>>WELCOME TO
THE NINTH SESSION IN THE 23rd
YEAR IN THE COURSE OF THE NATION
INSTITUTES OF HEALTH CALLED
DEMYSTIFYING MEDICINE.
I'M WIN ARIAS A SENIOR SCIENTIST
EMERITUS AT NIH AND PLEASED TO
BE YOUR HOST FOR THE PROGRAM
THIS AFTERNOON.
THIS COURSE IS A COURSE IN
BRIDGE BUILDING.
AS EXEMPLIFIED BY OUR LOGO WHICH
IS THE BROOKLYN BRIDGE.
AND THE TWO INDIVIDUALS ON THE
CATWALK ARE EXEMPLIFIED BY OUR
TWO SPEAKERS TODAY WHO WILL BE
ADDRESSING ONE OF THE MAJOR
PROBLEMS IN ALL OF MEDICINE.
THE ABILITY TO PREDICT, DETECT,
DIAGNOSE AND EVENTUALLY TREAT
MEDICAL DISEASES.
TODAY, THE SUBJECT IS CANCER.
SO THE PURPOSE OF DEMYSTIFYING
MEDICINE IS TO BRIDGE THE
EXCITING DEVELOPMENTS IN BIOLOGY
AND ENGINEERING WITH MEDICINE.
TODAY'S PRESENTATION KINDS OF
REMINDED ME OF SEVERAL GENERAL
THEMES THAT GO WAY BEYOND
ACTUALLY MEDICINE AND BEST
REFLECTED PERHAPS IN LITERATURE.
THERE ARE FOUR QUOTES.
WE'RE SUCH STUFF AS DREAMS ARE
MADE ON FROM THE TEMPEST BY
SHAKESPEARE.
WHO WOULD HAVE DREAMED THAT 15,
20 OR SO YEARS AGO WE WOULD BE
TALKING ABOUT THE TOPIC OF
PREDICTING, DETECTING AND
DIAGNOSING CANCER USING THE
TECHNOLOGY THAT KEEPS FLOWING TO
US.
IT WAS SORT OF LIKE IT WAS IN
THE REALM OF SCIENCE FICTION.
THINK STAR TREK.
THEN WE HAVE A BRAVE NEW WORLD
WITH SUCH CREATURES IN IT AND
THE CHALLENGES PRESENTED IB
BRIDGING THIS INCREDIBLE SERIES
OF ISSUES BROUGHT ABOUT AT THE
PRESENT TIME REQUIRE INDIVIDUALS
WHO HAVE EXPERTISE AND THAT'S
THE REAL CHALLENGE TO DEVELOP.
HOWEVER, NONE OF THIS IS SIMPLE.
AND MY FAVORITE RESPONSE TO THAT
IS FROM A QUOTE BY A WONDERFUL
DANISH CARTOONIST GROEKS WHO
WROTE PROBLEMS WORTH OF ATTACK
PROVE THEIR WORTH BY STRIKING
BACK.
YOU'LL HEAR ABOUT THIS IN
TODAY'S TALKS.
THEN THERE'S THE PURPOSE OF
DEMYSTIFYING MEDICINE AS
EXEMPLIFIED IN A WONDERFUL
STATEMENT BY A SWISS
NUTRITIONIST, MUCH IS KNOWN BUT
UNFORTUNATELY IN DIFFERENT
HEADS.
SO TODAY'S TOPIC IS REALLY EARLY
CANCER AND CAN WE DETECT EARLY
CANCER.
TO DISCUSS THIS WE ARE FORTUNATE
IN HAVING TWO EXPERT COLLEAGUES
WHO REPRESENT SOMEWHAT DIFFERENT
ASPECTS.
THE FIRST SPEAKER IS PHILIP
CASTLE.
HE'S THE DIRECTOR OF THE
DIVISION OF CANCER PREVENTION AT
THE NATIONAL CANCER INSTITUTE AT
THE NIH.
HE RECEIVED HIS Ph.D. FROM
HOPKINS IN BIO PHYSICS AND THEN
TOOK A MIXED POST-DOCTORAL
FELLOWSHIP AND GAINED A MASTER'S
IN PUBLIC HEALTH BETWEEN HOPKINS
AND THE CANCER PREVENTION
PROGRAM HERE IN BETHESDA.
IT WAS THE BEGINNING OF A LONG
AND HIGHLY PRODUCTIVE CAREER AT
THE NCI WHERE HE HAS BECOME A
SENIOR INVESTIGATOR AND WAS IN
2010.
THERE WAS A BRIEF INTERLUDE FROM
2014 WHEN HE WAS RECRUITED TO
THE ALBERT EINSTEIN COLLEGE OF
MEDICINE AS PROFESSOR OF
EPIDEMIOLOGY AND POPULATION
HEALTH.
THEN IN 2020 RETURNED TO NIH TO
HIS PRESENT POSITION AS DIRECTOR
OF THE DIVISION OF CANCER
PREVENTION.
NOW, HE HAS AN EXCEPTIONAL
CAREER INITIATING, CONDUCTING
AND LEADING MAJOR, HUGE NCI
MOLECULAR AND CLINICAL
EPIDEMIOLOGY RESEARCH MAINLY
INVOLVING HUMAN PAPILLOMA VIRUS
RELATED CANCERS.
HIS INTERESTS ARE IN EARLY
CANCER DIAGNOSIS AND DEVELOPMENT
OF NEW TECHNIQUES, GREENING,
DISPARITIES IN CANCER PREVENTION
AND EVIDENCE-BASED MEDICINE.
HE'S RECEIVED MANY AWARDS AND IS
HIGHLY HONORED IN THE NCI HAVING
RECEIVED THE DISTINGUISHED
ALUMNI AWARD AND FLEMING AWARD
FOR GOVERNMENT SERVICE AND HAS
BEEN A CHIEF SCIENTIFIC
INDIVIDUAL FOR THE AMERICAN
SOCIETY OF CLINICAL PATHOLOGY.
AND PHILIP IS GOING TO DISCUSS
TESTS FOR EARLY CANCER, FACT
VERSUS OPINIONS.
NOW, OUR SECOND SPEAKER IS
ROBERT NUSSBAUM WHO IS ALSO VERY
WELL KNOWN AND RESPECTED AT THE
NATIONAL INSTITUTES OF HEALTH.
HE IS CURRENTLY THE CHIEF
MEDICAL OFFICER OF THE INVITIME
COMPANY IN SUCCESS AND RECEIVED
HIS M.D. FROM HARVARD IN APPLIED
MATHEMATIC AND HIS UNDERGRADUATE
DEGREE AND THEN M.D. IN THE
HARVARD M.I.T. COMBINED PROGRAM
FOR HEALTH SCIENCE AND
TECHNOLOGY.
THEN WAS IN ST. LOUIS AND THEN
STUDIED GENETICS AT BAYLOR AND
BE THE WAS RECRUITED TO THE
FACULTY AT THE UNIVERSITY OF
PENNSYLVANIA WHERE EVENTUALLY HE
BECAME PROFESSOR OF GENETICS,
PEDIATRICS AND MEDICINE.
AND IN 1993 FRANCIS COLLINS WHO
HEADED THE HUMAN GENOME
INSTITUTE AT THE NIH RECRUITED
DR. NUSSBAUM TO HELP LAUNCH THE
INTRAMURAL PROGRAM OF THE NIH
GRI.
WHICH BOB DID WITH DISTINCTION.
HE IDENTIFIED ALSO THE FIRST
INHERITED FORM OF PARKINSON'S
DISEASE INVOLVING MUTATIONS IN
THE ALPHA-SYNUCLEIN GENE AND
LOOKED FOR INHERITABLE DISORDERS
OF THE LIKE OF PARKINSON'S AND
OTHERS.
IN 2006, HE WAS RECRUITED TO THE
UNIVERSITY OF CALIFORNIA SAN
FRANCISCO WHERE HE WAS THE CHIEF
OF THE DIVISION OF HUMAN
GENETICS.
HE CONTINUED THE ACTIVITY IN
2015 WHEN HE BECAME THE CHIEF
MEDICAL OFFICER OF INVITA.
HIS GOAL WAS TO DEVELOP,
EVALUATE AND EVENTUALLY MARKET
GENETIC TESTS FOR CANCER AND
OTHER DISEASES WORLDWIDE.
DR. NUSSBAUM HAS MANY MANY
ACCOMPLISHMENTS AND AWARDS.
HE'S A MEMBER OF THE NATIONAL
ACADEMY OF MEDICINE AND WAS
PRESIDENT OF THE AMERICAN
SOCIETY OF HUMAN GENETICS.
HE DESCRIBES HIMSELF AS A
BOARD-CERTIFIED GENETICIST.
WE KNOW HE'S AN OUTSTANDING
TEACHER AND A LEADER IN BRIDGING
BASIC GENETICS WITH ACCURATE
WIDELY AVAILABLE PREDICTIVE
DIAGNOSTIC TESTS.
SO WE WILL BEGIN FIRST WITH
DR. CASTLE.
PHILIP, YOU'RE ON.
>>THANK YOU SO VERY MUCH.
THANK YOU FOR THE OPPORTUNITY
AND HONOR, REALLY, TO PRESENT TO
THIS AUDIENCE.
TODAY WE'LL TALK ABOUT TEST FOR
EARLY CANCER AND TALK ABOUT
CANCER SCREENING AND NOT JUST
FOR EARLY CANCER BUT FOR
PRECANCER.
>>A FEW DISCLAIMERS AND
DISCLOSURES.
HE'S ARE MY OPINIONS AND DON'T
REPRESENT ANYBODY ELSE'S
INCLUDING THE NIH, NCI AND THE
DIVISION OF CANCER PREVENTION.
MY COMMENTS SHOULD NOT BE TAKEN
FOR FUNDING.
IF I MENTION SPECIFIC PRODUCTS
I'M NOT ENDORSING THEM.
FOR DISCLOSURE I RECEIVED FROM
THE FOLLOWING COMPANIES, ROCHE,
CEPHEID, BECTON DICKINSON AND
ARBOR VITA CORPORATION.
WE RECOGNIZE THERE'S LIMITATIONS
TO BOTH OBSERVATIONAL STUDIES AS
WELL AS RANDOMIZED CONTROL
TRIALS.
THIS ILLUSTRATES WITH
OBSERVATIONAL STUDIES WE CAN'T
ALWAYS GLEAN CAUSAL
RELATIONSHIPS BETWEEN WHAT WE
SURVEY AND WHAT WE THINK IS
GOING ON BUT WE CAN'T DO
ANYTHING BY RANDOMIZED CLINICAL
TRIALS.
THIS IS AN ARTICLE BY A BRITISH
MEDICAL JOURNAL ENTITLED
PARACHUTE USE TO PREVENT DEATH
AND MAJOR TRAUMA RELATED TO
GRAVITATIONAL CHALLENGES
SYSTEMIC REVIEW OF RANDOMIZED
CONTROLLED TRIALS AND THEY FOUND
NO CONTROL TRIALS.
THE RANDOMIZED CONTROL TRIAL IS
THE GOLD STANDARD.
SOMETIMES WE CAN USE IT AND
SOMETIMES WE CAN'T AND RECOGNIZE
WHEN WE CAN'T, OBSERVATIONAL
TRIALS MAY LEAD TO ERRONEOUS
CAUSAL RELATIONSHIPS BETWEEN THE
INTERVENTION AND THE OUTCOME.
SO I'M GOING TO TALK A LITTLE
BIT ABOUT SCREENING.
I'LL REMIND YOU WHAT ARE THE
CURRENT CANCER SCREENING
RECOMMENDATIONS.
I'M GOING TO ILLUSTRATE SOME OF
THE ONE PAST SUCCESS AND FAILURE
AND TALK ABOUT THE EMERGENCE OF
MULTI-CANCER DETECTION WHICH I
THINK ROBERT WILL TALK ABOUT
AFTER ME A LITTLE BIT AND HOW DO
WE AVOID THE PAST MISTAKE.
I DO WANT TO TOUCH UPON CANCER
HEALTH DISPARITIES AND SCREENING
AND MAKE A FEW FINAL COMMENTS.
SO WHAT IS SCREENING?
SO THIS IS THE HEALTH.gov
DEFINITION.
SCREENINGS ARE MEDICAL TESTS
DOCTORS USING TO CHECK FOR
DISEASES AND HEALTH CONDITIONS
BEFORE THERE'S ANY SIGNS OR
SYMPTOMS AND THERE'S THE WEBSITE
YOU CAN SEE YOURSELF.
I'D LIKE TO MODIFY THIS A LITTLE
BIT.
I'M GOING GIVE YOU MY OWN
DEFINITION.
SO SCREENS ARE PROCESSES THAT
INCLUDE MEDICAL TESTS AND
FOLLOW-UP CARE THAT A HEALTH
CARE PROVIDERS USE TO FIND AND
AVERT DISEASES AND HEALTH
CONDITIONS BEFORE THERE'S SIGNS
OR SYSTEMS WITH THE GOAL OF
INTERVENING TO IMPROVE HEALTH
OUTCOMES AND QUALITY OF LIFE.
THE IMPORTANT THING HERE IS THAT
SCREENING IS NOT JUST A TEST.
THAT IS PART OF IT.
IT'S AN IMPORTANT PART.
IT'S A RISK STRATIFIER AND
THAT'S WHAT WE'RE TALK BECOME
WHEN WE DO A TEST, SCREENING
TEST.
WE'RE SCATTEREDFYING --
STRATIFYING THE POPULATION AND
PEOPLE AT HIGHER AND LOWER RISK
AND RUNNING A TEST ALONE IS NOT
ENOUGH.
WE HAVE TO PROVIDE TEST FOR
THOSE WHO SCREEN POSITIVE OR THE
TESTING YOU'VE DONE IS
COMPLETELY USEFUL.
AND SCREENING AS I'LL ILLUSTRATE
IN THE NEXT SLIDE WITH
ARITHMETIC IS THE MOST
CHALLENGING APPLICATION OF A
DIAGNOSTIC WHICH IS TO USE IT IN
A HEALTHY PERSON TO KEEP
HEALTHY.
MOST DIAGNOSTIC DONE IN THOSE
WHO HAVE SOME SORT OF SYMPTOM OR
SIGN OR SOMETHING AMISS TO MAKE
A DIFFERENTIAL DIAGNOSIS OR
IDENTIFY THE CAUSE OF THE
SYMPTOM.
AS ILLUSTRATED HERE, THIS IS AN
EXAMPLE, A GENERAL EXAMPLE IT
PARALLELS THE USE OF HUMAN
PAPILLOMA VIRUS TESTING FOR
CERVICAL CANCER.
I'D SAY WE GO INTO A POPULATION
WHERE THERE'S A PREVALENCE OF
DISEASE FOR 1% AND FOR CERVICAL
CANCER WOULD BE PRECANCER AND
CANCER.
LET'S SAY YOU HAVE A TEST LIKE
HPV WHICH IS 90% SENSITIVE AND
90% SPECIFIC WHICH IS A REALLY
GOOD TEST.
AND BY THE WAY, TO PUT IT IN
PERSPECTIVE FOR THE
GENEOLOGISTS, THAT'S AN ODDS
RATIO OF 81.
I DON'T KNOW ABOUT THE REST OF
YOU BUT I'VE RARELY SEEN ODDS
RATIOS OF 81 EXCEPT FOR A FEW
AND MOST BIOMARKERS DON'T
ACHIEVE THAT LEVEL OF
ASSOCIATION.
LET'S LOOK AT THE NUMBERS.
LET'S TAKE THE THEORETICAL
POPULATION OF 10,000 PEOPLE AND
APPLY THE TEST AND 1% PREVALENCE
OF DISEASE.
IF THERE'S 100 CASES IN THE
10,000.
GUESS WHAT?
THE POSITIVE PREDICTIVE VALUE
FOR THAT TEST, SO THE NUMBER OF
PEOPLE WHO TEST POSITIVE AND THE
NUMBER OF CASES WITHIN THAT TEST
POSITIVE POPULATION, THE RISK OR
POSITIVE PREDICTIVE VALUE IS
ONLY 8.3%.
THAT MEANS 11 OUT OF 12 WHO
TESTED POSITIVE WILL BE FALSE
POSITIVE.
