GOOD AFTERNOON EVERYONE,
WELCOME TO THE WEDNESDAY
AFTERNOON LECTURE SERIES.
I AM EMILY CHU, CHIEF
INVESTIGATOR AT NIH INSTITUTE.
ON BEHALF OF NEI AND WSA, I AM
THRILLED TO INTRODUCE OUR WAL
SPEAKER TODAY Dr. BRENDA
GALLIE.
BUT BEFORE I DO, I WANT TO GIVE
YOU A QUICK ANNOUNCEMENT,
HOPEFULLY THE SLIDES WILL GO
BACK TO THE CME CREDIT.
THE CODE IS 57,667, REPEAT THAT
AGAIN, 57,667 AND FOR THOSE OF
YOU WHO ARE WATCHING REMOTELY,
YOU CAN SEND QUESTIONS TO THE
SPEAKER ANY TIME DURING THE
LECTURE AND SIMPLY CLICK ON THE
BUTTON THAT SAYS SEND LIVE
FEEDBACK WHICH IS BELOW THE
VIDEOCAST WINDOW AND TYPE IN
YOUR MESSAGE AND WE WILL RELAY
THAT TO THE SPEAKER AT THE END
OF THE LECTURE.
IT IS A REAL PLEASURE FOR ME TO
INTRODUCE Dr. BRENDA GALLIE.
UNIVERSITY OF TORONTO.
SHE DIRECTS THE RETINOBLASTOMA
PROGRAM FOR CHILDREN CALLED "THE
SICK KIDS".
THE FOCUS ON HER RESEARCH CAREER
HAS BEEN ON RETINOBLASTOMA,
CHILDREN'S EYE CANCER AND
INTERESTED IN TOP PATHOGENESIS
AND IMPACT.
HER LAB IS INVOLVED WITH
IDENTIFYING RG1 WHICH CAN DEPICT
RETINOBLASTOMA AND THE PRECURSOR
CALLED THE RETINOMA.
THEY ALSO SHOW THE KIDS GENE
OVER EXPRESSION CORRESPONDS TO
POOR OUTCOME IN LUNG AND OVARIAN
CANCERS SO IT GOES BEYOND THIS.
ON THE CRITICAL SIDE, Dr.
BALLIE'S TEAM HAS DEVELOPED
HIGHLY DEMONSTRATIVE IMPACT ON
PERSONAL MEDICINE.
SHE FOUND THE GENETIC TEST LAB
CALLED IMPACT GENETICS TO
PROVIDE THE HIGHEST MUTATIONS TO
FAMILIES AROUND THE WORLD WHICH
IMPARTS A INTERNATIONAL TEAM IN
2013 DISCOVERED AND RECOGNIZED
RETINOBLASTOMA WITHOUT THE
MUTATION ITSELF.
SO THIS IS AN IMPORTANT PART OF
HER YEAR WITH DISCOVERY AND HAS
RECEIVED MANY ACCOLADES FROM THE
CANADIAN OPHTHALMOLOGY SOCIETY,
KIDS RESEARCH AND ONTARIO ORDER
OF CANADA FOR DELIVERING
MEDICINE AND IS ONE OF MY
MENTORS.
SHE ACTUALLY GOT ME INTO
OPHTHALMOLOGY WHEN SHE TOLD ME
YOU SHOULD BE DOING THIS INSTEAD
OF SOMETHING ELSE SO HERE I AM,
Dr. BRENDA.
THE TITLE TODAY IS
RETINOBLASTOMA CAN WE REACH
EVERY CHILD AND I HOPE THAT
ANSWER IS YES.
Dr. GALLIE, GOOD TO SEE YOU.
$$TRANSMIT
>> THANK YOU VERY MUCH, EMILY.
EMILY UNDERSTATED HER
CONTRIBUTION TO MY WORK.
SHE HAS HAD TREMENDOUS INFLUENCE
ON ME.
SO THANK YOU FOR INVITING ME
HERE.
I THANK THE NIH DIRECTOR WHO IS
TOO BUSY TODAY AND I UNDERSTAND
THAT BUT I AM REALLY HONORED TO
BE HERE TODAY.
ALL THE SYMBOLS ACROSS THE
BOTTOM ARE CHARITIES THAT
SUPPORTED THE WORK IN DIFFERENT
WAYS AND I THINK THERE ARE
PROBABLY A FEW I HAVE NOT GOTTEN
ON THERE AND THE TOP THREE
INSTITUTIONS I WORK IN, SICK
KIDS, UHN, UNIVERSITY TORONTO
AND IRBC IS A CHARITY YOU WILL
HEAR MUCH MORE ABOUT AND REALLY
PUSHING FORWARD TO REACH EVERY
CHILD.
SOME WISE PERSON TOLD ME I
SHOULD SAY THE FIVE POINTS OF
WHAT YOU ARE GOING TO HEAR AND
WHAT TO LEARN SO WE WILL GO
QUICKLY THROUGH CANCERS AND
GENETIC DISEASE.
LASS OF PROSPECTIVE DATA OVER 30
YEARS FOR RECOGNITION OF SERIOUS
HARM FOR CARE I WAS RESPONSIBLE
GIVING TO PATIENTS.
RETINOBLASTOMA IS STILL THE ONLY
CANCER TO INCLUDE A
PREDISPOSITION IN THIS WORLD
STAGING RISK FACTOR SYSTEM AND
EARLY TERMS OF THESE BABIES NOW
LABELED H1 CARRYING THE GENETIC
PREDISPOPPING OPTIMIZES VISION
AND MINIMIZES THERAPY.
AND SUSTAINED RELEASE OF CHEMO
PLAQUE DELIVERS ONLY TO THE EYE
LEADING TO THE FIRST AND ONLY
CLINICAL TRIAL I HAD TO DO WITH
IT, A PHASE 1 STUDY WITH THREE
CONCEPTS IN CLINICAL TRIALS
THERE, COMPLETE RESPONSE,
CONSEQUENCE SCORE AND PRO PENS
AT THE MATCHING.
AND LOOKING FORWARD TO THE WHOLE
WORLD, THE DATA TO EVALUATE
INTERVENTION AND FULL VIEW OF
LIFE FOR PATIENTS TO BE ABLE TO
SEE THEIR WHOLE LIFE LONG
EVERYWHERE THEY ARE WITH
EVERYTHING THAT HAS HAPPENED TO
THEM WITH RESPECT TO
RETINOBLASTOMA AND PARTICULARLY
LOOKING FOR SUBSEQUENT CANCER.
SO I STARTED IN RETINOBLASTOMA
AND ALL THE FELLOWS I HAD A
WONDERFUL LUNCH WITH KNOW ALL
ABOUT THIS.
I WAS A THIRD YEAR RESIDENT IN
OPHTHALMOLOGY CALLED SICK KIDS
CALLED TO EMERGE WITH A RECENT I
AM GRANT WHO CAME IN WITH A
DIAGNOSIS OF CATARACT AND HAD
RED EYE AND YOU CAN SEE THE
PICTURE ON THE LEFT HAS A TUMOR
IN FRONT OF HIS IR IRIS AND
THAT EYE WAS NUKE UNITED AND
THIS IS THE TUMOR GOING DOWN THE
OPTIC NERVE.
SO WE HAD METASTATIC TUMOR ALL
OVER.
HE WAS TREATED WITH EXTERNAL
BEAM RADIATION AND HORRIBLE
CHEMOTHERAPY BECAUSE IN 1973,
OUR MISSION WAS TO SAVE LIFE AND
HE DIED A YEAR LATER WHEN HE
SHOULD HAVE BEEN DYING
PEACEFULLY AT HOME WITH PROPER
PALLIATION WHICH WOULD HAPPEN
TODAY I THINK.
SO WE BUILT A DATABASE WHICH I
WILL COME BACK TO AND CALLED E
CANCER RD AND EVERY TIME WE SEE
A KID WITH RETINOBLASTOMA WE
ENTER DIRECTLY INTO THIS
DATABASE SO I RETROSPECTIVELY
FOUND HIS REAL CHART WHEN I HAD
TO MOVE OUT OF OUR OFFICES AND
YOU CAN SEE THIS IS A SLIDE,
YOUNG PEOPLE WON'T KNOW WHAT A
SLIDE IS BUT THAT IS A PIECE OF
FILM ON CARDBOARD AND I WROTE
1973 ON IT AND THIS IS THE DATA
ENTERED FROM HIS CHART IN E
CANCER CARE SHOWING YOU THE
YELLOW TRIANGLE MEANS
ENUCLEATION AND THE ORANGE
ROUNDED SQUARE IS EXTERNAL BEAM
RADIATION SO THROUGHOUT I WILL
ASK WHAT WE HAVE DONE WITH THE
EYE AND YOU WILL BE ABLE TO TELL
ME WITH THOSE SYMBOLS.
