEMENT IN OUTCOMES? 1794 01:15:06,680 --> 01:15:10,040 THIS WILL ADD TO THE COST OF 1795 01:15:10,040 --> 01:15:10,400 TREATMENT. 1796 01:15:10,400 --> 01:15:11,640 THE ECONOMICS ARE IT'S PROBABLY 1797 01:15:11,640 --> 01:15:15,640 A SMALL ADDITION TO THE COST 1798 01:15:15,640 --> 01:15:18,280 OVER ALL COST OF CANCER 1799 01:15:18,280 --> 01:15:18,640 TREATMENT. 1800 01:15:18,640 --> 01:15:22,040 CANCER THERAPY IS VERY COSTLY. 1801 01:15:22,040 --> 01:15:24,920 THIS WILL ADD TO IT. 1802 01:15:24,920 --> 01:15:26,840 IF IT'S VALUABLE AND REALLY 1803 01:15:26,840 --> 01:15:28,040 SAVES SOME PEOPLE FROM HAVING 1804 01:15:28,040 --> 01:15:29,760 CERTAIN TREATMENTS OR DETECTS 1805 01:15:29,760 --> 01:15:34,040 CANCER EARLIER ENOUGH TO BE 1806 01:15:34,040 --> 01:15:36,320 SURGICALLY RECEPTABLE AND 1807 01:15:36,320 --> 01:15:40,720 TREATABLE IT'S PROVEN ITS VALUE. 1808 01:15:40,720 --> 01:15:42,440 THERE'S A RECENT PRIVATE 1809 01:15:42,440 --> 01:15:43,880 INSURANCE COMPANY THAT ISSUED A 1810 01:15:43,880 --> 01:15:47,520 STATEMENT THAT THE USE OF 1811 01:15:47,520 --> 01:15:49,000 PERSONALIZED TUMOR-INFORMED CT 1812 01:15:49,000 --> 01:15:52,840 DNA PLASMA-BASED TESTS ARE 1813 01:15:52,840 --> 01:15:53,520 CONSIDERED MEDICALLY NECESSARY 1814 01:15:53,520 --> 01:15:56,760 WHEN BOTH FOLLOWS ARE MET. 1815 01:15:56,760 --> 01:15:59,600 AN INDIVIDUAL STAGE 1 THROUGH 4 1816 01:15:59,600 --> 01:16:03,120 AFTER SURGICAL INTERVENTION WITH 1817 01:16:03,120 --> 01:16:05,400 CURATIVE INTENT IT IS JUSTIFIED 1818 01:16:05,400 --> 01:16:07,600 TO PROVIDE INFORMATION FOR ANY 1819 01:16:07,600 --> 01:16:10,080 OF THE FOLLOWING. 1820 01:16:10,080 --> 01:16:12,080 ADJUVANT FOR TARGETED THERAPY, 1821 01:16:12,080 --> 01:16:13,720 MONITORING FOR RELAPSE OF 1822 01:16:13,720 --> 01:16:14,680 PROGRESSION, INCLUDING BUT NOT 1823 01:16:14,680 --> 01:16:17,080 LIMITED THE USE OF IMMUNOTHERAPY 1824 01:16:17,080 --> 01:16:21,960 AND IMMUNE CHECKPOINT 1825 01:16:21,960 --> 01:16:22,240 INHIBITORS. 1826 01:16:22,240 --> 01:16:26,760 AS LONG AS YOU DON'T USE THE 1827 01:16:26,760 --> 01:16:28,080 TESTING MORE FREQUENTLY THAN THE 1828 01:16:28,080 --> 01:16:31,600 MONITORING GUIDELINES. 1829 01:16:31,600 --> 01:16:32,840 THIS IS A BIG STEP. 1830 01:16:32,840 --> 01:16:38,160 I BRING THIS HERE BECAUSE IN 1831 01:16:38,160 --> 01:16:41,480 MANY WAYS ADOPTION AS MUCH AS 1832 01:16:41,480 --> 01:16:44,080 PHIL POINTED OUT, SCIENCE AND 1833 01:16:44,080 --> 01:16:48,480 EVIDENCE ARE IMPORTANT BUT WHAT 1834 01:16:48,480 --> 01:16:50,640 ALLOWS ADOPTION TO OCCUR IS WHEN 1835 01:16:50,640 --> 01:16:54,640 HEALTH INSURERS AND MEDICARE 1836 01:16:54,640 --> 01:16:58,080 DECIDE THEY ARE GOING TO 1837 01:16:58,080 --> 01:17:01,320 REIMBURSE FOR THE TESTING. 1838 01:17:01,320 --> 01:17:03,600 THEY BASE THEIR JUDGMENT ON WHAT 1839 01:17:03,600 --> 01:17:06,480 WE HOPE IS GOING TO BE STRONG 1840 01:17:06,480 --> 01:17:09,840 EVIDENCE AND I BELIEVE PERMLY 1841 01:17:09,840 --> 01:17:11,640 THE MORE EVIDENCE NEEDS TO BE 1842 01:17:11,640 --> 01:17:11,880 DEVELOPED. 1843 01:17:11,880 --> 01:17:15,880 I BRING THIS UP BECAUSE THIS IS 1844 01:17:15,880 --> 01:17:16,120 COMING. 1845 01:17:16,120 --> 01:17:17,760 IT'S NOT SCIENCE FICTION. 1846 01:17:17,760 --> 01:17:19,320 IT'S HERE TODAY AND OVER THE 1847 01:17:19,320 --> 01:17:21,200 NEXT FEW YEARS WE'LL SEE A LOT 1848 01:17:21,200 --> 01:17:28,520 MORE DATA ON THE USES OF CT DNA 1849 01:17:28,520 --> 01:17:31,360 MONITORING FOR CANCER PATIENTS 1850 01:17:31,360 --> 01:17:32,960 AS WELL AS HERE MORE ABOUT 1851 01:17:32,960 --> 01:17:35,040 SCREENING IN PERHAPS PATIENT 1852 01:17:35,040 --> 01:17:36,320 WHO'S ARE AT GREATER RISK 1853 01:17:36,320 --> 01:17:40,040 BECAUSE THE GERM LINE MUTATIONS 1854 01:17:40,040 --> 01:17:40,680 AND BECAUSE PERHAPS EVEN IN THE 1855 01:17:40,680 --> 01:17:42,720 WHOLE POPULATION. 1856 01:17:42,720 --> 01:17:49,080 IF AND WHEN THIS TESTING BECOMES 1857 01:17:49,080 --> 01:17:51,120 SPECIFIC ENOUGH TO NOT HAVE 1858 01:17:51,120 --> 01:17:54,440 FALSE POSITIVE RATES THAT ARE 1859 01:17:54,440 --> 01:17:54,760 UNACCEPTABLE. 1860 01:17:54,760 --> 01:17:55,600 WITH THAT I'LL STOP. 1861 01:17:55,600 --> 01:18:00,960 THANK YOU FOR YOUR ATTENTION WE 1862 01:18:00,960 --> 01:18:02,360 CAN PROCEED WITH ANY QUESTIONS 1863 01:18:02,360 --> 01:18:03,480 YOU HAVE. 1864 01:18:03,480 --> 01:18:05,520 >>THANK YOU BOTH VERY MUCH FOR 1865 01:18:05,520 --> 01:18:10,400 VERY EXCITING AND PROVOCATIVE 1866 01:18:10,400 --> 01:18:11,600 PRESENTATIONS OF A FIELD THAT I 1867 01:18:11,600 --> 01:18:14,360 HOPE WILL HAVE MANY MORE 1868 01:18:14,360 --> 01:18:16,840 SESSIONS ON IN THE COMING YEARS 1869 01:18:16,840 --> 01:18:19,600 IN DEMYSTIFYING MEDICINE. 1870 01:18:19,600 --> 01:18:23,960 I THINK THIS IS A RAPIDLY 1871 01:18:23,960 --> 01:18:25,320 UNFOLDING SITUATION. 1872 01:18:25,320 --> 01:18:29,840 WE HAVE A WHOLE SERIES OF 1873 01:18:29,840 --> 01:18:31,080 QUESTIONS THAT FORMED DIFFERENT 1874 01:18:31,080 --> 01:18:39,600 CATEGORIES I WILL TRY TO PUT 1875 01:18:39,600 --> 01:18:43,600 TOGETHER. 1876 01:18:43,600 --> 01:18:46,960 PHILLIP, MANY QUESTIONERS ASKED 1877 01:18:46,960 --> 01:18:51,600 WHAT ARE WE DOING ABOUT THE 1878 01:18:51,600 --> 01:18:54,320 MISSISSIPPI DELTA? 1879 01:18:54,320 --> 01:18:58,480 IT WOULD APPLY TO ANY AREA OF AN 1880 01:18:58,480 --> 01:19:00,200 ENORMOUS HOT SPOT. 1881 01:19:00,200 --> 01:19:04,520 IT OBVIOUSLY SPILLS OVER INTO 1882 01:19:04,520 --> 01:19:05,520 SOCIO ECONOMIC, POLITICAL HEALTH 1883 01:19:05,520 --> 01:19:11,280 SYSTEMS BUT WHAT IF ANYTHING IS 1884 01:19:11,280 --> 01:19:13,360 BEING DONE REGARDING CERVICAL 1885 01:19:13,360 --> 01:19:14,880 CANCER OR ANY CANCER IN THE 1886 01:19:14,880 --> 01:19:15,600 MISSISSIPPI DELTA? 1887 01:19:15,600 --> 01:19:25,200 CAN YOU COMMENT ABOUT THAT? 1888 01:19:25,200 --> 01:19:26,680 >>CERTAINLY THE INTRAMURAL 1889 01:19:26,680 --> 01:19:29,760 PROGRAM I STARTED DOING RESEARCH 1890 01:19:29,760 --> 01:19:31,400 IN THE MISSISSIPPI DELTA AROUND 1891 01:19:31,400 --> 01:19:31,600 2005. 1892 01:19:31,600 --> 01:19:35,600 THE INTRAMURAL PROGRAM HAS 1893 01:19:35,600 --> 01:19:37,760 CONTINUED TO DEVELOP STRATEGIES 1894 01:19:37,760 --> 01:19:39,120 TO REACH WOMEN AND DO RESEARCH 1895 01:19:39,120 --> 01:19:43,680 ON HOW TO REACH WOMEN LIVING IN 1896 01:19:43,680 --> 01:19:47,200 THE MISSISSIPPI DELTA WITH 1897 01:19:47,200 --> 01:19:48,360 CERVICAL CANCER. 1898 01:19:48,360 --> 01:19:51,600 MORE BROADLY MORE CANCER CENTERS 1899 01:19:51,600 --> 01:19:53,240 ARE INCREASINGLY ASKED TO DO 1900 01:19:53,240 --> 01:19:55,000 WHAT THEY CALL COE WHICH IS 1901 01:19:55,000 --> 01:19:55,680 COMMUNITY OUTREACH AND 1902 01:19:55,680 --> 01:20:02,400 ENGAGEMENT. 1903 01:20:02,400 --> 01:20:07,600 AND SO PART IS REACHING UNDER 1904 01:20:07,600 --> 01:20:09,120 SERVED POPULATIONS AND GETTING 1905 01:20:09,120 --> 01:20:10,280 THEM ON STUDIES HOW TO REACH 1906 01:20:10,280 --> 01:20:11,600 THEM. 1907 01:20:11,600 --> 01:20:15,200 IT'S MANY LEVELS. 1908 01:20:15,200 --> 01:20:18,560 SOME OF THE THINGS WE'RE TRYING 1909 01:20:18,560 --> 01:20:20,040 TO SPONSOR IS USING TECHNOLOGIES 1910 01:20:20,040 --> 01:20:25,120 PARTICULARLY SOME TECHNOLOGIES 1911 01:20:25,120 --> 01:20:28,640 THAT CAME OUT OF COVID TO 1912 01:20:28,640 --> 01:20:31,600 DEMOCRATIZE AND CENTRALIZE 1913 01:20:31,600 --> 01:20:33,080 CANCER SCREENING. 1914 01:20:33,080 --> 01:20:34,200 FOR EXAMPLE, WE'VE BEEN 1915 01:20:34,200 --> 01:20:36,200 INTERESTED IN THE COVID ANTIGEN 1916 01:20:36,200 --> 01:20:38,560 TEST AND WHETHER THEY COULD BE 1917 01:20:38,560 --> 01:20:42,720 REPURPOSED FOR E-6 SEROLOGY FOR 1918 01:20:42,720 --> 01:20:45,040 HPV TESTING FOR HEAD AND NECK 1919 01:20:45,040 --> 01:20:45,320 CANCER? 