NOW, A TEST LIKE THIS ACTUALLY
THE REAL VALUE OF THIS OR THE
STRENGTH OF THIS TEST IN A LOW
PREVALENCE CIRCUMSTANCE IS THE
NEGATIVE PREDICTIVE VALUE SHOWN
HERE WHICH IS 99.9%.
THAT MEANS WHEN A PERSON TESTS
NEGATIVE YOU'LL HAVE ONLY MISSED
ONE CASE AND THERE'LL ONLY BE
ONE CASE IN 1,000 OUT OF THIS
HYPOTHETICAL SITUATION.
SO WHAT HAPPENS IF WE APPLY A
SECOND TEST TO THE SCREEN
POSITIVE OR GOING BACK TO THE
EXAMPLE BEFORE LET'S SAY THEY
HAVE A SYMPTOM?
SO HERE WE'RE STARTING WITH A
HIGHER PREVALENCE OF DISEASE
8.3% AND WE JUST USE IN THIS
CASE FOR THIS EXAMPLE ACYTOLOGY
ACYTOLOGY -- A CYTOLOGY TEST
AND BECAUSE IT'S ALMOST AN ORDER
OF MAGNITUDE GREATER THE
POSITIVE PREDICTIVE VALUE IS
ALMOST 50%.
SO THIS ILLUSTRATED WHEN WE CAN
SCREEN THE GENERAL HEALTHY
POPULATION IS BEST SERVED BY A
RULE OUT WHICH IS WHAT WE SHOW
ABOVE IF YOU'RE HPV NEGATIVE
YOU'RE UNLIKELY TO HAVE DISEASE
AND THE RULE END SHOWN AT THE
BOTTOM WHICH IS ONCE YOU KNOW
HAVE YOU A HIGHER RISK COHORT TO
USE A VERY SPECIFIC TEST TO
IDENTIFY THOSE WHO ARE BEARING
DISEASE.
JUST BECAUSE WE'RE NOT GOING TO
ACT ON THE SCREEN POSITIVES WHO
TRIAGE NEGATIVE DOESN'T MEAN
THEY'RE COMPLETELY LOST BECAUSE
WE ALREADY KNOW THEY'RE SCREEN
POSITIVE AND WILL FOLLOW THEM
MORE CLOSELY.
THIS IS ILLUSTRATING AN
IMPORTANT CONCEPT WHICH IS RISK
STRATIFICATION.
WE CAN'T DO EVERYTHING FOR
EVERYBODY.
WE'D LIKE TO BUT WE CAN'T,
PRACTICALLY, SO WE HAVE TO
DECIDE WHO'S AT THE HIGHEST RISK
AND LOWEST RISK AND ACT
ACCORDINGLY.
SO REALLY WHEN YOU THINK ABOUT
THE SCREENING CARE CONTINUUM IT
FALLS INTO FIVE STEPS.
SOME ARE COMBINED.
I'LL GIVE AN EXAMPLE HERE RISK
ASSESSMENT.
SO WE DON'T DO ALL CANCER
SCREENING ON EVERYBODY.
WE OFTEN USAGE AS ONE WAY TO
ASSESS RISK.
WE DON'T DO CERVICAL CANCER
SCREENING IN MEN BECAUSE THEY
DON'T HAVE A CERVIX SO THEY'RE
AT ZERO RISK.
WE SHOULDN'T BE DOING CERVICAL
CANCER SCREENING IN WOMEN WHO
HAVE HAD A HYSTERECTOMY BECAUSE
THEY DON'T HAVE A CERVIX AND WE
APPLY THE SCREENING TEST AND THE
FIRST LINE OF TEST IS TO RULE
OUT AND TELL HEALTHY PEOPLE
THEY'RE HEALTHY AND AMONG THE
TEST POSITIVES WE CAN DO
MANAGEMENT OR WHAT WE CALL
TRIAGE TO SAY WE'LL CAN GET A
BIOPSY FOR EXAMPLE.
FOR THOSE WHO INDICATE
PRECANCER, CANCER, WE MAY TREAT
YOU FOR PRECANCER.
SOME GETS COMBINED IF YOU THINK
ABOUT COLONOSCOPY AND THE
DIAGNOSIS ARE ALL PART OF ONE.
I WANTED TO ILLUSTRATE THIS
BECAUSE THE CHALLENGE GOING
FORWARD FOR ANY CANCER SCREENING
OR INTERVENTION IS HOW DO YOU
MAXIMIZE THE BENEFITS AND
MINIMIZE THE HARMS?
THE REASON I'M EMPHASIZING THIS
IS THAT MOST PEOPLE WHO COME IN
FOR CANCER SCREENING DON'T HAVE
CANCER.
SO WHAT WE DO TO THEM ONLY
CONTRIBUTES TO THE HARMS.
SO WHEN YOU TALK ABOUT A
POPULATION INTERVENTION IT'S
REALLY IMPORTANT TO CONSIDER
WHO'S GOING TO BENEFIT WHICH IS
ONLY A SMALL TRACTION AND WHO IS
GOING TO BE HARMED.
SO COMING BACK TO THE EXAMPLE OF
CERVIX, THE LIFE TIME RISK OF
CERVICAL CANCER IF WE DIDN'T DO
ANY SCREENING OR HAVE HPV
VACCINATION IS 2%.
THAT MEANS ONE OUT OF 50 WOMEN
WILL GET CERVICAL CANCER AND 49
OUT OF 50 WOULD BE PERFECTLY
FINE IF WE LEFT THEM ALONE.
WE HAVE TO BE COGNITIVE OF THE
49 WHILE WE'RE SAVING THE ONE
WHO MAY GET CANCER.
SO WHAT ARE THE CURRENT
RECOMMENDATIONS?
I PUT THIS UP TO SAY, YES, WE
CAN DO SCREENING AND TO REMIND
THE AUDIENCE THERE'S
EVIDENCE-BASED SCREENING THAT
WILL SAVE LIVES.
THESE ARE THE U.S. PREVENTIVE
SERVICES RECOMMENDED CANCER
RELATED SCREENING AND BREAST
CANCER FOR WOMEN AGE 50 TO 74
ILLUSTRATING WE DON'T DO BREAST
CANCER SCREENING IN EVERYBODY
BECAUSE THE RISK IS TO LOW ON
THE OTHER SIDE OR THE HARMS ARE
TOO GREAT.
SO IT'S 50 TO 74 YEARS OF AGE
AND THAT'S BIENNIAL OR EVERY TWO
YEARS AND CERVIX WE SCREEN FROM
21 TO 66 AND EXIT SCREENING AT
65 IF THERE'S NO HISTORY AND
FROM 30 TO 65 THEY CAN GET HPV
TESTING WITH OR WITHOUT CI
CYTOLOGY.
WHEN YOU HAVE MANY CHOICES YOU
WANT TO WORK WITH YOUR PROVIDER
TO WORK WHAT'S BEST FOR YOU BUT
EVERYBODY BETWEEN 75 MEN AND
WOMEN NEED THEIR COLORECTAL
CANCER SCREENING.
AND THERE'S THE EXACT SCIENCE
TECHNOLOGY THAT MEASURES GENOMIC
CHANGES IN STOOL.
THERE'S SIGMOIDOSCOPY AND THE
GOLD STANDARD IS COLONOSCOPY AND
WE HAVE -- THESE ARE NOT
DIRECTLY CANCER SCREENING BUT
SCREENING FOR HEPATITIS B AND C
ARE TWO MAJOR CAUSES OF LIVER
CANCER AND SURPRISINGLY FOR
HEPATITIS B THERE'S STILL A
FRACTION OF PEOPLE IN THE UNITED
STATES WHO HAVE NOT BEEN
VACCINATED AGAINST HBV.
SO FOR HIGH-RISK INDIVIDUALS
THEY SHOULD BE SCREENED FOR
HEPATITIS B AND HEPATITIS C, 18
TO 79 YEARS ALL YOU NEED IS ONE
ROUND OF SCREENING BUT YOU'D BE
SURPRISED AT HOW FEW PEOPLE KNOW
THE RECOMMENDATION AND HOW FEW
HAVE GOTTEN HEPATITIS C VIRUS
SCREENING.
AND LUNG CANCER SCREENING FOR
HEAVY SMOKERS.
THIS IS ANOTHER PROBLEM IN THE
UNITED STATES THAT ONLY ABOUT 5%
TO 10% OF THE HE WILL POPULATION
FOR LUNG CANCER SCREENING BY
TOMOGRAPHY HAVE GOTTEN IT AND
LUNG CANCER'S A MAJOR KILLER IN
THE UNITED STATES.
I CAN'T ENCOURAGE PEOPLE ENOUGH
WHO ARE AT HIGH RISK WHO HAVE 20
PACK YEAR SMOKING HISTORY AND
ARE CURRENT OR QUIT IN THE LAST
15 YEARS TO GET THEIR CANCER
SCREENING.
HERE'S THE CITATION AND THE
WEBSITE TO SEE THE
RECOMMENDATIONS.
AND THE STUDY I LEARNED SO MUCH
FROM AND I CONTINUE TO SEE NEW
THINGS ALL THE TIME AND CONTINUE
TO LEARN FROM IT.
THE BUT THE FIRST THING TO
RECOGNIZE IS WHY WAS THE CERVIX
OR CERVICAL CANCER SCREENING THE
LOW HANGING FRUIT OF CANCER
PREVENTION?
FIRST, IT'S A SLOW GROWING
CANCER.
THE TIME FROM HPV EXPOSURE TO
CANCER IS 20 TO 25 YEARS ON
AVERAGE.
WE'RE LUCKY WE HAVE A SINGLE
ET
ET -- ETIOLOGY AND MOST WOMEN
WILL TOLERATE GETTING A PAP
SAMPLE WHETHER FOR CYTOLOGY OR
HPV AND THERE'S NO ISSUE.
THERE'S A SMALL AREA OF
SUSCEPTIBILITY.
THE MOST CANCERS HAPPEN IN A
SMALL TISSUE OF SKRAUMAL TISSUE
AND IT'S LIKELY TO BE INFECTED
BY HPV AND BIGGER SURFACE AREA
SO IT'S A UNIQUE BIOLOGICAL
INTERACTION BETWEEN THE SMALL
AREA OF SUSCEPTIBILITY AND THE
HUMAN PAPILLOMA INFECTION.
AND THE TEST IS NOT NECESSARILY
GOOD BUT HELPED ELUCIDATE THE
NATURAL HISTORY AND
IDENTIFICATION OF THE PRECURSOR
OF THE CIN3 THAT SERVES AS A
SURROGATE FOR CANCER.
WHY'S THAT IMPORTANT?
BECAUSE IT'S ALLOWED US TO CYCLE
THROUGH DIFFERENT INTERVENTIONS
QUICKLY WITHOUT HAVING TO WAIT
FOR THE ACCUMULATION OF CANCER
WE CAN SAY IT WORKS OR DOESN'T
WORK AND WE CAN STOP PURSUING
THAT WITHOUT GOING TOO CANCER
END POINT WHICH TAKES MUCH
LONGER AND IS MUCH MORE
EXPENSIVE.
OVER THE LAST 25 YEARS AND
STARTED WITH TO THE DISCOVERY OF
HPV IN CANCERS IN THE LATE '80s
AND THE FOUNDER GOT A NOBEL
PRIZE LAUREATE IN 2008 AND YOU
SEE WHAT A CYTOPATHOLOGIST HAS
SEE AND IT'S COME TO FOUR
STAGES.
NORMAL INFECTED, PRECANCER AND
CANCER.
UP TOP YOU SEE CYTOLOGY AND IN
THE MIDDLE YOU SEE WHAT THE
COLPOSCOPIST SEES AND THE
CYTOLOGY IS JUST INFECTION
TYPICALLY WE SEE HPV INFECTION
PEAK ABOUT FIVE YEARS AFTER THE
AGE OF FIRST SEXUAL INITIATION.
IN THIS COUNTRY IT'S AROUND 20,
25 YEARS OF AGE BECAUSE THE
MEDIAN AGE OF SEXUAL INITIATION
IN THE UNITED STATES IS AROUND
16.
PRE CANCER OCCURS A FEW YEARS
AFTER THAT WHEN WE GO IN THE
POPULATION.
WE TEND TO SEE A PEAK AROUND 25
TO 30 AND CANCER IS ANOTHER 10
TO 15 TO 20 YEARS AFTER THAT.
FOR THE PATHOLOGISTS ON THE
LINE, YOU OBVIOUSLY YOU CAN SEE
VERY CLEARLY HERE THE OLD
CYTOLOGIC CITOSYS AND SO WE'VE
BEEN LOOKING AT HPV FOR OVER 50
YEARS SINCE THE AMERICAN CANCER
SOCIETY RECOMMENDED PAP SMEARS
BACK IN THE EARLY '50s.
NOW WE HAVE THE MEC MOLECULAR
BASIS ONE LEADING TO VACCINATION
AND SCREENING.
WE MOVED FROM THE OLD STRATEGY
FOR PREVENTION WHICH IS TO DO
REPEATED PAP TESTS AND HIGH
FREQUENT AND TRY TO VACCINE
BEFORE SEXUALLY ACTIVITY AND
APPLY A FEW HPV TESTS ON THE
LIFE TIME DEPENDING ON THE
RESOURCES OF THE COUNTRY TO FIND
THE HPV INFECTIONS THAT
DEVELOPED INTO CANCER AND PRE
CANCER.
THIS HAS PLAYED OUT AND I WON'T
SHOW YOU HPV VACCINATION IT'S
NOT PART OF THE TALK BUT WHEN WE
LOOK AT DATA LIKE THIS A
RANDOMIZED CONTROL TRIAL DATA
FROM EUROPE FROM FOUR CLINICAL
TRIALS.
IN THE RED IS THE CYTOLOGY ARM
AND IN THE BLUE IS THE HPV ARM.
ON THE LEFT IS ALL WOMEN, YOU
SEE A 50% REDUCTION IN THE
INCIDENTS OF INVASIVE CERVICAL
CANCER WITH ONE ROUND OF HPV
TESTING ED COMPARED TO
CYTOLOGY.
ON THE WHITE SIDE YOU SEE WOMEN
WHO TESTED NEGATIVE AND COMES
BACK TO THE RULE OUT I SAID
BEFORE ONCE YOU SAID THEY'RE HPV
NEGATIVE THEIR RISK IS REALLY
LOW.
WHY IS THAT IMPORTANT?
IF THEY'RE HPV NEGATIVE WE DON'T
NEED TO SCREEN YOU EVERY ONE,
TWO OR THREE YEARS, WE CAN
SCREEN YOU FIVE OR MORE YEARS
WHICH REDUCES THE HARMS.
GOING BACK TO THE SCALE OF
TRYING TO MAXIMIZE BENEFIT AND
MINIMIZE HARMS.
SCREEN THOSE PEOPLE AT RISK MORE
HEAVILY, MORE FREQUENTLY AND
SCREEN THOSE AT LOW RISK LESS
FREQUENTLY.
HERE'S THE BAD NEWS OR THE
FAILURE WHICH IS PSA TESTING.
SO BACK IN 1986 PSA TESTING WAS
USED FOR MONITORING PROSTATE
CANCER PROGRESSION.
BY 1988 IT WAS INTRODUCED FOR
SCREENING DESPITE THE LACK OF
EVIDENCE.
THE NCI IN 1990s START THE
PROSTATE LUNG, COLORECTAL AND
LUNG TRIAL AND THE EUROPEANS DID
LIKEWISE AND BY 2000 THEY FOUND
LITTLE TO NO MORTALITY REDUCTION
AND OVERDIAGNOSIS.
THERE WAS CONTAMINATION OF THE
CONTROL ARM OVER ALL IT WAS A
LITTLE BIT OF A MORTALITY
REDUCTION DUE TO THE PSA BUT THE
HARMS ASSOCIATED THAT HAS GIVEN
POSITIVE PSA AND THEY SAID DON'T
DO PSA SCREENING AND NOW THEY
BROUGHT IT BACK IN 2018 TO DO IT
IN AN INFORMED DECISION MAKE
PROCESS WITH YOUR PROVIDER AND
THE IDEA IS THAT THERE ARE SOME
PEOPLE WHO ARE AT HIGHER RISK
AND WOULD BENEFIT.