IN 1973, I WAS INSTRUCTED TO
PRESENT THIS CASE OF
RETINOBLASTOMA TO CITY-WIDE
ROUNDS AND I WENT TO THE
HOSPITAL LIBRARY AND I FOUND A
NEWLY PUBLISHED PAPER FROM AL
KNUDSON SHOWING A MATHEMATICAL
ANALYSIS THAT THIS WAS BILATERAL
CAUSING ONLY ONE EVENT IN
CHILDREN WITH BILATERAL DISEASE
WHERE THE UNILATERAL WAS A MORE
COMPLICATED CURVE.
HE CALLED THIS A TWO-HIT CURVE.
IN REANALYZING HIS OWN DATA WE
THINK THIS IS MORE OF A
THREE-HIT BUT THAT IS A MINOR
POINT.
AND THAT SHOWED TO ME CANCER IS
A GENETIC DISEASE AND NOW WE ALL
KNOW IT CONTROLS CELL DIVISION,
GENOMIC DIVISION, ET CETERA AND
THE RB1 MUTATION, MY WORK
SUBSEQUENTLY CONTRIBUTED TO
DETECTION TO OFFER PRECISE CARE
FOR FAMILIES WITH
RETINOBLASTOMA.
SO GOING BACK STILL INTO HISTORY
TO IMPORTANT THINGS, IN 1969 AND
1982, THE NEW YORK GROUP WHO
WERE THE CENTER OF
RETINOBLASTOMA PATIENT CARE AT
THAT TIME AND THAT IS WHY I DID
MY FELLOWSHIP IN NEW YORK,
BECAUSE I WANTED TO PURSUE
RETINOBLASTOMA.
THEY WROTE IN THOSE PAPERS,
RADIO THERAPY THE MOST VALUABLE
WEAPON AGAINST RETINOBLASTOMA
AND THE MAINSTAY OF TREATMENT
HAS BEEN EXTERNAL BEAM RADIO
THERAPY.
AND THAT WAS QUITE A FEW YEARS,
30 YEARS MORE BEFORE THE
BRILLIANT SCIENTISTS HERE AT NIH
SHOWED THAT THEY NEEDED TO
REALLY LOOK AT DATA.
AND THEY LOOKED AT RETROSPECTIVE
DATA COLLECTED IN BOSTON AND NEW
YORK.
LOTS OF PATIENTS SHOWED THAT
THOSE THAT WERE H1 HAD A
50 PERCENT, GREATER THAN
50 PERCENT RISK OF A SECOND
SUBSEQUENT MALIGNANT NEO PLASM
BY AGE 50.
THAT HAD NOT BEEN RECOGNIZED
BECAUSE NO DATA WAS COLLECTED
FROM THERE TO NOW AND THE SAME
PATIENTS WHO WERE H1 CARRIED THE
MUTATION DIDN'T HAVE EXTERNAL
BEAM RADIATION STILL HAD A HIGH
RISK OF SUBSEQUENT MALIGNANT NEO
PLASMS BUT NOTHING LIKE THE
IMPACT OF RADIATION.
SO JUMPING AHEAD TO 2017, THE
CANCER STAGING BOOK THAT CAME
OUT FOR EVERY CANCER AND THE
ONLY CANCER IN THAT BOOK THAT
MENTIONS GENETICS HAVING A
IMPACT ON PROGNOSIS IS
RETINOBLASTOMA.
AND THIS DATA THAT WENT INTO THE
NEW WAY, THE LEVEL OF DISEASE IN
THE EYE, IS BASED ON DATA I HAD
COLLECTED OVER 2001 TO 2011 AND
ANALYZING THAT DATA SAID THAT
THE PREVIOUS WAYS TO STAGE
CANCER STARTING WITH CELLS FOR
CLASSIFICATION AND THE OTHER
CLASSIFICATIONS WEREN'T AS GOOD
AS LOOKING AT THE DATA THAT CAME
OUT OF HERE AND THAT IS THE
CANCER STAGING TMM.
AND THAT WORK IS SUPPORTED IN
THE CLINICAL SURVEY BY THE I
CANCER FOUNDATION LED BY A
DOCTOR IN NEW YORK WHO IS A
BRILLIANT DEDICATED PERSON TO
WORLD EYE CANCER.
SO THIS IS THE H1 STATUS IN THAT
CHAPTER IN THE 8TH EDITION OF
TNM WHICH IS TNM1 WHICH
REPRESENTS THE H MEANING DON'T
KNOW, NO EVIDENCE OF A
CONSULTATIONAL GENE MUTATION.
H1 MEANS BILATERAL, TRY LATERAL
FAMILY HISTORY OR GENOME
IDENTIFIED WITH THAT PATIENT.
H0 IS APPLIED WHEN YOU KNOW THE
RELEVANT MUTATION AND YOU PROVED
THE BABY IN FRONT OF YOU DOES
NOT CARRY THAT MUTATION.
BUT IF I TESTED A UNILATERAL WHO
MIGHT BE EITHER ONE AS KNUDSEN
SHOWED AND DON'T FIND ANY
MUTATION, WE CALL THAT H1
ASTERISK BECAUSE IT CAN'T GO
BELOW THE 1 PERCENT MOST SAME
DIVISION.
IF THAT WERE LESS THAN
1 PERCENT, THE BABIES IN THE
FUTURE WOULD HAVE BILATERAL
RETINOBLASTOMA BECAUSE THEY
WOULD HAVE BEEN DESCENDED FROM
THE SPERM THAT CARRIED THE
MUTATION SO THAT IS WHY THE
ASTERISK IS ON SOME OF THEM.
SO JUMPING BACK TO NAME HISTORY,
I HAVE CARED FOR NOT THE FIRST,
NOT THE GRANDMOTHER BUT YOU KNOW
THE GRANDMOTHER IN 1949 HAD BOTH
EYES ENUCLEATED AND YOU CAN TELL
THAT BY YELLOW TRIANGLES FOR
HER.
SHE IS ALIVE AND WELL, I TALK TO
HER OFTEN THROUGHOUT HER LIFE.
SHE HAD FOUR CHILDREN.
I DIDN'T CARE FOR THE FIRST ONE
BECAUSE I WAS TOO YOUNG AT THAT
TIME BUT ALL OF THOSE -- THAT
CHILD WAS BILATERALLY
ENUCLEATED.
BUT ALL THE REST OF HER CHILDREN
WERE TREATED BY ME, MANAGING
THEIR RETINOBLASTOMA WITH
EXTERNAL BEAM RADIATION, THE
SQUARE THERE.
AND WE DID THAT BECAUSE WE KNEW
AS ELSEWHERE WAS POINTED OUT IN
PAPERS, WE COULD SAVE VISION AND
SAVE EYES.
WE HAD NO IDEA WHAT WE WERE
DOING TO THEM IN SECOND CANCER
RISKS AND YOU SEE THE
GRANDMOTHER IS ALIVE AND WELL
BUT HER TWO OLDEST CHILDREN HAVE
ALREADY DIED OF THEIR SECOND
CANCERS AND THESE TWO REMAINING
DO NOT HAVE THEIR SECOND CANCER
DIAGNOSED YET AND ARE VERY
CONCERNED ABOUT THAT BECAUSE
HERE IS THE THIRD GENERATION
NOW.
THE FIRST CHILD LOOKING FOR THE
PRECISE H1 MUTATION IN EACH
PREGNANCY, THE FIRST AND THIRD
ARE H0 BECAUSE WE KNOW IT CAN BE
PRECISE, DON'T NEED AN ASTERISK
BUT THE MIDDLE ONE IS H1.
AND NOW YOU CAN SEE BECAUSE WE
KNOW OF THAT CHILD, JUST GOING
BACK TO THE RADIATION RISKS, NOW
IN CANADA, ALL H1 BABIES ARE
DELIVERED AT 36 WEEKS WHICH IS
EARLY TERM.
THAT IS ONLY IN CANADA.
IT IS NOT HAPPENING IN THE
STATES UNLESS A FAMILY THAT WE
HAVE MANAGED AND KNOW ABOUT THIS
DEMAND IT.