1920 01:20:45,320 --> 01:20:47,280 CAN YOU USE THE COVID ANTIGEN 1921 01:20:47,280 --> 01:20:50,400 TECHNOLOGY TO SCREEN FOR PSA FOR 1922 01:20:50,400 --> 01:20:52,120 HIGH-RISK MEN AND MONITOR THEM 1923 01:20:52,120 --> 01:21:01,440 FOR THAT MATTER. 1924 01:21:01,440 --> 01:21:03,040 THERE ARE THINGS WE CAN DO AT 1925 01:21:03,040 --> 01:21:07,600 THE POINT OF CARE THAN WE'VE 1926 01:21:07,600 --> 01:21:11,120 EVER BEEN ABLE TO DO THEM. 1927 01:21:11,120 --> 01:21:13,120 WE'RE WORKING ON THAT ACTIVELY. 1928 01:21:13,120 --> 01:21:14,120 >>THERE'S BEEN SEVERAL 1929 01:21:14,120 --> 01:21:19,080 QUESTIONS THAT DEAL WITH THE 1930 01:21:19,080 --> 01:21:29,600 ISSUE OF A PATIENT WITH FAMILY 1931 01:21:33,800 --> 01:21:35,920 HISTORY AND IF YOU LOOK AT THE 1932 01:21:35,920 --> 01:21:37,840 SLIDE WITH THE DIFFERENT 20 1933 01:21:37,840 --> 01:21:39,440 COMPANY'S TECHNIQUES AND 1934 01:21:39,440 --> 01:21:40,080 PROBABLY THEY'RE ADVERTISING AND 1935 01:21:40,080 --> 01:21:46,080 MAYBE HYPES IT UP, WHAT'S THAT 1936 01:21:46,080 --> 01:21:50,080 PERSON SUPPOSED TO DO? 1937 01:21:50,080 --> 01:21:51,640 >>WHAT YOU HIGHLIGHT IS THE 1938 01:21:51,640 --> 01:21:53,840 THING THAT SCARES ME. 1939 01:21:53,840 --> 01:21:55,360 THINK ABOUT IT THIS WAY. 1940 01:21:55,360 --> 01:21:57,560 IF YOU WALK DOWN THE STREET AND 1941 01:21:57,560 --> 01:22:00,480 SAY LISTEN, I HAVE A TEST THAT 1942 01:22:00,480 --> 01:22:03,560 DETECTS 50 CANCERS -- IF YOU 1943 01:22:03,560 --> 01:22:06,080 DIDN'T KNOW ANY BETTER YOU'D BE 1944 01:22:06,080 --> 01:22:08,000 LIKE WHERE DID I SIGN UP BUT 1945 01:22:08,000 --> 01:22:09,720 JUST BECAUSE IT DETECTS CANCER 1946 01:22:09,720 --> 01:22:11,440 DIDN'T MEAN IT WILL GIVE YOU A 1947 01:22:11,440 --> 01:22:11,640 BENEFIT. 1948 01:22:11,640 --> 01:22:13,280 IT MAY FIND THE CANCER EARLIER 1949 01:22:13,280 --> 01:22:16,480 BUT MAY STILL KILL YOU. 1950 01:22:16,480 --> 01:22:19,640 THAT'S CALLED LEAD TIME 1951 01:22:19,640 --> 01:22:21,400 DETECTION OR BIAS. 1952 01:22:21,400 --> 01:22:23,600 RIGHT NOW WE CAN'T RECOMMEND ANY 1953 01:22:23,600 --> 01:22:25,640 OF THESE TESTS BECAUSE THEY 1954 01:22:25,640 --> 01:22:27,600 HAVEN'T BEEN PROVEN TO BENEFIT A 1955 01:22:27,600 --> 01:22:28,760 SINGLE PERSON. 1956 01:22:28,760 --> 01:22:31,560 THEY HAVEN'T PREVENTED A SINGLE 1957 01:22:31,560 --> 01:22:31,760 DEATH. 1958 01:22:31,760 --> 01:22:34,920 >>I WOULD SAY FOR SOMEONE WHO 1959 01:22:34,920 --> 01:22:36,440 HAS FAMILY HISTORY AND IS 1960 01:22:36,440 --> 01:22:37,760 CONCERNED ABOUT THEIR RISK, 1961 01:22:37,760 --> 01:22:39,600 FIRST AND FOREMOST THEY SHOULD 1962 01:22:39,600 --> 01:22:42,600 HAVE GERM LINE TESTING FOR 1963 01:22:42,600 --> 01:22:45,480 HEREDITARY CANCER SYNDROMES. 1964 01:22:45,480 --> 01:22:47,600 THAT'S THE FIRST STEP. 1965 01:22:47,600 --> 01:22:54,040 THEN IF THEY ARE NEGATIVE 1966 01:22:54,040 --> 01:22:55,600 THERE'S MORE DEVELOPING 1967 01:22:55,600 --> 01:22:58,480 INFORMATION ON POLY GENIC RISK 1968 01:22:58,480 --> 01:22:58,720 SCORES. 1969 01:22:58,720 --> 01:22:59,360 THERE'S A LITTLE BIT MORE OF A 1970 01:22:59,360 --> 01:23:02,040 PROBLEM IN THAT WE HAVE TO MAKE 1971 01:23:02,040 --> 01:23:03,240 SURE THEY'RE APPROPRIATE FOR 1972 01:23:03,240 --> 01:23:05,160 PEOPLE OF ALL ANCESTRIES. 1973 01:23:05,160 --> 01:23:07,600 RIGHT NOW MOST POLY GENIC RISK 1974 01:23:07,600 --> 01:23:09,960 SCORES HAVE BEEN DEVELOPED IN 1975 01:23:09,960 --> 01:23:12,040 PEOPLE OF EUROPEAN ANCESTRY AND 1976 01:23:12,040 --> 01:23:12,960 THIS IS AN ISSUE. 1977 01:23:12,960 --> 01:23:14,480 STEP ONE IS DO YOU HAVE A CHANGE 1978 01:23:14,480 --> 01:23:16,360 IN YOUR GERM LINE THAT REFLECTS 1979 01:23:16,360 --> 01:23:19,160 WHAT IT IS GOING ON IN YOUR 1980 01:23:19,160 --> 01:23:19,560 FAMILY. 1981 01:23:19,560 --> 01:23:22,480 BECAUSE THERE I THINK WE CAN 1982 01:23:22,480 --> 01:23:25,880 PREVENT CANCER IF PEOPLE HAVE 1983 01:23:25,880 --> 01:23:28,720 HIGH RISK VARIANTS THROUGH THE 1984 01:23:28,720 --> 01:23:30,840 USE OF PROPHYLACTIC SURGERY 1985 01:23:30,840 --> 01:23:31,120 PRIMARILY. 1986 01:23:31,120 --> 01:23:32,920 >>I THINK MY POINT ROBERT WAS 1987 01:23:32,920 --> 01:23:35,600 NOT TO USE THESE UNPROVEN TESTS 1988 01:23:35,600 --> 01:23:39,960 UNTIL WE HAVE EVIDENCE THAT THEY 1989 01:23:39,960 --> 01:23:40,160 WORK. 1990 01:23:40,160 --> 01:23:44,440 I'M GLAD YOU WHAT SAID ABOUT THE 1991 01:23:44,440 --> 01:23:45,320 FDA AND CMS. 1992 01:23:45,320 --> 01:23:46,600 I'M NOT ALLOWED IT TALK ABOUT 1993 01:23:46,600 --> 01:23:48,760 THEM BUT YOU ARE SO I'M GLAD YOU 1994 01:23:48,760 --> 01:23:50,240 SAID ALL THAT. 1995 01:23:50,240 --> 01:23:51,200 I AGREE UNDERSTANDING YOUR 1996 01:23:51,200 --> 01:23:53,840 RISK -- THAT'S A WHOLE TOPIC. 1997 01:23:53,840 --> 01:23:55,880 WE CAN DO A WHOLE SESSION ON 1998 01:23:55,880 --> 01:23:57,240 UNDERSTANDING YOUR RISK AND WHAT 1999 01:23:57,240 --> 01:23:58,480 IT MEANS AND WHAT IT DOESN'T 2000 01:23:58,480 --> 01:23:59,600 MEAN. 2001 01:23:59,600 --> 01:24:02,960 AND ONE OF THE CHALLENGES -- AND 2002 01:24:02,960 --> 01:24:06,160 I DIDN'T FULLY APPRECIATE THIS 2003 01:24:06,160 --> 01:24:08,920 EARLIER IN MY CAREER IS THAT IF 2004 01:24:08,920 --> 01:24:10,720 WE DON'T AS AN INDIVIDUAL 2005 01:24:10,720 --> 01:24:12,680 UNDERSTAND RISK PARTICULARLY 2006 01:24:12,680 --> 01:24:14,320 WELL AND I THINK COVID 2007 01:24:14,320 --> 01:24:15,000 HIGHLIGHTED THAT THE INDIVIDUAL 2008 01:24:15,000 --> 01:24:16,400 DOESN'T REALLY UNDERSTAND WHEN 2009 01:24:16,400 --> 01:24:19,840 YOU SAY YOU'RE AT A 10% RISK AND 2010 01:24:19,840 --> 01:24:21,080 FROM THEIR PERSPECTIVE WHAT IS 2011 01:24:21,080 --> 01:24:21,960 10% RISK MEAN? 2012 01:24:21,960 --> 01:24:23,520 YOU EITHER GET CANCER OR YOU 2013 01:24:23,520 --> 01:24:24,160 DON'T, RIGHT? 2014 01:24:24,160 --> 01:24:27,600 YOU'RE NOT A POPULATION. 2015 01:24:27,600 --> 01:24:30,080 YOU'RE A POPULATION OF ONE. 2016 01:24:30,080 --> 01:24:31,480 IT'S HARD TO TRANSLATE 2017 01:24:31,480 --> 01:24:33,160 POPULATION RISK TO WHAT 2018 01:24:33,160 --> 01:24:34,120 INDIVIDUALS ARE GOING TO DO AND 2019 01:24:34,120 --> 01:24:36,120 TO MAKE SURE THEY UNDERSTAND. 2020 01:24:36,120 --> 01:24:38,200 I AGREE FAMILY HISTORY AND THE 2021 01:24:38,200 --> 01:24:39,720 FIRST THING THAT SHOULD GO UP, 2022 01:24:39,720 --> 01:24:41,760 THE FLAG SHOULD GO UP. 2023 01:24:41,760 --> 01:24:45,760 YOU DO -- YOU LOOK FOR 2024 01:24:45,760 --> 01:24:49,360 PREDISPOSITION AND AFTER THAT IT 2025 01:24:49,360 --> 01:24:53,160 GETS MORE GEARED BUT HOPEFULLY 2026 01:24:53,160 --> 01:24:55,080 NEW TOOLS ARE COMING SO WE DON'T 2027 01:24:55,080 --> 01:24:58,320 HAVE TO REPLY ON PROPHYLACTIC AS 2028 01:24:58,320 --> 01:25:01,160 OUR ONLY MEANS. 2029 01:25:01,160 --> 01:25:02,280 I TOLD COLLEAGUES WE'LL LOOK 2030 01:25:02,280 --> 01:25:04,640 BACK 50 YEARS FROM NOW AND 2031 01:25:04,640 --> 01:25:07,400 SOMEBODY WILL SAY HOW DID YOU 2032 01:25:07,400 --> 01:25:08,320 DEAL WITH BRCA? 2033 01:25:08,320 --> 01:25:11,120 WE CUT OUT PARTS OF PEOPLE'S 2034 01:25:11,120 --> 01:25:12,880 BODIES AND THEY'LL SAY YOU GUYS 2035 01:25:12,880 --> 01:25:23,160 WERE BARBARIANS. 2036 01:25:25,080 --> 01:25:34,000 CURRENTLY THAT'S IT. 2037 01:25:34,000 --> 01:25:37,200 >>THERE'D BE PUBLIC INTEREST IN 2038 01:25:37,200 --> 01:25:42,080 CANCER AND THE ISSUES YOU BOTH 2039 01:25:42,080 --> 01:25:42,760 RAISED TODAY. 