AGAIN, THAT BENEFITS THE HARMS.
THAT'S WHAT WE ALWAYS COME BACK
TO WHEN WE COME BACK TO
SCREENING.
HOW MANY PEOPLE WILL BENEFIT AND
HOW MANY WILL BE HARMED?
THE SUMMARY OF THE STORY IS WHEN
WE THINK ABOUT INTRODUCING
SOMETHING INTO THE POPULATION,
WE NEED TO UNDERSTAND IT.
WE NEED TO MAXIMIZE THE BENEFITS
TO HARMS.
RANDOMIZED TRIALS ARE NOT
PERFECT AS I'VE ILLUSTRATED OR
CAN'T ALWAYS BE DONE AND THEY
CAN BE LIMITED AND THE ANSWERS
MAY NOT BE STRAIGHTFORWARD
PARTICULARLY WHEN YOU THINK
ABOUT ISSUES OF COMPLIANCE AND
CONTAMINATION IN YOUR CONTROL
ARM.
YOU CAN'T SIMPLY COMPARE
INCIDENTS OF SCREEN AND CONTROL
ARMS.
OUTCOMES OF SCREENING DEPEND ON
DISEASE NATURAL HISTORY AND MUST
UNDERSTAND IT TO SCREEN SMARTLY.
THAT WAS ILLUSTRATED WITH THE
CERVIX MODEL BY UNDERSTANDING
THAT NATURAL HISTORY WE KNOW --
WE WANT TO VACCINE YOUNG KIDS,
PRE TEENS BECAUSE THEY DON'T
HAVE HVP VET -- YET AND YOUNG
PEOPLE IT'S BETTER TO SCREEN
THAN VACCINE BECAUSE SOME
ALREADY HAVE HPV THAT ABOUT TO
GO ON TO CANCER.
OUTCOMES OF SCREENING DEPEND HOW
YOU USE THE TEST IN PRACTICE.
YOU CAN TURN A POSITIVE INTO A
NEGATIVE TEST IF YOU DON'T
SCREEN SMARTLY.
I THINK THE PSA CAN BE REVISED.
THE WAY IS BY USING A
RISK-INFORMED STRATEGY WHERE YOU
TAKE A BAYESIAN VIEW AND
CONTINUE TO UPDATE THE RISK
BASED ON THE INFORMATION YOU
HAVE AND YOU DECIDE WHETHER
TREATMENT BIOPSY AND INCREASED
SURVEILLANCE OR ROUTINE
SCREENING ARE APPROPRIATE.
AND WE USE THE PSA AS A LEAD-IN
TO MULTI-CANCER DETECTION
BECAUSE I'M AFRAID THIS HAS A
TREMENDOUS POTENTIAL.
THERE'S A LOT OF HOPE BUT
THERE'S A LOT OF HYPE AND WHAT'S
TRUE IS WE DON'T KNOW HOW THE
TESTS WILL WORK IN THE GENERAL
POPULATION.
THIS IS A GRAPHIC FROM MY
COMMUNICATIONS TEAM WITH CANCER
PREVENTION AND A WONDERFUL
ILLUSTRATION THERE'S MANY
TECHNOLOGIES EMERGING WE DON'T
KNOW HOW WELL THEY WORK AND THIS
IS A SUBSET AND THERE'S PROBABLY
DOUBLE THE NUMBER BEING
DEVELOPED AND SOME WHICH WE
DON'T KNOW AND PROBABLY ANOTHER
20 TO 50 ACADEMIC CENTERS
DEVELOPING A TEST.
THIS IS A WHOLE NEW FIELD.
WE'VE NEVER SEEN ANYTHING LIKE
IT AND THE CARTOON ON THE RIGHT
SAYS I THINK I'D LIKE TO HAVE AN
MCED TEST, DOC, BUT I DON'T KNOW
WHICH ONE AND RIGHT NOW WE DON'T
HAVE ADVICE FOR ANYONE.
BACKGROUND IN ASSAY.
EACH MEASURES DIFFERENT
MOLECULAR PROFILES IN BLOOD FOR
DIFFERENT SET OF CANCERS.
A POSITIVE RESULT IS A SIGNAL
FOR CANCER BUT NOT DIAGNOSED
CANCER.
SOME TESTS SUGGEST TISSUE OF
ORIGIN, SOME TESTS REQUIRE
EXTENSIVE IMAGING.
THEY'RE UNDER DEVELOPMENT SO
GETTING THEM LOCKED DOWN AND
KNOWING HOW THEY PERFORM IS A
MOVING TARGET.
THIS IS A SUBSET OF A SUBSET I
SHOWED YOU AND YOU CAN SEE THE
COMPLEXITY OF THE FIELD.
I LISTED HERE A HANDFUL OF THESE
THAT ARE DIFFERENT COMPANIES,
DIFFERENT NAMES, DIFFERENT
TECHNOLOGIES.
EVERYTHING FROM CFDNA ROBERT
WILL BE TALKING ABOUT TO
PRAGMA
PRAGMATTOMICS AND WHICH ONE IS
BEST FOR YOU?
I DON'T KNOW WHICH IS BEST FOR
ME BUT SAY A BRCA PATIENT WOULD
PROBABLY WANT FOR PANCREAS,
BREAST AND OVARIES.
I THINK IT'S EXCITING FOR
CANCERS FOR WHICH WE DON'T HAVE
TESTS LIKE PANCREAS AND OVARY
WHICH ARE LETHAL CANCERS BUT
HAVE NO DATA TO SHOW THEY YET
WORK I'LL TALK ABOUT IN THE NEXT
SLIDE.
IT'S UNKNOWN IF A SYMPTOMATIC
PEOPLE WITH CANCER WITH ASSAYS
WILL RESULT IN MORTALITY
REDUCTION OF CANCER.
THE WHOLE POINT OF SCREENING, IS
TO REDUCE MORTALITY.
FOR MANY OF THESE WE HAVE NO
DATA.
ALL THEY'VE SHOWN IS WE CAN
DETECT CANCER.
CAN WE SAVE LIVES?
THAT'S THE KEY ISSUES.
THERE'S POTENTIAL HARMS
ASSOCIATED WITH THE ASSAYS.
HOW MANY DIAGNOSTIC TESTS ARE
NEEDED TO MAKE THE CANCER
DIAGNOSIS?
WHAT HAPPENS FOLLOWING A
POSITIVE MCED TEST IF YOU DON'T
FIND A CANCER, HOW MANY INVASIVE
PROCEDURES AND WHAT WILL BE THE
HARMS AND COMPLICATIONS
ASSOCIATED WITH THE PROCEDURES?
WILL PEOPLE STOP GETTING THE
STANDARD OF CARE SCREENING?
NAY GET -- IF THEY GET A
NEGATIVE AND WILL IT LEAD TO
OVER DIAGNOSIS OF UNKNOWN
CANCERS?
WE HAVE STOOD UP A MULTI-PRONGED
RESEARCH PROGRAM.
A MULTI-LEVEL RESEARCH PROGRAM
AT THE NCI TO STUDY THESE FROM
BASIC SCIENCE TO CLINICAL
TRIALS.
OF COURSE IF ANY OF THESE WORK
BECAUSE WITH A LITTLE KNOW ABOUT
MORE ABOUT THE NATURAL HISTORY
WE'LL BE ABLE TO MAKE BETTER
MCED TESTS AND WILL PROBABLY
SPUR THE DEVELOPMENT OF NEW
THERAPIES BECAUSE WE'LL SEE
CANCERS AT A MOLECULAR STAGE
WE'VE NEVER SEEN BEFORE.
THIS IS A CARTOON OF THE TRIAL
WE'RE PROPOSING COMPARING MCEDs
VERSUS DIFFERENT ARMS AND THEY
DETECT DIFFERENT TISSUES FOR
CANCER AND SO THEY'RE NOT REALLY
DIRECTLY COMPARABLE.
ONLY DIRECTLY COMPARABLE TO THE
STANDARD OF CARE ARM FOR MANY
CANCERS THERE'S NO SCREENING
TEST.
AND MORTALITY WILL BE THE
PRIMARY OUTCOME.
THAT'S UNEQUIVOCAL.
YOU CAN'T ARGUE IF YOU REDUCE
MORTALITY RELATED TO THESE
CANCERS.
NOBODY CAN ARGUE WHETHER OR NOT
THOSE WERE THE RIGHT CANCERS TO
FIND.
SO I WANT TO TALK ABOUT CANCER
HEALTH DISPARITIES AND I'LL COME
BACK TO HPV AND CERVICAL CANCER.
YOU SEE MORTALITY RATES FOR THE
WORLD AND THE TREMENDOUS
DISPARITIES ACROSS THE WORLD.
IT'S REALLY AN ORDER OF
MAGNITUDE DIFFERENCE BETWEEN THE
RATES IN AFRICA AND IN THE
WESTERN WORLD ILLUSTRATED IN THE
UNITED STATES IN THE LIGHT PINK
FOR RED VERSUS THE DARK RED IN
AFRICA.
WE HAVE IMPORTANT HEALTH
DISPARITIES HERE IN THE UNITED
STATES.
YOU CAN SEE THAT IN THE SOUTHERN
STATES PARTICULARLY AROUND THE
MISSISSIPPI DELTA AND THE STATE
OF MISSISSIPPI THEY HAVE MUCH
HIGHER RATES THAN YOU WOULD SEE
IN OTHER PARTS OF THE COUNTRY.
SO DESPITE OUR ADVANCES IN
UNIVER
UNDERSTANDING CERVICAL KAECANCE
AND TARGETING HUMAN PAPILLOMA
STRATEGY THERE'S THE HAVEs AND
HAVE-NOTs.
ONE WAY TO INCREASE SCREENING IN
THE POPULATIONS IS TO USE
SELF-COLLECTION.
THOUGH WOMEN WILL UNDER GO
PELVIC EXAMS, NOT ALL WOMEN WILL
AND IT REQUIRES OBVIOUSLY TRAVEL
AND APPOINTMENT AND THINGS LIKE
THAT.
IT'S A REAL CHALLENGE FOR MANY
WOMEN TO UNDER GO CERVICAL
CANCER SCREENING AND WHAT WE
FOUND IS DNA APPLICATION A PCR
TEST TO OFFER SELF-COLLECTION TO
WOMEN AND ACHIEVE THE SAME
CLINICAL PERFORMANCE AS IF THE
PROVIDER WAS PROVIDING A PELVIC
EXAM AND GETTING A BIOPSY FROM A
CERVIX AND WOMEN PREFER IT AND
WHEN YOU PROVIDE THE
SELF-COLLECTION KIT YOU CAN
INCREASE PARTICIPATION IN
ABSOLUTE NUMBERS BY ALMOST 40%.
THE OTHER METRIC IS BY DOING SO
YOU INCREASE THE NUMBERS OF
PRECANCERS YOU FIND IN THE
POPULATION.
FOR EVERY 1,000 WOMEN SCREENED
YOU FIND ALMOST 2.5 MORE
PRECANCERS COMPARED TO OFFERING
A PROVIDER-COLLECTED SAMPLE TO
POPULATIONS THAT DON'T PAR
PARTICIPATE IN SCREENING.
THE NCI IS WORKING WITH THE FDA
TO GET SELF-COLLECTION TESTING
APPROVED AND CAN REACH UNDER
SERVED POPULATIONS THROUGH A
VARIETY OF METHODS.
THEY MAY NOT WANT TO COME TO THE
CLINIC.
THEY MAY WANT TO GO TO CVS OR
ANOTHER PHARMACY AND GET THEIR
SELF-COLLECTION KIT, DO IT IN
THE COMFORT OF THEIR HOME
WITHOUT A PELVIC EXAM AND HAVE
IT TESTED AND IF IT'S POSITIVE
BRING THEM TO THE CLINIC FOR THE
REST OF THE CARE.
I WANT TO HIGHLIGHT PLACES LIKE
THE MISSISSIPPI DELTA ARE NOT
THE ONLY DISEASES THEY HAVE A
DISPROPORTIONATE BURDEN.
HERE COLORECTAL CANCER, BREAST,
LUNG, NOT SO MUCH LUNG BUT YOU
CAN SEE SLIGHTLY LIGHTER AND
PROSTATE CANCER THEY EXPERIENCE
A HIGHER BURDEN THAN MANY OTHER
PLACES IN THE COUNTRY.
SO WE REALLY HAVE TO THINK ABOUT
NOT JUST CERVICAL CANCER BUT HOW
WE PROVIDE A PACKAGE OF CARE TO
THESE POPULATIONS WHO ARE IN
NEED.
SO MY FINAL COMMENTS, NATURAL
HISTORY INFORMS, PERIOD.
BUT NATURAL HISTORY INFORMS
INTERVENTIONS AND HOW BEST TO
USE THEM.
HAVING A GOOD SURROGATE ALLOWS
RAPID CYCLING THROUGH
INTERVENTIONS.
INTERVENTION AND SCREENING
MODALITIES CAN CAUSE HARMS LIKE
THE INTRODUCTION OF PSA AND
LESSER INTERVENTION PATH LEADS
IT A BETTER ONE.
PREDICATE TESTS ARE FOR
UNDERSTANDING THE NATURAL
HISTORY.
IN MY OPINION SCREENING WORKS
BEST AS A TWO-STEP PROCESS, RULE
OUT AND RULE IN AND RULE OUT
DISEASE IN THE HEALTHY WHICH SAY
BENEFIT NOBODY TALKS ABOUT AND
CREATING AN ENRICHED POPULATION
FOR THE RULE-IN TEST.
HIGHER PREVALENCE LEADS TO
BETTER PREDICTIVE VALUES.
IMPLEMENTING BEST PRACTICES YOU
SAW IN MISSISSIPPI NOT EVERYBODY
GETS THE SAME BENEFITS.
IMPLEMENTING BEST PRACTICE IS
DIFFICULT AND SLOW EVEN WHEN THE
SCIENCE AND EVIDENCE IS ROBUST.
ESPECIALLY IN DISORGANIZED
HEALTH CARE SYSTEMS LIKE WE HAVE
IN THE UNITED STATES.
THE DEVELOPMENT OF INTRODUCTION
AND NEW TECHNOLOGIES HAS
HISTORICALLY EXACERBATED RATHER
THAN MITIGATED HEALTH
DISPARITIES.
WE NEED TO DO BETTER.
AND MY FINAL POINT IS PREVENTION
SCREENING WILL BE KEY TO
REDUCING CANCER MORTALITY IN 15
TO 25 YEARS AND INCREASING
UPTAKE OF EVIDENCE-BASED
PREVENTION AND SCREENING
PRACTICES IN UNDER SERVED
POPULATION AND LOOKING AT THE
MOST LETHAL CANCERS SUCH AS
PANCREAS AND OVARY.
THANK YOU VERY MUCH.
I'LL LET YOU ENJOY THE TWO
CARTOONS.
ON THE LEFT IT SAID I'LL HAVE AN
OUNCE OF PREVENTION AND MANY ARE
AWARE OF THAT SAYING.
AND SAYING WHAT COULD WE ACHIEVE
WITH A POUND OF PREVENTION?
ON THE RIGHT, THERE'S AN '80s
BAND CALLED THE CURE AND THE
CARTOON SAYS APPARENTLY THE
PREVENTION IS BETTER THAN THE
CURE.
I'LL TURN IT OVER TO ROBERT TO
BRING US HOME.
>>HELLO, EVERYONE.
THANK YOU FOR JOINING US TODAY.
IT'S A GREAT HONOR TO BE ABLE TO
PARTICIPATE IN THE DEMYSTIFYING
MEDICINE SERIES.
THESE ARE MY OWN OPINIONS, NOT
NECESSARILY THOSE OF MY
EMPLOYER, THE INVITA CORPORATION
AND I'M AN EMPLOYEE AND SERVED
AS A CONSULTANT FOR PFIZER AND
GENOME MEDICAL.
AND I LIKE THE SCREENINGS.
THEY'RE MEDICAL TESTS DOCTORS
USE TO LOOK FOR HEALTH DISEASES
BEFORE THERE'S SIGNS AND
SYMPTOMS AND IT'S NOT JUST A
TEST BUT THE PROVISION OF CARE.