AND I KNOW OF ONE DELIVERED IN
BOSTON EARLY BECAUSE THEY SAID
WE MUST HAVE EARLY DELIVERY TO
LOOK AT OUR BABY'S EYES.
AND THIS IS A PICTURE OF A
36-YEAR-OLD, THERE IS THE OPTIC
NERVE RIGHT THERE, THESE ARROWS
POINT TO WHERE THE TUMOR IS
IDENTIFIED BUT LOOKING IT THE
OPTHOMOSCOPE OR CAMERA, YOU
CAN'T SEE IT AT ALL BUT LOOKING
THROUGH THE HTC, YOU CAN SEE
THAT IS WHERE THE RETINOBLASTOMA
EMERGES.
AND THEN WE DON'T KNOW WHERE
THAT IS SO WE FOLLOW THE BLOOD
VESSELS FROM THE NERVE AND SAY
WE THINK IT IS THERE AND PUT IN
A LASER BURN.
AND WE PUT IN ANOTHER OT C
IMMEDIATELY AND NOW YOU CAN SEE
THE TUMOR, THAT LITTLE ROUND
THING THERE AND GOING BACK TO
THE RTE IS SHOWING THE LASER
BURN SO WE HAVE HIT IT
CORRECTLY.
NOW WE SEE THE SPOT ON THE
RETINA AND CAN CONTINUE TREATING
THAT BECAUSE WE CAN SEE IT USING
THE LASER.
AND WE KEEP TREATING IT UNTIL WE
HAVE GOT IT THOROUGHLY EVALUATED
THAT WAY.
THIS IS, THEN ON THIS CHILD, FOR
EXAMPLE, WE DID ALL THAT LASER,
AND THIS IS A LASER TREATED
TUMOR IN HER EYE SOMEWHERE NEAR
THE PERIPHERY BUT WITH A VERY
GOOD OC T SHOWING OUR LASERS
CAUSED A PROBLEM.
THAT IS A VITREOUS SEED.
IT IS A GOOD PICTURE OF ONE
BECAUSE THEY ARE HOLLOW IN THE
CENTER.
ALL THE NUTRITION FOR THAT CLUMP
OF SELLS COMES FROM THE VITREOUS
WHERE THE CELLS DIE AND HAVE
THAT PART THAT YOU CAN SEE.
SO THEN WE NEEDED SOMETHING ELSE
TO DO AND WHAT WE DID WAS THE
CHEMO PLAQUE AND WE WILL SHOW
YOU MORE OF THAT.
THIS IS AFTER THE CHEMOPLAQUE
LATER AND KEPT FOLLOWING THAT
AND THERE HAS BEEN NO RECURRENCE
FURTHER.
SO THE E CANCER DATABASE, I
SHOWED YOU ON MY PATIENT 1
LOADED RETROSPECTIVELY BUT WE
USE THIS ONLY IN THE KIDS, A
BEAUTIFUL PROGRAM MADE BY
DEVELOPERS AT PRINCESS MARGARET
HOSPITAL WHICH WE TALKED ABOUT
OVER LUNCH AND WORK OVER EXACTLY
THIS.
AND THAT IS A PROTECTIVE IN THE
OR EVERY TIME WE SEE A PATIENT
OR IN THE CLINIC, AT THE POINT
OF CARE AND REPOSITORY OF DATA.
SO E CANCER CARE, THE
PROSPECTIVE PART IS FROM 2001 TO
'25, STILL USING IT IN SICK KIDS
BUT IT IS OLD, THE SERVER IS
GOING TO DIE BECAUSE IT IS ON
OLD SOFTWARE AND TECHNOLOGY SO
WE REALLY BACK IT UP REGULARLY
BECAUSE WE DON'T KNOW WHEN IT IS
GOING TO FAIL.
WE THEN ACTUALLY PUT THAT
DATABASE INTO KENYA WHERE THE
OPHTHALMOLOGISTS LOVED IT, USED
IT BUT WOULD PHONE US TO SAY IT
IS NOT WORKING, WE WOULD FIND
OUT THERE WAS A POWER FAILURE,
THE SERVER WASN'T TURNED ON AND
REALIZED WE CAN'T GO GLOBALLY
THAT WAY, CANCER CARE CAN'T DO
THAT.
SO WE BUILT A BRAND-NEW MODEL
CALLED DEPICT HEALTH, FULL VIEW
FOR LIFE AS YOU WILL SEE AND
PROSPECTIVE POINT OF CARE
REPOSITORY OF DATA.
THIS IS THE CHARITY THAT RUNS
THIS.
THE CHARITY PAYS THE UNIVERSITY
HEALTH NETWORK EVERY YEAR FOR
EXCLUSIVE LICENSE TO USE MY
DATABASE THAT IS OWNED BY THE
PRINCESS MARGARET CANCER CENTER.
$$TRANSMIT T H I S IS DEPICT
HEALTH.
WHAT IT LOOKS LIKE, THIS IS A
BEAUTIFUL TOOL TO USE.
I COULD DO A DEMO AFTER IF YOU
WANT BECAUSE WE HAVE NOW GOT
THIS RUNNING LIVE BUT I HAVEN'T
TIME TO DO THAT NOW.
AND ANY TIME YOU POINT TO ANY OF
THESE, IT SHOWS THE DATE, YOU
DOUBLE CLICK AND IT OPENS THE
WHOLE EVENT AND YOU CAN SEE
EVERYTHING.
YOU CAN SEE HERE IS THE STAGING
FOR THIS PARTICULAR CHILD, THE
STAGING OF THE EYE, NO NODES, NO
METATASTISIS.
BUT THE LINES THAT CROSS BOTH
EYES ARE SYSTEMIC SO THE GENETIC
TESTING IS GREEN AND ALL THE
BLUE LINES ARE SYSTEMIC
CHEMOTHERAPY.
THINKS ARE ONLY TO THIS EYE AND
WHAT DID WE DO TO THE LEFT EYE?
WE NUCLEATED YOU SEE RIGHT THERE
AFTER THE CHEMOTHERAPY BECAUSE
IT WAS THREATENING THE OPTIC
NERVE.
SO THEN WE DID MORE CHEMO AND WE
ARE NOT WAITING HERE.
SO I WENT TO A WORLD CONGRESS,
SAT IN HIS.HAVING COFFEE WITH
LYNN MURFREE WHO IS MY COLLEAGUE
IN CHILDREN'S LA AND SAID THAT
LITTLE DEVICE I HAVE BEEN
WORKING ON TO GET DRUG ONLY INTO
THE EYE WITHOUT BEING ABSORBED
INTO SYSTEMIC CIRCULATION HAS
BEEN APPROVED BY THE FDA TO PUT
IN A HUMAN.
AND I SAID I HAVE THE PATIENT
WHO NEEDS IT.
WE WENT BACK TO TORONTO, CHASING
ALL THESE TINY DATA FROM
SURGERY, THE RETINAL DETACHMENT
OBVIOUSLY AFFECTED HIS VISION,
AND YOU HAVE ALL THESE BEAUTIFUL
TOOLS TO UPLOAD TO DEPICT HEALTH
KEY IMAGES THAT SUPPORT THE
STORY FROM THAT EVENT, BUT NOT
ALL THE IMAGES.
AND OH BY THE WAY, ALL THE DATA
IS GOING INTO DEPICT HEALTH,
DEPICT HEALTH IS NOT THE
CUSTODIAN OF THAT DATA BUT A
COMMUNICATION SERVER ACROSS THE
WHOLE CIRCLE OF CARE AND THE
SITE SICK KIDS IS STILL MAIN
CUSTODIAN OF THE DATA.
SO OUR CHOICES FOR THIS CHILD
WERE TO ENUCLEATE HIS LAST EYE
OR DO EBT, HE HAS 20/20 VISION
AND SO WHAT WE DID WAS SPEND A
WEEK WITH HEALTH CANADA GETTING
SPECIAL ACCESS AUTHORIZATION TO
PUT THIS CHEMO PLAQUE IN THIS
CHILD'S EYE, THE FIRST HUMAN IN
THE WORLD TO HAVE A CHEMOPLAQUE.
THIS IS THE CHEMOPLAQUE INVENTED
BY THE IDEAS OF LIN MURPHY AND
RICARDO CLAVELLO NOW IN BRAZIL
AND DAVID CARKEY RUNS THE
COMPANY.