2040 01:25:42,760 --> 01:25:48,520 HAS IT HAD SOME BACKGROUND IN 2041 01:25:48,520 --> 01:25:51,080 TERMS OF OUR EDUCATIONAL SYSTEM 2042 01:25:51,080 --> 01:25:52,120 BOTH FOR YOUNG PEOPLE 2043 01:25:52,120 --> 01:25:59,400 PARTICULARLY ADOLESCENTS AND 2044 01:25:59,400 --> 01:26:03,600 THINKING ABOUT VACCINATION FOR 2045 01:26:03,600 --> 01:26:06,120 HUMAN PAPILLOMA VIRUS OR 2046 01:26:06,120 --> 01:26:15,600 ANYTHING ELSE IS THERE A WAY TO 2047 01:26:15,600 --> 01:26:18,600 EDUCATION PEOPLE SOMETHING ABOUT 2048 01:26:18,600 --> 01:26:20,640 CANCER BECAUSE PROBABLY THE VAST 2049 01:26:20,640 --> 01:26:22,360 MAJORITY OF PEOPLE ONLY KNOW IT 2050 01:26:22,360 --> 01:26:28,120 IN ITS MOST TERRIFYING ASPECTS. 2051 01:26:28,120 --> 01:26:29,960 >>I THINK THERE'S A TREMENDOUS 2052 01:26:29,960 --> 01:26:30,800 OPPORTUNITY TO EDUCATE WHAT YOU 2053 01:26:30,800 --> 01:26:33,080 CAN DO TO REDUCE YOUR RISK. 2054 01:26:33,080 --> 01:26:36,240 IT'S NOT JUST THE KIDS, IT'S THE 2055 01:26:36,240 --> 01:26:41,560 PARENTS, IT'S THE PROVIDERS. 2056 01:26:41,560 --> 01:26:43,640 WHAT IS AVAILABLE TO YOU AND 2057 01:26:43,640 --> 01:26:45,040 DEBUNKING SOME OF THE STORIES. 2058 01:26:45,040 --> 01:26:46,080 THE OTHER DAY SOMEBODY MENTIONED 2059 01:26:46,080 --> 01:26:49,680 TO ME THE OLD STORY THAT 2060 01:26:49,680 --> 01:26:55,600 VACCINATION CAUSES AUTISM WHICH 2061 01:26:55,600 --> 01:26:58,040 HAS BEEN DEBUNK NOW FOR FOUR 2062 01:26:58,040 --> 01:26:59,080 YEARS AND THERE'S BEEN A LEGAL 2063 01:26:59,080 --> 01:27:02,000 CASE FOR THE PERSON SUGGESTING 2064 01:27:02,000 --> 01:27:04,800 IT AND NOT PROVING OTHERWISE. 2065 01:27:04,800 --> 01:27:07,040 IT STILL LINGERS. 2066 01:27:07,040 --> 01:27:09,680 PEOPLE STILL WORRY ABOUT AUTISM 2067 01:27:09,680 --> 01:27:10,320 LINKED TO VACCINATION. 2068 01:27:10,320 --> 01:27:11,880 AND THERE'S JUST NO EVIDENCE FOR 2069 01:27:11,880 --> 01:27:16,400 THAT. 2070 01:27:16,400 --> 01:27:17,720 HAVE TO PROVIDE EDUCATION AND 2071 01:27:17,720 --> 01:27:22,720 RESOURCES AND THE OTHER PROBLEM 2072 01:27:22,720 --> 01:27:26,040 HERE IS DEALING WITH SOCIAL 2073 01:27:26,040 --> 01:27:26,520 MEDIA. 2074 01:27:26,520 --> 01:27:28,120 WE'RE IN A DIFFERENT WORLD AND 2075 01:27:28,120 --> 01:27:29,400 THE MANY SOURCES OF 2076 01:27:29,400 --> 01:27:29,760 MISINFORMATION. 2077 01:27:29,760 --> 01:27:34,920 HOW DO WE GUIDE THE PUBLIC TO GO 2078 01:27:34,920 --> 01:27:38,000 TO THE -- BACK IN OUR DAY YOU 2079 01:27:38,000 --> 01:27:41,560 WENT TO THE LIBRARY AND WENT TO 2080 01:27:41,560 --> 01:27:44,440 THE ENCYCLOPEDIA AND LEARN 2081 01:27:44,440 --> 01:27:45,040 WHATED 2082 01:27:45,040 --> 01:27:46,280 WHAT IS KNOWN AND HOW DO WE 2083 01:27:46,280 --> 01:27:47,360 CARVE OUT THE RIGHT INFORMATION 2084 01:27:47,360 --> 01:27:48,560 AND PROVIDE IT TO THE GENERAL 2085 01:27:48,560 --> 01:27:48,800 PUBLIC? 2086 01:27:48,800 --> 01:27:50,680 I DON'T HAVE AN ANSWER. 2087 01:27:50,680 --> 01:27:52,720 BUT MISINFORMATION IS AS 2088 01:27:52,720 --> 01:27:54,360 DANGEROUS AS -- WE'VE NEVER 2089 01:27:54,360 --> 01:27:55,600 EXPERIENCED THE LEVEL OF 2090 01:27:55,600 --> 01:27:57,040 MISINFORMATION THAT WE 2091 01:27:57,040 --> 01:27:58,360 EXPERIENCED NOW. 2092 01:27:58,360 --> 01:27:59,920 LOOK AT COVID. 2093 01:27:59,920 --> 01:28:01,760 THERE WAS A LOT OF 2094 01:28:01,760 --> 01:28:03,600 MISINFORMATION WHICH REALLY HURT 2095 01:28:03,600 --> 01:28:14,160 A LOT OF PEOPLE IN THE PROCESS. 2096 01:28:16,440 --> 01:28:19,520 >>I'D LIKE IT ADD A FEW THINGS. 2097 01:28:19,520 --> 01:28:23,600 THE AWARENESS OF AND CONCERN FOR 2098 01:28:23,600 --> 01:28:26,720 HEREDITY BREAST CANCER SYNDROMES 2099 01:28:26,720 --> 01:28:29,520 IS MUCH HIGHER THAN HEREDITARY 2100 01:28:29,520 --> 01:28:31,600 COLON CANCER THOUGH THE 2101 01:28:31,600 --> 01:28:34,120 HEREDITARY BREAST CANCER 2102 01:28:34,120 --> 01:28:43,280 SYNDROMES ARE APPROVXIMATELY SAE 2103 01:28:43,280 --> 01:28:46,120 PREVALENCE AND MEN TEND TO NOT 2104 01:28:46,120 --> 01:28:50,760 SEEK OUT MEDICAL CARE AND WE 2105 01:28:50,760 --> 01:28:54,000 HAVE THE ABILITY TO DO A BETTER 2106 01:28:54,000 --> 01:28:58,000 JOB WITH SCREENING AND WE HAVE 2107 01:28:58,000 --> 01:29:00,880 MAMMOGRAPHY AND WOMEN ARE MUCH 2108 01:29:00,880 --> 01:29:03,440 MORE AWARE IN EVERY GENETIC 2109 01:29:03,440 --> 01:29:06,840 STUDY I'VE EVER SEEN THE UPTAKE 2110 01:29:06,840 --> 01:29:10,120 OF WOMEN IS HIGHER THAN MEN. 2111 01:29:10,120 --> 01:29:11,600 WE HAVE A PARTICULAR CHALLENGE 2112 01:29:11,600 --> 01:29:15,240 IN EDUCATING MEN ABOUT THEIR 2113 01:29:15,240 --> 01:29:19,600 RISKS BUT THE ENTIRE POPULATION 2114 01:29:19,600 --> 01:29:20,120 POPULATION COULD USE MORE 2115 01:29:20,120 --> 01:29:24,240 EDUCATION. 2116 01:29:24,240 --> 01:29:27,680 >>BOB, IN ONE OF YOUR SLIDES 2117 01:29:27,680 --> 01:29:31,600 AND A LISTENER RAISED A QUESTION 2118 01:29:31,600 --> 01:29:36,600 I'LL BRING TO YOU, SURGERY 2119 01:29:36,600 --> 01:29:40,120 RESULTED IN A DRAMATIC FLOW OF 2120 01:29:40,120 --> 01:29:43,560 THE CIRCULATING DNA. 2121 01:29:43,560 --> 01:29:46,120 IT DIDN'T DISAPPEARED IT JUST 2122 01:29:46,120 --> 01:29:55,600 FELL TO A LOWER LEVEL. 2123 01:29:55,600 --> 01:29:58,080 BIOLOGICALLY IS THE CIRCULATING 2124 01:29:58,080 --> 01:30:00,760 DNA SUGGEST METASTASES ALREADY 2125 01:30:00,760 --> 01:30:01,040 OCCURRED? 2126 01:30:01,040 --> 01:30:04,720 >>THE ANSWER IS NO AND THE 2127 01:30:04,720 --> 01:30:10,120 REASON IS BECAUSE DEPENDING THE 2128 01:30:10,120 --> 01:30:14,160 THERAPY, THERE'S STILL DYING 2129 01:30:14,160 --> 01:30:15,960 CANCER CELLS AND THEY'RE 2130 01:30:15,960 --> 01:30:18,600 RELIEVING CT DNA AND WHETHER IT 2131 01:30:18,600 --> 01:30:21,000 CONSTITUTES AN ACTIVE METASTASIS 2132 01:30:21,000 --> 01:30:25,920 THAT WILL LEAD TO RELAPSE IS NOT 2133 01:30:25,920 --> 01:30:26,560 CLEAR. 2134 01:30:26,560 --> 01:30:27,200 THAT'S WHY SERIAL MONITORING IS 2135 01:30:27,200 --> 01:30:34,080 IMPORTANT. 2136 01:30:34,080 --> 01:30:36,440 >>IS THERE A CIRCADIAN RHYTHM 2137 01:30:36,440 --> 01:30:39,680 TO CIRCULATING DNA? 2138 01:30:39,680 --> 01:30:42,560 >>THAT'S INTERESTING. 2139 01:30:42,560 --> 01:30:45,520 I DON'T KNOW THE ANSWER TO THAT. 2140 01:30:45,520 --> 01:30:46,680 IT'S CLEARED VERY RAPIDLY WHEN 2141 01:30:46,680 --> 01:30:51,560 THE SOURCE OF IT IS REMOVED IT'S 2142 01:30:51,560 --> 01:30:54,320 CLEARED RAPIDLY. 2143 01:30:54,320 --> 01:30:56,680 WE KNOW THAT BETTER FROM FETAL 2144 01:30:56,680 --> 01:30:59,040 CELL-FREE DNA WHERE YOU CAN 2145 01:30:59,040 --> 01:31:01,240 REMOVE THE FETAL CONTRIBUTION TO 2146 01:31:01,240 --> 01:31:03,600 THE SERUM BY DELIVERING AND WHEN 2147 01:31:03,600 --> 01:31:06,840 THE BABY'S DELIVERED AND THE 2148 01:31:06,840 --> 01:31:16,040 PLACENTA IS OUT SINCE THE TROPE 2149 01:31:16,040 --> 01:31:19,120 OBLAST IS THE MAIN SOURCE IT 2150 01:31:19,120 --> 01:31:19,840 DROPS PRECIPITOUSLY. 2151 01:31:19,840 --> 01:31:20,760 IF IT HANGS AROUND IT'S BECAUSE 2152 01:31:20,760 --> 01:31:23,600 THERE'S A SOURCE BUT I DON'T 2153 01:31:23,600 --> 01:31:27,600 KNOW ABOUT CIRCADIAN RHYTHM. 2154 01:31:27,600 --> 01:31:30,200 PHIL, DO YOU KNOW ANYTHING ABOUT 2155 01:31:30,200 --> 01:31:30,400 THAT? 2156 01:31:30,400 --> 01:31:31,040 NO. 2157 01:31:31,040 --> 01:31:32,320 >>THERE'S A QUESTION 2158 01:31:32,320 --> 01:31:35,440 CIRCULATING TUMOR DNA STUDIES IN 2159 01:31:35,440 --> 01:31:39,440 ANIMALS, IS IT POSSIBLE TO USE 2160 01:31:39,440 --> 01:31:44,840 THAT AS A WAY OF EVALUATING 2161 01:31:44,840 --> 01:31:46,680 FACTOR ACCELERATE ASSUMER GROWTH 2162 01:31:46,680 --> 01:31:55,600 OR MAYBE NOT TUMOR GROWTH BUT 2163 01:31:55,600 --> 01:31:58,120 TOUMER RELEASE OF CIRCULATING 2164 01:31:58,120 --> 01:32:01,120 DNA THAT REGULATE THE TUMOR 2165 01:32:01,120 --> 01:32:02,400 AUTONOMOUS TO SOME DEGREE BUT 2166 01:32:02,400 --> 01:32:07,480 INTERACTING WITH FACTORS AND ALL 2167 01:32:07,480 --> 01:32:11,840 OF THAT. 2168 01:32:11,840 --> 01:32:14,560 IS THAT A REASONABLE RESEARCH TO 2169 01:32:14,560 --> 01:32:14,800 PURSUE? 