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>>OUR SPEAKER TODAY
IS DR. ANDREA HAYES-DIXON.
ON OCTOBER 22 SHE WAS APPOINTED
AS DEAN OF MEDICINE AND SERVES
AS ASSOCIATE CANCER CENTER AT
HOWARD.
SHE EARNED HER MD DEGREE FROM
DARTMOUTH COLLEGE.
SHE ALSO COMPLETED A MOLECULAR
BIOLOGY FELLOWSHIP AT THE
UNIVERSITY OF CALIFORNIA
SAN FRANCISCO AND WENT ON TO
COMPLETE A PEDEIATIC
PHARMACOLOGY RESIDENCE IN
MEMPHIS, TENNESSEE.
SHE CONTINUED HER ACADEMIC
JOURNEY BY COMPLETING HER
PEDIATRIC SURGERY FOALSHIP AT
THE TORONTO HOSPITAL FOR SICK
CHILDREN.
AND IN 2002, DR. HAY ESTIMATE
THAD DIXON BECAME THE FIRST
BLACK PEDIATRIC BOARD CERTIFIED
SURGEON IN THE UNITED STATES,
SHE WENT WENT ON TO COMPLETE A
MELANOMA AND SARCOMA FELLOWSHIP
IN TEXAS AT M. D. ANDERSON
CANCER CENTER WHILE SHE WAS
RECRUITED TO STAY ONAC FACULTY,
WHILE THERE SHE WAS AWARDED
ROBERT WOOD JOHNSON FOUNDATION
THAT ALLOWED HER TO FUND HER
RESEARCH IN MELANOMA SARCOMA AND
ANGIOGENESIS.
SHE SIGN SIMULTANEOUSLY
CONDUCTED CLINICAL RESEARCH AND
COMPLEELTED THE FIRST
CYTOREDUCTIVE SURGERY AND HYPER
THERMOGENESISSIC INTRA PERO TON
EEL CHEMO TERRAPY WITH
SARICOSEIS IN 2005.
SHE LATER ESTABLISHED SAFE CHEMO
THERAPY DOSING USING HIPECKS FOR
PATIENTS.
SHE CONTINUED TO IMPACT THE
FIELD OF SARCOMA BY MASSING THE
LARGE OF RESEARCH INFORMATION.
IT'S AN AGGRESSIVE FORM OF
CANCER AND VIA RESECTION AND
HYPO[INDISCERNIBLE] HAS IMPROVED
SURVIVAL FROM 30-60% IN THIS
POPULATION.
DR. DIXON CONTINUES TO RECEIVE
FUNDING IF ARE HER RESEARCH AND
IS NATIONALLY AND INTERNATIONAL
KNOWN FOR PIONEERING WORK FOR
[INDISCERNIBLE] CHILDREN.
DURING HER TIME AT M. D.
ANDERSON SHE SERVED AS CHIEF THE
SURGERY AND SHE WENT ON TO
BECOME THE SURGEON AND CHIEF AND
DIVISION AND CHIEF AT THE
PEDIATRIC UNIVERSITY AT UNC
CHILDREN'S HOSPITAL PRIOR TO
RETURNING HER CURRENT ESTEEMED
ROLE AT HOWARD.
ADDITIONALLY SHE SERVED ON THE
EXECUTIVE COMMITTEE OF THE
COMRN'S ONCOLOGY GROUP SARCOMA
COMMITTEE FOR THE PAST 10 YEARS,
A POSITION SHARED BY ONLY 2
OTHER PEDIATRIC SURGEONS IN THE
COUNTRY.
SHE EARNED MEMBERSHIP INTO THE
AMERICAN SURGICAL ASSOCIATION
AND SERVED AS THE CHAIR OF THE
CANCER COMMITTEE FOR THE
AMERICAN PEDIATRIC SURGICAL
ASSOCIATION.
SHE HAS ALSO BEEN SELECTED TO
THE PEDIATRIC DISEASE QUERY, A
NATIONAL COMMITTEE THAT VETS
EVERY PUBLICATION ON PEDIATRIC
CANCER AND SUMMARIZES THEM FOR
THE NATIONAL CANCER INSTITUTE.
SHE SERVED AS A PAST PRESIDENT
FOR THE SOCIETY OF BLACK
ACADEMIC SURGEONS AND IS A
REGION OF THE AMERICAN COLLEGE
OF SURGEONS.
DR. HAY ESTIMATE THAD DIXON WAS
APPOINTED BY FORMER PRESIDENT
TRUMP TO THE NATIONAL CANCER
ADVISORY BOARD WHICH REPORTS TO
THE DIRECTOR OF THE NATIONAL
CANCER INSTITUTE AND THE
SECRETARY OF HEALTH.
FINALLY DR. HAYES-DIXON HAS
PUBLISHED DOZENS OF BOOKS AND
PUBLICATIONS AND ENJOYS FAC ULGT
EXPE RESIDENTS.
NOW PLEASE HELP ME WELCOME OUR
SPEAKER DR. HAYES-DIXON WHOSE
PRESENTATION IS ENTITLED THE
JOURNEY TO DISCOVERING A NOVEL
PROCEDURE FOR CHILDREN WITH
ADVANCE ABDOMINAL TUMORS.
>>THANK YOU FOR THE PHENOMENAL
INTRODUCTION, AND I'M VERY
PLEASED TO BE WITH YOU TODAY TO
TALK ABOUT MY JOURNEY IN TRYING
TO ACHIEVE SOME UNDERSTANDING OF
A VERY RARE CANCER THAT I TAKE
CARE OF.
WHAT I WANT TO SHARE WITH YOU
TODAY IS WHAT'S HAPPENED OVER
THE LAST 20 YEARS OR SO OF MY
CAREER AND IN THAT I HAVE REALLY
LEARNED A LOT AND HOPE TO SHARE
THAT WITH YOU.
FIRST OF ALL I HAVE NO
DISCLOSURES AND I HOPE BY THE
END OF THE TALK, YOU WOULD BE
ABLE TO UNDERSTAND HOW IT IS IN
DEVELOPING A PATH TO DISCOVERING
SOMETHING THAT'S NEW, HOW DO YOU
INNOVATE.
WHAT QUESTIONS DO YOU ASK TO
UNDERSTAND A DISEASE THAT HASN'T
BEEN OOBD IN THE PAST.
HOW TO APPROACH WHAT HAS BEEN
CALLED AN IMPOSSIBLE TASK, WHAT
IS THIS RARE TUMOR I TAKE CARE
OF CAUSE TD DESMODEL CITIZEN
PLASTIC SMALL ROUND CELL TUMOR,
SO WHAT ARE THE OUTCOMES OF
THESE APPLICATIONS.
SO BILET END OF THE TALK, I HOPE
YOU WILL UNDERSTAND OF HOW I
THOUGHT THROUGH THE PROCESS OF
UNDERSTANDING THE ORIGIN OF THE
BASIC TUMOR, TAKING THE SCIENCE
BACK TO MY LABORATORY AND
FIGURING OUT HOW THE TUMOR GROWS
AND SPREADS.
SO MULTIPLE ABDOMINAL IMPLANTS
IS HOW I WAS INTRODUCED TO THIS
DISEASE.
SO WHEN I WAS IN TRAINING I MET
A 12 YEAR-OLD BOY WHO WE OPENED
THROUGH THE OPERATING ROOM
THROUGH A LONG MIDLINE INCISION
AND ENCOUNTERED HUNDREDS OF
THOUSANDS OF TUMORS IN THE
ABDOMEN, AND MY TEACHER SAID
THERE'S NOTHING WE CAN DO FOR
THIS CHILD AND I WAS TASKED WITH
LETTING THE PARENTS KNOW THERE
WERE NO OPTIONS MEDICALLY OR
SURGICALLY.
AND I DEPARTMENT LIKE THE
FEELING AND I WANTED TO
UNDERSTAND WHAT DOES IT MEAN
WHEN A PATIENT HAS MULTIPLE
ABDOMINAL TUMOR IMPLANTS AND WHY
IS IT SOMETHING THAT IS
IMPOSSIBLE TO TAKE CARE OF?
SO WHAT I LEARNED IS THAT THIS
INTRA DOMAININAL METASTASIS IS A
RARE FORM OF TUMOR DISSEMINATION
IN CHILDREN, CALLED
SARCOMATOSEIS AND UP UNTIL I
STARTED MANAGING THESE PATIENTS
IT WAS REALLY THOUGHT THAT IT
WAS IMPOSSIBLE TO REMOVE
HUNDREDS OR THOUSANDS OF TUMORS
IN 1 PATIENT AND RESTORE THEM TO
HEALTH.
AND CHILDREN WHO HAVE THIS
DISEASE WERE BASICALLY ALWAYS
OFFERED PALLIATIVE CARE BECAUSE
THERE REALLY WASN'T ANY
TREATMENT OPTIONS.
SO I DEVELOPED A NEW APPROACH
FOR SOME OF THESE ABDOMINAL
CANCERS IN CHILDREN WHEN I WAS
AT M. D. ANDERSON CANCER CENTER
AND WHAT I LEARNED WAS THAT AN
AGGRESSIVE SURGICAL APPROACH CAN
BE COMPLETED AND IS WARRANTIED.
I HAVE DONE AND REMOVED TUMORS
AND UP TO A COUPLE THOUSAND
TUMORS IN PATIENTS, TONIGHT.
TAKE A LONG TIME IN THE
OPERATING ROOM, SOMETIMES UP TO
APPROXIMATE 20 OR 22 HOURS.
BUT REMOVING ALL THESE LARGE MA
LIGNABT IMPLANTS CAN RESULT IN A
GOOD OUTCOME AND THAT'S WHAT I
WANT TO SHARE WITH YOU TODAY.
SO IN DEVELOPING THIS,A PROACH
WHERE WE PROVIDE
HYPOTHERMOGENESISSIC CHEMO
THERAPY, I PERFORMEDLET FIRST 1
IN 2006.
THAT'S THE FIRST 1 DONE IN A
CHILD IN THE WORLD.
AND SUBSEQUENTLY HAD TO DO A
PHASE 1 TRIAL, FOLLOWED BOO I A
PHASE 2 TRIAL BUT IN BETWEEN
ANALYZE THE TOXICITY SO THAT WE
COULD UNDERSTAND MORE ABOUT HOW
IT AFFECTED PATIENTS AND AVOID
ANY TOXICITYS THAT MIGHT BE.