THIS IS IN YELLOW FORM THAT WE
DIFFUSE IN THE EYE AND ALL OF
THE PEOPLE WHO HAD LUNCH WITH ME
COULD FEEL IT IN MY HAND.
SORRY?
ABOUT AS BIG AS YOUR BABY FINGER
NAIL, VERY SMALL.
AND I WILL SHOW YOU.
THIS IS PUTTING THE CRAZY GLUE
AND THE BLUE DYE IN THAT LITTLE
GROOVE RIGHT THERE, MUST NOT PUT
ANY OVER TOP OF THE DRUG OR IT
WON'T DO THE JOB.
SO WE PUT THIS IN AT 70 DAYS
BECAUSE IT DIDN'T SEEM TO BE
CAUSING ANY PROBLEM AT ALL AND
WE LOOKED IN BETWEEN AND THE
TUMORS WERE GETTING SMALLER AND
SMALLER AND WE TOOK IT OUT AND
THE ONLY ACTIVE TUMOR HERE IS
STILL WHERE HIS PRIMARY TUMOR
WAS WITH THE CALCIFICATION AND
ALL THE REST HAD DISAPPEARED
COMPLETELY.
ULTIMATELY WE TOOK OUT THIS
TUMOR WITH ANOTHER NEW PROCEDURE
THAT HAS BEEN PROMOTED AND DONE
WITH MY COLLEAGUE JOHN CHAO IN
CHINA AND THAT IS JUST TO TAKE
OUT THE ACTIVE TUMOR.
WE HAD TROUBLE PUBLISHING THAT
BECAUSE TOP EDITORS FOR
OPHTHALMOLOGY JOURNAL SAID YOU
CAN'T OPEN AN EYE WITH
RETINOBLASTOMA BUT THE DATA
WIDELY PUBLISHED NOW FROM CHILD
AND MANY OTHER COLLABORATORS ON
THE PAPER SHOWED THAT BY TAKING
OUT THE TUMOR THAT FAILED MANY
TREATMENTS AND THEREFORE BECOME
MORE GENOMICLY RESISTANT, THAT
THAT ACTUALLY SAVES LIVES AND
EYES.
IT IS BETTER THAN LEAVING THE
DEN HOME IN MICKLY MUTE TRAITING
PROGRESSIVE TUMOR IN THE EYE
WITHOUT TRYING TO TREAT IT.
SO THIS KID IS NOW FOUR YEARS
OUT WITH 20/40 VISION.
SO HEALTH CANADA SAID YOU CAN
ONLY DO THREE OF THOSE.
TWO OF THEM WERE NOT AS WELL
SELECTED AS HE WAS AND THEN YOU
HAVE TO DO A CLINICAL TRIAL.
I HAD NEVER DONE A CLINICAL
TRIAL IN MY LIFE BEFORE THIS ONE
BUT WITH THE HELP OF THE COMPANY
MANAGING AND BUILDING THE
CHEMOPLAQUES AND CHILDREN'S
STUDY JOINED US AND SO THE
DOCTORS AND MY TEAM JOINED US
FOR THE PHASE 1 STUDY.
THIS IS THE DESIGN, THREE
ESCALATING DOSES.
TWO BLACKS, ONE WITH 1.6 AND ONE
WITH .9 AND THE ONE I WILL SHOW
YOU IS THE .9 WHICH I LIKE BEST
OF ALL OF THEM.
AND THEN ESCALATING DOSES THAT
REQUIRE TUBE CHEMOPLAQUES.
THEY STAY IN PLACE FOR SIX WEEKS
AND WE PICKED THAT BECAUSE IN 50
DAYS WITH THE RABBITS THERE WAS
NO DRUG LEFT AND WE PICKED THAT
SO THE PATIENTS WOULD HAVE A
MORE CONSTANT DOSE LEVEL AT SIX
WEEKS.
THEN WE MONITORED THEM WITH
THREE YEARS FOLLOW-UP AND THIS
SHOWS THE CHEMOPLAQUE PUT IN THE
MUSCLES AND IT CAUSES A
FOOTPRINT SCAR SO WE REMEMBER
THE THAT BE AN INTERIOR SCLETOMA
THAN EXTERNAL.
SO THIS IS WHAT I WILL USE MANY
TIMES THROUGHOUT THE REST OF MY
TALK AND THIS WAS ACTUALLY
INVENTED BY AN UNDER GRAD SUMMER
STUDENT WHO LOVED TO EXCEL AND
PRETTY SMART AND SHE BUILT THIS
WAY TO TAKE OUR DATA FROM THE E
CANCER DATABASE AND DISPLAY IT.
THE ONLY DATA HERE IS WHAT IS
THE TREATMENT AND THE DATE IT
WAS DELIVERED.
AND THAT COMES FROM OUR PRO
EXPECT SIEVE DATABASE.
SO THAT DATA GOES INTO THE
SWIMMER PLOT AND THIS IS THE
DOSES OF THE DRUGS SO YOU CAN
SEE THE BLUE DOWN HERE IS THE
6MG, ET CETERA, AND UP TO THE
HIGHER DOSES.
$$TRANSMIT T H E N WE
INVENTED ANOTHER THING BECAUSE
CANS S-R STAGING -- AND TO SAY
YOUR TREATMENT, YOUR THERAPY,
WHATEVER IT IS, IS WORKING, YOU
HAVE TO HAVE SOME MEASUREMENT
THAT IS STANDARD FOR THE CANCER.
FOR RETINOBLASTOMA, IT IS REALLY
HARD BECAUSE OF THE LITTLE
PIECES OF TUMOR ALL OVER THE
PLACE AND HOW CAN YOU KNOW WHAT
TO MEASURE.
SO WE SAID LET'S GET SIMPLE AND
FOLLOW ALONG THE SWIMMER AND
AFTER RESPONSE, THERE IS NO
OTHER CANCER TO THE PATIENT AND
THE EYE AND THAT IS WHAT IS
SHOWED THERE.
DOSE SAME TOXICITY THERE AND NOW
IT IS MORE EXPANDED SO
AUTOMATICALLY PUTS IN THE CRS
AND ALL THOSE EXTRA THINGS SO I
DON'T HAVE TO FILL THEM IN
ANYMORE.
AND THEN WE HAVE THE KEY AND I
WILL SHOW YOU THE DATA BEHIND IT
BUT YOU CAN SEE A LOT OF CRS
HERE, A LOT MORE IN THE SMALLER
OR HIGHER DOSES AND A LOT MORE
DLTS AT THE HIGHER DOSES WHICH
IS WHY WE ARRIVED AT THE
RECOMMEND *EZ PHASE 2 DOSE OF .9
AND 1.2.
SO MERE IS ANOTHER APPROACH TO
THIS.
WE THOUGHT WE WOULD HAVE TO
DESIGN A RANDOMIZED TRIAL TO GET
FDA TO LET US GO FORWARD BUT
THEN WE REALIZED BURIED IN OUR E
CANCER CARE DATA IS THE
RETROSPECTIVE DIAGNOSIS AND HERE
IS THE VIEW OF THE CANS S-R
TREATMENT FOR RETINOBLASTOMA.
BEFORE 2010 AND MUCH LONGER THAN
THAT BUT WE'RE ONLY SHOWING THAT
HERE, IT IS MAINLY EXTERNAL'
RADIATION AND IF WE WENT FURTHER
THAN THAT, I DON'T HAVE THAT
DATA AVAILABLE.
AND THEN Dr. HELEN CHEN WHO IS
A ENTHUSIASTIC, ENERGETIC
CHEMOPLAQUE ONCOLOGIST DEVELOPED
CHEEP THERAPY FOR RETINOBLASTOMA
AND THAT WAS CONSIDERED HERE SY.
AND MORE RECENTLY, THINKING THE
CHEMOTHERAPY THAT YOU GIVE IT
ONLY TO THE EYE OR NEAR THE
OPHTHALMIC WORLD OR NEAR THE
ARTERY AND THAT IS DOMINATING
THE WORLD FOR RETINOBLASTOMA.
CHEMOTHERAPY IS STILL THE MAIN
TREATMENT WITH LOTS OF RISKS TO
THE EYE AND THE PATIENT.
HERE ARE THE RISKS TO ADULTS
SHOWING WHY WE RECOMMEND THE
PHASE 2 DOSE AND COMBINED
TOGETHER AT 77 PERCENT COMPLETE
RESPONSE RATE.
AND THAT IS SUSTAINED COMPLETE
RESPONSE AS LONG AS WE FOLLOWED
THE PATIENT.