2170 01:32:14,800 --> 01:32:18,480 >>I THINK IT WOULD BE VERY 2171 01:32:18,480 --> 01:32:22,000 VALUABLE BECAUSE THE AMOUNT OF 2172 01:32:22,000 --> 01:32:22,640 CIRCULATING TUMOR DNA DIFFERS 2173 01:32:22,640 --> 01:32:25,720 FROM THE TUMOR TYPE AND FROM THE 2174 01:32:25,720 --> 01:32:27,360 MASS OF THE TUMOR BUT ALSO THERE 2175 01:32:27,360 --> 01:32:29,520 ARE OTHER BIOLOGICAL FACTORS 2176 01:32:29,520 --> 01:32:35,600 ABOUT THE TUMOR PROBABLY THINGS 2177 01:32:35,600 --> 01:32:39,600 INVOLVED WITH HOW GOOD IS THE 2178 01:32:39,600 --> 01:32:44,640 BLOOD SUPPLY AND HOW ACTIVE IS 2179 01:32:44,640 --> 01:32:48,360 IT AND HOW MUCH TURNOVER AND 2180 01:32:48,360 --> 01:32:49,920 IMMUNE RESPONSE AND LYMPHOCYTE 2181 01:32:49,920 --> 01:32:51,640 INFILTRATION THERE IS IN THE 2182 01:32:51,640 --> 01:32:52,000 TUMOR. 2183 01:32:52,000 --> 01:32:54,120 ALL THOSE WILL PROBABLY A PLAY A 2184 01:32:54,120 --> 01:32:56,080 ROLE AND ANIMALS WOULD BE IDEAL 2185 01:32:56,080 --> 01:32:58,000 AS A WAY OF BEING ABLE TO 2186 01:32:58,000 --> 01:33:00,040 MANIPULATE THE HOST FACTORS IN 2187 01:33:00,040 --> 01:33:02,240 WAYS WE CAN'T IN HUMANS. 2188 01:33:02,240 --> 01:33:03,880 >>I WOULD SAY THAT'S AN 2189 01:33:03,880 --> 01:33:06,360 IMPORTANT ENDEAVOR BECAUSE WE 2190 01:33:06,360 --> 01:33:08,520 DON'T FOR ALL WE DO KNOW ABOUT 2191 01:33:08,520 --> 01:33:10,400 CIRCULATING DNA THERE'S A LOT WE 2192 01:33:10,400 --> 01:33:12,720 DON'T KNOW. 2193 01:33:12,720 --> 01:33:14,000 ALSO WE WON'T BE ABLE TO ANSWER 2194 01:33:14,000 --> 01:33:16,120 ALL THE QUESTIONS IN ANIMAL 2195 01:33:16,120 --> 01:33:18,440 MODELS BECAUSE WE CAN'T MIMIC 2196 01:33:18,440 --> 01:33:20,280 THE HETEROGENEITY OF HUMANS IN 2197 01:33:20,280 --> 01:33:22,000 THE PROCESS. 2198 01:33:22,000 --> 01:33:24,760 IT HAS TO BE A COMBINED ANIMAL 2199 01:33:24,760 --> 01:33:27,600 MODEL AND HUMAN MODEL, IF YOU 2200 01:33:27,600 --> 01:33:29,680 WILL, GETTING BLOOD FROM CANCER 2201 01:33:29,680 --> 01:33:31,360 PATIENTS AND SAYING WHY DOES 2202 01:33:31,360 --> 01:33:33,040 THIS PATIENT HAVE MORE OF THIS 2203 01:33:33,040 --> 01:33:34,120 OR LESS OF THAT. 2204 01:33:34,120 --> 01:33:36,360 WHAT ARE THEIR CHARACTERISTICS 2205 01:33:36,360 --> 01:33:43,600 WE HAVE TO DO SORT OF A 2206 01:33:43,600 --> 01:33:46,120 MOLECULAR EPIDEMIOLOGIC ANALYSIS 2207 01:33:46,120 --> 01:33:47,160 ON HUMANS TO UNDERSTAND THE 2208 01:33:47,160 --> 01:33:51,320 STAGE AND THE TUMOR AND THE 2209 01:33:51,320 --> 01:33:56,640 MOLECULAR PROFILE AND THE PERSON 2210 01:33:56,640 --> 01:33:58,640 THEMSELVES CONTRIBUTE TO THE 2211 01:33:58,640 --> 01:33:58,880 PROFILE? 2212 01:33:58,880 --> 01:34:02,760 >>THE STRENGTH OF THE HUMAN 2213 01:34:02,760 --> 01:34:05,120 STUDIES ARE PEOPLE ARE 2214 01:34:05,120 --> 01:34:06,160 HETEROGENEOUS THE PROBLEM IS 2215 01:34:06,160 --> 01:34:07,760 THAT PEOPLE ARE HETEROGENEOUS. 2216 01:34:07,760 --> 01:34:18,000 >>EXACTLY. 2217 01:34:19,200 --> 01:34:20,080 THERE'S SEVERAL ISSUES WITH 2218 01:34:20,080 --> 01:34:27,600 REPORTS AND I'M LOOKING AT EXTRA 2219 01:34:27,600 --> 01:34:31,560 CELLULAR VESICLES SECRETED FROM 2220 01:34:31,560 --> 01:34:33,640 TISSUES AND THEY CONTAINED 2221 01:34:33,640 --> 01:34:36,680 UNEXPECTED THINGS, I WOULD 2222 01:34:36,680 --> 01:34:37,520 THINK. 2223 01:34:37,520 --> 01:34:42,480 IS DNA ONE OF THE THINGS THAT IS 2224 01:34:42,480 --> 01:34:42,720 PRESENT? 2225 01:34:42,720 --> 01:34:48,800 TUMORS THROUGH THEIR VESICLE 2226 01:34:48,800 --> 01:34:49,400 RELEASE -- 2227 01:34:49,400 --> 01:34:51,600 >>DNA AND RNA. 2228 01:34:51,600 --> 01:34:56,760 DID YOU WANT TO COMMENT ON THIS? 2229 01:34:56,760 --> 01:34:58,800 >>EXTRA CELLULAR VESICLES IS 2230 01:34:58,800 --> 01:35:00,160 THE NEW FRONTIER. 2231 01:35:00,160 --> 01:35:01,360 THERE'S SO MUCH -- AND THE CELLS 2232 01:35:01,360 --> 01:35:05,200 USE THAT TO COMMUNICATE IN WAYS 2233 01:35:05,200 --> 01:35:10,120 WE STILL WE'RE AT THE NICE 2234 01:35:10,120 --> 01:35:13,240 UNDERSTANDING OF THAT. 2235 01:35:13,240 --> 01:35:15,000 AND PROBABLY ALSO INFLUENCES 2236 01:35:15,000 --> 01:35:16,160 IMMUNE RESPONSE AND OTHER 2237 01:35:16,160 --> 01:35:16,920 BIOLOGICAL FACTOR AND MANY 2238 01:35:16,920 --> 01:35:19,600 COMPANIES ARE NOW SPRINGING UP 2239 01:35:19,600 --> 01:35:22,080 TO TAKE ADVANTAGE OF EXTRA 2240 01:35:22,080 --> 01:35:23,600 CELLULAR VESICLES FROM 2241 01:35:23,600 --> 01:35:26,600 EVERYTHING FROM DRUG DELIVERY -- 2242 01:35:26,600 --> 01:35:27,920 IT'S A FIELD COMING INTO ITS OWN 2243 01:35:27,920 --> 01:35:32,040 NOW. 2244 01:35:32,040 --> 01:35:34,520 BUT I WOULD SUSPECT THERE'S A 2245 01:35:34,520 --> 01:35:36,120 TREMENDOUS AMOUNT OF BASIC 2246 01:35:36,120 --> 01:35:39,080 UNDERSTANDING STILL MISSING. 2247 01:35:39,080 --> 01:35:40,520 >>I THINK IT'S LIKELY OPPOSED 2248 01:35:40,520 --> 01:35:43,600 TO THE CIRCULATING TUMOR DNA 2249 01:35:43,600 --> 01:35:46,120 PART OF THE CELL-FREE DNA THAT'S 2250 01:35:46,120 --> 01:35:49,800 A REFLECTION OF CELL AND RELEASE 2251 01:35:49,800 --> 01:35:54,680 OF DNA FRAGMENTS. 2252 01:35:54,680 --> 01:36:00,000 THE EXOSOME THAT'S LIVING CELLS. 2253 01:36:00,000 --> 01:36:01,240 I THINK IT WILL SHED A DIFFERENT 2254 01:36:01,240 --> 01:36:02,240 LIGHT ON THE BIOLOGY. 2255 01:36:02,240 --> 01:36:05,560 >>IT'S GOING TO TELL US MORE 2256 01:36:05,560 --> 01:36:09,840 ABOUT HOW THE TUMOR MANIPULATES 2257 01:36:09,840 --> 01:36:11,800 THE LOCAL MICROENVIRONMENT IN 2258 01:36:11,800 --> 01:36:13,280 WAYS THAT WILL TAKE PROBABLY 2259 01:36:13,280 --> 01:36:15,600 SOME NEW TECHNOLOGIES TO REALLY 2260 01:36:15,600 --> 01:36:19,440 BE ABLE TO STUDY THAT BUT 2261 01:36:19,440 --> 01:36:21,960 CLEARLY WHEN JIM ANDERSON'S WORK 2262 01:36:21,960 --> 01:36:24,040 AND OTHERS CAME OUT ON 2263 01:36:24,040 --> 01:36:25,280 IMMUNOTHERAPY AND THE ROLE OF 2264 01:36:25,280 --> 01:36:30,160 IMMUNE SYSTEM, IT'S VERY CLEAR 2265 01:36:30,160 --> 01:36:39,600 THIS WAS HAPPENING EARLY IN C 2266 01:36:39,600 --> 01:36:43,240 CAR -- CARCINOGENESIS AND IT'S 2267 01:36:43,240 --> 01:36:45,680 PART OF THE STRATEGY OF THE 2268 01:36:45,680 --> 01:36:47,240 TUMOR TO MANIPULATE THE 2269 01:36:47,240 --> 01:36:50,040 ENVIRONMENT FOR ITS OWN 2270 01:36:50,040 --> 01:36:51,160 EVOLUTIONARY ADVANTAGE. 2271 01:36:51,160 --> 01:36:56,200 >>WE HAVE SEVERAL FOLKS 2272 01:36:56,200 --> 01:36:59,560 INTERESTED IN KNOWING WHERE DOES 2273 01:36:59,560 --> 01:37:03,600 THE CIRCULATING TUMOR DNA NO. 2274 01:37:03,600 --> 01:37:05,240 GO? 2275 01:37:05,240 --> 01:37:06,440 -- TUMOR DNA GO? 2276 01:37:06,440 --> 01:37:10,120 HOW IS IT DEGRADED OR IS THERE A 2277 01:37:10,120 --> 01:37:11,440 CELL SPECIFICITY? 2278 01:37:11,440 --> 01:37:15,600 DO WE KNOW ABOUT ITS 2279 01:37:15,600 --> 01:37:15,880 DEGRADATION? 2280 01:37:15,880 --> 01:37:17,800 IT'S REMOEFL? 2281 01:37:17,800 --> 01:37:18,760 -- REMOVAL. 2282 01:37:18,760 --> 01:37:22,120 IT'S REMOVED PRETTY RAPIDLY IN 2283 01:37:22,120 --> 01:37:31,600 THE DNA SYSTEM. 2284 01:37:31,600 --> 01:37:34,160 >>IT'S PROBABLY JUST CLEANING 2285 01:37:34,160 --> 01:37:39,600 HOUSE. 2286 01:37:39,600 --> 01:37:45,960 [AUDIO DIGITIZING] 2287 01:37:45,960 --> 01:37:48,680 THERE'S NO CIRCULATING TUMOR DNA 2288 01:37:48,680 --> 01:37:59,360 IN 10 OF 10 RECURRENCES IMPLYING 2289 01:38:00,960 --> 01:38:03,560 THEY'RE NOW EXPRESSING DIFFERENT 2290 01:38:03,560 --> 01:38:03,760 GENES. 