AND EMPHASIZE AS WITH THE
NEWBORN SCREENING IT'S NOT JUST
A TEST, IT'S A PROGRAM THAT NOT
ONLY PROVIDES THE TEST BUT THE
FOLLOW-UP NECESSARY.
FOR THE PURPOSE OF THIS
DEMYSTIFYING MEDICINE TALK I'D
LIKE TO EXPAND THE DEFINITION TO
INCLUDE NOT ONLY TESTING DESIGN
TO LOOK FOR CANCER IN
ASYMPTOMATIC HEALTHY INDIVIDUALS
IN THE POPULATION BUT ALSO
MONITOR NEW PATIENTS FOR
RESPONSE OR RELAPSE FOLLOWING
INTENT TO CURE THERAPY.
CFDNA AND CIRCULATED TUMOR DNA.
WHAT WAS DISCOVERED NOW A COUPLE
DECADES AGO A FASCINATING AND
INTERESTING OBSERVATION WAS THAT
PLASMA CONTAINED CELL-FREE DNA.
THE FRAGMENT DERIVED MAINLY FROM
DYING WHITE BLOOD CELLS.
BUT WITHIN THE CELL-FREE DNA
COMPARTMENT IN PATIENTS WITH
CANCER THERE'S CIRCULATING TUMOR
DNA FRAGMENTS SHED FROM THE
TUMOR AND MIXED WITH THE
CELL-FREE DNA.
THE LEVELS OF CT DNA CAN DIFFER
FROM HOW MUCH CANCER IS IN THE
BODY AND WHAT SITES THE PRIMARY
AND MANY METASTATIC SITES AND
THERE'S PROBABLY OTHER ASPECTS
OF TUMOR BIOLOGY THAT GOVERN
WHAT THE LEVEL OF CT DNA WOULD
BE.
HERE'S A COUPLE EXAMPLES OF THE
AMOUNT OF CT DNA SHED.
BLADDER IS ONE THAT PRODUCES
QUITE A BIT OF CT DNA AND
COLORECTAL AND PANCREATIC AND
OVARIAN.
THESE ARE EXAMPLES PHIL
MENTIONED, GASTROESOPHAGEAL MAY
BE DIFFICULT TO DETECT IN
CERTAIN KINDS OF GASTRIC CANCER
BUT THEY DO SHED DETECTABLE
AMOUNTS OF CT DNA AND BREAST AND
MELANOMA AND HEAD AND NECK,
ETCETERA, DOWN TO GLIOMA TUMOR
THAT HAS THE FREQUENCY OF CASES
THAT HAVE DETECTABLE CT DNA IS
SMALL BUT WE THINK IT HAS TO DO
WITH THE BLOOD BRAIN BARRIER BUT
THERE MAY BE OTHER REASONS WITH
THE BIOLOGY OF GLIOMA THAT
INTERFERES.
THYROID IS A HIGHLY WELL
VASCULARIZED TISSUE.
YOU CAN SEE IT'S NOT ALWAYS
OBVIOUS WHICH CANCERS ARE GOING
TO BE FREQUENTLY DEMONSTRATING
DETECTABLE CT DNA AND WHICH ARE
NOT.
THERE ARE SOME CONFOUNDING
FACTORS TO KEEP IN MIND WHEN
MEASURES CT DNA.
IN PREGNANCY, A COUPLE YEARS AGO
WE HEARD A TALK FROM DR. BIANCHI
THE INSTITUTE DIRECTOR OF THE
NATIONAL INSTITUTE OF CHILD
HEALTH WHO TALKED ABOUT THE USE
OF FETAL CELL FREE DNA IN THE
MATERNAL PLASMA AND PREGNANCY
WILL BE A CONFOUNDING FACTOR IF
WHAT YOU'RE LOOKING FOR IS CT
DNA.
ACTIVE MALIGNANCIES AND IF YOU
HAD A BLOOD TRANSFUSION IN THE
LAST TWO WEEKS THERE'LL BE CELL
FREE DNA DERIVED FROM THE
TRANSFUSED BLOOD WHICH CAN
INTERFERE AND OBSCURE, CONFOUND
YOUR ABILITY TO DETECT IN THE
INDIVIDUAL.
ANOTHER DEFINITION CALLED
MINIMAL RESIDUAL DISEASE.
THE PRESENCE OF RESIDUAL TUMOR
CELLS FOLLOWING THERAPY THAT
CANNOT BE DETECTED BY STANDARD
IMAGING STUDIES OR OTHER ROUTINE
METHODS.
THIS IS ONE OF THE AREAS WHERE
CT DNA WILL COME INTO ITS OWN.
THE DETECTING CT DNA IS EVIDENCE
OF MINIMAL RESIDUAL DISEASE AND
MRD IS FREQUENTLY CALLED
MOLECULAR RESIDUAL DISEASE OR
MEASURABLE RATHER THAN MINIMAL
BECAUSE IT WILL BE DETECTABLE BY
MOLECULAR METHODS.
AND A LOT OF TRADITIONAL METHODS
LIKE IMAGING OR PATHOLOGICAL
FEATURES OR BLOOD MARKERS HAVE A
PROBLEM PREDICTING RISK OF
RELAPSE OR DETECTING TUMOR
GROWTH OR MRD UNTIL AFTER THEY
HAVE ALREADY METASTASIZED.
THE ISSUE IS WHETHER CT DNA
OFFERS INCREASED SENSITIVITY AND
IS THAT AN ADVANTAGE?
SO THIS IS AN EXAMPLE OF A TIME
COURSE OF WHAT HAPPENS TO CT DNA
BASED ON DISEASE BURDEN AND THE
PASSAGE OF TIME FROM THE
DIAGNOSIS.
YOU BEGIN WITH SAY A TUMOR THAT
HAS AND THIS IS OVER SIMPLIFIED
BUT THE IDEA IS TO DEMONSTRATE
YOU HAVE A VARIANT, MUTATION 1,
THEY CALL IT, A MARKER FOR THE
CANCER DISTINCT FROM A MARKER
PRESENT IN THE PATIENT'S OWN
GERM LINE DNA.
IT IS A DISTINGUISHING FEATURE
AND THE AMOUNT OF CT DNA
CONTAINING THIS MUTATION
INCREASES OVER TIME AND AT SOME
POINT THERE'S BE AN INTENT TO
CURE SURGICAL INTERVENTION SHOWN
BY THE ARROW AND THE AMOUNT OF
CT DNA DROPS VERY QUICKLY
BECAUSE YOU'VE REMOVED THE VAST
MAJORITY OF THE TUMOR.
BUT IF IT HASN'T ALL BEEN
REMOVED OR BEEN A METASTASIS
THAT WAS NOT REMOVED, OVER
MUTATION NUMBER ONE IT WILL
INCREASE AND WILL START TO
INCREASE AND ON TOP OF IT,
THERE'S GOING TO BE CLONAL
EVOLUTION OF THE CANCER.
SO THAT ANOTHER MUTATION,
MUTATION NUMBER 2 MAY START
RISING IN ITS LEVELS.
AND FURTHER ON DOWN THERE MAY BE
ADDITIONAL MUTATIONS REQUIRED BY
THE CANCER AS IT EVOLVES AND
DEVELOPS.
SO YOU END UP WITH HIGHER LEVELS
OF CT DNA WITH MULTIPLE
MUTATIONS PRESENT OVER TIME.
NOW, ONE OF THE USES FOR CT DNA?
THERE'S A COUPLE OF
POSSIBILITIES.
ONE SETTING IS TO SCREEN FOR
CANCER.
AND PHIL TOUCHED ON THIS AND I
THINK GAVE A CLEAR EXPLANATION
FOR HOW DIFFICULT IT IS TO USE
CT DNA TO SCREEN DE NOVO FOR
UNDETECTED CANCER IN A SETTING
OF A POPULATION.
IT COMES DOWN TO A KEY CONCEPT I
HOPE EVERYONE UNDERSTANDS OR BY
THE END OF THE SESSION FULLY
UNDERSTANDS AND THAT IS THE
DIFFERENCE BETWEEN FALSE
POSITIVE RATE OR SPECIFICITY OF
A TEST DOES NOT GIVE YOU A FIXED
PREDICTIVE VALUE OF THAT TEST.
IT DEPENDS ON THE PREVALENCE OF
THE DISORDER YOU'RE TRYING TO
DETECT IN THE POPULATION.
SO A GIVEN TEST WITH A GIVEN
SENSITIVITY AND GIVEN
SPECIFICITY WILL HAVE A
DIFFERENT POSITIVE PREDICTIVE
VALUE AND NEGATIVE PREDICTIVE
VALUE DEPENDING ON THE
PREVALENCE.
SO THE SETTING IN WHICH YOU'RE
TRYING TO APPLY ONE OF THESE
TESTS MATTERS A LOT.
SO SCREENING FOR CANCER, YOU CAN
LOOK FOR SINCE YOU ACTUALLY
DON'T KNOW WHAT SPECIFIC
VARIANCE OR CHANGES MIGHT BE
PRESENT IN A CANCER, YOU HAVEN'T
BIOPSIED OR REMOVED A PIECE OR
BEEN ABLE TO LOOK AT IT.
YOU GENERALLY TRY TO DEVELOP
SOME KIND OF A PANEL THAT
CONTAINS MOST THE COMMON
VARIANTS FOUND IN CANCER.
THE WELL KNOWN DRIVER MUTATIONS
FOUND IN THE CANCERS AND TRY TO
DETECT THEM IN AN INDIVIDUAL.
THEN YOU HAVE SAY A CANCER
DEVELOPS AND YOU DO A SURGICAL
INTERVENTION AND NOW YOU
ACTUALLY HAVE TISSUE.
SO YOU CAN SEQUENCE THAT TISSUE
AND AT THAT POINT ASK THE
QUESTION, FOLLOWING SURGICAL
INTERVENTION, WHAT'S THE RISK OF
RELAPSE?
CAN WE USE CT DNA TO DETECT
MINIMAL RESIDUAL DISEASE OR
MOLECULAR RESIDUAL DISEASE
FOLLOWING THE SURGICAL
INTERVENTION AND IF SO, IS THAT
PREDICTIVE OF THE POSSIBILITY
THAT THIS CANCER WILL ACTUALLY
RECUR?
IF IT DOES RECUR, WILL CT DNA
GIVE YOU AN EARLIER DETECTION OF
THAT RECURRENCE BEFORE ANY OTHER
IMAGING OR OTHER SORTS OF
MARKERS SO YOU HAVE GREATER LEAD
TIME TO BE ABLE TO DETECT IT?
AND THEN FINALLY YOU THEN
INSTITUTE SAY KEEM --
CHEMOTHERAPY CAN YOU FOLLOW THE
PROGRESSION USING CT DNA HOW
WELL IS THE CANCER RESPONDING TO
THE THERAPY YOU INSTITUTED?
SO THERE'S SCREENING, THERE'S
PROGNOSIS FOLLOWING INTENT TO
CURE SURGICAL INTERVENTION.
THERE'S DETECTING A REOCCURRENCE
IF A REOCCURRENCE DOES OCCUR AND
THERAPY RESPONSE.
OF COURSE, DEPENDING ON HOW YOU
DO THE CT DNA IF YOU'RE ACTUALLY
LOOKING FOR DRIVER MUTATIONS OR
OTHER TARGETS FOR TREATMENT OR
OTHER MARKERS FOR TREATMENT SUCH
AS SAY A TUMOR MORE LIKELY TO
RESPOND TO THE CHECKPOINT
THERAPY BECAUSE OF A HIGHER
TUMOR MUTATION BURDEN THEN YOU
ALSO HAVE THAT AS A FIFTH
PURPOSE, A FIFTH USE OF CT DNA.
THAT'S OUTLINED IN THE BULLET
POINT ON THE LEFT.
ONE OF THE BIG PROBLEMS RIGHT
NOW IS WE DON'T NO WHICH
PATIENTS HAVE BEEN CURED POST
THERAPY.
SURGERY CURES A PORTION OF
PATIENTS BUT HARD TO KNOW WHO'S
BEEN CURED.
MOST GO ON ADJUVANT THERAPY
THOUGH WE RECOGNIZE PROBABLY
DON'T NEED TO GO ON ADJUVANT
THERAPY AFTER SURGERY SO IT'D BE
GREAT TO HAVE A TOOL TO
DETERMINE WHO NEEDS TO BE
EXPOSED TO THE COMPLICATIONS AND
PROBLEMS OF ADJUVANT THERAPY AND
WHO DOESN'T.
SOME PATIENTS CAN BENEFIT FROM
ADJUVANT THERAPY.
WHO NEEDS IT?
AND WOULD PATIENTS DECLINE
ADJUVANT THERAPY NOT KNOWING
THEY'RE AT HIGHER RISK.
CAN CT DNA PROVIDE INSIGHT INTO
A BETTER CHOICE OF WHO NEEDS TO
GO POST SURGERY ON ADJUVANT
THERAPY AND SOME PATIENTS CANNOT
BE CURED BY THERAPY AND ADJUVANT
THERAPY SO WHO IS STILL AT HIGH
RISK AFTER SUCH TREATMENT AND
CAN WE FOLLOW THEM PERHAPS ALTER
THEIR THERAPY IF THERE'S
EVIDENCE THAT THEY ARE RECURRING
AND ARE RELAPSING AND THE
CURRENT REGIMENT IS NOT HOLDING
THEIR CANCER IN CHECK.
CAN WE FIND THAT EARLIER AT A
TIME WHEN PERHAPS IT MAY BE
EASIER TO TREAT?
AS I'LL TALK ABOUT LATER, THERE
ARE STILL MANY QUESTIONS AROUND
THE USE OF CT DNA IN THESE
VARIOUS SETTINGS THAT NEED TO BE
ADDRESSED.
SO HOW DO WE DETECT RELAPSE
CURRENTLY?
ONCE A TUMOR IS LARGE ENOUGH TO
BE DETECTED ON IMAGING.
AT THIS POINT THE TUMOR MAY HAVE
METASTASIZED.
THE CONCERN IS WE HAVE FOUND IT
TOO LATE AND TUMOR MARKERS, CEA
ARE SURROGATES FOR DISEASE.
THIS IS CEA THEY FREQUENTLY
DON'T CORRELATE WITH A TUMOR
VOLUME AND NOT THE BEST WAY TO
ASSESS THE STATUS OF THE PATIENT
UNDERGOING A RELAPSE.
SO WHAT CT DNA INVOLVES IS THE
LOOKING AT VARIANTS.
LOOKING AT VARIANTS IN THE TUMOR
THAT ARE NOT PRESENT IN THE
NORMAL DNA AND THEREFORE YOU CAN
IDENTIFY THE SUBSET, THE
FRACTION OF TOTAL CELL-FREE DNA
THAT IS DERIVED FROM THE TUMOR,
CT DNA.
AND THE SENSITIVITY OF SUCH
VARIANT-BASED TEST IS TO FIND BY
ITS ABILITY TO DETECT A
PARTICULAR VARIANT OR SET OF
VARIANTS EVEN WHEN PRESENT AT
VERY LOW AMOUNTS.
THERE ARE SOME CT DNAs THAT CAN
DETECT THE PRESENCE OF A
CIRCULATING TUMOR DNA DOWN TO
LEVELS AS LOW AS .08% OF THE
TOTAL ALLELE FREQUENCY.
THEY CAN BE VERY SENSITIVE.
AND CT DNA SURVEILLANCE CAN
DETECT RELAPSE AND POSITIVITY
CAN CAPTURE THE MAJORITY OF
RELAPSE EVENTS AHEAD OF STANDARD
CARE METHODS POTENTIALLY -- I
WANT TO STRESS, POTENTIALLY,
ALLOWING FOR EARLIER
INTERVENTION.
CT DNA MAY BE UNDETECTABLE
SHORTLY AFTER SURGERY OR SHORTLY
AFTER THERAPY AND LONGITUDINAL
TESTS INCREASES THE SENSITIVITY
OF THE ABILITY TO DETECT MINIMAL
RESIDUAL DISEASE AND THE FACT
THE TUMOR IS AT RISK FOR
RELAPSING.