SO HERE IS RED THROW RESPECTIVE
CONTROLS TREATED WITH INTERIOR
ARTERIAL CHEMOTHERAPY IN A
EQUIVALENT TIME WINDOW WHEN THE
CHEMOPLAQUES HAD THEIR DIAGNOSIS
AND YOU CAN SEE THE BEST
RESPONSE RATE COMPARED TO
77 PERCENT FOR THE CHEMOPLAQUE
WHICH IS SUSTAINED RELEASE.
AND THAT MAKES SENSE.
AS SOON AS YOU GIVE A PULSE, IT
KILLS LOTS OF CELLS, IT CAN GET
SMALLER BUT THE CELLS THAT
SURVIVE HAVE ACQUIRED HUGE
CHANGES AND BECOME MORE AND MORE
RESISTANT THE MORE YOU GIVE THEM
A PULSE BUT THE SUSTAINED
DELIVERY TO THE WHOLE EYE
DOESN'T GIVE THEM ANY CHANCE TO
ESCAPE WHICH I THINK IS PART OF
THE ANSWER.
THEN WE LOOKED BACK ON THIS AND
SAID IF WE LOOK ON OUR SWIMMER
PLOT, WE CAN SEE HOW MANY EYES
HAVE BEEN ENUCLEATED AND YOU CAN
SEE HERE IT WOULD SCORE ON THE
YELLOW TRIANGLE AND THERE WERE
TWO FROM THE CHEMO FLAK
ROTATIONS AND MANY MORE FROM THE
IAC.
SO NOW WE WANT TO DO
RETROSPECTIVE PROPER COMPARISON
SO THE E CANCER CARE PATIENTS IN
THIS RETROSPECTIVE WINDOW
COMPARED TO THE .9 AND 1.2
CHEMOPLAQUE STUDY.
HERE WE HAD 22 EYES BUT CAN'T
SCORE FOR THIS MATCH BECAUSE
THEY HAD NO OTHER TREATMENT OR
THEY WERE A LOT OLDER.
SO THE STUDY FOR EYES MATCHING
WERE 18 AND THEN WE WENT THROUGH
A PATH STARTING WITH 97 EYES AND
WORKING OUR WAY DOWN TO ONES
THAT COULD REASONABLY MATCH THE
CONTROL EYE OF 45 AND WE THOUGHT
WE SHOULD BE RANDOMIZING UP WITH
OF THESE EYES FROM ONE OF THESE
BUT I LEARNED LAST NIGHT THAT IS
NOT THE CASE AND WE SHOULD HAVE
MANY AS POSSIBLE.
SO THIS WILL BE REVISED SOON.
AND THIS IS ANOTHER CANADIAN
REFUGEE, WE HAVE MANY GREAT
REFUGEES IN CANADA AND CONTROL
EYES FOR MATCH, WE HIRED HIM AS
A RESEARCH ASSISTANT FROM HONG
KONG, HE IS ABSOLUTELY BRILLIANT
AND HAS DONE ALL OF THIS WORK
MAKING THE SWIMMER PLOT BETTER
AND VERY MUCH A KEY PERSON TO
THE WHOLE STUDY.
SO THE PROPENSITY MATCH IS
MATCHING THE PATIENTS ACROSS
HERE AND THE PLAN IS TO
CALCULATE THE CONSEQUENCE SCORE
FOR EACH EYE.
YOU HAVEN'T HEARD ABOUT
CONSEQUENCE SCORE, HAVE YOU?
WE JUST INVENTED OUT OF OUR
HEADS THE CONSEQUENCE SCORE AND
SAID IT IS ARBITRARY BUT
INTENDED TO ESTIMATE THE
PERCEIVED RELATIVE HARMFUL SIDE
EFFECTS OF ANY OF THESE
TREATMENTS AND YOU CAN SEE THE
ONES THAT HIT THE TOP ARE EBRT
AND ENUCLEATION OF THE EYE AND
THAT WOULD BE ONE TREATMENT, NOT
COUNTING THE NUMBER OF BURNS IN
THE EYE BUT THAT EPISODE THAT
SCORES ON THE SWIMMER PLOT.
AND THAT IS WHAT WE DECIDED WE
WOULD USE.
IT DOESN'T MATTER WHAT THE REAL
NUMBERS ARE BECAUSE IN ALL THE
CALCULATIONS, THE NUMBERS ARE
THE SAME ON BOTH SIDES.
IT JUST LETS US QUANTITATE
OUTCOMES AND EVENTS AND
PROPENSITY MATCHING.
SO HERE WE ARE THE CHEMOPLAQUE
AND COUNT THE SCORE BY THREE
ARTERIALS, THAT GIVES THE TOTAL
OF 12 TOTAL CONSEQUENCE SCORE
BEFORE CHEMOPLAQUE IN THAT STUDY
OF KIDS UNDER 25.
THEN WE LOOKED THROUGH OUR OTHER
CONTROLS AND FIND OTHERS WITH A
CONSEQUENCE SCORE OF 12, THEN WE
PICK THE DAY ZERO THAT MIGHT BE
THE NEXT TREATMENT, THAT MIGHT
HAVE GOTTEN THE CHEMOPLAQUE BUT
DIDN'T.
DOES THAT MAKE SENSE?
HOPE SO.
SO THIS GIVES US A NEW MATCHING
SET BY THAT CRITERIA, THEN WE
ALSO IMPROVED THE MATCH BY
LOOKING AT THE TREATMENT
PATTERN.
SO YOU CAN SEE HERE OUR
CHEMOPLAQUE CITATION HAS FOUR
EYES OF MATERIALS, THIS PATIENT
HAD 12 BUT ONLY THREE ARTERIAL
AND THREE LASER.
SO THAT WOULD FIT IF WE'RE
MATCHING ONLY BY TUMOR PATTERN,
BUT THIS ONE FITS BETTER BECAUSE
THESE ARE INTRAARTERIAL THAT
MATCH THE OTHER INTRAARTERIAL
THERE AND IN A MOMENT WE SAID WE
WOULD DO RANDOM SELECTION BUT
LEARNED LAST NIGHT WE WILL USE
BOTH OF THEM BECAUSE WE WANT TO
ENRICH THE NUMBERS IN OUR
RETROSPECTIVE CONTROL.
SO HERE WE ARE LOOKING AT THE RB
TD FOR ONE-TO-ONE MATCHES
BETWEEN THE CHEMOPLAQUES AND
THEN THE OUTCOME MATCHED BETWEEN
THE GROUPS AND DON'T HAVE ANY
DIFFERENCE BETWEEN THEM.
AND THE PROPENSITY MATCH AT WEEK
ZERO, HERE IS THE INSERTION OF
THE CHEMOPLAQUE.
SO IF YOU LOOK AT THE RESULTS,
THE MATCHED RETROSPECTIVE FOR
CONTROL VERSUS THE CHEMOPLAQUE,
THAT SHOWS A VERY SIGNIFICANT
VALUE TO THE CHEMOPLAQUE
COMPARED TO MATCHED CONTROLS.
I WILL SHOW YOU ONE BEAUTIFUL
LITTLE PATIENT.
THIS IS STEP RB AND THE CHILD
SHOULD HAVE BEEN DIAGNOSED AT
WEEK 30.
DIAGNOSED NOW AT GESTATIONAL
WEEK 36 WHICH WE DO COMMONLY IN
CANADA BUT GOT MISSED BECAUSE
THE PASSING BACK AND FORTH
BETWEEN GENETIC LABS AND
FAMILIES AND TESTING FOR
GENETICS WAS DELAYED SO NO ONE
RECOGNIZED HER COUSIN, BOTH
FATHERS FROM IDENTICAL TWINS WHO
ACTUALLY HAD NEVER HAD RED
RETINOBLASTOMA SO THIS CHILD
ALREADY HAD THIS TUMOR AT THAT
POINT IN TIME.
AND THIS IS THE ONLY PICTURE I
HAVE BUT IT IS AN ULTRASOUND
DONE ACROSS THERE SHOWING TUMOR
AND CHEMOPLAQUE ON ULTRASOUND.
YOU CAN SEE HOW IT IS GLUED WITH
CRAZY GLUE HERE AT THE FRONT OF
THE EYE AND FITS THE PROFILE
THERE.