2291 01:38:03,760 --> 01:38:05,040 IS THAT THE CORRECT 2292 01:38:05,040 --> 01:38:05,400 INTERPRETATION. 2293 01:38:05,400 --> 01:38:08,240 >>NOT GENES BUT VARIANTS. 2294 01:38:08,240 --> 01:38:14,440 THEY REPRESENT NEW PRIMARIES. 2295 01:38:14,440 --> 01:38:16,360 THE PROFILE BEING USED TO 2296 01:38:16,360 --> 01:38:18,440 IDENTIFY THE ORIGINAL CANCER AND 2297 01:38:18,440 --> 01:38:19,640 THE PROFILE OF VARIANTS BEING 2298 01:38:19,640 --> 01:38:21,080 USED TO IDENTIFY THE ORIGINAL 2299 01:38:21,080 --> 01:38:24,360 CANCER DON'T APPLY, DON'T WORK 2300 01:38:24,360 --> 01:38:30,000 IN THESE NEW PRIMARIES. 2301 01:38:30,000 --> 01:38:32,880 >>ONE THING WORTH MENTIONING TO 2302 01:38:32,880 --> 01:38:35,320 THE AUDIENCE IS THAT 20% OF NEW 2303 01:38:35,320 --> 01:38:38,080 CANCERS, NEW PRIMARIES OCCUR IN 2304 01:38:38,080 --> 01:38:39,560 CANCER SURVIVORS. 2305 01:38:39,560 --> 01:38:41,640 SO THIS IS A HIGH RISK 2306 01:38:41,640 --> 01:38:43,600 POPULATION NOT JUST FOR THE 2307 01:38:43,600 --> 01:38:47,600 RECURRENCE BUT CANCER BURDEN 2308 01:38:47,600 --> 01:38:58,040 RELATED TO NEW PRIMARIES. 2309 01:39:11,560 --> 01:39:15,600 >>DIFFERENT CANCERS HAVE 2310 01:39:15,600 --> 01:39:17,040 DIFFERENT DISTRIBUTION AND RISK 2311 01:39:17,040 --> 01:39:19,440 FACTORS IN DIFFERENT PARTS OF 2312 01:39:19,440 --> 01:39:22,160 THE WORLD AND DIFFER AMONG 2313 01:39:22,160 --> 01:39:26,480 SEXES, SOCIO ECONOMIC DISPARITY 2314 01:39:26,480 --> 01:39:28,320 HOW DO YOU QUANTIFY THE FACTORS 2315 01:39:28,320 --> 01:39:32,000 WHEN YOU'RE TRYING TO DEVELOP A 2316 01:39:32,000 --> 01:39:34,120 PROGRAM THAT ULTIMATELY WILL 2317 01:39:34,120 --> 01:39:43,800 AFFECT HEALTH CARE? 2318 01:39:43,800 --> 01:39:46,160 >>SO YOU'RE TOUCHING ON AND I 2319 01:39:46,160 --> 01:39:51,440 THINK BOB MENTIONED THIS TOO. 2320 01:39:51,440 --> 01:39:53,320 YOU'RE TOUCHING ON INCLUSIVITY 2321 01:39:53,320 --> 01:39:55,600 ON THE RESEARCH WE DO. 2322 01:39:55,600 --> 01:39:57,320 IF YOU WANT TO REFLECT EVERYBODY 2323 01:39:57,320 --> 01:39:59,600 YOU HAVE TO INCLUDE EVERYBODY 2324 01:39:59,600 --> 01:40:03,240 OTHERWISE YOU GET THE KINDS OF 2325 01:40:03,240 --> 01:40:06,760 BIASES WHERE WE HAD PRIMARILY OF 2326 01:40:06,760 --> 01:40:07,480 EUROPEAN DECENT INVOLVED IN THE 2327 01:40:07,480 --> 01:40:11,640 RESEARCH AND CONS CONSEQUENTLY 2328 01:40:11,640 --> 01:40:13,240 IT WORKED FOR EUROPEANS BUT 2329 01:40:13,240 --> 01:40:15,760 WE'RE NOT ALL WHITE COMING BACK 2330 01:40:15,760 --> 01:40:18,760 TO THE HETEROGENEITY AND COMING 2331 01:40:18,760 --> 01:40:19,600 BACK TO THE HPV VACCINE WHICH 2332 01:40:19,600 --> 01:40:24,960 WORKED SO WELL. 2333 01:40:24,960 --> 01:40:28,160 WE'VE BEEN DOING EPIDEMIOLOGICAL 2334 01:40:28,160 --> 01:40:31,600 STUDIES BUT THE VACCINES OF 2335 01:40:31,600 --> 01:40:32,640 FIRST GENERATION THAT TARGET 16 2336 01:40:32,640 --> 01:40:35,200 AND 18 AND THE NEXT GENERATION 2337 01:40:35,200 --> 01:40:40,240 TARGETS SEVEN CARCINOGENIC TYPE 2338 01:40:40,240 --> 01:40:42,600 AND IN THE WORLD IT CAUSES 2% OF 2339 01:40:42,600 --> 01:40:43,520 CERVICAL CANCER. 2340 01:40:43,520 --> 01:40:44,640 IT'S IMPORTANT BUT NOT ONE OF 2341 01:40:44,640 --> 01:40:50,160 THE BIG PLAYERS. 2342 01:40:50,160 --> 01:41:00,720 OF PEOPLE OF AFRICAN DESCENT AND 2343 01:41:08,000 --> 01:41:12,360 SOME WORK WELL BETWEEN 2344 01:41:12,360 --> 01:41:15,600 CAUCASIANS AND PEOPLE OF AFRICAN 2345 01:41:15,600 --> 01:41:17,920 AMERICAN DESCENT. 2346 01:41:17,920 --> 01:41:19,040 EVERYBODY'S GOT TO BE INVOLVED 2347 01:41:19,040 --> 01:41:22,040 TO WORK WELL ON EVERYBODY AND 2348 01:41:22,040 --> 01:41:24,520 COMES TO ANOTHER POINT POINT AND 2349 01:41:24,520 --> 01:41:27,360 SOMETHING THE NCI STRUGGLES WITH 2350 01:41:27,360 --> 01:41:28,320 WHICH IS GETTING PARTICIPATION 2351 01:41:28,320 --> 01:41:31,600 BY THE PUBLIC IN THE TRIALS AND 2352 01:41:31,600 --> 01:41:40,560 RESEARCH. 2353 01:41:40,560 --> 01:41:43,800 IT'S TEAM WORK. 2354 01:41:43,800 --> 01:41:45,480 PEOPLE HAVE TO BE WILLING TO 2355 01:41:45,480 --> 01:41:46,680 PARTICIPATE TO MAKE SURE WE MAKE 2356 01:41:46,680 --> 01:41:47,600 SOMETHING THAT WORKS FOR 2357 01:41:47,600 --> 01:41:47,880 EVERYBODY. 2358 01:41:47,880 --> 01:41:54,400 THAT'S WHAT WE REALLY WANT. 2359 01:41:54,400 --> 01:41:55,920 IT'S GOING TO TAKE A TEAM 2360 01:41:55,920 --> 01:41:56,160 EFFORT. 2361 01:41:56,160 --> 01:41:57,600 WE HAVE TO BE MORE SENSITIVE AND 2362 01:41:57,600 --> 01:41:59,360 AWARE AND THE PUBLIC HAS TO BE 2363 01:41:59,360 --> 01:42:00,720 WILLING TO SAY I'M GOING GIVE MY 2364 01:42:00,720 --> 01:42:04,000 SPECIMENS AND PARTICIPATE IN THE 2365 01:42:04,000 --> 01:42:05,400 TRIAL. 2366 01:42:05,400 --> 01:42:07,280 IN ORDER FOR US TO BE MORE 2367 01:42:07,280 --> 01:42:08,400 SUCCESSFUL AND MORE INCLUSIVE IN 2368 01:42:08,400 --> 01:42:10,160 THE DEVELOPMENT OF NEW 2369 01:42:10,160 --> 01:42:18,400 TECHNOLOGIES. 2370 01:42:18,400 --> 01:42:21,840 >>IF I CAN CLIMB UP ON MY 2371 01:42:21,840 --> 01:42:22,760 SOAPBOX FOR A BRIEF PERIOD. 2372 01:42:22,760 --> 01:42:25,720 THIS IS ONE OF THE MOST 2373 01:42:25,720 --> 01:42:30,560 CONTENTIOUS ISSUES FACING US 2374 01:42:30,560 --> 01:42:37,400 TODAY, THAT IS THE FOUND AND 2375 01:42:37,400 --> 01:42:39,600 CONFUSION AROUND THE TERM LACE 2376 01:42:39,600 --> 01:42:43,120 AND ETHNIC AND ANCESTRAL ORIGIN. 2377 01:42:43,120 --> 01:42:45,160 AND THE EXTENT TO WHICH THAT 2378 01:42:45,160 --> 01:42:49,840 REFLECTS AT ALL DIFFERENCES IN 2379 01:42:49,840 --> 01:42:51,480 GENETIC MAKEUP VERSUS HOW MUCH 2380 01:42:51,480 --> 01:42:53,480 IT REFLECTS DIFFERENCES IN 2381 01:42:53,480 --> 01:42:54,760 SOCIETAL AND ENVIRONMENTAL 2382 01:42:54,760 --> 01:42:55,840 EXPOSURES, CULTURAL DIFFERENCES, 2383 01:42:55,840 --> 01:42:59,120 WHATEVER. 2384 01:42:59,120 --> 01:43:01,480 THOSE TWO HAVE BEEN CONFOUNDED 2385 01:43:01,480 --> 01:43:03,560 TO OUR DETRIMENT FOR DECADES. 2386 01:43:03,560 --> 01:43:08,040 WE HAVE TO FINALLY GET OVER THIS 2387 01:43:08,040 --> 01:43:10,520 AND REALLY START TO IDENTIFY 2388 01:43:10,520 --> 01:43:17,080 WHAT ARE THE FACTORS. 2389 01:43:17,080 --> 01:43:19,080 THE HPV SUBTYPE THAT'S MORE 2390 01:43:19,080 --> 01:43:22,120 COMMON IN PEOPLE IN AFRICA, WHY? 2391 01:43:22,120 --> 01:43:24,080 IS THAT A COFOUNDER AFFECT? 2392 01:43:24,080 --> 01:43:27,840 >>A CO-EVOLUTION CASE IN THAT 2393 01:43:27,840 --> 01:43:32,840 CASE. 2394 01:43:32,840 --> 01:43:34,200 WHY DO AFRICAN AMERICAN 2395 01:43:34,200 --> 01:43:41,840 INCIDENTS OF THE APOLL A1 IN 2396 01:43:41,840 --> 01:43:43,160 KIDNEY DISEASE? 2397 01:43:43,160 --> 01:43:46,200 WE NEED TO STOP IN FERRING A 2398 01:43:46,200 --> 01:43:48,400 GENETIC DIFFERENCE BECAUSE 2399 01:43:48,400 --> 01:43:50,880 PEOPLE ARE AT DIFFERENT 2400 01:43:50,880 --> 01:43:52,160 ANCESTRAL BACKGROUNDS AND AT THE 2401 01:43:52,160 --> 01:43:55,400 SAME TIME WE HAVE TO STOP 2402 01:43:55,400 --> 01:43:57,960 ASSUMING THAT THE ONLY REASON 2403 01:43:57,960 --> 01:44:00,680 THERE'S A DIFFERENCE IN RESPONSE 2404 01:44:00,680 --> 01:44:03,080 IN PEOPLE OF DIFFERENT 2405 01:44:03,080 --> 01:44:07,520 BACKGROUNDS AND SOCIETAL AND 2406 01:44:07,520 --> 01:44:08,000 ENVIRONMENTAL EXPOSURES. 2407 01:44:08,000 --> 01:44:08,280 IT'S BOTH. 2408 01:44:08,280 --> 01:44:09,160 UP FIGURING OUT THE CONTRIBUTION 2409 01:44:09,160 --> 01:44:14,000 OF ONE OVER THE OTHER, THE 2410 01:44:14,000 --> 01:44:15,600 RELATIVE CONTRIBUTION IS THE 2411 01:44:15,600 --> 01:44:15,800 SCIENCE. 