CT DNA ALSO CAN BE A MEASURE OF
THERAPY RESPONSE.
THE ABSENCE OF CT DNA DURING
THERAPY COULD BE INDICATIVE TO
RESPONSE TO THERAPY IF IT HAS
PREVIOUSLY BEEN DETECTED.
IT WAS THERE BEFORE AND NOW HAD
THE PATIENT GO THROUGH THERAPY
AND IT'S NO LONGER THERE.
BUT CT DNA DYNAMICS ARE A
GROWING FIELD AND THERE NEEDS TO
BE A LOT MORE RESEARCH DONE TO
DOCUMENT AND UTILIZE CT DNA
TRAJECTORIES TO KNOW WHAT THEY
MEAN DURING AND FOLLOWING CANCER
TREATMENT.
THERE ARE SITUATIONS WHERE YOU
CAN EASILY IMAGINE THE CT DNA IS
NOT DETECTED BECAUSE IT'S
ACTUALLY LOOKING FOR VARIANTS
THAT PERHAPS ARE NO LONGER
PRESENT IN LARGE AMOUNTS IN THE
CANCER AND THERE MAY BE OTHER
VARIANTS THAT ARE NOT BEING USED
TO DETECT THE CT DNA WHICH NOW
ARE STARTING TO DEVELOP THESE
ADDITIONAL MUTATIONAL BURDENS
THAT'S OCCURRING SO THEREFORE
YOU ARE NOT LOOKING AT THE
VARIANTS MOST REPRESENTATIVE OF
THE CANCER AT ITS CURRENT STATE.
SO HERE'S A SUMMARY.
WITHIN CELL FREE DNA IN PATIENTS
WITH CANCER HAVE CT DNA CELLS
THAT SHED AND THERE ARE METHODS
THAT WILL DETECT MAGNITUDES LESS
AND CAN HELP INFORM RISK
STRATIFICATION FOR PATIENTS.
MANY STUDIES HAVE SHOWN CT DNA
DETECTION IS PROGNOSTIC FOR HOW
LIKELY A PERSON'S CANCER WILL
RECUR FOLLOWING INTENT TO CURE
THERAPY.
SURVEILLANCE.
THERE ARE MANY STUDIES THAT SHOW
CT DNA DETECTS RELAPSE AHEAD OF
STANDARD OF CARE METHODS
POTENTIALLY, ONCE AGAIN,
POTENTIALLY, ALLOWING FOR
EARLIER INTERVENTION AND IT
NEEDS TO BE PROVEN AND THERAPY
RESPONSE.
THE ABSENCE OF CT DNA DETECTED
DURING THERAPY MAY BE INDICATIVE
OF RESPONSE TO THERAPY IN A MORE
SENSITIVE WAY THAN SOME OF THE
STANDARD TOOLS USED FOR
MEASURING RESPONSE.
HERE'S AN EXAMPLE OF CT DNA USED
FOR RISK STRATIFICATION.
THIS IS AN AMALGAMATION ACROSS
MANY STUDIES THAT WAS SUMMARIZED
IN THE PAPER ACROSS 20 STUDIES,
PATIENTS DETECTED TO HAVE CT DNA
FOLLOWING CURATIVE SURGERY WERE
AT A HIGHER RISK OF RELAPSE THAN
THOSE NOT DETECTED TO HAVE CT
DNA.
IN THE GRAPH YOU CAN SEE IS
FREEDOM FROM PROGRESSION AS A
PERCENTAGE AND THE YELLOW LINE
ARE THE PATIENTS WHO HAD CT DNA
FOLLOWING SURGERY AND THE BLUE
LINE ARE PATIENTS WHO DID NOT
HAVE CT DNA DURING SURGERY --
AFTER SURGERY.
YOU CAN SEE THE VERY SIGNIFICANT
DIFFERENCE IN THE FREEDOM FROM
PROGRESSION INDICATING FOLLOWING
SURGERY IN THE STUDIES THE CT
DNA WAS STRONGLY PROGNOSTIC FOR
WHO IS LIKELY TO RELAPSE AND WHO
IS NOT.
I THINK IT'S INTERESTING TO SEE
THAT 20% OF THE PATIENTS WHO DID
NOT HAVE CT DNA DETECTED STILL
PROGRESSED.
IT WAS 80%.
BUT FAR FEWER THAN THE ONES WHO
HAD DETECTABLE CT DNA FOUR TO
SIX WEEKS AFTER SURGERY.
SO THERE'S A NUMBER OF DIFFERENT
TEST TYPES USED FOR A CT DNA.
THEY FULL TO TWO MAIN
CATEGORIES.
ONE IS WHAT ARE CALLED TUMOR
AGNOSTIC.
THESE ARE ASSAYS DESIGN TO FIND
COMMON ALTERATION IB CANCER AND
SET ON A PRE SET VARIANT PANEL.
THEY'RE LESS SENSITIVE BECAUSE
THEY'RE NOT REALLY TAILORED TO
THE SPECIFIC CANCER THE PATIENT
HAS BUT DON'T REQUIRE TUMOR
SEQUENCE.
SO THESE ASSAYS ARE DESIGN TO
FIND COMMON ALTERATIONS IN
CANCER.
THE OTHER IS TUMOR INFORMED.
YOU HAVE TO HAVE AT LEAST SOME
DNA REPRESENTATIVE OF THE
PATIENT'S TUMOR AND USE IT TO
IDENTIFY VARIANTS.
THERE ARE DIFFERENT ASSAYS -- I
DON'T WANT TO GO INTO ALL THE
DETAILS BUT GENERALLY INVOLVE
MULTIPLE VARIANTS THAT INCREASE
THE SENSITIVITY AND SPECIFICITY
AND CHARACTERISTIC OF THE
TUMOR'S DNA AND NOT THE
PATIENT'S OWN GERM LINE DNA AND
HAVE HIGHER SPECIFICITY BUT
REQUIRE UP FRONT TUMOR
SEQUENCING.
IN BOTH CASES THEY CAN BE USED
TO DETECT AND MONITOR
ALTERATIONS.
EACH HAS CERTAIN PROS AND CONS
IN TERMS OF HAVING TO HAVE A
PIECE OF TUMOR VERSUS A BETTER
SPECIFICITY FOR THE
TUMOR-INFORMED TYPE OF TEST.
FOR THE TUMOR-INFORMED, THE
ALTERATIONS COULD BE THE DRIVING
MUTATIONS THAT CAN THEN SERVE AS
THERAPEUTIC TARGETS OR TUMOR,
PASSENGER MUTATIONS CHOSEN TO
IMPROVE THE SENSITIVITY OF THE
TEST.
THERE ARE CERTAIN FORMS OF CT
DNA TESTING THAT ARE DESIGN TO
IMPROVE SENSITIVITY AND NOT
NECESSARILY THE DRIVER
MUTATIONS.
THEY WOULD NOT SERVE AS A
THERAPY SELECTION ASSAY BUT
SERVE AS A VERY SENSITIVE
MONITORING TEST FOR THE CANCER.
CT DNA DETECTION CAN BE IMPROVED
BY TARGETING MANY VARIANTS IN
THE TUMOR AS YOU INCREASE THE
NUMBER OF VARIANTS YOU CAN LOOK
AT WITH THE TUMOR-INFORMED PANEL
YOU CAN DETECT THESE AT A LOWER
LEVEL THAN TUMOR AGNOSTIC PANEL
WHICH REQUIRES MORE PRE SET
VARIANTS TO BE PRESENT FOR YOU
TO BE ABLE TO DETECT.
YOU ALSO NEED A LOT OF
SPECIFICITY.
THIS IS THE POINT THAT PHIL MADE
WELL.
ON LEFT IS THE GRAPH OF THE
AFFECT OF SPECIFICITY ON FALSE
POSITIVE RATES DURING
MONITORING.
SO HERE'S THE FALSE POSITIVE
RATE THE Y AXIS AROUND ON THE X
AXIS IS HOW MANY TIME POINTS OF
CT DNA OR MRD DETECTION YOU ARE
DOING?
YOU CAN SEE THE FALSE POSITIVE
RATE GOES UP QUITE A BIT WHEN
YOUR SPECIFICITY IS 97% BUT AS
IT INCREASES TO 99% OR 99. 9%
YOU ELIMINATE THE FALSE POSITIVE
RATE BY HAVING HIGH SPECIFICITY.
EVEN SO JUST WANT TO REMIND YOU
APPLYING A TEST WITH HIGH
SPECIFICITY TO A POPULATION THAT
HAS A VERY LOW PREVALENCE OF THE
DISEASE YOU'RE SCREENING FOR
STILL GENERATES A POSITIVE
PREDICTIVE VALUE LESS THAN 100%
AND WILL STILL FLAG PEOPLE WHO
ARE FALSE POSITIVES FOR THAT
TEST DESPITE HIGH SPECIFICITY.
WHICH IS WHY A LOT OF WHAT I'VE
BEEN TALKING ABOUT TODAY ARE
PEOPLE AT HIGH RISK OF RELAPSE
OF THEIR CANCER OR MINIMAL
RESIDUAL DISEASE FOLLOWING
THERAPY.
I'VE NOT BEEN TALKING ABOUT WHAT
HAPPENS WHEN YOU TAKE ONE OF
THESE STEPS AND APPLY IT TIE
POPULATION WHERE 1% OR LESS OF
PEOPLE IN THAT POPULATION HAVE A
CANCER YOU'LL DETECT.
WHAT ARE SOME LIMITATIONS?
WHAT ARE REASONS A CT DNA OR
MRNA MAY BE DETECTED?
NO RESIDUAL TUMOR CELLS WHICH
REMAIN, THAT IS GOOD OR IT MAY
BE A POOR SHEDDER.
DIFFERENT TYPES HAVE DIFFERENT
AMOUNTS AND IT MAY BE BELOW THE
DETECTION AND SOME HAVE MORE
SENSITIVITY THAN OTHERS AND THE
TUMOR-INFORMED ASSAY IS
CALIBRATED TO A SPECIFIC
MOLECULAR SIGNATURE AND
THEREFORE MAY NOT DETECT A NEW
CANCER WITH A DIFFERENT SET OF
MARKERS THAT AFFECTS THE
PATIENT.
THESE ARE ALL THINGS TO KEEP IN
MIND.
THE CT DNA PARTICULARLY THE
TUMOR-INFORMED DNA AND ALL THESE
TESTS WHETHER TUMOR-INFORMED OR
NOT ARE CUSTOMIZED TO PARTICULAR
CANCERS EITHER BY CHOOSING
PARTICULAR DRIVER MUTATIONS OR
DERIVING THEM FROM SEQUENCING OF
THE PATIENT'S OWN TUMOR.
AND THEY ARE NOT SOME SORT OF
TOTAL SOLUTION.
ALL CANCER'S DETECTABLE.
THEY DO NOT OPERATE THAT WAY AND
WE HAD TRACER X WITH PEOPLE WITH
TUMOR STAGE NON-CELL LUNG CANCER
AND A CT DNA TEST CUSTOMIZED TO
EACH PATIENT WITH TIME POINTS
AND THEN THE PATIENTS WERE
FOLLOWED WITH STANDARD OF CARE
IMAGING, ETCETERA, THOUGH IT
VARIED FROM SITES FROM WHICH THE
STUDY WAS DONE.
IT'S A NINE-YEAR PROSPECTIVE
STUDY TO FIND THE CLONAL
EVOLUTION OF EARLY STAGE NON
-SMALL LUNG CANCER AND THE
INITIAL FINDINGS ARE CT DNA
DETECTED BEFORE RELAPSE IN 37
OUT OF 45 CLINICAL RELAPSING
PATIENTS WITH A MEDIAN LEAD TIME
BEFORE CLINICAL EVIDENCE FOR
RELAPSE OF 151 DAYS.
NO CT DNA WAS DETECTED IN 190
OUT OF 199 PLASMA SAMPLES IN THE
23 PATIENT WHO'S DIDN'T RELAPSE
AND REINFORCES THE POINT PHIL
MADE WHICH IS NEGATIVE SCREENING
TESTS ARE VERY POWERFUL PIECES
OF INFORMATION.
IT COULD BE HAVE ALL IN PREDICT
OFFICER HIGH VALUES AND HAVING
NO CT DNA DETECTED IN 10 OUT OF
10 PATIENTS WITH SECOND PRIMARY
TUMORS AND REFLECTING THE TEST
IS SPECIFIC TO THE PRIMARY
TUMOR.
THAT'S IMPORTANT TO KEEP IN
MIND.
THERE'S ALSO OTHER LANDMARK
DATA, THE PRESENCE OF CT DNA
MOST CURATIVE IN PATIENTS WITH
METASTATIC COLORECTAL CANCER AND
THE CT DNA PREDICTED RISK OF
RELAPSE IN PATIENTS WITH EARLY
STAGE DISEASE, LONGITUDINAL
MONITORING AND SENSITIVE AND THE
LEAD TIME ACROSSIES VARIED WITH
MOST IT WAS A MEDIAN OF SIX
MONTHS OR GREATER LEAD TIME
COMPARED TO STANDARD OF CARE.
I THINK THE CT DNA WORKS FOR
FINDING RELAPSES EARLIER AND IT
BEGS THE QUESTION, DOES THAT
IMPROVE OUTCOMES?
THAT STILL NEEDS TO BE
DETERMINED.
THIS WAS CT DNA DETECTION MOST
INITIAL TRANS URETHRA DETECTION
AND ON THE LEFT IS PROBABILITY
OF DISEASE-FREE SURVIVAL.
ON THE TOP TWO, RED AND BLUE IS
THE CT DNA NEGATIVE.
AND IN THE BOTTOM IS THE CT DNA
POSITIVE.
THE DIFFERENCE BETWEEN THE TWO
LINES WERE THE PATIENTS WHO
RECEIVED ADJUVANT THERAPY.
YOU CAN SEE THE PATIENTS WHO
WERE CT DNA POSITIVE POST
SURGERY RECEIVED GREATER BENEFIT
FROM THE ADJUVANT THERAPY THAN
PATIENTS WHO WERE CT DNA
NEGATIVE.
THE PROBABILITY OF DISEASE
SURVIVAL WAS MUCH GREATER IF THE
CT DNA WAS NEGATIVE AND THE
PATIENTS REALLY DIDN'T SHOW
SIGNIFICANT RESPONSE TO ADJUVANT
THERAPY COMPARED TO THOSE WHO
RECEIVED THE ONE LOWER POSITIVE
AND ON THE RIGHT IS SIMILAR
EXCEPT THE PROS PROBABILITY OF
OVER ALL SURVIVAL.
AND SAME THING, CT DNA POSITIVE
HAD WORSE SURVIVAL AND A
POSITIVE RESPONSE COMPARED TO
THE CT DNA NEGATIVE PATIENTS IN
THE TOP TWO CURVES.
SO THERE'S KEY REMAINING
QUESTIONS AMONG OTHERS.
ONE IS CAN CT DNA BECOME
SPECIFIC ENOUGH TO ALLOW
DETECTION IN THE GENERAL
POPULATION?
I THINK PHIL MADE THE POINT AND
I'VE TRIED TO HAMMER IT HOME
BECAUSE I THINK IT'S A KEY POINT
TO MAKE HERE AND THAT IS YOU
NEED AN AMAZINGLY SPECIFIC TEST
IF YOU'RE GOING TO APPLY IT TO A
POPULATION WHERE THE PREVALENCE
IS LOW.
AND IF YOU END UP WITH A FALSE
POSITIVE YOU NOW HAVE CREATED A
GROUP OF PEOPLE IN WHOM IT'S GO
BE TO BE HARD TO FIND A POSITIVE
A LOT OF THEM ARE FALSE
POSITIVES AND VERY WORRIED
INDIVIDUALS WHEN IT WAS A FALSE
POSITIVE.
THIS IS OPEN FOR FURTHER
DEVELOPMENT.
HOWE ABOUT HIGH RISK PEOPLE?
HOW ABOUT THE PEOPLE WHO ARE
POSITIVE FOR BRCA1 AND 2
PATHOGENIC VARIANTS OR FOR ATM
PATHOGENIC VARIANTS WITH
PANCREATIC AND OVARIAN CANCERS.