THIS IS WEEK 9 OF TOXICITY AND
SHOWS THE MAJOR TOXICITY, THE
GREEN DOTTED CIRCLE IS THE
FOOTPRINT OF THE CHEMO PLAQUE
AND SOMETIMES SHOWS MORE TIRATIS
AND ULTIMATELY THE RETINA IS
DESTROYED BUT THIS SHOWS THAT
ACTIVE TUMOR SITTING RIGHT THERE
ON TOP OF THE CALCIUM.
BUT WE JUST KEPT FOLLOWING THAT
AND DID NOT DO ANY
INTERVENTIONAL TREATMENT AND BY
WEEK 35 AT 3.3 YEARS FOLLOW-UP,
IT LOOKS JUST LIKE THAT.
THIS IS THE SCAR WHICH WILL BE
IN HER SUPERIOR FIELD AND THEY
ALL HAVE THIS OUTCOME FROM THE
CHEMOPLAQUE FOOTPRINT AND NOW
THERE IS NO LONGER A TUMOR
THERE.
AND THE TIMELINE IS CHEMOPLAQUE
AND NO OTHER TREATMENT SO SHE IS
STILL IN COMPLETE RESPONSE AT
3.3 YEARS AND THIS METHOD AND CR
LEAVES NOT MUCH ROOM FOR
DISCUSSION AROUND IT.
ACTUALLY IF I GO BACK HERE TO
THIS, HERE IS A LITTLE DROPDOWN
WAY OVER HERE AT 90-SOMETHING
WEEKS.
THAT WAS ONE PARTICIPANT IN THE
STUDY WHO SHOWED A HOT SPOT ON
THE SOFT PART OF THE REGRESSED
TUMOR AND WE LASERED IT BECAUSE
THE WHOLE TEAM MAKES THE
DECISION THAT IS THE SAFEST
THING TO DO FOR HIS EYE EVEN
THOUGH IT MAY NOT HAVE BEEN A
TUMOR.
WE DID ONE TREATMENT AND THAT
DROPPED HIM DOWN ONE POINT AND
HE NO LONGER IS A COMPLETE
RESPONSE BECAUSE WE TREATED HIM
BUT THAT IS NO PROBLEM AS WE PUT
PATIENT CARE FIRST.
SO NOW WE ARE OUT HERE AND THIS
LITTLE GIRL WHO TAUGHT US
SOMETHING WE DIDN'T THINK OF
BEFORE.
THIS IS EVA, VERY PROUD OF BEING
IN MY TALK SO I CAN USE HER
PICTURE WITH PERMISSION AND HER
VISION MEASURES POORLILY BECAUSE
HER CENTRAL VISION IS RIGHT
THERE SO SHE WILL NEVER HAVE
GOOD VISION OUT OF THIS EYE.
BUT SHE IS PATCHED TO THE BETTER
EYE SO SHE WILL HAVE OPTIMIZED
VISION OF THIS EYE.
BUT WISE PEOPLE SAID WHY ARE YOU
BOTHERING TO PATCH, THERE IS NO
CHANCE TO CHANGE HER CENTRAL
VISION AND YOU ARE RIGHT BUT SHE
RUNS AROUND WITH HER PATCH AND
CATCHES BALANCE BECAUSE SHE IS
USING ALL THE REST OF THE
RETINA AND SO WE SAY KEEP
PATCHING FOREVER, MAYBE THE REST
OF YOUR LIFE BECAUSE YOU DON'T
WANT TO LOSE THE FUNCTION OF
THIS BEAUTIFUL RETINA THAT SHE
CAN USE TO DO A LOT OF THINGS IN
LIFE.
SO WE HAVE NEVER PAID ATTENTION
TO THE VISUAL FIELD AND THAT IS
A NEW STUDY.
PLEASE COME AND FOLLOW THIS
STUDY WITH PATIENTS WITH SCARS
ALL OVER THE PLACE FROM INFANCY
AND HOW THAT VISION FIELD
CHANGES CORRELATING TO THEIR JOB
PROSPECTS AND WHAT THEY LIKE TO
DO IN THE WORLD AND THAT IS VERY
IMPORTANT FOR FOLLOW-UP FOR THE
FAMILIES.
SO YOU CAN SEE I HAVE USED THE
DATA IN MANY WAYS.
I WILL JUST POINT OUT THAT THIS
DATA HERE -- NO, THIS DATA FROM
NEW YORK AND BOSTON, I COMMENTED
ON THAT, AND THAT EVENTUALLY LED
TO THE RECOGNITION THAT EBRT WAS
NOT A GOOD THING TO DO TO H1
PATIENTS.
THE RETROSPECTIVE REPOSITORY
WHICH I BUILT FROM 2001 TO 2013
AT UNIVERSITY HEALTH NETWORK,
THAT FED INTO THE CANCER STAGING
AND NOW A J.C. CANCER STAGING
INCLUDING H1.
AND ANOTHER EVEN OLDER REGISTRY
FROM THE NETHERLANDS THAT THEY
PULLED FANTASTIC DATA OUT OF.
SO HAVING REALLY RETROSPECTIVE
REPOSITORIES IS VERY USEFUL.
THE CHINESE GROUP WORK WITH
MANY, MANY PATIENTS JOINING 28
CENTERS TOGETHER BUT ALL THE
PATIENTS IN ONE DATABASE, AND I
HAVE HAD THE PRIVILEGE TO WORK
WITH Dr. CHAO IN CHINA AND NOW
A MEDICAL STUDENT WHO WAS
ORIGINALLY BORN IN CHINA BUT IS
NOW A RESIDENT IN OTTAWA,
CANADA, AND WORKS THROUGH THE
STATE WITH THE THREE OF US
WRITING ALL SORTS OF PAPERS OUT
OF THIS REPOSITORY WHICH SHOW
FOR EXAMPLE THE SAFEST WAY TO
SAVE A CHILD'S LIFE IS TO
ENUCLEATE.
PRIMARY ENUCLEATION IS A REALLY
IMPORTANT TREATMENT FOR THE
WHOLE WORLD.
THIS IS THE E CANCER CARE
REPOSITORY AND I WILL COME BACK
TO THAT.
SO DEPICT WORLDWIDE, WE NEED TO
KNOW HOW TO REACH CENTERS
WORLDWIDE.
HELEN DIMARAS WHO WAS IMPORTANT
IN THE RB SITES WORLDWIDE HAS
BUILT A TUMOR BANK FOR THE WORLD
ALL BASED IN SICK KIDS AND MANY
YEARS AGO SET UP THIS MAP, YOU
CAN GO FROM THAT URL AND JUMP
RIGHT TO THIS MAP AND ANY TIME
YOU POINT TO A GREEN SPOT, IT
WILL TELL YOU PRETTY UP-TO-DATE
HOW MANY PATIENTS THEY ARE
SEEING THERE, WHAT KIND OF
TREATMENT TUMORS DO THEY HAVE
AVAILABLE IN THAT SITE AND WHO
ARE THE ACTIVE ONCOLOGISTS AND
OPHTHALMOLOGISTS AND ANYONE
INVOLVED IN THE CARE IN THOSE
SITES.
AND WE KNOW MOST OF THESE
PEOPLE, NOT ALL OF THEM OF
COURSE BUT KNOW LOTS OF THEM AND
THOSE ARE HOW WE HAVE BEEN ABLE
TO EXPEDITE MOVING DEPICT HEALTH
THROUGH THE WORLD.
SO THIS IS DEPICT HEALTH WHICH
ANCHORS THE CIRCLE OF CARE AND
THAT IS THE BLUE CIRCLES WHICH
INCLUDES FAMILIES, PATIENTS,
Dr., ET CETERA, THEY CAN VIEW
ALL THE DATA.
BUT ALL THE PEOPLE IN THE BLUE
CIRCLE HERE ARE CLINICIANS OF
ALL DESCRIPTIONS WHO WOULD ENTER
DATA INTO DEPICT HEALTH.
THIS IS NOT IN THE E MR OF A
HOSPITAL SITE, IT IS FILLED OUT
BY THE CLINICIANS OF ALL
DIFFERENT TYPES BUT VERY SIMPLE,
VERY EASY AND BECOMES A
COMMUNICATION SERVICE ACROSS
THIS CIRCLE OF CARE.
THEY PUT IN THE ACCURATE DATA
BUT THE AUDITORS IS TO SAY DID
THEY MAKE A MISTAKE ARE THE
PATIENTS AND PARENTS BECAUSE
THEY CAN WATCH THIS IN THE
WAITING ROOM, READY FOR THIS
WHILE WE'RE ACTUALLY PUTTING THE
DATA INTO DEPICT HEALTH IN THE
OR.