2412 01:44:15,800 --> 01:44:17,000 WE SHOULD FIGURE THAT OUT. 2413 01:44:17,000 --> 01:44:18,240 I'M DONE WITH MY SOAPBOX. 2414 01:44:18,240 --> 01:44:27,600 >>I'LL GET BACK ON IT. 2415 01:44:27,600 --> 01:44:31,600 UNDERLYING A LOT OF THIS IS JUST 2416 01:44:31,600 --> 01:44:38,840 POVERTY ACCESS TO CARE AND I WAS 2417 01:44:38,840 --> 01:44:41,720 TELLING STUDENTS, POVERTY KILLS. 2418 01:44:41,720 --> 01:44:44,560 YOU CAN'T UNDERESTIMATE THE 2419 01:44:44,560 --> 01:44:45,760 IMPORTANCE OF POVERTY AND SOCIAL 2420 01:44:45,760 --> 01:44:46,560 DETERMINATES OF HEALTH IN THE 2421 01:44:46,560 --> 01:44:51,200 PROCESS OF DEVELOPING NEW 2422 01:44:51,200 --> 01:44:52,600 TECHNOLOGY AND PARTICIPATING IN 2423 01:44:52,600 --> 01:44:58,160 THE RESEARCH THAT INFORMS THAT 2424 01:44:58,160 --> 01:45:00,040 DEVELOPMENT. 2425 01:45:00,040 --> 01:45:01,560 PRESIDENT A REAL CHALLENGE TO 2426 01:45:01,560 --> 01:45:02,880 OVERCOME THE BIASES IN THE 2427 01:45:02,880 --> 01:45:06,600 SYSTEM AND WE HAVE TO OPEN OUR 2428 01:45:06,600 --> 01:45:08,840 EYES TO IT AND OPEN OUR HEARTS, 2429 01:45:08,840 --> 01:45:12,120 IN A WAY, IF YOU WILL, TO TAKING 2430 01:45:12,120 --> 01:45:21,040 THIS ON IN A GLOBAL WAY RATHER 2431 01:45:21,040 --> 01:45:21,760 THAN WITH MYOPIA 2432 01:45:21,760 --> 01:45:23,760 >>IF YOU WANT TO GO IN THIS 2433 01:45:23,760 --> 01:45:27,400 AREA, HOW DO EITHER OF YOU 2434 01:45:27,400 --> 01:45:29,880 PROPOSE WHAT ARE YOUR THOUGHTS 2435 01:45:29,880 --> 01:45:35,240 ABOUT CROSSING THE BRIDGE YOU'VE 2436 01:45:35,240 --> 01:45:36,680 BEEN TALKING ABOUT FROM THE 2437 01:45:36,680 --> 01:45:39,280 STANDPOINT OF MAJOR CHANGES IN 2438 01:45:39,280 --> 01:45:44,600 THE SOCIO ECONOMICS, POLITICS 2439 01:45:44,600 --> 01:45:47,160 AND THE HEALTH SYSTEMS? 2440 01:45:47,160 --> 01:45:51,240 I MEAN EVERYONE TALKS ABOUT THIS 2441 01:45:51,240 --> 01:45:53,160 BUT HOW DO YOU VISUALIZE THIS 2442 01:45:53,160 --> 01:45:55,000 MAY ACTUALLY HAPPEN AND SPIN OFF 2443 01:45:55,000 --> 01:45:58,200 INTO THE RESEARCH AND CLINICAL 2444 01:45:58,200 --> 01:46:04,840 AREAS THAT YOU INVESTIGATE? 2445 01:46:04,840 --> 01:46:08,280 >>I'LL TAKE OF MAKE A COMMENT. 2446 01:46:08,280 --> 01:46:15,480 I'D DRAW THE ANALOGY YOU HAVE, 2447 01:46:15,480 --> 01:46:19,160 WIN, FOR DEMYSTIFYING AND PEOPLE 2448 01:46:19,160 --> 01:46:21,080 WHO DO RESEARCH AND THE TWO 2449 01:46:21,080 --> 01:46:23,600 GROUPS NEED TO MEET AND THERE 2450 01:46:23,600 --> 01:46:25,960 ARE SILOS NOW BETWEEN FOLKS 2451 01:46:25,960 --> 01:46:28,080 INTERESTED IN THE GENETIC 2452 01:46:28,080 --> 01:46:29,120 DETERMINATES OF HEALTH AND 2453 01:46:29,120 --> 01:46:29,800 PEOPLE INTERESTED IN THE SOCIAL 2454 01:46:29,800 --> 01:46:31,560 DETERMINATES OF HEALTH. 2455 01:46:31,560 --> 01:46:32,360 THEY'RE BOTH IMPORTANT. 2456 01:46:32,360 --> 01:46:33,680 THOSE ARE TWO GROUPS THAT IN MY 2457 01:46:33,680 --> 01:46:35,600 EXPERIENCE ARE NOT TALKING TO 2458 01:46:35,600 --> 01:46:39,800 EACH OTHER AS MUCH AS THEY 2459 01:46:39,800 --> 01:46:42,000 SHOULD BE THAT'S ONE OF THE 2460 01:46:42,000 --> 01:46:47,400 AREAS I THINK IS IMPORTANT TO 2461 01:46:47,400 --> 01:46:48,680 BRIDGE THE TWO FIELD THEY'RE 2462 01:46:48,680 --> 01:46:52,960 VERY IMPORTANT AND TO BE BLUNT I 2463 01:46:52,960 --> 01:46:55,600 THINK THERE'S SOME ANTAGONISM 2464 01:46:55,600 --> 01:46:57,760 BETWEEN THE TWO GROUPS. 2465 01:46:57,760 --> 01:46:59,600 NOT JUST LACK OF UNDERSTANDING 2466 01:46:59,600 --> 01:47:02,200 BUT ACTUAL ANTAGONISM. 2467 01:47:02,200 --> 01:47:03,480 THAT NEEDS TO BE OVERCOME 2468 01:47:03,480 --> 01:47:04,480 BECAUSE I DON'T THINK MAKE 2469 01:47:04,480 --> 01:47:07,480 PROGRESS WITHOUT IT. 2470 01:47:07,480 --> 01:47:15,840 >>IT'S LIKE THE HIV SCENARIO OF 2471 01:47:15,840 --> 01:47:21,520 WHEN THE RESEARCH COMMUNITY AND 2472 01:47:21,520 --> 01:47:24,600 THE PUBLIC FINALLY GOT THE 2473 01:47:24,600 --> 01:47:31,920 POLITICAL SYSTEM TO RESPOND. 2474 01:47:31,920 --> 01:47:34,160 WE ALL KNOW THE HISTORY WE HAVE 2475 01:47:34,160 --> 01:47:36,080 ANOTHER COUPLE GENERAL QUESTIONS 2476 01:47:36,080 --> 01:47:37,320 FOR YOU. 2477 01:47:37,320 --> 01:47:39,240 ONE IS WHAT IS THE CONTRIBUTION, 2478 01:47:39,240 --> 01:47:46,880 IF ANYTHING OF THE GWAS STUDY TO 2479 01:47:46,880 --> 01:47:52,200 THESE QUESTIONS OF PREDICTION, 2480 01:47:52,200 --> 01:47:54,400 DETECTION OF CANCER? 2481 01:47:54,400 --> 01:47:57,320 >>WELL, FOR DETECTION OF CANCER 2482 01:47:57,320 --> 01:47:59,320 I DON'T THINK IT HAS MUCH 2483 01:47:59,320 --> 01:48:00,520 CONTRIBUTION AT THIS POINT. 2484 01:48:00,520 --> 01:48:03,560 THE MAIN VALUE OF THE GWAS IS TO 2485 01:48:03,560 --> 01:48:08,480 BE ABLE TO GENERATE A POLY GENIC 2486 01:48:08,480 --> 01:48:11,120 RISK SCORE WHICH HELPS YOU 2487 01:48:11,120 --> 01:48:12,080 DETERMINE PEOPLE'S RISK FOR 2488 01:48:12,080 --> 01:48:15,600 DEVELOPING CERTAIN CANCERS. 2489 01:48:15,600 --> 01:48:17,080 THERE ARE POLY GENIC RISK SCORES 2490 01:48:17,080 --> 01:48:19,600 INVOLVED IN MANY COMMON 2491 01:48:19,600 --> 01:48:20,640 DISEASES, BREAST CANCER AND 2492 01:48:20,640 --> 01:48:23,600 PROSTATE CANCER BEING TWO OF THE 2493 01:48:23,600 --> 01:48:25,720 CANCERS MOST COMMONLY DONE. 2494 01:48:25,720 --> 01:48:30,560 THEY ARE STARTING TO BE USED 2495 01:48:30,560 --> 01:48:34,160 CLINICALLY MY HESITATION WITH 2496 01:48:34,160 --> 01:48:37,120 THEM IS MAKING SURE THEY'RE 2497 01:48:37,120 --> 01:48:38,880 APPLICABLE TO PEOPLE OF ALL 2498 01:48:38,880 --> 01:48:40,680 BACKGROUNDS AND MIXED 2499 01:48:40,680 --> 01:48:42,000 BACKGROUNDS BECAUSE MIXED 2500 01:48:42,000 --> 01:48:43,600 BACKGROUNDS IS VERY COMMON. 2501 01:48:43,600 --> 01:48:54,120 SO FIGURING OUT HOW TO ADAPT AND 2502 01:48:55,080 --> 01:48:59,880 THE OTHER ASPECT IS GWAS MAY 2503 01:48:59,880 --> 01:49:00,520 HIGHLIGHT THE CONTRIBUTION OF 2504 01:49:00,520 --> 01:49:02,680 CERTAIN GENES OR REGIONS IF 2505 01:49:02,680 --> 01:49:07,080 WE'RE SMART ENOUGH WE CAN DEDUCE 2506 01:49:07,080 --> 01:49:08,880 THE MECHANISTIC RELATIONSHIP 2507 01:49:08,880 --> 01:49:11,480 BETWEEN THE CHANGES AND 2508 01:49:11,480 --> 01:49:12,280 DEVELOPMENT OF CANCER AND 2509 01:49:12,280 --> 01:49:14,400 THEREFORE MIGHT POSSIBLY BE USED 2510 01:49:14,400 --> 01:49:20,280 FOR FINDING NEW THERAPIES, NEW 2511 01:49:20,280 --> 01:49:25,840 TARGETS, NEW TREATMENTS. 2512 01:49:25,840 --> 01:49:31,440 GWAS IN ITS PUREST FORM IS 2513 01:49:31,440 --> 01:49:32,240 SIMPLY STATISTICALLY SIGNIFICANT 2514 01:49:32,240 --> 01:49:34,760 ASSOCIATION BETWEEN VARIANTS, 2515 01:49:34,760 --> 01:49:38,000 CHANGES IN THE GENE DNA AND A 2516 01:49:38,000 --> 01:49:39,560 PARTICULARLY CLINICAL PHENOTYPE. 2517 01:49:39,560 --> 01:49:41,920 BUT WHEN YOU DIG IN YOU CAN 2518 01:49:41,920 --> 01:49:46,160 START TO INFER IMPORTANT 2519 01:49:46,160 --> 01:49:46,800 MECHANISTIC RELATIONSHIPS AND 2520 01:49:46,800 --> 01:49:49,200 THAT I THINK CAN HELP WITH 2521 01:49:49,200 --> 01:49:51,200 UNDERSTANDING THE BIOLOGY IN 2522 01:49:51,200 --> 01:49:52,000 THESE CANCERS. 2523 01:49:52,000 --> 01:49:53,880 SO THAT I GUESS IS WHERE I SEE 2524 01:49:53,880 --> 01:49:55,080 THE ROLE OF GWAS. 2525 01:49:55,080 --> 01:50:02,280 >>LET ME ADD TO THAT IN SAYING 2526 01:50:02,280 --> 01:50:03,600 THAT UNDERSTANDING THE BIOLOGY 2527 01:50:03,600 --> 01:50:06,560 OF CANCER AND CARCINOGENESIS IS 2528 01:50:06,560 --> 01:50:12,320 CRITICAL TO THE NCI'S COMMITMENT 2529 01:50:12,320 --> 01:50:14,160 TO DEVELOPING NEW STRATEGIES. 