AND THE TRIAL WAS PUBLISHED IN
MAY OF 2018.
SO REALLY WHAT THAT TOLD US IS
THAT IF YOU LOOK AT THIS, WITH
THE STUDENTS THAT PAY ATTENTION
TO THE TIMELINE THAT IT TOOK,
DECADES REALLY TO ESTABLISH A
NEW TREATMENT IN A NOVEL SURGERY
IN A YOUNG POPULATION.
SO LET'S FIRST START OFF TALKING
ABOUT THE PATIENTS AND WHAT THE
PATIENTS WOULD LOOK LIKE.
SO THIS IS A FIRST PATIENT, SO 5
YEAR-OLD MALE, PRECEPTS WITH
ABNORMALITIES DOLLINAL
DISTENTION AND DISCOMFORT FOR 1
WEEK.
THEY PRESENT TO AN EMERGENCY
ROOM WHERE A CT SCAN WAS
OBTAINED AND THE PHYSICIAN ON
CALL THOUGHT THE PATIENT HAD
CONSTIPATION, HOWEVER, I WILL
SHOW YOU THE SCAN WHERE THERE
WERE MULTIPLE MASSES AND
ASCITES, AND THE ER DOCTOR TOLD
THE PATHWAY GIVES PARENTS THERE
WAS NOT ANYTHING THAT COULD BE
DONE WITH THIS NEW PROGNOSIS.
I KNOW MANY OF YOU ARE NOT
FAMILIAR WITH CT SCANS BUT THIS
IS FLUID BETWEEN THE LIVER AND
ALL THESE GRAYISH CIRCLINGS ARE
TUMOR IMPLANTS IN THIS CROSS
SECTION OF THE ABDOMEN.
IF YOU LOOK OVER HERE TO THE
RIGHT SIDE, YOU SEE THERE'S A
LARGE AMOUNT OF FLUID, THE BOWEL
FLOATING IN THE TUMOR AND TINY
TINY TUMOR IMPLANTS ON THE PERO
TON EEL SURFACE.
NOW IN 5 YEAR-OLD BOY WAS 1 OF
THE FIRST PATIENTS, ACTUALLY WAS
THE FOURTH PATIENT WE TOOK ON
OUR CLINICAL TRIAL AND WE WERE
ABLE TO SUCCESSFULLY REMOVE ALL
THESE HUNDREDS OF TUMORS AND
THIS IS HIS CAT SCAN AFTER
SURGERY AND AFTER THE PROCEDURE
WHERE YOU CAN SEE THERE'S
ABSOLUTELY NO TUMORS AND THAT
THERE'S NOW FLUID NO ASCITES,
AND HE WENT ON TO GEORGETOWN
UNIVERSITY, I BELIEVE SHE SHOULD
BE GRADUATING IN A YEAR OR 2.
THIS IS ANOTHER EXAMPLE OF AN 8
YEAR-OLD BOY, SAME TUMOR.
WHAT I'M TRYING TO POINT OUT AND
WHY THIS DISEASE IS SO DIFFICULT
TO UNDERSTAND AND TREAT IS IT
LOOKS VERY DIFFERENT IN EVERY
SINGLE PATIENT.
IT'S NOT LIKE COLON CANCER WHERE
THERE'S A LUMP IN THE COLON OR
BREAST CANCER WHERE YOU THERE'S
1 LUMP IN THE BREAST, YOU KNOW
WHERE IT COMES FROM, YOU PREDICT
WHAT IT'S GOING TO DO.
THIS TUMOR PRESENTS IN MANY
DIFFERENT WAYS IN DIFFERENT
PATIENTS AND HERE'S THE SAME
DISEASE INSTEAD OF WITH MANY OF
HUNDREDS OF STIEWMORS AND
ASCITES, AND YOU SEE 1, 2, 3,
AND I LABELED IT HERE AND 1, 2,
3, OF JUST 3 LARGE TUMORS, 1 OF
THEM BEING WEDGED PARTICULARLY
BETWEEN THE BLADDER AND THE RUCT
UMKC AND I WILL SHOW YOU MORE
IMAGES OF THAT SUBSIDIARY
QUEBTLY.
SO ANOTHER EXAMPLE OF A 13
YEAR-OLD MALE WHO WAS IN A
SURFING ACCIDENT AND THOUGHT
THAT HIS ABDOMINAL PAIN WAS FROM
SURFING.
HE HAD ABDOMINAL DISTENTION, NO
FATIGUE, NO VOMITING, NO FEVER,
NO CONS TIARASIPATION OR
DIARRHEA, HE HAD A CT SCAN AND
AGAIN IT LOOKS VERY DIFFERENT.
WE HAVE THE LIVER FLOATING IN
THE MIDDLE OF THE
ASCITEXPECTATIONS S, ABOUT YOU A
THICKENED AREA IN THE TUMOR OF
THE RIGHT DIAPHRAGM.
AND I WILL SHOW YOU ISHT
OPERATIVE IMAGES OF THIS
SHORTLY.
AND IN ADDITION TO BEING INTRA
ABDOMINAL, AND PERO TON EEL AS
WELL, SO AGAIN A CONFUSING
PICTURE OF HOW TO UNDERSTAND
THIS DISEASE.
HERE'S A 22 YEAR-OLD.
THIS PATIENT HAS NO FLUID, NO
ASCITES, AND HERE'S THE LIVER,
THIS IS THE RIGHT DIAPHRAGM AND
THE GRAYISH AREA IS TUMOR ON THE
RIGHT DIAFRAM.
WHEN YOU LOOK IN THE PELVIS, YOU
SEE THIS TUMOR WEDGED BETWEEN
THE BLADDER AND THE RECTUM AND
THE WAY I WAS TOUT IN RESIDENCY
WAS WHEN YOU HAVE A PATIENT
WHERE YOU CAN'T IDENTIFY A SPACE
BETWEEN THE ORGANS AND THE ORGAN
HAS TO BE REMOVED IN ORDER TO
GET NEGATIVE MARGINS AND BE ABLE
TO PROVIDE THE PATIENT WITH GOOD
LONG-TERM OUTCOME.
IN FACT, IN THIS PATIENT AND IN
MANY OTHERS I SEE WITH THIS
DISEASE, I WAS ABLE TO TAKE THIS
TUMOR OUT IN THE RECTUM AND
BRADDER REMAIN INTACT, THAT'S
PART OF THE TECHNIQUE I HAD TO
TEACH MYSELF OVER THE YEARS.
HERE'S ANOTHER REASON THIS IS SO
DIFFICULT, HERE'S A RADIOLOGIST
IMPRESSION OF A CT SCAN, THEY
ARE POINTING OUT THE NUMBER OF
LESIONS THEY SEE, THE SIZE OF
THE LESIONS AND WHAT THEY
ACTUALLY--WHAT I ACTUALLY FOUND
WHEN I WENT TO SURGERY WAS MUCH
MORE THAN THAT, OF ALMOST 3000
TUMORS IT TOOK ME 17 HOURS, NO
FAULT OF THE THE RADIOLOGIST,
THIS IS JUST A VERY EVASIVE
DISEASE.
AND THE NEXT IRMPAGS WILL BE
INTEROPERATIVE IMAGES AND THIS
IS THAT SAME PATIENT, THE
SPLEEN, THE DISTAL PANCREAS AND
THE [INDISCERNIBLE], ALL THOSE
WHITE SPOTS ARE TUMORS, AGAIN
IT'S A SLICER VIEW OF THE SAME
THING, WITH THE MEASUREMENT TAPE
OF ABOUT 15-CENTIMETERS FOR
CONTEXT AND MULTIPLE, MULTIPLE
TUMORS, TOO NUMEROUS TO COUNT IN
THIS IMAGE.
HERE'S ANOTHER IMAGE OF THE
PATIENT WITH THE SAME DISEASE,
WE ARE LOOKING DOWN INTO THE
PELVIC CAVITY, THE PATIENTS FEET
ARE AT THE TOP OF THE SCREEN,
HEAD IS AT THE BOTTOM, THIS IS
LEFT, THIS IS RIGHT AND INCISION
IS DOWN THE LEFT OF THE ABDOMEN,
MY HAND IS ON THE COLON AND
RECTUM AND THE SMALL TUMOR
NODULES HERE ARE THE DISEASE AND
YOU SEE THEY ARE WHITE IN COLOR
WHICH IS IMPORTANT TO RECOGNIZE
IS THAT MEANS THAT THEY HAVE
VERY LITTLE ANGIOGENESIS, THEY
HAVE VERY--THE TUMORS ARE NOT
MAKING THEIR OWN BLOOD VESSELS
AS WELL SO THEY WILL USUALLY
STOP GROWING AND I WILL SHOW YOU
LATER ABOUT WHY THIS IS
IMPORTANT.
THIS PATIENT RECEIVED CHEMO
THERAPY AND THEREFORE THE TUMORS
ARE THESE WHITE COLOR BUT IF YOU
LOOK CAREFULLY, ESPECIALLY THOSE
OF YOU ON A SCREEN THAT YOU CAN
GET CLOSER TO, THERE'S A TUMOR
NODULE HERE AND HERE AND HERE,
ALL OF THESE ARE TUMOR NODULES,
OWL OF THESE HERE ARE TUMOR
NODULES AS WELL AS HERE AND IF
YOU LOOK CLOSELY THERE'S A TINY
TINY WHITE DOT, SO JUST IN THE
IMAGE IT'S PROBABLY ABOUT 40
TUMORS.
NOW WE'RE LOOKING UP INTO A
DIFFERENT PATIENT ON THE RIGHT
UPPER AREA OF THE ABDOMINAL
CAVITY.
SO THE HEAD OF THE PATIENT IS TO
THE RIGHT, THE FEET ARE TO YOUR
LEFT.
THE LIVER IS UP TO THE RIGHT.
THIS IS THE DIAPHRAGM.
THIS IS PAISKLY HOW THE INITIAL
PATIENT THAT I SAW LOOKED WHEN
WE SAID THERE WAS NOTHING THAT
COULD BE DONE AND THAT'S BECAUSE
WE'RE TAUGHT WHEN YOU SEE THIS
MUCH DISEASE ON AN ORGAN THAT
THE ENTIRE ORGAN NEEDS TO BE
REMOVED AND I WILL SHOW YOU HOW
I REMOVE THIS TUMOR WITHOUT
REMOVING THE DIAPHRAGM.