THEY'RE HARD CANCERS TO LOOK
FOR.
THEY'RE PRIOR PROBABILITY IS NOT
THE SAME AS THE GENERAL
POPULATION.
THEY'RE AT GREATER RISK SO A
TEST WITH A GIVEN SPECIFICITY
WILL HAVE A HY POSITIVE
PREDICTIVE VALUE THAN IN THE
GENERAL POPULATION.
MIGHT WE HAVE A ROLE TO PLI IN
THOSE S PATIENTS?
IS VARIANT CT DNA THE BEST WAY
TO SCREEN OR AS DEVELOPED BY A
NUMBER OF INVESTIGATORS,
METHYLATION SIGNATURES ON THE CT
DNA FRAGMENTS?
WOULD THEY ADD TO THE
SPECIFICITY AND MIGHT I HELP
IDENTIFY THE TISSUE OF ORGAN?
THAT'S ONE THING BEING LOOKED
AT.
JUST THE PRESENCE OF CT DNA
THERE'LL GOING TO BE MORE
DEVELOPMENT LOOKING AT DNA AND
METHYLATION.
BIG QUESTION, DOES EARLIER
DETECTION OF RELAPSE IMPROVE
SURVIVAL S&P -- SURVIVAL?
I THINK THE CT DNA IN MANY
SITUATIONS IS CLEARLY
OUTPERFORMING CLINICAL RELAPSE
DOES IT MAKE A DIFFERENCE?
THAT NEEDS TO BE PROVEN.
WILL CT DNA BE EFFECTIVE IN THE
SHARED DECISION MAKING BETWEEN
THE ONCOLOGIST AND PATIENT.
SAY I'M NOT SURE IF POST SURGERY
THE PATIENT WILL ASK THE
SURGEON, DOC, DID YOU GET IT
ALL?
THE SURGEON IS LEFT WITH THE
SITUATION WHERE, I THINK I GOT
IT ALL.
I DON'T SEE EVIDENCE BUT MAYBE
JUST TO BE ON THE SAFE SIDE WE
SHOULD USE ADJUVANT CHEMOTHERAPY
BECAUSE I CAN'T BE SURE AND THE
CHANCE OF REOCCURRENCE IS
SIGNIFICANT IN THE CANCER.
WILL CT DNA BE ACCEPTED AND
PROVEN TO ALLOW PEOPLE WHO DON'T
NEED ADJUVANT CHEMOTHERAPY TO
SKIP IT AND THE PEOPLE WHO NEED
IT TO FEEL CONFIDENT, YES, THIS
IS THE RIGHT NEXT STEP.
FINALLY WE HAVE TO TALK ABOUT
THE COST OF CT DNA MONITORING?
IS IT JUSTIFIED JUST BY THE
IMPROVEMENT IN OUTCOMES?
THIS WILL ADD TO THE COST OF
TREATMENT.
THE ECONOMICS ARE IT'S PROBABLY
A SMALL ADDITION TO THE COST
OVER ALL COST OF CANCER
TREATMENT.
CANCER THERAPY IS VERY COSTLY.
THIS WILL ADD TO IT.
IF IT'S VALUABLE AND REALLY
SAVES SOME PEOPLE FROM HAVING
CERTAIN TREATMENTS OR DETECTS
CANCER EARLIER ENOUGH TO BE
SURGICALLY RECEPTABLE AND
TREATABLE IT'S PROVEN ITS VALUE.
THERE'S A RECENT PRIVATE
INSURANCE COMPANY THAT ISSUED A
STATEMENT THAT THE USE OF
PERSONALIZED TUMOR-INFORMED CT
DNA PLASMA-BASED TESTS ARE
CONSIDERED MEDICALLY NECESSARY
WHEN BOTH FOLLOWS ARE MET.
AN INDIVIDUAL STAGE 1 THROUGH 4
AFTER SURGICAL INTERVENTION WITH
CURATIVE INTENT IT IS JUSTIFIED
TO PROVIDE INFORMATION FOR ANY
OF THE FOLLOWING.
ADJUVANT FOR TARGETED THERAPY,
MONITORING FOR RELAPSE OF
PROGRESSION, INCLUDING BUT NOT
LIMITED THE USE OF IMMUNOTHERAPY
AND IMMUNE CHECKPOINT
INHIBITORS.
AS LONG AS YOU DON'T USE THE
TESTING MORE FREQUENTLY THAN THE
MONITORING GUIDELINES.
THIS IS A BIG STEP.
I BRING THIS HERE BECAUSE IN
MANY WAYS ADOPTION AS MUCH AS
PHIL POINTED OUT, SCIENCE AND
EVIDENCE ARE IMPORTANT BUT WHAT
ALLOWS ADOPTION TO OCCUR IS WHEN
HEALTH INSURERS AND MEDICARE
DECIDE THEY ARE GOING TO
REIMBURSE FOR THE TESTING.
THEY BASE THEIR JUDGMENT ON WHAT
WE HOPE IS GOING TO BE STRONG
EVIDENCE AND I BELIEVE PERMLY
THE MORE EVIDENCE NEEDS TO BE
DEVELOPED.
I BRING THIS UP BECAUSE THIS IS
COMING.
IT'S NOT SCIENCE FICTION.
IT'S HERE TODAY AND OVER THE
NEXT FEW YEARS WE'LL SEE A LOT
MORE DATA ON THE USES OF CT DNA
MONITORING FOR CANCER PATIENTS
AS WELL AS HERE MORE ABOUT
SCREENING IN PERHAPS PATIENT
WHO'S ARE AT GREATER RISK
BECAUSE THE GERM LINE MUTATIONS
AND BECAUSE PERHAPS EVEN IN THE
WHOLE POPULATION.
IF AND WHEN THIS TESTING BECOMES
SPECIFIC ENOUGH TO NOT HAVE
FALSE POSITIVE RATES THAT ARE
UNACCEPTABLE.
WITH THAT I'LL STOP.
THANK YOU FOR YOUR ATTENTION WE
CAN PROCEED WITH ANY QUESTIONS
YOU HAVE.
>>THANK YOU BOTH VERY MUCH FOR
VERY EXCITING AND PROVOCATIVE
PRESENTATIONS OF A FIELD THAT I
HOPE WILL HAVE MANY MORE
SESSIONS ON IN THE COMING YEARS
IN DEMYSTIFYING MEDICINE.
I THINK THIS IS A RAPIDLY
UNFOLDING SITUATION.
WE HAVE A WHOLE SERIES OF
QUESTIONS THAT FORMED DIFFERENT
CATEGORIES I WILL TRY TO PUT
TOGETHER.
PHILLIP, MANY QUESTIONERS ASKED
WHAT ARE WE DOING ABOUT THE
MISSISSIPPI DELTA?
IT WOULD APPLY TO ANY AREA OF AN
ENORMOUS HOT SPOT.
IT OBVIOUSLY SPILLS OVER INTO
SOCIO ECONOMIC, POLITICAL HEALTH
SYSTEMS BUT WHAT IF ANYTHING IS
BEING DONE REGARDING CERVICAL
CANCER OR ANY CANCER IN THE
MISSISSIPPI DELTA?
CAN YOU COMMENT ABOUT THAT?
>>CERTAINLY THE INTRAMURAL
PROGRAM I STARTED DOING RESEARCH
IN THE MISSISSIPPI DELTA AROUND
2005.
THE INTRAMURAL PROGRAM HAS
CONTINUED TO DEVELOP STRATEGIES
TO REACH WOMEN AND DO RESEARCH
ON HOW TO REACH WOMEN LIVING IN
THE MISSISSIPPI DELTA WITH
CERVICAL CANCER.
MORE BROADLY MORE CANCER CENTERS
ARE INCREASINGLY ASKED TO DO
WHAT THEY CALL COE WHICH IS
COMMUNITY OUTREACH AND
ENGAGEMENT.
AND SO PART IS REACHING UNDER
SERVED POPULATIONS AND GETTING
THEM ON STUDIES HOW TO REACH
THEM.
IT'S MANY LEVELS.
SOME OF THE THINGS WE'RE TRYING
TO SPONSOR IS USING TECHNOLOGIES
PARTICULARLY SOME TECHNOLOGIES
THAT CAME OUT OF COVID TO
DEMOCRATIZE AND CENTRALIZE
CANCER SCREENING.
FOR EXAMPLE, WE'VE BEEN
INTERESTED IN THE COVID ANTIGEN
TEST AND WHETHER THEY COULD BE
REPURPOSED FOR E-6 SEROLOGY FOR
HPV TESTING FOR HEAD AND NECK
CANCER?
CAN YOU USE THE COVID ANTIGEN
TECHNOLOGY TO SCREEN FOR PSA FOR
HIGH-RISK MEN AND MONITOR THEM
FOR THAT MATTER.
THERE ARE THINGS WE CAN DO AT
THE POINT OF CARE THAN WE'VE
EVER BEEN ABLE TO DO THEM.
WE'RE WORKING ON THAT ACTIVELY.
>>THERE'S BEEN SEVERAL
QUESTIONS THAT DEAL WITH THE
ISSUE OF A PATIENT WITH FAMILY
HISTORY AND IF YOU LOOK AT THE
SLIDE WITH THE DIFFERENT 20
COMPANY'S TECHNIQUES AND
PROBABLY THEY'RE ADVERTISING AND
MAYBE HYPES IT UP, WHAT'S THAT
PERSON SUPPOSED TO DO?
>>WHAT YOU HIGHLIGHT IS THE
THING THAT SCARES ME.
THINK ABOUT IT THIS WAY.
IF YOU WALK DOWN THE STREET AND
SAY LISTEN, I HAVE A TEST THAT
DETECTS 50 CANCERS -- IF YOU
DIDN'T KNOW ANY BETTER YOU'D BE
LIKE WHERE DID I SIGN UP BUT
JUST BECAUSE IT DETECTS CANCER
DIDN'T MEAN IT WILL GIVE YOU A
BENEFIT.
IT MAY FIND THE CANCER EARLIER
BUT MAY STILL KILL YOU.
THAT'S CALLED LEAD TIME
DETECTION OR BIAS.
RIGHT NOW WE CAN'T RECOMMEND ANY
OF THESE TESTS BECAUSE THEY
HAVEN'T BEEN PROVEN TO BENEFIT A
SINGLE PERSON.
THEY HAVEN'T PREVENTED A SINGLE
DEATH.
>>I WOULD SAY FOR SOMEONE WHO
HAS FAMILY HISTORY AND IS
CONCERNED ABOUT THEIR RISK,
FIRST AND FOREMOST THEY SHOULD
HAVE GERM LINE TESTING FOR
HEREDITARY CANCER SYNDROMES.
THAT'S THE FIRST STEP.
THEN IF THEY ARE NEGATIVE
THERE'S MORE DEVELOPING
INFORMATION ON POLY GENIC RISK
SCORES.
THERE'S A LITTLE BIT MORE OF A
PROBLEM IN THAT WE HAVE TO MAKE
SURE THEY'RE APPROPRIATE FOR
PEOPLE OF ALL ANCESTRIES.
RIGHT NOW MOST POLY GENIC RISK
SCORES HAVE BEEN DEVELOPED IN
PEOPLE OF EUROPEAN ANCESTRY AND
THIS IS AN ISSUE.
STEP ONE IS DO YOU HAVE A CHANGE
IN YOUR GERM LINE THAT REFLECTS
WHAT IT IS GOING ON IN YOUR
FAMILY.
BECAUSE THERE I THINK WE CAN
PREVENT CANCER IF PEOPLE HAVE
HIGH RISK VARIANTS THROUGH THE
USE OF PROPHYLACTIC SURGERY
PRIMARILY.
>>I THINK MY POINT ROBERT WAS
NOT TO USE THESE UNPROVEN TESTS
UNTIL WE HAVE EVIDENCE THAT THEY
WORK.
I'M GLAD YOU WHAT SAID ABOUT THE
FDA AND CMS.
I'M NOT ALLOWED IT TALK ABOUT
THEM BUT YOU ARE SO I'M GLAD YOU
SAID ALL THAT.
I AGREE UNDERSTANDING YOUR
RISK -- THAT'S A WHOLE TOPIC.
WE CAN DO A WHOLE SESSION ON
UNDERSTANDING YOUR RISK AND WHAT
IT MEANS AND WHAT IT DOESN'T
MEAN.
AND ONE OF THE CHALLENGES -- AND
I DIDN'T FULLY APPRECIATE THIS
EARLIER IN MY CAREER IS THAT IF
WE DON'T AS AN INDIVIDUAL
UNDERSTAND RISK PARTICULARLY
WELL AND I THINK COVID
HIGHLIGHTED THAT THE INDIVIDUAL
DOESN'T REALLY UNDERSTAND WHEN
YOU SAY YOU'RE AT A 10% RISK AND
FROM THEIR PERSPECTIVE WHAT IS
10% RISK MEAN?
YOU EITHER GET CANCER OR YOU
DON'T, RIGHT?
YOU'RE NOT A POPULATION.
YOU'RE A POPULATION OF ONE.
IT'S HARD TO TRANSLATE
POPULATION RISK TO WHAT
INDIVIDUALS ARE GOING TO DO AND
TO MAKE SURE THEY UNDERSTAND.
I AGREE FAMILY HISTORY AND THE
FIRST THING THAT SHOULD GO UP,
THE FLAG SHOULD GO UP.
YOU DO -- YOU LOOK FOR
PREDISPOSITION AND AFTER THAT IT
GETS MORE GEARED BUT HOPEFULLY
NEW TOOLS ARE COMING SO WE DON'T
HAVE TO REPLY ON PROPHYLACTIC AS
OUR ONLY MEANS.
I TOLD COLLEAGUES WE'LL LOOK
BACK 50 YEARS FROM NOW AND
SOMEBODY WILL SAY HOW DID YOU
DEAL WITH BRCA?
WE CUT OUT PARTS OF PEOPLE'S
BODIES AND THEY'LL SAY YOU GUYS
WERE BARBARIANS.
CURRENTLY THAT'S IT.
>>THERE'D BE PUBLIC INTEREST IN
CANCER AND THE ISSUES YOU BOTH
RAISED TODAY.
HAS IT HAD SOME BACKGROUND IN
TERMS OF OUR EDUCATIONAL SYSTEM
BOTH FOR YOUNG PEOPLE
PARTICULARLY ADOLESCENTS AND
THINKING ABOUT VACCINATION FOR
HUMAN PAPILLOMA VIRUS OR
ANYTHING ELSE IS THERE A WAY TO
EDUCATION PEOPLE SOMETHING ABOUT
CANCER BECAUSE PROBABLY THE VAST
MAJORITY OF PEOPLE ONLY KNOW IT
IN ITS MOST TERRIFYING ASPECTS.
>>I THINK THERE'S A TREMENDOUS
OPPORTUNITY TO EDUCATE WHAT YOU
CAN DO TO REDUCE YOUR RISK.
IT'S NOT JUST THE KIDS, IT'S THE
PARENTS, IT'S THE PROVIDERS.
WHAT IS AVAILABLE TO YOU AND
DEBUNKING SOME OF THE STORIES.
THE OTHER DAY SOMEBODY MENTIONED
TO ME THE OLD STORY THAT
VACCINATION CAUSES AUTISM WHICH
HAS BEEN DEBUNK NOW FOR FOUR
YEARS AND THERE'S BEEN A LEGAL
CASE FOR THE PERSON SUGGESTING
IT AND NOT PROVING OTHERWISE.
IT STILL LINGERS.
PEOPLE STILL WORRY ABOUT AUTISM
LINKED TO VACCINATION.
AND THERE'S JUST NO EVIDENCE FOR
THAT.
HAVE TO PROVIDE EDUCATION AND
RESOURCES AND THE OTHER PROBLEM
HERE IS DEALING WITH SOCIAL
MEDIA.
WE'RE IN A DIFFERENT WORLD AND
THE MANY SOURCES OF
MISINFORMATION.
HOW DO WE GUIDE THE PUBLIC TO GO
TO THE -- BACK IN OUR DAY YOU
WENT TO THE LIBRARY AND WENT TO
THE ENCYCLOPEDIA AND LEARN
WHATED
WHAT IS KNOWN AND HOW DO WE
CARVE OUT THE RIGHT INFORMATION
AND PROVIDE IT TO THE GENERAL
PUBLIC?