2530 01:50:14,160 --> 01:50:15,480 IF WE UNDERSTAND EARLIER AND 2531 01:50:15,480 --> 01:50:16,920 EARLIER WHAT GOES WRONG WE CAN 2532 01:50:16,920 --> 01:50:18,320 POTENTIALLY TARGET IT IN A 2533 01:50:18,320 --> 01:50:20,040 NUMBER OF WAYS. 2534 01:50:20,040 --> 01:50:21,960 AT LATEST FOR HIGH- RISK 2535 01:50:21,960 --> 01:50:23,600 POPULATIONS AND MAYBE EVENTUALLY 2536 01:50:23,600 --> 01:50:24,640 FOR THE GENERAL POPULATION. 2537 01:50:24,640 --> 01:50:26,360 SO WE WORK CLOSELY WITH THE 2538 01:50:26,360 --> 01:50:29,520 DIVISION OF CANCER BIOLOGY ON A 2539 01:50:29,520 --> 01:50:31,720 NUMBER OF INITIATIVES TO 2540 01:50:31,720 --> 01:50:33,360 ELUCIDATE THE EARLY PROCESSES 2541 01:50:33,360 --> 01:50:35,560 WHERE IT'S CLEARLY GONE OFF 2542 01:50:35,560 --> 01:50:39,640 TRACK HERE AND HOW DO WE 2543 01:50:39,640 --> 01:50:41,160 REFERRING THAT UNDERSTANDING. 2544 01:50:41,160 --> 01:50:43,520 I THINK THE POLY GENIC RISK 2545 01:50:43,520 --> 01:50:45,240 SCORE IS AN INTERESTING TOPIC. 2546 01:50:45,240 --> 01:50:46,200 WE'VE BEEN TALKING ABOUT IT 20 2547 01:50:46,200 --> 01:50:49,880 YEARS. 2548 01:50:49,880 --> 01:50:52,280 THERE ARE SOME ACADEMIC CENTERS 2549 01:50:52,280 --> 01:50:56,360 THAT USE IT BUT AS BOB POINTED 2550 01:50:56,360 --> 01:50:58,200 OUT IT'S HARD TO KNOW WHETHER 2551 01:50:58,200 --> 01:51:00,160 IT'S REPRESENTATIVE AND 2552 01:51:00,160 --> 01:51:00,400 VALIDATED. 2553 01:51:00,400 --> 01:51:02,720 THEY'VE DONE IT INTERNALLY BUT 2554 01:51:02,720 --> 01:51:03,680 WHAT'S THE OUTCOME? 2555 01:51:03,680 --> 01:51:09,080 WE NEED IN MY OPINION A 2556 01:51:09,080 --> 01:51:11,480 DEMONSTRATION WHEN WE HAVE A 2557 01:51:11,480 --> 01:51:13,280 POLY GENIC RISK SCORE THAT'S 2558 01:51:13,280 --> 01:51:14,480 REPRESENTATIVE AND I KNOW SOME 2559 01:51:14,480 --> 01:51:18,360 GROUPS HAVE WORKED ON PROSTATE 2560 01:51:18,360 --> 01:51:21,960 AND IN PARTICULARLY OF AFRICAN 2561 01:51:21,960 --> 01:51:23,040 AMERICANS BECAUSE OF THE HIGHER 2562 01:51:23,040 --> 01:51:24,240 RISK OF MORTALITY IN THE GROUP 2563 01:51:24,240 --> 01:51:26,000 BUT WE NEED TO PUT IT TO THE 2564 01:51:26,000 --> 01:51:26,200 TEST. 2565 01:51:26,200 --> 01:51:28,200 CAN WE USE RISK SCORES AND IT 2566 01:51:28,200 --> 01:51:30,000 MAY INCLUDE POLY GENIC RISK 2567 01:51:30,000 --> 01:51:32,520 SCORES NORT TO IMPROVE 2568 01:51:32,520 --> 01:51:34,200 SCREENING? 2569 01:51:34,200 --> 01:51:36,240 THE EXAMPLE I ALWAYS GIVE IS FOR 2570 01:51:36,240 --> 01:51:40,760 MORE THAN TWO DECADES DR. MITCH 2571 01:51:40,760 --> 01:51:42,080 GAIL IN THE INTRAMURAL PROGRAM 2572 01:51:42,080 --> 01:51:43,360 HAD THE GAIL MODEL. 2573 01:51:43,360 --> 01:51:45,360 WE NEVER USED THAT TO INFORM WHO 2574 01:51:45,360 --> 01:51:50,520 SHOULD GET SCREENING AT WHAT 2575 01:51:50,520 --> 01:51:50,680 AGE. 2576 01:51:50,680 --> 01:51:55,560 SUBSEQUENTLY LY AND NOW WE CAN 2577 01:51:55,560 --> 01:51:56,280 BETTER. 2578 01:51:56,280 --> 01:51:57,600 THAT WAS A LARGE MARK PAPER BUT 2579 01:51:57,600 --> 01:51:59,240 WE NEVER APPLIED THAT. 2580 01:51:59,240 --> 01:52:00,680 WHAT HAPPENED IS WE APPLIED JUST 2581 01:52:00,680 --> 01:52:01,080 AGE. 2582 01:52:01,080 --> 01:52:03,080 WHAT'S THE PROBLEM WITH AGE? 2583 01:52:03,080 --> 01:52:06,520 A NEW STUDY OR DATA COMES OUT 2584 01:52:06,520 --> 01:52:08,720 THAT SHOWS A CERTAIN RISK IN A 2585 01:52:08,720 --> 01:52:10,200 CERTAIN GROUP. 2586 01:52:10,200 --> 01:52:12,320 THE GUIDELINES CHANGE FOR BREAST 2587 01:52:12,320 --> 01:52:15,600 CANCER, START AT 50, START AT 2588 01:52:15,600 --> 01:52:18,560 45, DO EVERY YEAR, DO EVERY TWO 2589 01:52:18,560 --> 01:52:18,880 YEARS. 2590 01:52:18,880 --> 01:52:21,280 I'M TELLING YOU NOW, THERE'S SIX 2591 01:52:21,280 --> 01:52:23,440 OR SEVEN GUIDELINE GROUPS IN THE 2592 01:52:23,440 --> 01:52:27,520 UNITED STATES THAT HAVE 2593 01:52:27,520 --> 01:52:28,160 RECOMMENDATIONS NOT EXACTLY THE 2594 01:52:28,160 --> 01:52:28,360 SAME. 2595 01:52:28,360 --> 01:52:30,280 SO WOMEN ARE CONFUSED WHAT KIND 2596 01:52:30,280 --> 01:52:32,080 OF BREAST CANCER SCREENING THEY 2597 01:52:32,080 --> 01:52:33,600 SHOULD GET AT WHAT AGE. 2598 01:52:33,600 --> 01:52:34,160 WE'VE DONE OURSELVES A 2599 01:52:34,160 --> 01:52:37,040 DISSERVICE. 2600 01:52:37,040 --> 01:52:39,600 WE CAN DO BETTER. 2601 01:52:39,600 --> 01:52:41,400 WE CAN TAKE THE DATA. 2602 01:52:41,400 --> 01:52:43,240 AGE IS NOT A GREAT PROXY FOR 2603 01:52:43,240 --> 01:52:44,240 CANCER RISK. 2604 01:52:44,240 --> 01:52:45,640 IT'S AN IMPORTANT RISK FACTOR 2605 01:52:45,640 --> 01:52:48,080 BUT IT'S NOT EVERYTHING WE KNOW. 2606 01:52:48,080 --> 01:52:49,880 WE'RE NOT APPLYING ALL WE KNOW 2607 01:52:49,880 --> 01:52:51,400 ABOUT BREAST CANCER TO IMPROVE 2608 01:52:51,400 --> 01:52:56,680 IT AND I THINK NOW'S THE TIME 2609 01:52:56,680 --> 01:52:57,960 PARTICULARLY FOR PROSTATE AND 2610 01:52:57,960 --> 01:53:00,440 IT'S A HIGH-BURDEN CANCER WE CAN 2611 01:53:00,440 --> 01:53:02,480 APPLY OUR KNOWLEDGE. 2612 01:53:02,480 --> 01:53:03,760 ALL THIS INVESTMENT INTO DOING 2613 01:53:03,760 --> 01:53:06,720 BETTER CANCER SCREENING. 2614 01:53:06,720 --> 01:53:09,640 THAT'S FOR THESE TWO DISEASES. 2615 01:53:09,640 --> 01:53:13,200 >>THERE ARE AT LEAST TWO VERY 2616 01:53:13,200 --> 01:53:15,840 LARGE NHGRI AND NIH FUNDED 2617 01:53:15,840 --> 01:53:19,520 PROGRAMS HERE LOOKING AT PRS 2618 01:53:19,520 --> 01:53:19,920 SCORES. 2619 01:53:19,920 --> 01:53:22,880 ONE IS CALLED PRIMID AND THE 2620 01:53:22,880 --> 01:53:23,200 EMERGE 4. 2621 01:53:23,200 --> 01:53:25,280 I'M HOPING OVER THE NEXT FOUR 2622 01:53:25,280 --> 01:53:30,520 YEARS WE'RE GOING TO HAVE 2623 01:53:30,520 --> 01:53:31,560 MULTI-ANCESTRY RELIABLE 2624 01:53:31,560 --> 01:53:35,560 DEPENDABLE PRS SCORES WE CAN 2625 01:53:35,560 --> 01:53:35,720 USE. 2626 01:53:35,720 --> 01:53:40,760 THAT WOULD BE MY HOPE. 2627 01:53:40,760 --> 01:53:44,560 IT'S A GREAT GROUP OF 2628 01:53:44,560 --> 01:53:45,000 INVESTIGATORS. 2629 01:53:45,000 --> 01:53:49,320 >>WELL, OUR TIME RAN OUT THE 2630 01:53:49,320 --> 01:53:50,400 BASIC QUESTION IS FROM THE ROLE 2631 01:53:50,400 --> 01:53:53,920 OF THE INSURANCE COMPANY AND IN 2632 01:53:53,920 --> 01:53:55,120 OUR SOCIETY WHERE THERE'S A SO 2633 01:53:55,120 --> 01:53:56,080 MANY DIFFERENT INSURANCE 2634 01:53:56,080 --> 01:53:57,080 COMPANIES AND THEY HAVE THEIR 2635 01:53:57,080 --> 01:54:02,440 OWN RULES, REGULATIONS AND 2636 01:54:02,440 --> 01:54:03,880 EVERYTHING ELSE, SOME SUPPORT 2637 01:54:03,880 --> 01:54:06,360 PET SCANS, SOME DON'T, SOME 2638 01:54:06,360 --> 01:54:07,720 SUPPORT APPARENTLY ACCORDING TO 2639 01:54:07,720 --> 01:54:14,800 THE PERSON WHO SUBMITTED THE 2640 01:54:14,800 --> 01:54:19,600 QUESTION, ACTUALLY ENCOURAGE 2641 01:54:19,600 --> 01:54:24,800 TUMOR DNA ANALYSIS. 2642 01:54:24,800 --> 01:54:27,600 IT REMINDS ME OF MANY YEARS AGO, 2643 01:54:27,600 --> 01:54:29,600 BILL SCHWARTS THE CHAIRMAN OF 2644 01:54:29,600 --> 01:54:31,080 MEDICINE AT TUFTS UNIVERSITY AND 2645 01:54:31,080 --> 01:54:37,000 HE WAS THE ONE WHO COINED THE 2646 01:54:37,000 --> 01:54:39,320 TERM RATIONED CARE BECAUSE HE 2647 01:54:39,320 --> 01:54:40,000 SPENT A YEAR AT THE RAND 2648 01:54:40,000 --> 01:54:42,840 CORPORATION AND TOLD ME ONE DAY, 2649 01:54:42,840 --> 01:54:44,360 HE SAID THE MOST INCREDIBLE 2650 01:54:44,360 --> 01:54:46,160 THING COULD HAPPEN IS IF SOMEONE 2651 01:54:46,160 --> 01:54:48,880 CAME UP WITH A FOOL-PROOF 2652 01:54:48,880 --> 01:54:49,840 DIAGNOSTIC TEST FOR CANCER AND 2653 01:54:49,840 --> 01:54:54,760 IT HAD TO BE TAKEN EVERY DAY IT 2654 01:54:54,760 --> 01:54:59,600 WOULD BREAK THE BANK. 2655 01:54:59,600 --> 01:55:03,480 I'M WONDERING WOULD YOU WANT TO 2656 01:55:03,480 --> 01:55:04,560 MAKE SOME COMMENTS ABOUT WHO 2657 01:55:04,560 --> 01:55:06,520 PAYS FOR THIS? 2658 01:55:06,520 --> 01:55:12,920 HOW ARE WE GOING DO IT IN A 2659 01:55:12,920 --> 01:55:13,720 PROFIT-DRIVEN SOCIETY AND HOW 2660 01:55:13,720 --> 01:55:15,760 FREE ARE THE INSURANCE COMPANIES 2661 01:55:15,760 --> 01:55:18,600 OR SHOULD THEY BE? 2662 01:55:18,600 --> 01:55:22,200 CAN THE NCI MAKE A 2663 01:55:22,200 --> 01:55:23,160 RECOMMENDATION EVERYBODY HAS TO 2664 01:55:23,160 --> 01:55:23,960 GO ALONG WITH? 2665 01:55:23,960 --> 01:55:24,480 DON'T THINK SO. 2666 01:55:24,480 --> 01:55:29,840 >>THE NCI DOESN'T MAKE POLICY 2667 01:55:29,840 --> 01:55:30,480 OR GUIDELINES. 