THIS IS ANOTHER IMAGE OF OF THE
SMALL BOWEL, THIS INSTRUMENT,
THIS FORCEP IS ABOUT 3-INCHES IN
DIAMETER AND YOU CAN SEE HOW
SMALL THESE TUMORS ARE.
YOU CAN SEE THREAR IN THE SMALL
INTESTINE AND THESE ARE PURPLE
IN COLOR BECAUSE I LIFTED UP THE
PERITONEUM AND REMOVED THE BLOOD
SUPPLY AND THAT'S WHY IT'S THE
PURPLE COLOR AND IN THIS
PARTICULAR PATIENT I REMOVED THE
NODULES WITHOUT REMOVING THE
INTESTINE.
THIS IS AN IMAGE OF THE OMENTA,
THE FATTY DRAPE THAT COVERS THE
BOWEL AND YOU CAN SEE SMALL
WHITE DOTS AND TUMORS IN THAT AS
WELL.
SO BACK TO THE PATIENT, I WAS
SHOWING YOU WITH A TUMOROT
DIAPHRAGM.
THE HEAD IS TO YOUR RIGHT, FEET
ARE ON THE LEFT.
THIS IS THE BELLY BUTTON, THE
INCISION IS RIGHT DOWN THE
MIDDLE, THESE RETRACT TRACTORS
ARE HOLDING UP THE ABDOMINAL
WALL SO I CAN SEE A BIT BETTER,
THIS IS THE LIVER SO IF YOU LOOK
CAREFULLY HERE, THIS IS THE
TENDON OF THE DIAPHRAGM, THIS IS
DIAPHRAGM MUSCLE, AND I'M
DISSECTING IT OFF OF THIS AREA.
YOU CAN SEE THAT THERE'S--TUMOR
NODULES ARE ALL IN THE SHEET OF
PERITONEUM AND THE DIAPHRAGM IS
INTACT, SO AT THE END OF THAT,
YOU HAVE A SHEET OF TUMORS ON
THE PERITONEUM.
AND YOU CAN SEE I REMOVED THE
TUMOR WITHOUT REMOVING THE
BLADDER AND RECTUM.
SO THIS IS THE LARGE TUMOR MASS,
THIS IS THE THIN LAYER OF
PERITONEUM, AND YOU CAN SEE THE
GREEN TOWEL THROUGH THIS VERY
THIN LAYER AND THE PERITONEUM,
THAT COVERS ALL OF THE ORGANS IN
THE ABDOMINAL CAVITY AND GOD IT
THERE TO KEEP THE ORGANS FROM
TICKING TOGETHER SO THAT YOUR
BLADDER DOESN'T TICK TO YOUR
RECTUM, THE LIVER DOESN'T STICK
TO THE STOMACH, ET CETERA, AND
FOR REASONS I'M TRYING TO LEARN,
IT SITS ON TOP, IT DOES NOT
INVADE INTO THE ORGANS AND'S WHY
WE'RE ABLE TO REMOVE THIS WHOLE
PERITONEUM, THIS WAS ON THE
BLADDER AND THIS IS RIGHT AND
LEFT AND LEAVE THE MAJOR ORGANS
IN INTACT AND WHAT THAT LOOKS
LIKE AFTER THE RESECTION IN THE
PATIENT, AGAIN THIS PATIENT'S
FEET ARE AT THE TOP OF YOUR
SCREEN, HEADS AT THE BOTTOM OF
THE SCREEN, THIS CLAMP IS ON THE
BLADDER AND THE FORCEPS HERE IS
POINTING TO THIS IN THE MALE
PATIENT, THIS IS VERY IMPORTANT
LATER ON WHEN I TALK ABOUT
SCIENTIFICALLY HOW I FIGURED OUT
WHERE THIS TUMOR COMES FROM AND
HOW IT GROWS.
THIS IS THE SURFACE OF THE
RECTUM HERE, THIS IS THE RIGHT
VAS, DEFERENCE, AND THE GOING TO
THE RIGHT AND LEFT TESTICLE AND
SOME VASCULATURE INTERNAL ILIAT
ARTERIES.
SO THIS OBSERVATION THAT PRETTY
MUCH FOR EVERYBODY PATIENT I WAS
CUTTING TUMOR OFF THESE SEMINOLE
VESICLES LED TO A DISCOVERY I
WILL TELL YOU ABOUT LATER.
SO ALL THE IMAGES HAVE BEEN A
DIAGNOSIS OF DESMODEL CITIZEN
PLASTIC SMALL TUMOR AND THIS IS
WE DON'T KNOW THE TUMOR OF
ORINIGEIN.
IT'S QUITE RARE, THERE MIGHT BE
200 CASES IN THE UNITED STATES.
MOST PATIENTS ARE MALE AND THE
MEDIAN AGE IS ABOUT 18 RANGING
FROM ABOUT 5-25 YEARS OLD, MOST
COMMONLY.
THE PRESENTING--VERY, VERY POOR,
THEY MAY BE 10 OR 15% OF THE
PATIENTS WERE SURVIVING LONGER
THAN 5 YEARS AND THIS WAS
DESPITE AGGRESSIVE CHEMO
THERAPY, RADIATION THERAPY DONE
BY MY PREVIOUS COLLEAGUES.
INTERESTING THING IS THAT THIS
NEVER PRESENTS WITH 1 KIND.
EVERY PATIENT HAS METASTASIS,
WHICH IS A MISNOMER IN THIS
PARTICULAR CASE, BUT ALL OF THE
PEASHTS HAVE MORE THAN 1 TUMOR
AT THE TIME OF DIAGNOSIS.
IT'S A VERY YOUNG TUMOR FIRST
DESCRIBED BY [INDISCERNIBLE]
FROM 1989 FROM MEMORIAL SLOAN
KETTERRING CANCER CENTER AND IT
HAS A FUSION PROTEIN THAT'S VERY
CHARACTERISTIC, A TRANSLOCATION
BETWEEN THE 11th AND 13th
CHROMOSOME RESULTING IN A EWING
SARCOMA AND WILM'S TUMOR FUSION
PROTEIN SO BIOLOGICALLY THE
TUMOR BEHAVES LIKE A EWING SORRY
COMA AND A WILM'S TUMOR, AND
THIS IS THE TUMOR IN EVERY CASE.
AND EVERY TIME WE KNOW IS THAT
THE CHROMOSOME 22 TRANSLOCATES
TO 11 AND YOU GET A FUSION GENE
BUT WE DON'T KNOW HOW THE DSRCT
DEVELOPING AFTER THIS POINT.
WE THINK IT PROBABLY ARRIVES
FROM THE MESOTHELIOMA EPITHELIAL
CELLS AND DIFFERENTIATION
BECAUSE IT'S IN THE PERITONEUM
AND THE PLURIPOTENT CELLSA.
THE ORIGIN WE THINK ARE FROM
HIGHLY UNDIFFERENTIATED
MESSENTERIEN CHIMMAL CELLS AND
THAT'S BECAUSE WE SEE IT IN LATE
STAGES IN THE BONE AND BRAIN.
AS I SHOWED YOU THE TUMORS ARE
SOLID AND FIRM, THE YELLOWISH
GRAY SURFACE RESULTS AFTER CHEMO
THERAPY, PRIOR TO CHEMO THERAPY,
THEY'RE VERY HEMORRHAGIC AND
NECROTIC AND THEY CAN BE SMALL
AND LARGE.
THIS IS A BIOPSY I TOOK FROM 1
OF MY PATIENTS IN THE
[INDISCERNIBLE] TO SHOW THE
REASON THE TUMOR HAS THIS NAME
AND WHY IT'S SO CHALLENGING TO
TREAT AND UNDERSTAND.
YOU CAN SEE HERE A HIGH POWER,
THIS IS UCD SMALL ROUND BLUE
CELLS WHICH ARE MITOTICALLY
ACTIVE IN DIVIDING CELLS AND
THEN YOU SEE THESE LIGHTER
COLORED STROMAL COMPONENT THAT'S
FIBROTIC, IT'S NOT VERY
CELLULAR, THERE ARE NO CELLS
THAT ARE DIVIDING AND IT LOOKS
VERY QUIET SO TO SPEAK.
NOW THIS SMALL ROUND BLUE CELL
COMPONENT THAT IS RAPIDLY
DIVIDING ARE THE CELLS THAT ARE
TARGETED BY CYTOTOXIC CHEMO
THERAPY.
SO WHEN THE CHEMO THERAPY IS
GIVEN PRIOR TO SURGERY, THESE
CELLS DIE BECAUSE OF THE CHEMO
THERAPY ABOUT THESE FIBROTIC
BANDS IN BETWEEN 2 NOT IS THAT'S
WHY THE TUMORS HAVE THE WHITE
COLOR I SHOWED YOU BEFORE AND
THAT'S WHAT LEFT FOR THE SURGEON
TO RESECT BACK AFTER THE CHEMO
THERAPY HAS KILLED THESE SMALL
ROUND BLUE CELLS BETTER IN
MITOSIS.
SO THIS IS A SPECIMEN FROM A
PATIENT OF MINE AFTER CHEMO
THERAPY.
SO YOU CAN SEE THIS TUMOR IS
MAYBE ABOUT 2-3-MILLIMETERS BUT
LOOKING AT HIGH POWERED 1 FROM 4
X TO 4 D X, YOU SEE THAT THERE'S
A VERY SMALL NEST OF THESE ROUND
BLUE CELLS AND THE LARGE
COMPONENT OF THIS FIBROUS
STRANDS THAT HAVE NO CELLS IN
THEM AND THIS IS A RESULT OF
EFFECTIVE CHEMO THERAPY REDUCING
THOSE DIVIDING CELLS TO VERY
MINIMAL.
THIS IS ANOTHER TUMOR IMPLANT IN
THE PERITONEUM.
AND YOU SLEEP APNEA AND OBESITYY
IT ON EITHER SIDE.
--YOU SEE IT ON EITHER SIDE.