I DON'T HAVE AN ANSWER.
BUT MISINFORMATION IS AS
DANGEROUS AS -- WE'VE NEVER
EXPERIENCED THE LEVEL OF
MISINFORMATION THAT WE
EXPERIENCED NOW.
LOOK AT COVID.
THERE WAS A LOT OF
MISINFORMATION WHICH REALLY HURT
A LOT OF PEOPLE IN THE PROCESS.
>>I'D LIKE IT ADD A FEW THINGS.
THE AWARENESS OF AND CONCERN FOR
HEREDITY BREAST CANCER SYNDROMES
IS MUCH HIGHER THAN HEREDITARY
COLON CANCER THOUGH THE
HEREDITARY BREAST CANCER
SYNDROMES ARE APPROVXIMATELY SAE
PREVALENCE AND MEN TEND TO NOT
SEEK OUT MEDICAL CARE AND WE
HAVE THE ABILITY TO DO A BETTER
JOB WITH SCREENING AND WE HAVE
MAMMOGRAPHY AND WOMEN ARE MUCH
MORE AWARE IN EVERY GENETIC
STUDY I'VE EVER SEEN THE UPTAKE
OF WOMEN IS HIGHER THAN MEN.
WE HAVE A PARTICULAR CHALLENGE
IN EDUCATING MEN ABOUT THEIR
RISKS BUT THE ENTIRE POPULATION
POPULATION COULD USE MORE
EDUCATION.
>>BOB, IN ONE OF YOUR SLIDES
AND A LISTENER RAISED A QUESTION
I'LL BRING TO YOU, SURGERY
RESULTED IN A DRAMATIC FLOW OF
THE CIRCULATING DNA.
IT DIDN'T DISAPPEARED IT JUST
FELL TO A LOWER LEVEL.
BIOLOGICALLY IS THE CIRCULATING
DNA SUGGEST METASTASES ALREADY
OCCURRED?
>>THE ANSWER IS NO AND THE
REASON IS BECAUSE DEPENDING THE
THERAPY, THERE'S STILL DYING
CANCER CELLS AND THEY'RE
RELIEVING CT DNA AND WHETHER IT
CONSTITUTES AN ACTIVE METASTASIS
THAT WILL LEAD TO RELAPSE IS NOT
CLEAR.
THAT'S WHY SERIAL MONITORING IS
IMPORTANT.
>>IS THERE A CIRCADIAN RHYTHM
TO CIRCULATING DNA?
>>THAT'S INTERESTING.
I DON'T KNOW THE ANSWER TO THAT.
IT'S CLEARED VERY RAPIDLY WHEN
THE SOURCE OF IT IS REMOVED IT'S
CLEARED RAPIDLY.
WE KNOW THAT BETTER FROM FETAL
CELL-FREE DNA WHERE YOU CAN
REMOVE THE FETAL CONTRIBUTION TO
THE SERUM BY DELIVERING AND WHEN
THE BABY'S DELIVERED AND THE
PLACENTA IS OUT SINCE THE TROPE
OBLAST IS THE MAIN SOURCE IT
DROPS PRECIPITOUSLY.
IF IT HANGS AROUND IT'S BECAUSE
THERE'S A SOURCE BUT I DON'T
KNOW ABOUT CIRCADIAN RHYTHM.
PHIL, DO YOU KNOW ANYTHING ABOUT
THAT?
NO.
>>THERE'S A QUESTION
CIRCULATING TUMOR DNA STUDIES IN
ANIMALS, IS IT POSSIBLE TO USE
THAT AS A WAY OF EVALUATING
FACTOR ACCELERATE ASSUMER GROWTH
OR MAYBE NOT TUMOR GROWTH BUT
TOUMER RELEASE OF CIRCULATING
DNA THAT REGULATE THE TUMOR
AUTONOMOUS TO SOME DEGREE BUT
INTERACTING WITH FACTORS AND ALL
OF THAT.
IS THAT A REASONABLE RESEARCH TO
PURSUE?
>>I THINK IT WOULD BE VERY
VALUABLE BECAUSE THE AMOUNT OF
CIRCULATING TUMOR DNA DIFFERS
FROM THE TUMOR TYPE AND FROM THE
MASS OF THE TUMOR BUT ALSO THERE
ARE OTHER BIOLOGICAL FACTORS
ABOUT THE TUMOR PROBABLY THINGS
INVOLVED WITH HOW GOOD IS THE
BLOOD SUPPLY AND HOW ACTIVE IS
IT AND HOW MUCH TURNOVER AND
IMMUNE RESPONSE AND LYMPHOCYTE
INFILTRATION THERE IS IN THE
TUMOR.
ALL THOSE WILL PROBABLY A PLAY A
ROLE AND ANIMALS WOULD BE IDEAL
AS A WAY OF BEING ABLE TO
MANIPULATE THE HOST FACTORS IN
WAYS WE CAN'T IN HUMANS.
>>I WOULD SAY THAT'S AN
IMPORTANT ENDEAVOR BECAUSE WE
DON'T FOR ALL WE DO KNOW ABOUT
CIRCULATING DNA THERE'S A LOT WE
DON'T KNOW.
ALSO WE WON'T BE ABLE TO ANSWER
ALL THE QUESTIONS IN ANIMAL
MODELS BECAUSE WE CAN'T MIMIC
THE HETEROGENEITY OF HUMANS IN
THE PROCESS.
IT HAS TO BE A COMBINED ANIMAL
MODEL AND HUMAN MODEL, IF YOU
WILL, GETTING BLOOD FROM CANCER
PATIENTS AND SAYING WHY DOES
THIS PATIENT HAVE MORE OF THIS
OR LESS OF THAT.
WHAT ARE THEIR CHARACTERISTICS
WE HAVE TO DO SORT OF A
MOLECULAR EPIDEMIOLOGIC ANALYSIS
ON HUMANS TO UNDERSTAND THE
STAGE AND THE TUMOR AND THE
MOLECULAR PROFILE AND THE PERSON
THEMSELVES CONTRIBUTE TO THE
PROFILE?
>>THE STRENGTH OF THE HUMAN
STUDIES ARE PEOPLE ARE
HETEROGENEOUS THE PROBLEM IS
THAT PEOPLE ARE HETEROGENEOUS.
>>EXACTLY.
THERE'S SEVERAL ISSUES WITH
REPORTS AND I'M LOOKING AT EXTRA
CELLULAR VESICLES SECRETED FROM
TISSUES AND THEY CONTAINED
UNEXPECTED THINGS, I WOULD
THINK.
IS DNA ONE OF THE THINGS THAT IS
PRESENT?
TUMORS THROUGH THEIR VESICLE
RELEASE --
>>DNA AND RNA.
DID YOU WANT TO COMMENT ON THIS?
>>EXTRA CELLULAR VESICLES IS
THE NEW FRONTIER.
THERE'S SO MUCH -- AND THE CELLS
USE THAT TO COMMUNICATE IN WAYS
WE STILL WE'RE AT THE NICE
UNDERSTANDING OF THAT.
AND PROBABLY ALSO INFLUENCES
IMMUNE RESPONSE AND OTHER
BIOLOGICAL FACTOR AND MANY
COMPANIES ARE NOW SPRINGING UP
TO TAKE ADVANTAGE OF EXTRA
CELLULAR VESICLES FROM
EVERYTHING FROM DRUG DELIVERY --
IT'S A FIELD COMING INTO ITS OWN
NOW.
BUT I WOULD SUSPECT THERE'S A
TREMENDOUS AMOUNT OF BASIC
UNDERSTANDING STILL MISSING.
>>I THINK IT'S LIKELY OPPOSED
TO THE CIRCULATING TUMOR DNA
PART OF THE CELL-FREE DNA THAT'S
A REFLECTION OF CELL AND RELEASE
OF DNA FRAGMENTS.
THE EXOSOME THAT'S LIVING CELLS.
I THINK IT WILL SHED A DIFFERENT
LIGHT ON THE BIOLOGY.
>>IT'S GOING TO TELL US MORE
ABOUT HOW THE TUMOR MANIPULATES
THE LOCAL MICROENVIRONMENT IN
WAYS THAT WILL TAKE PROBABLY
SOME NEW TECHNOLOGIES TO REALLY
BE ABLE TO STUDY THAT BUT
CLEARLY WHEN JIM ANDERSON'S WORK
AND OTHERS CAME OUT ON
IMMUNOTHERAPY AND THE ROLE OF
IMMUNE SYSTEM, IT'S VERY CLEAR
THIS WAS HAPPENING EARLY IN C
CAR -- CARCINOGENESIS AND IT'S
PART OF THE STRATEGY OF THE
TUMOR TO MANIPULATE THE
ENVIRONMENT FOR ITS OWN
EVOLUTIONARY ADVANTAGE.
>>WE HAVE SEVERAL FOLKS
INTERESTED IN KNOWING WHERE DOES
THE CIRCULATING TUMOR DNA NO.
GO?
-- TUMOR DNA GO?
HOW IS IT DEGRADED OR IS THERE A
CELL SPECIFICITY?
DO WE KNOW ABOUT ITS
DEGRADATION?
IT'S REMOEFL?
-- REMOVAL.
IT'S REMOVED PRETTY RAPIDLY IN
THE DNA SYSTEM.
>>IT'S PROBABLY JUST CLEANING
HOUSE.
[AUDIO DIGITIZING]
THERE'S NO CIRCULATING TUMOR DNA
IN 10 OF 10 RECURRENCES IMPLYING
THEY'RE NOW EXPRESSING DIFFERENT
GENES.
IS THAT THE CORRECT
INTERPRETATION.
>>NOT GENES BUT VARIANTS.
THEY REPRESENT NEW PRIMARIES.
THE PROFILE BEING USED TO
IDENTIFY THE ORIGINAL CANCER AND
THE PROFILE OF VARIANTS BEING
USED TO IDENTIFY THE ORIGINAL
CANCER DON'T APPLY, DON'T WORK
IN THESE NEW PRIMARIES.
>>ONE THING WORTH MENTIONING TO
THE AUDIENCE IS THAT 20% OF NEW
CANCERS, NEW PRIMARIES OCCUR IN
CANCER SURVIVORS.
SO THIS IS A HIGH RISK
POPULATION NOT JUST FOR THE
RECURRENCE BUT CANCER BURDEN
RELATED TO NEW PRIMARIES.
>>DIFFERENT CANCERS HAVE
DIFFERENT DISTRIBUTION AND RISK
FACTORS IN DIFFERENT PARTS OF
THE WORLD AND DIFFER AMONG
SEXES, SOCIO ECONOMIC DISPARITY
HOW DO YOU QUANTIFY THE FACTORS
WHEN YOU'RE TRYING TO DEVELOP A
PROGRAM THAT ULTIMATELY WILL
AFFECT HEALTH CARE?
>>SO YOU'RE TOUCHING ON AND I
THINK BOB MENTIONED THIS TOO.
YOU'RE TOUCHING ON INCLUSIVITY
ON THE RESEARCH WE DO.
IF YOU WANT TO REFLECT EVERYBODY
YOU HAVE TO INCLUDE EVERYBODY
OTHERWISE YOU GET THE KINDS OF
BIASES WHERE WE HAD PRIMARILY OF
EUROPEAN DECENT INVOLVED IN THE
RESEARCH AND CONS CONSEQUENTLY
IT WORKED FOR EUROPEANS BUT
WE'RE NOT ALL WHITE COMING BACK
TO THE HETEROGENEITY AND COMING
BACK TO THE HPV VACCINE WHICH
WORKED SO WELL.
WE'VE BEEN DOING EPIDEMIOLOGICAL
STUDIES BUT THE VACCINES OF
FIRST GENERATION THAT TARGET 16
AND 18 AND THE NEXT GENERATION
TARGETS SEVEN CARCINOGENIC TYPE
AND IN THE WORLD IT CAUSES 2% OF
CERVICAL CANCER.
IT'S IMPORTANT BUT NOT ONE OF
THE BIG PLAYERS.
OF PEOPLE OF AFRICAN DESCENT AND
SOME WORK WELL BETWEEN
CAUCASIANS AND PEOPLE OF AFRICAN
AMERICAN DESCENT.
EVERYBODY'S GOT TO BE INVOLVED
TO WORK WELL ON EVERYBODY AND
COMES TO ANOTHER POINT POINT AND
SOMETHING THE NCI STRUGGLES WITH
WHICH IS GETTING PARTICIPATION
BY THE PUBLIC IN THE TRIALS AND
RESEARCH.
IT'S TEAM WORK.
PEOPLE HAVE TO BE WILLING TO
PARTICIPATE TO MAKE SURE WE MAKE
SOMETHING THAT WORKS FOR
EVERYBODY.
THAT'S WHAT WE REALLY WANT.
IT'S GOING TO TAKE A TEAM
EFFORT.
WE HAVE TO BE MORE SENSITIVE AND
AWARE AND THE PUBLIC HAS TO BE
WILLING TO SAY I'M GOING GIVE MY
SPECIMENS AND PARTICIPATE IN THE
TRIAL.
IN ORDER FOR US TO BE MORE
SUCCESSFUL AND MORE INCLUSIVE IN
THE DEVELOPMENT OF NEW
TECHNOLOGIES.
>>IF I CAN CLIMB UP ON MY
SOAPBOX FOR A BRIEF PERIOD.
THIS IS ONE OF THE MOST
CONTENTIOUS ISSUES FACING US
TODAY, THAT IS THE FOUND AND
CONFUSION AROUND THE TERM LACE
AND ETHNIC AND ANCESTRAL ORIGIN.
AND THE EXTENT TO WHICH THAT
REFLECTS AT ALL DIFFERENCES IN
GENETIC MAKEUP VERSUS HOW MUCH
IT REFLECTS DIFFERENCES IN
SOCIETAL AND ENVIRONMENTAL
EXPOSURES, CULTURAL DIFFERENCES,
WHATEVER.
THOSE TWO HAVE BEEN CONFOUNDED
TO OUR DETRIMENT FOR DECADES.
WE HAVE TO FINALLY GET OVER THIS
AND REALLY START TO IDENTIFY
WHAT ARE THE FACTORS.
THE HPV SUBTYPE THAT'S MORE
COMMON IN PEOPLE IN AFRICA, WHY?
IS THAT A COFOUNDER AFFECT?
>>A CO-EVOLUTION CASE IN THAT
CASE.
WHY DO AFRICAN AMERICAN
INCIDENTS OF THE APOLL A1 IN
KIDNEY DISEASE?
WE NEED TO STOP IN FERRING A
GENETIC DIFFERENCE BECAUSE
PEOPLE ARE AT DIFFERENT
ANCESTRAL BACKGROUNDS AND AT THE
SAME TIME WE HAVE TO STOP
ASSUMING THAT THE ONLY REASON
THERE'S A DIFFERENCE IN RESPONSE
IN PEOPLE OF DIFFERENT
BACKGROUNDS AND SOCIETAL AND
ENVIRONMENTAL EXPOSURES.
IT'S BOTH.
UP FIGURING OUT THE CONTRIBUTION
OF ONE OVER THE OTHER, THE
RELATIVE CONTRIBUTION IS THE
SCIENCE.
WE SHOULD FIGURE THAT OUT.
I'M DONE WITH MY SOAPBOX.
>>I'LL GET BACK ON IT.
UNDERLYING A LOT OF THIS IS JUST
POVERTY ACCESS TO CARE AND I WAS
TELLING STUDENTS, POVERTY KILLS.
YOU CAN'T UNDERESTIMATE THE
IMPORTANCE OF POVERTY AND SOCIAL
DETERMINATES OF HEALTH IN THE
PROCESS OF DEVELOPING NEW
TECHNOLOGY AND PARTICIPATING IN
THE RESEARCH THAT INFORMS THAT
DEVELOPMENT.