SO THE PATIENTS PARTICIPATE WITH
A COMMUNICATION CONSENT SIGNED
BY THEM TO THE HOSPITAL THAT IS
THE CUSTODIAN OF THE DATA,
ALBERTA HEALTH OR SICK KIDS AND
THEY HAVE TO HAVE ONE
COMMUNICATION SENT WITH EACH OF
THOSE INSTITUTIONS.
AND THEN IF THE PATIENT'S
PARENTS SIGN AN OPTIONAL
RESEARCH CONSENT, THEN CODED
AGGREGATE DATA CAN BE DELIVERED
BACK TO EACH SITE SO IN A
RESEARCH READY FORMAT, WE DON'T
STEAL THEIR DATA FROM THEM, THEY
CAN DO THEIR OWN RESEARCH AND
PASS THAT BACK TO THE SITE.
SO WE HELP THEM TO DO THEIR OWN
RESEARCH, BUT WE ALSO TAKE THAT
DATA FROM THERE AND TAKE IT
THROUGH GLOBAL REACH AND OTHER
MEANS BUT THE ONE THAT IS RIGHT
NOW REALLY FUNCTIONAL IS THIS
PEDIATRIC DATA COMMONS,
PEDIATRIC CANCER DATA COMMONS
BUILT BY A FANTASTIC GROUP IN
CHICAGO AND THEY DID NOT HAVE
ANY COMMONS FOR RETINOBLASTOMA.
ALL THE OTHER PEDIATRIC CANCER
CENTERS SAID WE WANT TO IoT
RETINOBLASTOMA, THIS HE CAME TO
US, THEY HEARD ABOUT DEPICT
HEALTH AND WE GIVE THEM THE
DATABASE SO IT IS MATCHED UP
REALLY WELL TO THE DATA WITH THE
COMMONS AND THAT CAN GO TO
REB-APPROVED RESEARCH.
SO WE DON'T HAVE TO JUDGE WHO IS
ALLOWED TO HAVE THE DATA BECAUSE
PEDIATRIC CANCER DATA COMMONS
HAVE ALL OF THAT IN PLACE WHICH
IS REALLY NICE.
BUT THE OTHER THING IS THAT DATA
CAN PRODUCE AND SUPPORT NATIONAL
GUIDELINES BECAUSE THE DATA IS
SPECIFIC TO WHATEVER SITES ARE
INVOLVED AND THAT CAN REFLECT
REGIONAL REALITY AND IN THAT WAY
PATIENTS BECOME ADVOCATES TO
HELP OTHER PATIENTS SO IT GOES
REALLY FULL CIRCLE AROUND.
AND AS I HAVE SHOWED YOU, THE
POWER OF THIS LONGITUDINAL DATA
GOING FORWARD HERE ALSO CAN BE
USED AS A PROPENSITY MATCH OUT
OF DEPICT HEALTH.
SO YOU CAN IMAGE AS THIS IS
REALLY SITE SPECIFIC, YOU CAN
TOOL WHICH DATA ARE YOU GOING TO
LOOK AT TO MATCH WHICH PATIENTS
IN WHICH LOCATION FOR WHICH KIND
OF CIRCUMSTANCES AND THAT IS
VERY EXCITING THINGS COMING
ARISING OUT OF OUR FIRST SITE
ONLY CLINICAL TRIAL.
SO JUMPING TO THIS PATIENT, YOU
MAY RECOGNIZE HIM BECAUSE ALL I
HAVE DONE IS TAKE HIS DEPICT
HEALTH TIMELINE TO MARCH 2036
ALL CONDENSET DOWN.
NOW HE IS ABOUT HERE, THAT SHOWS
HIS CHEMOPLAQUE THERE BUT HE IS
HERE WITH A WHOLE LIFE TO LEAD.
HE HAS HAD NO EXTERNAL RADIATION
BUT OTHER THINGS DONE TO HIS EYE
SO NOW WE CAN USE DEPICT HEALTH
TO FOLLOW HIS SECOND MALIGNANT
THAT WANT NEO ALARMS.
WE HOPE OUT OF THE DNA STUDIES
LED BY A COLLEAGUE OUT OF LA TO
ULTIMATELY DEVELOP BLOOD TESTS
THAT WILL SEE DNA COMING FROM
THE BLOOD FOR ANY CANCER
ANYWHERE, NOT JUST
RETINOBLASTOMA.
AND THAT CANCER SIGNAL, SO FAR
WE PUT A GRAB IN, DIDN'T GET IT
BECAUSE OUR PATIENTS AT RISK ARE
TOO RARE BUT FOR THE SYNDROME
THEY HAVE DATA TO SAY THIS CAN
PREDICT CANCER BEFORE IT IS
OTHERWISE EVIDENT.
SO THIS MEANS THIS IS A
SURVEILLANCE TEST THAT WILL BE
ORDERED BY A SIMPLE BLOOD TEST
ON SOME REGULAR INTERVAL BASED
ON THE DATA.
WE'RE GOING TO RESUBMIT THIS
WITH THE POWER OF PATIENTS WHO
ARE EAGER TO KNOW WHEN THEY ARE
GOING TO HAVE A SECOND CANCER.
SO THAT'S MY TALK.
I WOULD LOVE TO HEAR IF THERE
ARE QUESTIONS AND SUGGESTIONS
THAT COULD MAKE OUR WORK BETTER.
THANK YOU, AND ONLINE.
[APPLAUSE]
>> THANK YOU, CAUGHT ME A LITTLE
BIT OFFGUARD THERE.
WE WELCOME QUESTIONS AT THE MICS
OF COURSE.
I DO HAVE A FEW TO GET STARTED.
JUST ONE THAT CAME EARLY ON SO
YOU KIND OF ALLUDED TO IT, WHEN
DOES TUMOR FORMATION AND VISION
DETERIORATION START, IN UTERO?
AND HOW SOON CAN THE CHEMOPLAQUE
THERAPY START?
IS TIME OF THE ESSENCE OR IS
THERE A OPEN WINDOW FOR THERAPY
TO ACHIEVE SIGNIFICANT POSITIVE
OUTCOMES?
$$TRANSMIT
>> THAT IS A VERY GOOD
QUESTION/COMMENT.
WE AT 36 WEEKS GESTATION,
30 PERCENT WILL ALREADY HAVE A
TUMOR DETECTABLE BY INTENSE OC T
SCREENING.
SO SOME YOUNGER THAN THAT BEFORE
WE ARE READY TO DELIVER THEM AND
SOME OF THOSE IN THE STUDY WE
FIRST PUBLISHED ON THIS WERE
BORN EARLIER THAN THAT BECAUSE
THEY CHOSE TO BE BORN FOR OTHER
REASONS BUT THAT IS ABOUT THE
TIME WINDOW.
SO IF YOU LOOK AT THE BEAUTIFUL
WORK BY DAVID OOLBRENIK IN L.A.
ON HOW THE RETINOBLASTOMA FORMS
IN THE CODAL PRECURSORS AND THAT
IS HOW THEY START.
BUT PRESCREENING AT 36 WEEKS,
THAT IS A GOOD TIME AND WE DO
THAT ROUTINELY ACROSS CANADA BUT
THE U.S. DOES NOT DO THAT
BECAUSE OBSTETRICIANS SAY IF I
DELIVER AN EARLY TERM BABY
ELECTIVELY, I MIGHT BE SUED AND
THAT IS A PROBLEM BECAUSE IF
BORN AT 40 WEEKS, THEY COULD
HAVE A BIG TUMOR ALREADY.
THERE ARE OTHER WAYS TO FIND
TUMORS IN UTERO BY ULTRASOUND
AND PUBLISHED THAT BUT ANOTHER
FOUND ANOTHER ONE BY ULTRASOUND
AS IT IS A VERY DIFFICULT JOB.
LIN MURPHY DID A MRI STUDY ON
PREGNANT PEOPLE TO SEE IF HE
COULD FIND SOMETHING AND IT DID
NOT DELIVER NIGH USEFUL DATA.
SO THE BEST IS TO DELIVER THEM
AT 36 WEEKS AND SEE WHAT WE HAVE
GOT.
IN OUR NEXT STUDY, WE HAVE A .3
CHEMOPLAQUE DOSE AVAILABLE WHICH
WAS MANUFACTURED BUT NEVER USED.