I WAS SURPRISED FIRST TIME I SAW
THIS FROM A PATIENT I REMOVED
THE TUMOR FROM IS THIS THESE
CELLS NEXT TO THE TUMOR THAT
ACTUALLY IS TUMOR IN THERE AS
WELL, SO IF YOU LOOK AT THE
PERITONEUM HERE, YOU SEE THERE'S
ACTUALLY TUMOR ADJACENT TO THE
PERITONEUM NODULE WHICH IS WHAT
MAKES MOOY TAKE OUT A WIDER
PIECE WHEN I DO SURGERY, NOW
THESE OF COURSE I COULD NOTE SEE
WITH MY EYES AND I WANTED TO
KNOW EVEN MORE ABOUT WHAT I
COULDN'T SEE WITH MY EYES.
SO I REMOVED THIS PIECE OF
PERITONEUM AND VERY
INTERESTINGLY WHAT YOU FIND AND
GROWINGSLY AND WHEN YOU LOOK THE
TUMOR HERE WHERE YOU SEE THE
SMALLER IN BLUE AND DIVIDING
CELLS AND IMMUNE CELLS IN THERE
AS WELL.
SO HERE'S THE PROBLEM.
IF I AS A SURGEON GO IN AND
REMOVE ALL THESE TUMORS AND I
CAN'T SEE THESE MICROSCOPIC
CELLS, OBVIOUSLY THE TUMOR COULD
GROW BACK.
SO, WHAT THE HYPER
THERMOGENESISSIC CHEMO THERAPY
DOES IS PENETRATE THIS VERY THIN
LAYER OF PERITONEUM WHERE WE
DON'T SEE ANY GROSS TUMOR AND
KILLS THOSE MICROSCOPIC CELLS SO
THAT THE TUMOR DOES NOT REGROW.
SO THE WAY THE HYPER
THERMOGENESISSIC CHEMO THERAPY
WORKS THIS IS JUST A CARTOON
DIAGRAM AND ALL THE EQUIPMENT
LOOKS DIFFERENT FROM DIFFERENT
COMPANIES BUT THE CONCEPT IS
THAT THE PATIENT IS LYING IN THE
OPERATING ROOM, AN INCISION MADE
DOWN THE MIDDLE, THE SURGERY IS
DONE AS WE REMOVE THE TUMORS AS
I PREVIOUSLY SHOWED YOU AND THE
CHEMO THERAPY DRUG IS
INFISCHERRED INTO THIS TUBE,
COMES OUT OF THE OTHER TUBE, THE
ABDOMEN DISTENDS WITH FLUID.
YOU GENTLY PRESS ON THE
ABDOMINAL WALL TO AGITATE THE
FLUID SO IT EVENLY CIRCULES IN
THE CAVITY AND THERE'S A
TEMPERATURE PROBE CONNECTED TO A
MONITOR THAT TELLS ME THAT IN
EVERY PART OF THE ABDOMINAL
CAVITY THE HYPOTHERMOGENESISSIC
CHEMO THERAPY IS REACHING THAT
AREA.
AND OF COURSE IT HEATS IT AND
RECIRCULATES IT.
THIS HAPPENS FOR AN HOUR AND A
HALF IN THE OPERATE HAPPENING
ROOM WHILE THE PATIENT'S
SLEEPING IN THE OPERATING ROOM
AT 41-DEGREES CELSIUS, THIS IS
HOW IT LOOKS, THIS IS THE IN
FLOW, OUT FLOW AND PROBES, AND
FINE CONSTITUTURING THE 69 TO
KEEP IT WATER TIGHT DURING THE
PROCEDURE AND I CHOSE TO USE
THIS SIS PLATIN FOR THE FIRST
TIME IN CHILDREN BECAUSE IT HAD
NO LOCAL PERITONEUM TOXICITY, NO
TOXICITY FOR DRUGS GIVEN
PREVIOUSLY AND YOU GIVE ANN
NEUTRALIZING AGENT TO BIND UP
THE SIS PLATIN AND AG GREEN
CELLS IMAIT SIDE EFFECTS FROM
THE CHEMO THERAPY DRUG.
THE DIRECT CONTACT OF THE SIS
PLATIN TO THE TISSUES IS WHAT'S
VERY IMPORTANT AND THAT'S
BECAUSE VERY LITTLE OF IT GETS
ABSORBED INTO THE BLOOD STREAM.
SO HOW THIS WORKS IS THAT YOU
HAVE THIS RESPONSE TO
HYPOTHERMIA AND NORMAL TISSUES
ARE REALLY FINE UNTIL YOU GET UP
TO ABOUT 50-DEGREES CELSIUS,
REMEMBER I SAID WE'RE DOING THIS
AT 41.5-DEGREES CELSIUS, THE
BLOOD FLOW THROUGH CANCER
TISSUES INCREASES TO A LESSER
EXTENT AND STASIS OCCURS WHICH
CAN ADD TO CELLULAR TOXICITY AND
THE HEAT PLUS CHEMO THERAPY
SYNERGIZED TO KILL THE
MICROSCOPIC CELLS THAT ARE LEFT
BEHIND AFTER SURGICAL REMOVAL.
THERE ARE ONLY CERTAIN CHEMO
THERAPY DRUGS THAT ARE SINNER
GESTIC WITH HYPOTHERMIA, I CHOSE
SIS PLATIN BECAUSE IT HAD THE
LOWEST TOXICITY PROFILE AND A
HINT OF EFFICACY AND SARCOMAS.
ALSO, THE SIS PLATIN STAYS IN
THE ABDOMINAL CAVITY, SO THAT
VERY LITTLE OF IT GETS ABSORBED
IN THE BLOOD STREAM.
MAYBE ONLY 2-5% GETS ABSORBED IN
THE BLOOD STREAM.
SO WHAT TYPE OF PATIENTS MIGHT
NEED THIS PROCEDURE, THIS IS A
PATIENT OF MINE THAT I MET WHEN
I FIRST STARTED THE CLINICAL
TRIAL, SHE WAS ALMOST 3 YEARS
OLD AND THE ONCOLOGIST CALLED ME
A BIT SHEEPISHLY AND SAID I AM
SO SORRY TO BOTHER YOU, I TRIED
TO TREAT THIS PATIENT WITH CHEMO
THERAPY AND NOTHING'S WORKING
AND I'M ABOUT TO SEND THEM HOME
ON HOSPICE, THE MOTHER'S
INSISTING ON SPEAKING WITH A
SURGEON BEFORE LEAVING THE
HOSPITAL.
WOULD YOU MIND SPEAKING WITH
THEM.
THIS IS THE PET SCAN AND THE
IMAGING, YOU CAN SEE THE OUTLINE
OF THE SKELETON OF THE LITTLE
AND HERE'S THE SPOTS WITH THE
TUMORS IN THE ABDOMEN AND, THE
BLADDER'S THE ONLY THING NORMAL
IN THIS IMAGE, THE REST OF IT
THAT ARE LIT UP THERE ARE FROM
THE TUMORS AND YOU CAN SEE ON
THE CAT SCAN SHE HAS TONS OF
TUMORS IN HER LIVER.
I SAID WE'RE DOING THIS NEW
TRIAL, I DON'T KNOW IF WE WILL
WORK BUT WE WILL TRY IT IN YOUR
DAUGHTER AND WE DID AND WE WERE
ABLE TO REMOVE A HUNDRED PERCENT
OF HER TUMORS AND DO THE HYPACK,
AND I LOST TRACK OF HER WHEN SHE
GOT TO EIGHTH OR NINTH GRADE
BECAUSE SHE DID WELL FOR 10
YEARS PLUS AFTER THAT AND YOU
CAN SEE IN THIS IMAGE THERE'S NO
TUMOR JUST NORMAL KIDNEYS AND
BLADDER.
THIS IS ANOTHER EXAMPLE OF A 13
YEAR-OLD BOY WHO CAME TO ME
AFTER HE HAD BEEN OPERATED AT A
DIFFERENT HOSPITAL, AND HIS
TUMOR HAD ACTUALLY GREW AFTER
HIS OPERATION THAT THE SURGEON
TOOK OUT PAROF IT BUT NOT ALL OF
IT, THIS IS A INCISION FROM THE
SURGERY, WE HAD GIVEN HIM
MAXIMAL CHEMO THERAPY, WE ARE IN
A DILLAMY BECAUSE THIS WAS THE
ONLY TUMOR IN HIS BODY, AND HE
NEEDED TO DO IT QUICKLY BECAUSE
HE COULD BT REALLY BREATHE DUE
TO THE SIZE OF THE TUMOR.
SO THIS IS THE AT END OF THE
SURGERY WHERE I WAS ABLE TO
REMOVE THE WHOLE TUMOR IN 1
PIECE, THIS IS THE PATIENT
AFTERWARDS WAKING UP IN SURGERY.
AND IN THE OPERATING ROOM,
AGAIN, THE FEET ARE TO YOUR
LEFT, HEADS TO YOUR RIGHT,
YOU'RE LOOKING DOWN INTO WHERE
THE TUMOR WAS, MY HAND'S ON THE
SMALL BOWEL, THE COLON IS
TRANSECTOMYOSINNED SO A SMALL
PIECE OF COLON WAS REMOVED WITH
THE TUMOR YOU CAN SEE THE LEFT
AND RIGHT.
YOU CAN SEE THE BLOOD VESSELS
AND THERE WASN'T REALLY ANY
INVASION OF THE ORGANS AND THE
LARGE MASS WAS ABLE TO BE
REMOVED.
THIS IS ANOTHER EXAMPLE OF A 12
YEAR-OLD GIRL WITH A SIMILAR
TUMOR THAT WAS OVARIAN AND HAD A
RELAPSE AND I WENT TO KENYA TO
DO HER OPERATION--EXCUSE ME--AND
WAS ABLE TO REMOVE THE TUMOR AND
SEND HER BACK TO HER VILLAGE.
SO THE JOURNEY BEGAN IN TRYING
TO ESTABLISH THIS NEW APPROACH.
WE OPENED A PHASE 1 TRIAL.
AND WE TAKE THE FIRST 10
PATIENTS AND TRY TO
ESKACCTCULATE THE DOSE OF THE
SIS PLATIN TO SEE IF WE CAN GET
TO AN EFFICACIOUS AND SAFE DOSE,
NOW I'VE DONE OVER 200 PATIENTS
TO DATE BUT THIS IS THE RESULT
OF THE FIRST 27 HIPEC PROCEDURES
AND AT THE TIME WE TOOK ALL
COMERS, ALL DIAGNOSIS, AND IT
TOOK ME A WHILE TO FIGURE OUT
THAT THE DSRCT WAS PRETTY LOW.