PRESIDENT A REAL CHALLENGE TO
OVERCOME THE BIASES IN THE
SYSTEM AND WE HAVE TO OPEN OUR
EYES TO IT AND OPEN OUR HEARTS,
IN A WAY, IF YOU WILL, TO TAKING
THIS ON IN A GLOBAL WAY RATHER
THAN WITH MYOPIA
>>IF YOU WANT TO GO IN THIS
AREA, HOW DO EITHER OF YOU
PROPOSE WHAT ARE YOUR THOUGHTS
ABOUT CROSSING THE BRIDGE YOU'VE
BEEN TALKING ABOUT FROM THE
STANDPOINT OF MAJOR CHANGES IN
THE SOCIO ECONOMICS, POLITICS
AND THE HEALTH SYSTEMS?
I MEAN EVERYONE TALKS ABOUT THIS
BUT HOW DO YOU VISUALIZE THIS
MAY ACTUALLY HAPPEN AND SPIN OFF
INTO THE RESEARCH AND CLINICAL
AREAS THAT YOU INVESTIGATE?
>>I'LL TAKE OF MAKE A COMMENT.
I'D DRAW THE ANALOGY YOU HAVE,
WIN, FOR DEMYSTIFYING AND PEOPLE
WHO DO RESEARCH AND THE TWO
GROUPS NEED TO MEET AND THERE
ARE SILOS NOW BETWEEN FOLKS
INTERESTED IN THE GENETIC
DETERMINATES OF HEALTH AND
PEOPLE INTERESTED IN THE SOCIAL
DETERMINATES OF HEALTH.
THEY'RE BOTH IMPORTANT.
THOSE ARE TWO GROUPS THAT IN MY
EXPERIENCE ARE NOT TALKING TO
EACH OTHER AS MUCH AS THEY
SHOULD BE THAT'S ONE OF THE
AREAS I THINK IS IMPORTANT TO
BRIDGE THE TWO FIELD THEY'RE
VERY IMPORTANT AND TO BE BLUNT I
THINK THERE'S SOME ANTAGONISM
BETWEEN THE TWO GROUPS.
NOT JUST LACK OF UNDERSTANDING
BUT ACTUAL ANTAGONISM.
THAT NEEDS TO BE OVERCOME
BECAUSE I DON'T THINK MAKE
PROGRESS WITHOUT IT.
>>IT'S LIKE THE HIV SCENARIO OF
WHEN THE RESEARCH COMMUNITY AND
THE PUBLIC FINALLY GOT THE
POLITICAL SYSTEM TO RESPOND.
WE ALL KNOW THE HISTORY WE HAVE
ANOTHER COUPLE GENERAL QUESTIONS
FOR YOU.
ONE IS WHAT IS THE CONTRIBUTION,
IF ANYTHING OF THE GWAS STUDY TO
THESE QUESTIONS OF PREDICTION,
DETECTION OF CANCER?
>>WELL, FOR DETECTION OF CANCER
I DON'T THINK IT HAS MUCH
CONTRIBUTION AT THIS POINT.
THE MAIN VALUE OF THE GWAS IS TO
BE ABLE TO GENERATE A POLY GENIC
RISK SCORE WHICH HELPS YOU
DETERMINE PEOPLE'S RISK FOR
DEVELOPING CERTAIN CANCERS.
THERE ARE POLY GENIC RISK SCORES
INVOLVED IN MANY COMMON
DISEASES, BREAST CANCER AND
PROSTATE CANCER BEING TWO OF THE
CANCERS MOST COMMONLY DONE.
THEY ARE STARTING TO BE USED
CLINICALLY MY HESITATION WITH
THEM IS MAKING SURE THEY'RE
APPLICABLE TO PEOPLE OF ALL
BACKGROUNDS AND MIXED
BACKGROUNDS BECAUSE MIXED
BACKGROUNDS IS VERY COMMON.
SO FIGURING OUT HOW TO ADAPT AND
THE OTHER ASPECT IS GWAS MAY
HIGHLIGHT THE CONTRIBUTION OF
CERTAIN GENES OR REGIONS IF
WE'RE SMART ENOUGH WE CAN DEDUCE
THE MECHANISTIC RELATIONSHIP
BETWEEN THE CHANGES AND
DEVELOPMENT OF CANCER AND
THEREFORE MIGHT POSSIBLY BE USED
FOR FINDING NEW THERAPIES, NEW
TARGETS, NEW TREATMENTS.
GWAS IN ITS PUREST FORM IS
SIMPLY STATISTICALLY SIGNIFICANT
ASSOCIATION BETWEEN VARIANTS,
CHANGES IN THE GENE DNA AND A
PARTICULARLY CLINICAL PHENOTYPE.
BUT WHEN YOU DIG IN YOU CAN
START TO INFER IMPORTANT
MECHANISTIC RELATIONSHIPS AND
THAT I THINK CAN HELP WITH
UNDERSTANDING THE BIOLOGY IN
THESE CANCERS.
SO THAT I GUESS IS WHERE I SEE
THE ROLE OF GWAS.
>>LET ME ADD TO THAT IN SAYING
THAT UNDERSTANDING THE BIOLOGY
OF CANCER AND CARCINOGENESIS IS
CRITICAL TO THE NCI'S COMMITMENT
TO DEVELOPING NEW STRATEGIES.
IF WE UNDERSTAND EARLIER AND
EARLIER WHAT GOES WRONG WE CAN
POTENTIALLY TARGET IT IN A
NUMBER OF WAYS.
AT LATEST FOR HIGH- RISK
POPULATIONS AND MAYBE EVENTUALLY
FOR THE GENERAL POPULATION.
SO WE WORK CLOSELY WITH THE
DIVISION OF CANCER BIOLOGY ON A
NUMBER OF INITIATIVES TO
ELUCIDATE THE EARLY PROCESSES
WHERE IT'S CLEARLY GONE OFF
TRACK HERE AND HOW DO WE
REFERRING THAT UNDERSTANDING.
I THINK THE POLY GENIC RISK
SCORE IS AN INTERESTING TOPIC.
WE'VE BEEN TALKING ABOUT IT 20
YEARS.
THERE ARE SOME ACADEMIC CENTERS
THAT USE IT BUT AS BOB POINTED
OUT IT'S HARD TO KNOW WHETHER
IT'S REPRESENTATIVE AND
VALIDATED.
THEY'VE DONE IT INTERNALLY BUT
WHAT'S THE OUTCOME?
WE NEED IN MY OPINION A
DEMONSTRATION WHEN WE HAVE A
POLY GENIC RISK SCORE THAT'S
REPRESENTATIVE AND I KNOW SOME
GROUPS HAVE WORKED ON PROSTATE
AND IN PARTICULARLY OF AFRICAN
AMERICANS BECAUSE OF THE HIGHER
RISK OF MORTALITY IN THE GROUP
BUT WE NEED TO PUT IT TO THE
TEST.
CAN WE USE RISK SCORES AND IT
MAY INCLUDE POLY GENIC RISK
SCORES NORT TO IMPROVE
SCREENING?
THE EXAMPLE I ALWAYS GIVE IS FOR
MORE THAN TWO DECADES DR. MITCH
GAIL IN THE INTRAMURAL PROGRAM
HAD THE GAIL MODEL.
WE NEVER USED THAT TO INFORM WHO
SHOULD GET SCREENING AT WHAT
AGE.
SUBSEQUENTLY LY AND NOW WE CAN
BETTER.
THAT WAS A LARGE MARK PAPER BUT
WE NEVER APPLIED THAT.
WHAT HAPPENED IS WE APPLIED JUST
AGE.
WHAT'S THE PROBLEM WITH AGE?
A NEW STUDY OR DATA COMES OUT
THAT SHOWS A CERTAIN RISK IN A
CERTAIN GROUP.
THE GUIDELINES CHANGE FOR BREAST
CANCER, START AT 50, START AT
45, DO EVERY YEAR, DO EVERY TWO
YEARS.
I'M TELLING YOU NOW, THERE'S SIX
OR SEVEN GUIDELINE GROUPS IN THE
UNITED STATES THAT HAVE
RECOMMENDATIONS NOT EXACTLY THE
SAME.
SO WOMEN ARE CONFUSED WHAT KIND
OF BREAST CANCER SCREENING THEY
SHOULD GET AT WHAT AGE.
WE'VE DONE OURSELVES A
DISSERVICE.
WE CAN DO BETTER.
WE CAN TAKE THE DATA.
AGE IS NOT A GREAT PROXY FOR
CANCER RISK.
IT'S AN IMPORTANT RISK FACTOR
BUT IT'S NOT EVERYTHING WE KNOW.
WE'RE NOT APPLYING ALL WE KNOW
ABOUT BREAST CANCER TO IMPROVE
IT AND I THINK NOW'S THE TIME
PARTICULARLY FOR PROSTATE AND
IT'S A HIGH-BURDEN CANCER WE CAN
APPLY OUR KNOWLEDGE.
ALL THIS INVESTMENT INTO DOING
BETTER CANCER SCREENING.
THAT'S FOR THESE TWO DISEASES.
>>THERE ARE AT LEAST TWO VERY
LARGE NHGRI AND NIH FUNDED
PROGRAMS HERE LOOKING AT PRS
SCORES.
ONE IS CALLED PRIMID AND THE
EMERGE 4.
I'M HOPING OVER THE NEXT FOUR
YEARS WE'RE GOING TO HAVE
MULTI-ANCESTRY RELIABLE
DEPENDABLE PRS SCORES WE CAN
USE.
THAT WOULD BE MY HOPE.
IT'S A GREAT GROUP OF
INVESTIGATORS.
>>WELL, OUR TIME RAN OUT THE
BASIC QUESTION IS FROM THE ROLE
OF THE INSURANCE COMPANY AND IN
OUR SOCIETY WHERE THERE'S A SO
MANY DIFFERENT INSURANCE
COMPANIES AND THEY HAVE THEIR
OWN RULES, REGULATIONS AND
EVERYTHING ELSE, SOME SUPPORT
PET SCANS, SOME DON'T, SOME
SUPPORT APPARENTLY ACCORDING TO
THE PERSON WHO SUBMITTED THE
QUESTION, ACTUALLY ENCOURAGE
TUMOR DNA ANALYSIS.
IT REMINDS ME OF MANY YEARS AGO,
BILL SCHWARTS THE CHAIRMAN OF
MEDICINE AT TUFTS UNIVERSITY AND
HE WAS THE ONE WHO COINED THE
TERM RATIONED CARE BECAUSE HE
SPENT A YEAR AT THE RAND
CORPORATION AND TOLD ME ONE DAY,
HE SAID THE MOST INCREDIBLE
THING COULD HAPPEN IS IF SOMEONE
CAME UP WITH A FOOL-PROOF
DIAGNOSTIC TEST FOR CANCER AND
IT HAD TO BE TAKEN EVERY DAY IT
WOULD BREAK THE BANK.
I'M WONDERING WOULD YOU WANT TO
MAKE SOME COMMENTS ABOUT WHO
PAYS FOR THIS?
HOW ARE WE GOING DO IT IN A
PROFIT-DRIVEN SOCIETY AND HOW
FREE ARE THE INSURANCE COMPANIES
OR SHOULD THEY BE?
CAN THE NCI MAKE A
RECOMMENDATION EVERYBODY HAS TO
GO ALONG WITH?
DON'T THINK SO.
>>THE NCI DOESN'T MAKE POLICY
OR GUIDELINES.
I WILL SAY DESPITE THE EFFORT TO
DO COST-EFFECTIVENESS ANALYSIS
FOR SCREENING AND INTERVENTIONS
THEY'RE LARGELY IGNORED AND THE
CONSEQUENCE IS HIDDEN BY OUR
HEALTH CARE SYSTEM AND THE WAY
YOU RECEIVE REIMBURSEMENT.
YOU DON'T DIRECTLY SEE THE EXTRA
PROCEDURE YOU'VE DONE
EVENTUALLIES IN -- EVENTUALLY
EXACERBATES HIGHER PREMIUMS
GOING FORWARD.
IF YOU LOOK AT HOW OTHER
EUROPEAN COUNTRIES AND AUSTRALIA
DO IT, CERTAINLY FOR PREVENTIVE
SERVICE IT'S A UNIFIED PROCESS
AND UNIVERSAL HEALTH CARE
SYSTEM.
I CERTAINLY WOULD LOVE TO SEE
UNIVERSAL HEALTH CARE SYSTEM FOR
PREVENTIVE SERVICES WHERE IT'S
ABOUT POPULATION AND NUMBERS AND
NOT ABOUT PERSONALIZED CARE, PER
SE.
IT'S COMPLICATED.
YOU'RE STEALING FROM ONE PLACE
AND STEALING FROM PETER TO PAY
PAUL.
IT'S A REAL THING.
AT SOME POINT IT'S GOING TO
BREAK THE BANK BECAUSE WE HAVE
THE HIGHEST HEALTH CARE
EXPENDITURE PER CAPITA OF ANY
COUNTRY IN THE WORLD .
AND WE ARE LIKE 50th IN THE
WORLD IN OUTCOMES.
AND LIFE EXPECTANCY.
SO SOMETHING'S GOT TO GIVE.
>>BOB, DO YOU WANT TO MAKE A
FINAL --
>>YOU TALKED TO ONE PRIVATE
INSURANCE POLICY MAKER YOU
TALKED TO ONE INSURER.
IT'S ALL OVER THE PLACE.
AND WHETHER THEY USE EVIDENCE
BASE OR PRESSURE FROM
EMPLOYERS -- SOMETHING TO KEEP
IN MIND WHEN A BUNCH OF
EMPLOYEES FEEL SOMETHING SHOULD
BE COVERED AND THEY AGITATE WITH
THEIR EMPLOYER, THE EMPLOYER IS
ACTUALLY THE PERSON WHO
EMPLOYEES THE INSURANCE
COMPANIES.
THEY HAVE TREMENDOUS SWAY FOR
THE PRIVATE HEALTH INSURERS.
I THINK CMS AND MEDICARE HAS A
SOMEWHAT MORE RATIONAL SYSTEM
AND SOME INSURERS FOLLOW THE
LEAD WHAT MOLD EX.
IT'S MOLD-DX.
IT'S A SYSTEM.
AND THE PRESSURES THAT COME TO
BEAR ARE IRRATIONAL.
AMONG THE OTHER THINGS PEOPLE
CHANGE INSURANCE COMPANIES
OFTEN.
SO FOR INSURANCE COMPANY TO PAY
FOR SOMETHING WHICH IS GOING TO
PREVENT A MUCH MORE EXPENSIVE
PROBLEM FOR THIS PATIENT FIVE
YEARS OR 10 YEARS DOWN THE LINE
THAT'S NOT SOMETHING THEY'RE
THINKING ABOUT.
BECAUSE THAT'S NOT GOING TO BE
MY INSURED PERSON 5 OR 10 YEARS
FROM NOW.
IT'S GOING TO BE SOME OTHER
INSURANCE COMPANY'S PROBLEM.
THERE'S LOTS OF REASONS AND I
PERSONALLY AM VERY MUCH IN FAVOR
OF A RATIONAL ORGANIZED MEDICARE
SYSTEM THAT FOCUSES ON
PREVENTION BUT WE'RE A LONG WAY
AWAY FROM THAT.
>>WELL, LISTEN.
ON BEHALF OF ALL THE PEOPLE
LISTENING, WATCHING AND THOSE
WHO WILL LATER PICK THIS UP WHEN
IT'S ON THE VIDEO ARCHIVE --
WE'RE IN 38 DIFFERENT COUNTRIES
SO WE'RE INTERNATIONAL.
I WANT TO THANK YOU BOTH VERY
MUCH FOR REALLY VERY EXCITING
INFORMATIVE AND THOUGHT
PROVOKING.
I'D LIKE TO CALL ATTENTION TO
THE FACT THAT NEXT WEEK WE HAVE
ANOTHER EXCITING THOUGHT
PROVOKING ONE.
THE TOPIC IS NEURODEGENERATION
AND AGING.
SO HOW ARE THEY LINKED?
ARE THEY PREVENTIBLE?
ARE THEY REVERSIBLE?
AND THERE'S RESEARCH DEALING ON
ALL THESE AGENCY SPECTS WHICH IS
VERY EXCITING AND PROVOCATIVE.
SO WE LOOK FORWARD TO SEEING YOU
NEXT TUESDAY.
AND THANK YOU BOTH VERY MUCH FOR
A REMARKABLE AFTERNOON.
>>THANK YOU.
TAKE CARE, EVERYONE.