WE WOULD PUT THAT ON A BABY THAT
HAD A LARGER TUMOR, NOT ONE YOU
COULD LASER OR FIND A FOCAL
POINT BUT EVEN A MACULAR TUMOR
YOU WOULDN'T WANT TO LASER
BECAUSE IT WOULD DAMAGE VISION
AND WOULD BE GREAT FOR A .3,
WITH BUT HAS NOT BEEN DONE.
$$TRANSMIT
>> THAT WAS A GREAT TALK.
WONDERING WHAT YOUR UPCOMING
CONTROL GROUP IS FOR PHASE 1
CHEMOPLAQUE?
>> IT IS RETRO EXPERTIVE.
$$TRANSMIT RETROSPECTIVE.
$$TRANSMIT
>> AND THE FDA WILL ALLOW THAT
IN THIS CASE?
>> WELL, WE HAD ALREADY DESIGNED
A RANDOMIZED STUDY AND SOME SAID
YOU COULDN'T DO THAT BUT I
THOUGHT IT WAS MICE BECAUSE IT
HAD A CROSSOVER AND MA MADE IT
ALL RIGHT ETHICALLY, I THOUGHT.
BUT AS THEY WALKED THROUGH THE
DOOR, THEY STATE RETROSPECTIVE
CONTROLS ARE SO GOOD, IT WOULD
BE IMMORAL FOR US TO ASK FOR A
RANDOMIZED STUDY.
>> VERY COMFORTING, THANK YOU.
$$TRANSMIT
>> AND APPARENTLY THIS NEW LOGIC
HAS PERMEATED IN OTHER DISEASE
SO OUR PLAN PHASE 3 AND NOW I
LEARNED WE DON'T NEED TO DO A
PHASE 2 BECAUSE OUR DATA IS SO
GOOD AND CAN MOVE TO A PHASE 3.
NEVER DONE CLINICAL TRIALS
BEFORE AND DON'T KNOW WHAT A
PHASE 3 IS, I DON'T HAVE TO DO
ALL OF THIS MYSELF SO SOMEBODY
DOES AND THAT WILL BE USED IN
DEPICT HEALTH IF I JUMP BACK IN
THE SLIGHT -- I DON'T KNOW IF
YOU CAN SEE IT.
THIS PROPENSITY DATA FROM EVERY
PATIENT WILL COME FROM THAT SITE
FROM ALL THE PATIENTS WHO DID
NOT GET THE PERFECTLY MATCHED
FOR PATIENTS WHO DID NOT GET
CHEMOPLAQUE.
>> THAT IS GREAT, THANK YOU.
>> ANOTHER ONE, YOU MIGHT HAVE
BEEN EXPECTING THIS.
AMAZING WORK.
CAN YOU SPEAK MORE OF THE
CONSEQUENCE SCORE?
WHICH FACTORS GO INTO THE
ESTIMATE?
IS THIS MORE OF A INTUITION OR
SET OF CHECKLIST CHECKS?
$$TRANSMIT
>> THE CONSEQUENCE SCORE WAS
MADE UP BY ME.
THOSE NUMBERS, I SAID WE HAVE TO
MAKE THE WORST EBRT AND STANDARD
FOR FAILURE IN OPHTHALMOLOGY
LITERATURE FOR RETINOBLASTOMA
PATIENTS AND THAT IS IN THE
LITERATURE EVERYWHERE.
SO I PUT 30 ON IT, ADDED EUA'S
WHICH HAVE CONSEQUENCES TOO BUT
GAVE IT A .5 AND THEN WE DID
DESIGN A LITTLE STUDY TO SAY ARE
THESE NUMBERS THE RIGHT GUESSES
BUT IT DOESN'T MATTER THE WAY WE
ARE HE USING IT BECAUSE THEY ARE
MATCHED ON BOTH SIDES WITH THE
SAME NUMBERS.
SO JUST IMPACT COUNTING HOW MANY
EVENTS HAPPENED, A DIFFERENT
IMPACT COMPARING ENUCLEATION OF
THE EYES VERSUS CHEMOPLAQUE.
BUT I DON'T KNOW ANY OTHER
CANCER THAT SHOWS THAT
CONSEQUENCE SCORE.
$$TRANSMIT
>> IT COULD BE APPLICABLE TO --
>> ABSOLUTELY AND MAYBE
APPLICABLE TO AMD.
AND I WOULD LOVE TO HEAR FROM
EMILY MORE ABOUT THESE THINGS
BECAUSE THE CHEMOPLAQUE IS
SUSTAINED RELEASE.
THERE IS LOTS OF WAYS AND IN OUR
FANTASTIC LUNCH I HAD WITH ALL
THE FELLOWS AND STUDENTS, THERE
ARE LOTS OF DRUGS YOU GUYS ARE
INVENTING OR DISCOVERING OR
WORKING ON FOR THE EYE, THIS
BEAUTIFUL ORGAN, THE EYE, THAT
TEACHES SO MUCH ABOUT THE BODY,
A CONSEQUENCE SCORE COULD BE A
RELEVANT THING TO EVALUATE
OUTCOMES.
BUT YES, RETINOBLASTOMA
INVENTION IS OF CONSEQUENCE.
NICHE WHY IS EXTERNAL THEME
RADIATION SUCH A RISK FACTOR FOR
SUBSEQUENT NEO PLASMS?
$$TRANSMIT
>> BECAUSE RADIATION INDUCES
CANCER PRE DISPOSITION, CHANGES
IN THE AREA AND IF YOU GO TO THE
SUITE, YOU WEAR A ZILLION LAYERS
OF PROTECTION BECAUSE THERE IS
RADIATION EVERYWHERE AND THAT IS
WHAT THE DATA SHOWS.
I DON'T KNOW OF ANY SCIENCE
PROVING THAT BUT THE MOST COMMON
KAEPBS SERIOUS ARE MELANOMA AND
IN WHIM HIDDEN TILL VERY
RECENTLY WHEN WE LOOKED AT THE
DATA WAS OVARIAN BLASTOMA.
THAT WAS A PARTICULARLY NASTY
ONE BECAUSE OVARIAN CANCER GETS
MASKED AND CALLED FIBROIDS SO
THAT IS THE INHERENT RD1 DAMAGED
GENE.
>> ONE MORE QUESTION ONLINE.
THANK YOU FOR A WONDERFUL TALK.
PERHAPS NOT ENTIRELY RELEVANT
BUT CAN YOU SHARE ANYTHING ABOUT
THE CANADIAN HEALTH INSURANCE
LANDSCAPE?
THE THERAPY DOESN'T SEEM
EXTREMELY EXPENSIVE.
ARE THESE PROCEDURES COVERED OR
IS CHARITABLE SUPPORT NEEDED?
>> THE CANADIAN HEALTHCARE
SYSTEM COVERS BASIC CARE, NONE
OF THESE ARE CHARGED TO THE
PUBLIC.
THE CHEMOPLAQUE IS SO FAR
RESEARCH AND WE DON'T KNOW THE
PRICE OF THAT.
ONCE IT GETS THAT FAR AND IS
ALLOWED TO BE SOLD, I DON'T
THINK COMPARED TO THE COST OF
INTERVENTIONAL RADIOLOGY IN AN
INTERVENTIONAL SUITE WITH ALL
THE DIFFERENT THINGS IS PRETTY
PLUS.
SO I THINK IT IS A REALLY GOOD
THING FOR GLOBAL RED THOUGH
BLASTOMA BECAUSE IF YOU PUT IT
IN A PATIENT IN AFRICA, THE
CANCER JUST DISAPPEARS.
BUT COST IS, I AM SORRY, CAN'T
SPEAK TO THE U.S. AS IT IS VERY,
VERY DIFFERENT THERE.
$$TRANSMIT .
>> THANK YOU VERY MUCH FOR A
WONDERFUL TALK AND ALL YOUR
DISCUSSION AND THANK YOU ALL FOR
BEING HERE.
WE REALLY LOOK FORWARD TO YOUR
NEXT TRIAL TO SEE WHAT HAPPENS
WITH THESE LITTLE CHILDREN AND I
THINK IT IS HEART WARMING YOU
ARE DOING THIS GLOBALLY AROUND
THE WORLD AND THAT PEOPLE ARE
GETTING BENEFITS FROM YOUR
RESEARCH WHICH IS FANTASTIC.
I WELCOME ALL OF YOU TO A
RECEPTION OUTSIDE AND THANK YOU
VERY MUCH FOR ATTENDING AND FOR
ALL THESE QUESTIONS HERE AND
ONLINE AND THANK YOU FOR BEING
HERE, BRENDA, REALLY APPRECIATE.