WE START OFF WITH 45.41-DEGREES
CELSIUS AND WE TRY TO GO UP TO
150-MILLIGRAMS PER METERS
SQUARED AND WE ENCOUNTERED
TOXICITY THAT WE WILL FILE
SHORTLY AND WE FOLLOWED THE
PATIENTS FOR 5 YEARS, OPERATIVE
TIME AT THAT POINT WAS ABOUT 15
HOURS AT MAXIMUM.
AND THE AVERAGE HOSPITAL STAY IS
10-12 DAYS.
WE DID A PARALLEL QUALITY OF
LIFE STUDY THAT I DON'T HAVE
TIME TO SHARE ALL THE DETAILS
BUT SUFFICE IT TO SAY THAT WHAT
WE FOUND WAS FROM ANYWHERE FROM
30-60 DAYS THE PATIENT WAS BACK
TO THEIR NORMAL ACTIVITY AND
DOING EVERYTHING NORMALLY.
IN THE PHASE 1 STUDY, WE FOUND
THAT GRADE 3 RENAL FAILURE WAS
THE DOSE LIMITING TOXICITY AND
6% OF THE PATIENTS REQUIRED
DIALYSIS, THAT'S WHETHER I SHUT
THE PROTOCOL DOWN AND BEGAN TO
DO A VERY DETAILED EVALUATION:
THE OTHER TOXICITIES WERE VERY
MINIMAL, SUBCLINICAL DECREASE IN
HEARING, HEMOTO LOGIC TOXICITIES
THAT REVERSED OVER A FEW DAYS
TIME AND A PATIENT THAT HAD TO
COME BACK TO THE HOSPITAL FOR
ILEUS, TO AFTER THIS TRIAL AND
TO DATE I HAVE HAD NO MORE DEATH
IN CHILDREN.
ONE PATIENT HAD CARDIO MYOPATHY,
I TOOK OUT OVER A KILOOF TUMOR
IN THIS PATIENT AND THE
CARDIOLOGIST EXPLAINED TO ME
THAT THIS STUNS THE HEART,
ALTHOUGH HE HAD NO SYMPTOMS HE
REQUIRED BETA BLOCKERS IN ORDER
FOR HIM TO BE ABLE TO DO
ACTIVITY AND THEN PARTIAL SMALL
BOWEL OBSTRUCTION CAN OCCUR.
IN THIS COHORT OR TO TO DATE I
HAVE NOT HAD TO TAKE ANY
PATIENTS BACK TO THE OPERATING ROOM
WE'RE DRAWING SO AT A CANCER
CENTER, WE'RE ARGUELY HAVING
EXCELLENT CARE IF NOT THE BEST
CARE, FROM 1999-2003 YOU CAN SEE
IN THIS SURVIVAL CAP LANMIER
CURVE THAT ONLY 10% OF THE
PATIENTS WERE SURVIVINGA THE A
HUNDRED MONTHS.
I ARRIVED AT M. D. ANDERSON FROM
2004, FROM 2004-2010, IN THAT 6
YEAR TIME PERIOD I WAS ABLE TO
GET A 50% SURVIVAL IN THIS
COHORT OF DSRCT PATIENTS WITH MY
APPROACH.
SO ABOUT THE TOXICITY.
IT'S VERY CONCERNING TO ME, I
NEVER WANT TO HURT A PATIENT
DOING THIS BUT ONLY HELP THEM OF
COURSE.
SO I DID A VERY DETAILED
ANALYSIS WITH 21 DIFFERENT
VARIABLES, TO TRY TO UNDERSTAND
ANYTHING AND EVERYTHING THAT
COULD AFFECT THE KIDNEY
SO THIS RENAL TOXISITY IS
WHAT WE MEASURED IN 10 PATIENTS
AND THE 3 THAT REQUIRED DIALYSIS
WHICH IS WHY WE SHUT THE
PROTOCOL DOWN AND AFTER LOOKING
AT ALL OF THE VARIABLES, WHAT I
FOUND WAS THAT THE PREOPERATIVE
HYDRATION AND SODIUM SULFATE
CONTRIBUTED TO THE MOST TO THE
OUTCOME OR STATISTICALLY
SIGNIFICANT IN HOW THEY IMPACTED
THE RENAL FAILURE.
SO WHEN I THEY FIRST STARTED WE
WERE UNABLE TO ADMIT THE
PATIENTS TO THE HOSPITAL THE DAY
BEFORE AND WE HAD TO--THE
INSURANCE COMPANY ALLOW US TO
ADTHEM ON THE DAY BEFORE AND WE
CAN'T DO THAT, IT WAS VERY HARD
FOR RENAL FAILURE AND THE OTHER
VALUE THAT WAS STATISTICALLY
SIGNIFICANT WAS THE TIMING OF
THE DELIVERY OF THE SODIUM
THIOSULFATE WHICH BINDS UP THE
SIS PLATIN MOLECULES SO IF YOU
WAIT UNTIL THE END OF THE 90
MINUTE INFUSION OF SIS PLATIN
YOU WILL GET A HIGHER TOXICITY
AT THE BEGINNING OF THE DRUG OR
PROCEDURE AND THAT'S LAWEDDER
DALE WE STARTED DOING AND ONCE
WE MADE THE CHANGES WE HAVE NOT
HAD ANY INCIDENCE OF RENAL
INSUFFICIENCY OR RENAL FAILURE
FROM THESE PROCEDURES.
MY FIRST RESULTS I PUBLISHED IN
2013 SPECIFICALLY ON THE DSRCT
REMEMBER WE TOOK ALL HISTOLOGIES
FOR A WHILE, NARROWING IT DOWN
TO THE 1S THAT ARE EFFECTIVE AND
WHEN WE LOOKED WE SELECTED
PATIENTS THAT HAD NO DISEASE
OUTSIDE THE ABDOMINAL CAVITY.
THE PATIENTS WERE CYTOREDUCE TD
TO A SMALL TUMOR THAT MIGHT BE
AMENABLE TO RADIATION, REMEMBER
THIS IS A EWING TYPE SARCOMA
BIOLOGICALLY, SO EWING SARCOMA
RESPONDS WELL TO RADIATION.
SO WE PROVIDED RADIATION EITHER
IN 1 SPOT AND/OR THE WHOLE
ABDOMEN AND WITH THAT NEW
PARADIGM THE SURVIVAL IMPROVED
FROM 26 MONTHS TO 63 MONTHS.
MOVING FORWARD NOW TO THE PHASE
2 STUDY THAT WAS START INDEED
2016, WE NOW HAD LEARNED EXACTLY
WHICH PATIENTS TO SELECT AND WE
DID A PHASE 2 EFFICACY TRIAL
LOOKING AT PATIENTS FROM AGE 22
MONTHS TO 50 YEARS AND WE USED
SIS PLATIN AT A HUNDRED
MILLIGRAMS PER METER SQUARED.
WE DID LEARN THAT WE HAD TO
EXCLUDE PATIENTS WHO DID NOT
RESPOND TO CHEMO THERAPY THAT
WAS GIVEN IN A NEW ADJUVANT
STETTING, WE COULD NOT ACCEPT
PATIENTS THAT HAD ANY DISEASE
OUTSIDE THE ABDOMINAL CAVITY,
AND ANY PATIENTS THAT HAD POOR
PERFORMANCE STATUS OR ANY
PATIENTS WITH ORGAN DYSFUNCTION.
WE COULD NONAPOPTOTIC THE
RECEIVE--WE COULD NOT DO THIS
PROCEDURE IF WHEN I LOOKEDDA THE
IMAGING, I THOUGHT A HUNDRED% OF
THE DISEASE COULD NTD BE REMOVED
YOU HAVE TO REMOVE A HUNDRED
PERCENT OF WHAT YOU CAN SEE IN
ORDER TO SEE ANY CHANGE.
SO FROM 2012-2013 WE MET OUR
ACCRUAL.
FOURTEEN OF THE PATIENTS HAD
DSRCT AND 6 HAD OTHER DIAGNOSIS.
ALL PATIENTS HAD NEW ADJUVANT
CHEMO THERAPY FOLLOWED BY NEW
CYCLES FOLLOWED BY REDUCTIVE
SURGERY AND THE HIPEC, AND THEN
THEY HAD RADIATION THERAPY AND
AMILLIOY AND CHEMO THERAPY
BEFORE SURVEILLANCE.
THE ESTIMATED 1 YEAR SURVIVAL IS
93% FOR THE DSRCT PATIENTS AND
TD MEDIAN SURVIVAL WAS NOT
REACHED FOR THE DSRCT PATIENTS.
THE RAB DO MYOSARCOMA AND OTHER
PATIENTS IN THE STUDY DOES NOT
DO WELL AND DID NOT RESPOND TO
THE TREATMENT.
THIS IS ANOTHER KAPLAN MIER
CURVE WITH PATIENTS OF ALL
PATIENTS AT 63% AT 3 YEARS.
BUT WHEN YOU SEPARATE THE DSRCT
PATIENTS FROM THE OTHER
PATIENTS, YOU SEE A STRIKING
DIFFERENCE IN SURVIVAL.
THE BLACK LINE IS THE DSRCT
PATIENTS AND THIS IS SURVIVAL
CAP LANMIER CURVE SO CAN YOU SEE
THAT AT 30 MONTHS THAT THERE'S
80% SURVIVAL IN THE DSRCT
PATIENTS COMPARED TO THE OTHER
PATIENTS FOR WHICH ALL OF THEM
FOR 15 MONTHS.
AGAIN THIS IS THE DISEASE
SURVIVAL, THE BLACK LINE IS THE
DSRCT PATIENTS AND THE OTHER
LINES ARE PATIENTS WITH OTHER
DIAGNOSIS.