2668 01:55:30,480 --> 01:55:33,880 I WILL SAY DESPITE THE EFFORT TO 2669 01:55:33,880 --> 01:55:35,680 DO COST-EFFECTIVENESS ANALYSIS 2670 01:55:35,680 --> 01:55:41,840 FOR SCREENING AND INTERVENTIONS 2671 01:55:41,840 --> 01:55:46,680 THEY'RE LARGELY IGNORED AND THE 2672 01:55:46,680 --> 01:55:48,760 CONSEQUENCE IS HIDDEN BY OUR 2673 01:55:48,760 --> 01:55:49,760 HEALTH CARE SYSTEM AND THE WAY 2674 01:55:49,760 --> 01:55:54,160 YOU RECEIVE REIMBURSEMENT. 2675 01:55:54,160 --> 01:55:57,880 YOU DON'T DIRECTLY SEE THE EXTRA 2676 01:55:57,880 --> 01:55:59,600 PROCEDURE YOU'VE DONE 2677 01:55:59,600 --> 01:56:07,640 EVENTUALLIES IN -- EVENTUALLY 2678 01:56:07,640 --> 01:56:08,440 EXACERBATES HIGHER PREMIUMS 2679 01:56:08,440 --> 01:56:09,720 GOING FORWARD. 2680 01:56:09,720 --> 01:56:11,280 IF YOU LOOK AT HOW OTHER 2681 01:56:11,280 --> 01:56:13,000 EUROPEAN COUNTRIES AND AUSTRALIA 2682 01:56:13,000 --> 01:56:15,520 DO IT, CERTAINLY FOR PREVENTIVE 2683 01:56:15,520 --> 01:56:18,320 SERVICE IT'S A UNIFIED PROCESS 2684 01:56:18,320 --> 01:56:19,200 AND UNIVERSAL HEALTH CARE 2685 01:56:19,200 --> 01:56:19,480 SYSTEM. 2686 01:56:19,480 --> 01:56:22,360 I CERTAINLY WOULD LOVE TO SEE 2687 01:56:22,360 --> 01:56:23,960 UNIVERSAL HEALTH CARE SYSTEM FOR 2688 01:56:23,960 --> 01:56:25,120 PREVENTIVE SERVICES WHERE IT'S 2689 01:56:25,120 --> 01:56:26,960 ABOUT POPULATION AND NUMBERS AND 2690 01:56:26,960 --> 01:56:27,880 NOT ABOUT PERSONALIZED CARE, PER 2691 01:56:27,880 --> 01:56:35,040 SE. 2692 01:56:35,040 --> 01:56:39,600 IT'S COMPLICATED. 2693 01:56:39,600 --> 01:56:42,080 YOU'RE STEALING FROM ONE PLACE 2694 01:56:42,080 --> 01:56:43,600 AND STEALING FROM PETER TO PAY 2695 01:56:43,600 --> 01:56:43,800 PAUL. 2696 01:56:43,800 --> 01:56:45,960 IT'S A REAL THING. 2697 01:56:45,960 --> 01:56:46,880 AT SOME POINT IT'S GOING TO 2698 01:56:46,880 --> 01:56:50,320 BREAK THE BANK BECAUSE WE HAVE 2699 01:56:50,320 --> 01:56:51,600 THE HIGHEST HEALTH CARE 2700 01:56:51,600 --> 01:56:54,520 EXPENDITURE PER CAPITA OF ANY 2701 01:56:54,520 --> 01:56:55,000 COUNTRY IN THE WORLD . 2702 01:56:55,000 --> 01:56:56,920 AND WE ARE LIKE 50th IN THE 2703 01:56:56,920 --> 01:57:00,960 WORLD IN OUTCOMES. 2704 01:57:00,960 --> 01:57:02,800 AND LIFE EXPECTANCY. 2705 01:57:02,800 --> 01:57:06,600 SO SOMETHING'S GOT TO GIVE. 2706 01:57:06,600 --> 01:57:09,880 >>BOB, DO YOU WANT TO MAKE A 2707 01:57:09,880 --> 01:57:10,720 FINAL -- 2708 01:57:10,720 --> 01:57:12,480 >>YOU TALKED TO ONE PRIVATE 2709 01:57:12,480 --> 01:57:13,280 INSURANCE POLICY MAKER YOU 2710 01:57:13,280 --> 01:57:15,600 TALKED TO ONE INSURER. 2711 01:57:15,600 --> 01:57:23,520 IT'S ALL OVER THE PLACE. 2712 01:57:23,520 --> 01:57:25,920 AND WHETHER THEY USE EVIDENCE 2713 01:57:25,920 --> 01:57:28,320 BASE OR PRESSURE FROM 2714 01:57:28,320 --> 01:57:30,360 EMPLOYERS -- SOMETHING TO KEEP 2715 01:57:30,360 --> 01:57:32,080 IN MIND WHEN A BUNCH OF 2716 01:57:32,080 --> 01:57:33,080 EMPLOYEES FEEL SOMETHING SHOULD 2717 01:57:33,080 --> 01:57:35,200 BE COVERED AND THEY AGITATE WITH 2718 01:57:35,200 --> 01:57:38,800 THEIR EMPLOYER, THE EMPLOYER IS 2719 01:57:38,800 --> 01:57:39,840 ACTUALLY THE PERSON WHO 2720 01:57:39,840 --> 01:57:41,040 EMPLOYEES THE INSURANCE 2721 01:57:41,040 --> 01:57:41,360 COMPANIES. 2722 01:57:41,360 --> 01:57:42,720 THEY HAVE TREMENDOUS SWAY FOR 2723 01:57:42,720 --> 01:57:46,200 THE PRIVATE HEALTH INSURERS. 2724 01:57:46,200 --> 01:57:51,480 I THINK CMS AND MEDICARE HAS A 2725 01:57:51,480 --> 01:57:52,800 SOMEWHAT MORE RATIONAL SYSTEM 2726 01:57:52,800 --> 01:57:59,600 AND SOME INSURERS FOLLOW THE 2727 01:57:59,600 --> 01:58:03,440 LEAD WHAT MOLD EX. 2728 01:58:03,440 --> 01:58:05,800 IT'S MOLD-DX. 2729 01:58:05,800 --> 01:58:06,880 IT'S A SYSTEM. 2730 01:58:06,880 --> 01:58:12,680 AND THE PRESSURES THAT COME TO 2731 01:58:12,680 --> 01:58:17,200 BEAR ARE IRRATIONAL. 2732 01:58:17,200 --> 01:58:18,800 AMONG THE OTHER THINGS PEOPLE 2733 01:58:18,800 --> 01:58:20,720 CHANGE INSURANCE COMPANIES 2734 01:58:20,720 --> 01:58:21,200 OFTEN. 2735 01:58:21,200 --> 01:58:22,200 SO FOR INSURANCE COMPANY TO PAY 2736 01:58:22,200 --> 01:58:24,920 FOR SOMETHING WHICH IS GOING TO 2737 01:58:24,920 --> 01:58:26,800 PREVENT A MUCH MORE EXPENSIVE 2738 01:58:26,800 --> 01:58:28,080 PROBLEM FOR THIS PATIENT FIVE 2739 01:58:28,080 --> 01:58:31,600 YEARS OR 10 YEARS DOWN THE LINE 2740 01:58:31,600 --> 01:58:34,200 THAT'S NOT SOMETHING THEY'RE 2741 01:58:34,200 --> 01:58:35,000 THINKING ABOUT. 2742 01:58:35,000 --> 01:58:38,880 BECAUSE THAT'S NOT GOING TO BE 2743 01:58:38,880 --> 01:58:39,600 MY INSURED PERSON 5 OR 10 YEARS 2744 01:58:39,600 --> 01:58:40,800 FROM NOW. 2745 01:58:40,800 --> 01:58:42,160 IT'S GOING TO BE SOME OTHER 2746 01:58:42,160 --> 01:58:44,960 INSURANCE COMPANY'S PROBLEM. 2747 01:58:44,960 --> 01:58:48,240 THERE'S LOTS OF REASONS AND I 2748 01:58:48,240 --> 01:58:52,200 PERSONALLY AM VERY MUCH IN FAVOR 2749 01:58:52,200 --> 01:58:54,640 OF A RATIONAL ORGANIZED MEDICARE 2750 01:58:54,640 --> 01:58:55,600 SYSTEM THAT FOCUSES ON 2751 01:58:55,600 --> 01:58:58,280 PREVENTION BUT WE'RE A LONG WAY 2752 01:58:58,280 --> 01:58:58,720 AWAY FROM THAT. 2753 01:58:58,720 --> 01:59:00,600 >>WELL, LISTEN. 2754 01:59:00,600 --> 01:59:02,440 ON BEHALF OF ALL THE PEOPLE 2755 01:59:02,440 --> 01:59:03,680 LISTENING, WATCHING AND THOSE 2756 01:59:03,680 --> 01:59:05,680 WHO WILL LATER PICK THIS UP WHEN 2757 01:59:05,680 --> 01:59:10,200 IT'S ON THE VIDEO ARCHIVE -- 2758 01:59:10,200 --> 01:59:12,760 WE'RE IN 38 DIFFERENT COUNTRIES 2759 01:59:12,760 --> 01:59:15,040 SO WE'RE INTERNATIONAL. 2760 01:59:15,040 --> 01:59:16,000 I WANT TO THANK YOU BOTH VERY 2761 01:59:16,000 --> 01:59:19,480 MUCH FOR REALLY VERY EXCITING 2762 01:59:19,480 --> 01:59:23,440 INFORMATIVE AND THOUGHT 2763 01:59:23,440 --> 01:59:23,680 PROVOKING. 2764 01:59:23,680 --> 01:59:24,720 I'D LIKE TO CALL ATTENTION TO 2765 01:59:24,720 --> 01:59:27,640 THE FACT THAT NEXT WEEK WE HAVE 2766 01:59:27,640 --> 01:59:29,280 ANOTHER EXCITING THOUGHT 2767 01:59:29,280 --> 01:59:30,360 PROVOKING ONE. 2768 01:59:30,360 --> 01:59:33,760 THE TOPIC IS NEURODEGENERATION 2769 01:59:33,760 --> 01:59:35,080 AND AGING. 2770 01:59:35,080 --> 01:59:38,800 SO HOW ARE THEY LINKED? 2771 01:59:38,800 --> 01:59:40,200 ARE THEY PREVENTIBLE? 2772 01:59:40,200 --> 01:59:43,280 ARE THEY REVERSIBLE? 2773 01:59:43,280 --> 01:59:44,560 AND THERE'S RESEARCH DEALING ON 2774 01:59:44,560 --> 01:59:47,920 ALL THESE AGENCY SPECTS WHICH IS 2775 01:59:47,920 --> 01:59:49,760 VERY EXCITING AND PROVOCATIVE. 2776 01:59:49,760 --> 01:59:53,360 SO WE LOOK FORWARD TO SEEING YOU 2777 01:59:53,360 --> 01:59:56,120 NEXT TUESDAY. 2778 01:59:56,120 --> 01:59:57,440 AND THANK YOU BOTH VERY MUCH FOR 2779 01:59:57,440 --> 01:59:58,800 A REMARKABLE AFTERNOON. 2780 01:59:58,800 --> 01:59:59,360 >>THANK YOU. 2781 01:59:59,360 --> 00:00:00,000 TAKE CARE, EVERYONE.