SOPHISTICATED WHEN I LOOK AT THE
DATA MORE CAREFULLY AND FOLLOW
THE PATIENTS LONGER, WHAT I
FOUND WAS THAT HERE'S THE 80%
SURVIVAL AT 30 MONTHS ABOUT YOU
WHEN YOU WAIT LONGER THAN
30-MONTHS, THE DISEASE STARTS TO
OCCUR AND OTHER PARTS OF THE
BODY, SO THEY DON'T HAVE--I HAVE
1 PATIENT THAT A RECURRENCE IN L
ABDOMEN IN THEIR PATIENTS BUT
MOST OF THE TIME THEY DON'T
OCCUR AT ALL IN THE ABDOMEN, IT
STAYS PRISTINE BUT UNFORTUNATELY
THE TUMOR COMES BA IN THEIR
LYMPHNODES OR AREAS OF THE LUNGS
AND CHEST AND BONES AND BRAIN.
SO THIS REALLY MOTIVATED ME TO
UNDERSTAND THE DISEASE SO NOW WE
UNDERSTAND HOW TO TAKE CARE OF
THE LOCAL DISEASE BUT WE REALLY
WANT THE HOME RUN TO BE ABLE TO
CURE THE DISEASE ALTOGETHER.
SO I WILL TELL YOU BRIEFLY HOW
I'M TRYING TO CHANGE THE STAGING
OF THIS DISEASE AND THEN WE WILL
TALK ABOUT THE SCIENCE BEHIND
IT.
SO IF EVERY PATIENT PRESENTS
WITH MORE THAN A TUMOR, IN
SARCOMAS, WE CALL THAT A STAGE 4
PATIENT.
EVERY PATIENT CAN BE A STAGE 4
BECAUSE THEY'RE ALL DIFFERENT.
SO I KREALT A NEW STAGING SYSTEM
THAT HASN'T YET BEEN VALIDATED
THAT STAGE 1 TUMORS ARE JUST IN
THE [INDISCERNIBLE].
THEY HAVE SEVERAL OF THOSE THAT
ARE DOING VERY WELL.
STAGE 2 TUMORS DOESN'T HAVE MANY
TUMORS BUT THEY DON'T HAVE ANY
LIVER METASTASIS AND THEY DON'T
HAVE ANY LYMPHNODE OR ANY OTHER
REGIONAL METASTASIS OR ANYTHING
ELSE OUTSIDE THE ABDOMINAL
CAVITY.
SOPHISTICATEDY WHEN YOU LOOK
STATISTICALLY AT THIS DAT ATHIS
PLAYS OUT, THAT IT'S VERY
CONSISTENT THAT THE STAGE 1
PATIENTS HAD A HUNDRED%
SURVIVAL, THE STAGE 2 PATIENTS,
70% SURVIVAL AND THE STAGE 3 AND
4 PATIENTS REFLECT MORE HIOF
THORICALLY OF WHAT THESE
PATIENTS LOOK LIKE PRIOR TO ME
STUDYING THIS DISEASE AND
STATISTICALLY SIGNIFICANT.
SO WITH THE MULTIVARIANT
ANALYSIS SHOWED US STAGE 3 OR 4
RISK OF PATIENTS WITH HIGHER
DEATH, PATIENTS WITHOUT EXTRA
ABDOMINAL DISEASE DOES WELL, AND
INCOMPLETE RESECTION PROMOTED A
HIGHER RISK FOR RECURRENCE AND
PATIENTS WITHOUT LIVER DISEASE
DID BETTER WITH PATIENTS WITH
LIVER DISEASE.
SO NOW ON TO THE SCIENCE OF WHAT
IS A TUMOR AND HOW DOES IT
OCCUR.
SO WHEN I FIRST SAW THESE TUMORS
AND I REMEMBER I MENTIONED THAT
THE TUMORS ARE ALWAYS STUCK TO
THE SEMINAL VESICLE.
SO I WAS GETTING VERY COG COGNT
OF THE PATTERN THAT EVERY
PATIENT I WAS DOING SURGERY ON,
I WAS CUTTING OFF TUMOR VESICLES
AND NIEBT% OF THE PATIENTS WERE
MAIL MALE.
SO I THOUGHT IF IT HAD AN
ANDROGEN COMPONENT TO IT SO THE
FIRST THING I DID WAS TAKE THE
CELLS INTO THE DID WEST OTHER
THAN BLOT TO LOOK AT PROTEINS
AND COMPARED THEM WITH TC71.
COMPARING DSRCT TO THE EWING'S
SARCOMA, BUT THE SAME AMOUNT OF
RECEPTOR IN PROSTATE CANCER IS
FOUND IN DSRCT, AND SO, I BEGAN
TO ASK WHAT IS THE ROLE OF THIS
RECEPTOR SINCE IT'S VERY HIGHLY
EXPRESSED THIS THESE TUMOR
CELLS.
SO I COMPARED DSRCT TO THE
CANCER CELLS IN THE LABORATORY
AND I GREEN COLOR STAINING FOR
ANDROGEN RECEPTOR AND IF YOU
LOOK AT THE COMPARISON BETWEEN
THE PROOF THEASTY CANCER CELLS
AND THE DSRCT CELLS YOU SEE
THERE'S A SIGNIFICANT EXPRESSION
IN THE DSRCT CELLS ALMOST AS
STRONG AS IN PROOF THEASTY
CANCERREN.
THEN I TOOK DSRCT CELLS AND
ADDED TESTOSTERONE TO THE CELL
CULTURE AND WATCHED THE CELLS
PROLIFERATE WITH INCREASING
DOSES OF TESTOSTERONE.
SIMILARLY FOR DISCIPLINARY
HYDROTESTOSTERONE, WHEN YOU
ADDED IT, THE RED LINE ACROSS
THE CANCER CELLS INCREASED.
THE BLUE LINE IS THE EWING
SARCOMA CELLS THAT DIDN'T CHANGE
AT ALL AND THE BLACK LINE IS THE
DSRCT CELLS THAT INCREASED AT
THE SAME SLOPE AS A PROSTATE
CANCER CELLS.
SO THEN I BEGAN TO LOOK AT THE
PATHWAYS THAT PROSTATE CANCER
CELL DEVELOPED AND METASTASIZED
AND LOOK AT RNA HEAT SEEKING
MAPS TO UNDERSTAND HOW SIMILAR,
OR DIFFERENT THEY ARE WITH
RECAST RATE RESISTANT PROSTATE
CANCER.
SO THEN THE QUESTION IS, AGAIN
WRRKS DOES IT COME FROM, SO WHEN
YOU START TO LOOK AT WHERE
TISSUE--TUMORS COME FROM, YOU
LOOK AT LIKE TISSUE AND LIKE
PATHWAYS TO SEE IF YOU CAN PIECE
TOGETHER WHAT IT MIGHT LOOK LIKE
IN DIFFERENT TUMORS AND
DIFFERENT TISSUES.
SO THE BLUE DOTS ARE DSRCT
TUMORS, THE OTHER DOTS ARE
DIFFERENT TISSUE TYPES.
SO THE BLUE TISSUE HERE IS THE
LUNG, THE SKELETAL MUSCLE AND
SKIN ARE DOWN HERE AND THE
PURPLE DOTS ARE FAT.
SO CAN YOU SEE THAT THE DSRCT
TUMORS LOOK CLOSER TO FAT THAN
ANYTHING ELSE BUT REALLY DON'T
LOOK LIKE ANY LITTLER TISSUE
TYPE, THEY DON'T LOOK LIKE FAT,
OR LUNG OR MUSCLE OR SKIN.
AND THIS PANEL TO THE RIGHT
SHOWS HOW DIFFERENT IT IS THAN
OTHER SARCOMAS, SO THESE ARE A
LIST OF OTHER SARCOMAS THAT
OCCUROT ABDOMINAL CAVITY.
CHOND ROW, DOLPS, AND OTHERS,
CAN YOU SEE THAT THE DSRCT
TUMORS CLUSTER WAY OVER HERE,
NOWHERE NEAR ANY SIMILARITY
GENETICALLY TO ANY OF THESE
OTHER TUMORS.
AND WHEN YOU TRY TO LOOK AT THE
GENEX TREE, YOU SLEEP APNEA AND
OBESITYY A DIFFERENT STORY AS
WELL, SO EVERY 1 OF MY PATIENTS
I TOOK TISSUE FROM THE IN THE
OPERATING ROOM AND TOOK IT TO
THE LAB RADIO LABORATORY, AND
THESE THE COMMONALITY, IN THIS
TREE, IS EWINGS T1 AT THE BASE
OF THE TREE SO TO SPEAK BUT WHEN
YOU BRANCH UP FROM THAT, YOU SEE
THAT ALL OF THESE PATIENTS HAVE
DIFFERENT TUMOR EXPRESSION,
DIFFERENT PROTEIN EXPRESSIONS,
WHICH AGAIN MAKE ITS VERY
DIFFICULT TO FIND COMMONALITIES,
IN THESE TUMORS.
SO, I NEED TO HAVE AN ORTHOTOPIC
XENOGRAFTIC MODEL AND RECRETE
THE DISEASE IN A MOUSE IN ORDER
TO STUDY IT BETTER SO KNOWING
WHAT I KNEW ABOUT THE PROSTATE
CANCER AND THE ANDROGEN
SENSITIVITY, THESE DSRCT CELLS
INTO THE PERITESTICULAR PERRY
AND THE PELVIC REGION OF IMMUNO
COMPROMISED, AND WE LABELED THEM
OF THE LUCIFERASE AND IMAGE THEM
AT 6 WEEKS AND THEN EVERY WEEK
AFTERWARDS.
AND THIS IS WHAT THE MODEL LOOKS
LIKE.
THE MICE THAT HAVE NO TUMOR,
THIS IS OUR CONTROL.
THIS IS 2 MILLION TUMOR CELLS
EACH AND THIS IS 5 MILLION EACH
IN THESE 2 MICE.
AND IF YOU LOOK AT THE NECROPSY,
IT DUPLICATES THE DISEASE VERY,
VERY CLOSELY.
SO THIS WHRIET DOT HERE IS ON
THE SEMINOLE VESICLE, THIS IS
SEMINOLE VESICLE OF THE MOUSE
AND ALL THESE WHITE DOTS AGAIN
ARE TUMORS IN THE ABDOMINAL
CAVITY OF THIS MOUSE AND IF YOU
LOOK CAREFULLY YOU CAN SEE 1 ON
THE SURFACE OF THE LIVER AND
ANOTHER 1 HERE AND WHEN YOU
LOOKED MICROSCOPICALLY AT
VARIOUS TISSUES AND THE NECROPSY
OF THIS MOUSE, YOU FIND THERE IS
ABNORMALITIES DIAGRAMINAL
METASTASIS, REMEMBER THE
PANCREAS AND THE MOUSE IS A FREE
FLOATING AND THERE'S TUMOR NEXT
TO THE PANCREAS.
AND SUPER [INDISCERNIBLE]
METASTASIS WHICH IS A VERY
TYPICAL PRESENTATION OF THIS
DISEASE, CAN YOU SEE THAT IN THE
MICE AS WELL.
SO THEN I WENT ON TO DO SINGLE
CELL SEQUENCING TO UNDERSTAND
EVEN MORE ABOUT THIS TUMOR
GROWTH IN THE CONTEXT OF THIS
MOUSE MODEL.
SO THESE ARE DSRCT TUMOR CELLS
FROM 2 DIFFERENT PATIENTS, THE
BLUE IS AT 1 PATIENT, GREEN IS A
DIFFERENT PATIENT.
AND YOU CAN SEE WE'RE ABLE TO
TAKE 1 LOCAL TUMOR AND SEPARATE
ALL THE DIFFERENT TUMORS TO SEE
THOSE CELLS SO WE CAN FOCUS ON
JUST THE TUMOR CELLS.
SO CAN YOU SEE THERE'S
POPULATIONS OF MONOCYTES AND
MACROPHAGES, NUTRIFILLS, ET
CETERA WITHIN THE TUMORS.
AGAIN, THESE 2 CIRCLES ARE 2
DIFFERENT PATIENTS AND WE BEING
LOAMACY THEA WT1 AND ANDROGEN
RECEPTOR AND YOU SEE THAT ONLY
THE TUMOR CELLS OF BOTH PATIENTS
STAINED WITH TK1 ANDROGEN
RECEPTOR AND THE SMALL
POPULATION HERE TO THE SIDE IS
WHAT WE'RE TERMING THE CANCER
STEM CELLS FOR DSRCT SO YOU CAN
SEE THAT THE STEM CELLS, THE
SMALLER POPULATION THAT DRIVE
THE TUMOR GROWTH AND METASTASIS,
COMMONLY STAINED WITH WT1 AND
ANGIO RECEPTOR.
WHEN YOU LOOK AT AGAIN THE
SUBSET OF CELLS IN THE CANCER
STEM CELL POPULATION, YOU HAVE
ANGIO RECEPTOR, SOX 2 IS ANOTHER
MARKER AND THOSE ARE ONLY
PRESSENT IN THE SMALL POPULATION
OF CELLS.
SO I WON'T WON'T GO THROUGH
EVERY SINGLE PIECE OF DATA YOU
ABOUT I WILL SHOW YOU HOW WE
LOOKEDDA THE THIS TREE.
SO WE DEVELOPED A GENETIC TREE
FROM THE INFORMATION THAT WE
ACHIEVE WITH THE RNA SEQUENCE.
WE MADE SURE THAT THE CELLS WERE
PURE AND SO THIS JUST IS A
DOCUMENTATION OF THE RNA PURITY
AND THE PERCENT IN EACH SAMPLE.
THEN WE LOOKED AT THE DIFFERENT
PORTIONS OF THE TREE, THE
DIFFERENT CELLS AND WHAT
PROTEINS WERE EXPRESSED AND WHAT
GENES ARE IMRESESSED IN THOSE
CELLS AND TO LOOK AT IT MORE
CLOSELY SEE YOU CAN SEE IT
BETTER, THESE ARE THE DIFFERENT
CELL TYPES THAT WERE CIRCLES IN
THE SINGLE CELL SEQUENCING AND
THE GENETIC PANEL THAT RESULTED
FROM THE DIFFERENT CELL TYPES
AND WE TOOK THAT AND BROKE THAT
DOWN INTO WHAT WE WAS MOST
COMMONLY UP OR DOWN REGULATED
AND NARROWED IT DOWN TO THIS
GROUP OF GENES.
SO WE KNEW ABOUT WT1, WE KNEW
ABOUT ANGIO RECEPTOR, WE DIDN'T
KNOW ABOUT JJB2, WHICH IS WHAT
I'M LOOKING FORWARD FOR NOW IN
THE LABORATORY.
AND THIS IS A DIFFERENT COUNT OF
DIFFERENT GENES IN THE
SUBPOPULATIONS 1-12 OF THE
CIRCLES OF THE CANCER STEM
CELLS.
EXCUSE ME OF THE SINGLE CELL
SEQUENCING.
THEN WE WENT ON TO LOOK AT
PATIENT SAMPLES AND THE SHARED
GENETICS THAT WERE ANDROGEN
DEPEBDENT.
SO NOW WE'RE JUST LOOKING AT
ANDROGEN RECEPTOR DEPENDENT
PROTEINS AND GENES.
SO THESE ARE TUMORS FROM MY ISHT
PATHWAY GIVESS, THIS IS
14-EXCUSE ME DIFFERENT PATIENTS
COMPARED TO 6 DIFFERENT EWING
SARCOMA PATIENTS AND THIS SET OF
EXPERIMENTS SHOW THE PROTEIN
EXPRESSION IN THE DSRCT IN RED
VERSUS EWING SARCOMA IN BLUE.
SO YOU CAN SEE THE TUMORS
WHETHER YOU LOOK AT ANGIO
RECEPTOR OR OTHER 3 PROTEINS
HAVE A SIGNIFICANTLY HIGHER
EXPRESSION THAN EWING SARCOMA
TUMORS BUT THAT THESE TALENTS,
PROBABLY BECAUSE THEY CROSS THE
0 LINE MAY NOT BE EFFECTIVE
TARGETS SO ANGIO RECEPTOR LOOKS
LIKE IT'S STILL FALLING OUT AS
THE MOST EFFECTIVE TARGET AND WE
LOOKED AT THESE GENES HERE AND
THEIR EXPRESSION IN DSRCT
PATIENT TUMORS IN EWING SARCOMA,
COMPARING THE TUMORS AND FOUND
THE SAME THING, THAT THE RED
DSRCT PATIENTS HAVE MUCH HIGHER
EXPRESSION OF THESE 2 COMPARED
TO THE GENE.
SO WE'RE CONCENTRATING AGAIN ON
ANDROGEN RECEPTOR WHICH IS
LITTLE TO NONE IN THE EWING
SARCOMA GENE.
SO THIS IS THE MOST RECENT
PUBLICATION FROM NATURE, AND I
WANT YOU TO FOCUS ON THESE 2
COLUMNS IN THIS WAY.
SO THESE--THIS LEFT COLUMN IS A
XEEN O GRAPH MODEL, AND IN THE
RIGHT COLUMN OR PDXs OR
PATIENT DERIVED XEEN O GRAPHS SO
TAKEN THE CELLS FROM THE PATIENT
TUMOR WE TAKE A CHUNK OF TUMOR
IS PUT IT INTO THE MICE.
AND THE DARK ORANGE, FOCUS ON
THE DARK ORANGE LINE WHICH IS
THE ANTISENSE, SO MY
COLLABORATORS MADE AN ANTISENSE
WITH THE TUMOR AND WE COMPARED
THE TREATMENT IN THE MICE AND IN
THE PD ACCESS TO TREATMENT OF
PROSTATE CANCER SO ENZALUTAMIDE
IS A CONTRIBUTOR TO PREVENTION
OF PROSTATE CANCER.
SO IN ALL THE ANIMALS YOU CAN
SEE WHEN WE USE ANTISENSE, THEY
TUMORS DIDN'T GROW, THE GROWTH
OF THE TUMOR WAS SLOWER, THAN IN
THE ENZALUTAMIDE, AND IN THE PDX
NODDLE THE SAME THING, THE DORK
ORANGE, THE GROWTH OF THE TUMOR
VOLUNTEERS UMKC WAS LOWER, THE
GROWTH OF THE TUMOR WAS SLOWER
AND IN FACT SPHARTED TO DECREASE
AT THE END OF THE STUDY, AND
THERE WAS A HUNDRED% SURVIVAL
COMPARED TO SOME OR MOST OF ALL
OF THE OTHER MICE DYING, EXTEN O
GRAPH AND THE PDX MODELS.
SO IN CONCLUSION, IT IS POSSIBLE
TO GO FROM BENCH TO BEDSIDE.
IT IS POSSIBLE TO UNDERSTAND A
DISEASE THAT WAS NOT PREVIOUSLY
TREATABLE OR UNDERSTOOD.
AND THAT PERSISTENCE AND
PATIENCE ARE KEY AND THIS IS THE
GREEN AT HOWARD IN THE
BACKGROUND OF MY SLIDES AS WELL
AS MY VIRTUAL BACKGROUND SO I
WANT TO THANK YOU VERY MUCH FOR
YOUR ATTENTION AND GIVE THANKS
TO THE PERSONS WHO HELPED ME
ALONG THE WAY.
THANK YOU SO MUCH.
>>THANK YOU SO MUCH
DR. HAYES DIXON ON THIS VERY
RARE TUMOR TYPE AND LAWEDDER
DALE YOU'VE DONE SO FAR TO MOVE
THIS FIELD FORWARD AND LEARN
ABOUT THIS TUMOR.
IT'S OPEN FOR QUESTIONS FOR
THOSE WHO HAVE ANY QUESTIONS,
YOU CAN PUT IT AGAIN THROUGH AT
THE BOTTOM OF YOUR SCREEN, BUT
BEFORE WE HAVE ANY--WHILE PEOPLE
ARE STILL BRINGS QUESTIONS, FOR
THIS RARE TUMOR TYPE I KNOW YOU
TALKED ABOUT DEVELOPING THE
MOUSE MODEL WHICH IS VERY
IMPORTANT BECAUSE FOR CHILDREN,
YOU DO NEED A MODEL BECAUSE YOU
CAN'T ALWAYS DO SOME OF
THESE--TEST THESE THINGS ON
CHILDREN.
SO IT'S IMPORTANT TO UNDERSTAND
THE BIOLOGY THROUGH THESE
PRECLINNAL MODELS:
HAVE YOU EVER THOUGHT OF DOING
HIPEC IN YOUR MICE MODELS TO SEE
IF THERE'S A RESPONSE TO
ANDROGEN RECEPTOR OR ANTAGONIST
YOU TALKED ABOUT.
AND DO YOU KNOW OF ANY SAY,
EXVIVO MODELS THAT PROVIDE MORE
INSIGHT TO WHAT YOU'RE LOOKING
INTO.
WELL, THANK YOU FOR THAT
QUESTION.
CAN YOU HEAR ME OKAY?
ALL RIGHT.
>>I CAN HEAR YOU.
>>ALL RIGHT.
IT WOULD BE HELPFUL TO ACTUALLY
RECREATE HIPEC IN AN ANIMAL
MODEL AND THERE ARE RESEARCHERS
WHO ARE DOING SO, WHAT I'M
HOPING TO DO BEFORE I DO THAT IS
TO IDENTIFY SOME NOVEL DRUG
TARGETS WE CAN USE IN THE PIPE O
THERMOGENESISSIC CHEMO THERAPY
INFUSION.
ONE OF THE NUMBER OF GENES AND
PROTEINS I SHOWED IN THE LAST
COUPLE OF SLIDES, I WANT TO KNOW
IF WE CAN DEVELOP A NEW DRUG
THAT WILL SPECIFICALLY TARGET
THAT.
THE ANTISENSE THAT MY
COLLABORATOR, [INDISCERNIBLE]
MADE IS NOT SOMETHING THAT'S
IMMEDIATELY TRANSLATABLE TO A
DRUG AND SO, WE'VE GOT TO FIND
THAT PLUS OTHER TARGETS TO
DEVELOP AND ONCE WE GET THAT, I
THINK I WILL TRY DOING THE HIPEC
IN THE MICE THEMSELVES.
BUT THE OTHER POINT IS THAT
THERE MAY BE A SMARTER WAY TO DO
THINGS AS FAR AS INSTEAD OF
INFUSING HOT CHEMO THERAPY OVER
AN HOUR AND A HALF, MAYBE
THERE'S AN IMPLANT WE COULD PUT
INSIDE THE ABDOMINAL CAVITY THAT
WILL SLOWLY RELEASE CHEMO
THERAPY OR SOME TYPE OF DRUGS
OVER DAYS TO WEEKS, THAT WILL
ALLOW THE PATIENT NOT TO HAVE TO
BE SUBJECT TO THAT.
SO I'M LOOKING AT OTHER
ALTERNATIVES, I'M NOT BEING
NARROW MINDED ABOUT HIPEC BUT
OTHER WAY FOR CELL DEATH AT THE
MICROSCOPIC LEVEL.
>>THANK YOU.
>>I DON'T SEE ANY QUESTIONS IN
THE CHAT RIGHT NOW.
>>I DON'T SEE IT AS WELL.
BUT JUST AS A FOLLOW UP TO
LOOKING NOT JUST AT THE MODEL
BUT THE TUMOR BIOLOGY, HAVE YOU
NOTED ANY DIFFERENCES IN THE
BIOLOGY AS YOU SAID STAGE 1
VERSUS MORE ADVANCED BECAUSE AS
YOU SAID, THEY DEFINITELY HAVE
DIFFERENT MUTATIONAL STATUSES
WITHIN THE DIFFERENT TUMORS
WHICH MAKES IT DIFFICULT TO
TARGET THAT HETEROGENERATED AITY
MAKES IT DIFFICULT TO TARGET BUT
HAVE YOU NOTICED ANY
SIMILARITIES BETWEEN THOSE WHO
HAVE THE MORE FAVORABLE OUTCOME
VERSUS THOSE THAT DON'T.
>>I'M HOPING TO LOOK AT THAT
MOVING FORWARD, I HAVEN'T HAD A
CHANCE TO DO THAT JUST YET.
YOU NEED QUITE A FEW PATIENT
SAMPLES TO COMPARE 1 TO OTHER
AND SINCE IT'S SUCH A RARE
DISEASE, IT TAKES YEARS TO GET
ALL THE SAMPLES.
BUT YES, IT'S DEFINITELY
SOMETHING ON MYRA DART--DARTH TO
LOOK AT THE STAGE 1 PATIENTS AND
COMPARE THEM TO THE OTHER
PATIENTS.
THE OTHER COMMONALITY IN THE
STAGE 1 PATIENTS IS THEY ALL
HAVE DISEASE IN THE OMENTEM, SO
THE OTHER SORT OF IDEA THAT I'M
WORKING THROUGH IS HOW MUCH THE
OMENTUM PLAYS A ROLE IN THE
CONTROL OF THIS DISEASE OR THE
DISSEMINATION OF THIS DISEASE.
IT SEEMS LIKE THE OMENTA MIGHT
BE THE FIRST ORGAN OF ORIGIN
THAT IT MAY BE BECAUSE OF
GRAVITY THAT THE OMENTUM IS DOWN
IN THE PELVIS TOUCHING THE IT
WITH THE CELLS, I DON'T KNOW
IT'S A HYPOTHESIS RIGHT NOW BI I
THINK WE NEED MORE MORE TISSUE
FROM PATIENTS THAT ARE EARLY
STAGE DISEASE TO COMPARE THEM TO
LATER STAGES.
UNFORTUNATELY THERE'S
ONLY--THERE'S NO COMMERCIAL CELL
LINES FOR DSRCT WHICH ADDS AN
ADDITIONAL CHALLENGE.
SO YOU HAVE TO GET PATIENT
TUMORS TO STUDY IT.
THERE'S 1 CELL LINE THAT THE 1 I
WAS STUDYING THAT I BORROWED
FROM AN INVESTIGATOR IN JAPAN,
BUT THERE'S NO OTHER CELL LINES
IN THE WORLD RIGHT NOW TO STUDY
THIS DISEASE.
SO WE NEED SOME MORE PATIENT
TISSUES.
>>WE HAVE 1 REQUESTY THAT CAME
IN, WOULD YOU COMEBT ON THE
MOLECULAR GENETICS OF DSRCT?
>>WELL THE ONLY TECHNOLOGY
TRANSFER WE KNOW IS THE EWTS E1
FUSION GENE THAT,'S WHATY WOO
KNOW AND THEN THE PROTEINS I'M
LOOKING AT THROUGH THE SINGLE
CELL SEQUENCING SERIES, SO THE
PDGF RECEPTOR ALPHA IS 1 OF THE
TOP 1S AND BYS6 IS ANOTHER 1.
SO, I'M STILL WORKING THROUGH
WHICH THAT IS, WE DO KNOW
GENETICALLY THAT--NOT
GENETICALLY IMMUNOLOGICALLY THAT
DSRCT IS IMMUNE COLD AND SO WE
CAN'T USE OUR WONDERFUL NEW
IMMUNE THERAPY DRUGS THAT WE
HAVE FOR OTHER CANCERS, IT JUST
DOESN'T WORK ON THAT TUMOR SO A
LOT MORE WORK TO DO.
>>NO OTHER QUESTIONS, ALL
RIGHT?
>>DEFINITELY.
>>WELL I HOPE THAT WAS REALLY
HELPFUL TO EVERYONE.
>>ONE MORE QUESTION.
ONE MORE QUESTION.
>>OKAY.
>>SOMEONE SAID GREAT TALK, I
REMEMBER DR. HAYES DIXON SHOWING
A TUMOR SECTION IN THE GIRL IN
KENYA, WHAT OTHER GROABAL TUMOR
RESECTIONS HAVE YOU DONE FOR
THIS DSRCT?
>>THAT'S THE ONLY CASE I DID.
IT WAS QUITE CHALLENGING TO DO
THAT IN A COUNTRY THAT'S YOU
SHOULD RESOURCED BUT I'M NOT
OPPOSED TO DO IT AGAIN.
I THINK THAT, IN THAT PARTICULAR
CASE THAT CHILD AND THEIR FAMILY
COULDN'T TRAVEL TO THE UNITED
STATES AND SO I WENT THERE TO
HELP HER.
THERE ARE OTHER CHALLENGES.
YOU KNOW SOME OF THE PLACES
DON'T HAVE BLOOD BANKS, IT'S
DIFFICULT TO DO SURGERY WITHOUT
BLOOD AVAILABLE, SIMPLE THINGS
THAT WE TAKE FOR GRANTED LIKE
SUCTION AND CAUTERY ARE ARE
SPARSELY AVAILABLE AS WELL AS
SOME OF THE THINGS, LITTLER
THINGS WE TAKE FOR GRANTED LIKE
SUTURE AND TUBES AND DRAINS THAT
THEY JUST DON'T HAVE AVAILABLE
IN THOSE COUNTRIES.
DOESN'T MEAN IT CAN BE DONE, IT
JUST TAKES PLANNING AND THOUGHT
AND COMMITMENT BY THE PERSONS
THERE ON THE GROUND.
>>I SEE, NO FURTHER QUESTIONS.
THIS IS AGAIN, VERY EVOLVING
FIELD WHICH IS VERY EXCITING TO
SEE WHAT YOU ARE DOING AND WILL
CONTINUE TO DO AS YOU DEVELOP
MORE MODELS AND UNDERSTAND THE
DISEASE MORE.
BUT WITHOUT ANY FURTHER
QUESTIONS, IF YOU ANY ANY
CLOSING REMARKS WE WOULD LOVE TO
HEAR FROM YOU.
>>I WANT TO THANK YOU SO MUCH
FOR THE INVITATION AND I KNOW
THIS IS RECORDED SO PEOPLE CAN
WATCH IT LATER AND I HOPE TO
INSPIRE PEOPLE TO INNOVATE AND
QUESTION WHEN SOMEONE TELLS YOU
THERE'S NOTHING THAT CAN BE DONE
OR THE STABBED ARD OF CARE, THIS
IS THE BEST IT GETS, THINK ABOUT
IT, ASK ABOUT IT, THINK
CAREFULLY AND SCIENTIFICALLY
ABOUT SO THAT WE CAN CHANGE HOW
MEDICINE IS PRACTICED.
SO THANK YOU ALL FOR YOUR
ATTENTION.
>>THANK YOU DR. DIXON.
>>AND THANK YOU DR. TEKE, FOR
THE INTRODUCTION AND MODERATING,
I APPRECIATE IT AND EVERYONE
HAVE A WONDERFUL DAY.
>>PLEASURE.
THANK YOU.