>> GOOD AFTERNOON, OUR FIRST TALK IS ON RADIATION ONCOLOGY. SO WE HAVE ELIZABETH NICHOLS ASSOCIATE PROFESSOR UNIVERSITY OF MARYLAND. SO SHE WAS UNGRAD AT DUKE AND THEN WENT TO THE UNIVERSITY OF MARYLAND MEDICAL CENTER. AND SHE DID HER RESIDENCY THERE. SHE WILL TALK TO US TODAY ABOUT RADIATION ONCOLOGY. LIZ. >> THANK YOU, EVERYONE FOR HAVING ME TODAY. IT EAT MY PLEASURE TO TALK TO EVERYONE, I WILL TALK ABOUT RADIATION ONCOLOGY, HOW RADIATION WORKS IN THE BODY, PRINCIPLES WE THINK ABOUT FROM A THERAPEUTIC VIEWPOINT, QUESTION I'LL GO THROUGH THE PROCESS OF RADIATION THERAPY AS WELL AS THERE ARE SOME STEPS THAT MOST PEOPLE ARE NOT FAMILIAR WITH AND TALK A COUPLE OF CASES TO SOLIDIFY THAT KNOWLEDGE.& I HAVE NO DISCLOSURES. AGAIN, HERE IS OUR OUTLINE FOR TODAY TO TALK GOALS OF CANCER THERAPY, SPECIFICALLY FOCUS ON SOME OF THE GOALS OF RADIATION THERAPY, SOME OF THE BASICS OF RADIATION ONCOLOGY, AND THEN SOME OF THE EXCITING AREAS OF RESEARCH IN RADIATION ONCOLOGY AS WELL. AND HOW THEY MAY INTERACT WITH SOME OF THE WORK THAT'S BEEN DONE HERE AND ABROAD. IN TERMS OF PRINCIPLES OF CANCER THERAPY, THERE'S MULTIPLE PRINCIPLES WE OPERATE UPON. ONE IS TO MINIMIZE THERAPY, SO WE WANT TO GIVE PATIENTS THE MINIMUM NEEDED TO CURE THEIR CANCER OR MAKE THEM FEEL BETTER, THIS IS IMPORTANT WE WANT TO MINIMIZE OUR TOXICITIES OF THERAPY, WHICH CAN BE FROM SURGERY, CHEMOTHERAPY, RADIATION FROM IMMUNOTHERAPY MINIMIZE THE TIME PATIENTS ARE IN OUR CLINICS FOR THESE PIS AS WELL AS MINUTEMIZE COST OF THERAPY. AS MANY PEOPLE ARE FAMILIAR THERE'S INCREASING COSTS DUE TO NEW DRUGS AND MINIMIZE WILL MINIMIZE HEALTHCARE COSTS. WE ARE LOOKING TO MINIMIZE NEGATIVE IMPACT ON PATIENT QUALITY OF LIFE SO AND FUNCTION. WHEN WE TALK FUNCTION A LONG TIME AGO WHEN WHICH FIRST STARTED TREATING SARCOMA OF THE EXTREMITIES WE USED TO DO AMPUTATION. WE CAN NOW DO LIMB PRESERVING THERAPY. WITH PROSTHESIS, THE EXAMPLES WITH BREAST CANCER THINKING MASTECTOMY AS POPESSED TO LUMPECTOMY. WE ARE LOOKING TO IMPROVE PATIENT QUALITY OF LIFE FOR PATIENTS WITH METASTATIC OR STAGE 4 CANCER. OFTEN TIMES RADIATION THERAPY IS USED FOR PAILIATION VIEWPOINT WHERE A PATIENT MAY HAVE A BONE METASTASIS THAT IS CAUSING PAIN. WE CAN TREE THAT METASTASIS WITH RADIATION AND IMPROVE THE PATIENT PAIN AND NEED FOR NARCOTICS. ALSO LOOKING AT ORGAN PRESERVATION. IN BLADDER CANCER THEY REMOVE THE BLADDER OR A BLADDER PRESERVING APPROACH USING RADIATION AND CHEMOTHERAPY SO WE CAN PRESERVE THEIR ORGAN. WE ARE LOOKING TO MAXIMIZE IMPACT ON QUANTITY QUANTITIES OF LIFE, CARE AND OMISSION AND LOOKING TO ADVANCE CANCER OUTCOME WHICH OF COURSE INVOLVES RESEARCH IN MANY WORKS THAT ARE BEING DONE HERE. IN GENERAL DISCIPLINE OF RADIATION ONCOLOGY IS REALLY DIVIDED TO THREE SEPARATE GROUPS, FOCUSING ON RADIATION BIOLOGY, RADIATION THERAPY, AS WELL AS PHYSICS AND SPECIFICALLY WITH MEDICAL PHYSICS. THESE COMBINE TOGETHER TO ALLOW US TO TREAT PATIENTS. SO MOVING TO THE BASICS OF THE PHYSICS OF RADIATION ONCOLOGY, I WILL SAY THIS IS JUST THE BASICS, AGAIN THIS IS A WHOLE SEPARATE FIELD WHICH ALSO INCLUDES A MEDICAL PHYSICS RESIDENCY IN ORDER TO BECOME A MEDICAL PHYSICIST. SO WE THINK ABOUT WHAT ACTUALLY IS RADIATION? RADIATION IS THE COMPLETE PROCESS BY WHICH ENERGY IS EMITTED BY ONE BODY TRANSMITTED THROUGH INTERVENING MEME YUM AND ABSORBED BY ANOTHER BODY. THERE'S MULTIPLE TYPES OF RADIATION. INCLUDING ALPHA PARTICLES WHICH YOU CAN SEE HERE. BETA PARTICLES AND GAMMA RAYS SYNONYMOUS TO PHOTONS. ALPHA PARTICLES TRAVEL VERY SHORT DISTANCES AND CAN BE STOPPED BY VERY THIN THINGS. SO MOST PEOPLE ARE FAMILIAR WITH THE FUCK SHE MA DISASTER IN JAPAN -- P ONE THING THEY WERE TOLD IS TO WEAR LONG SLEEVES AND PANTS, KEEP YOUR SKIN COVERED. THAT CLOTHING CAN BLOCK THESE ALPHA PARTICLES SO IT PROTECTED PEOPLE'S SKIN. BETA PARTICLES CAN TRAVEL FURTHER, SO GENERALLY WE SAY BETA PARTICLES TRAVEL ABOUT TWO TO THREE MILLIMETERS, BEFORE THEY CAN STOP AND VERY -- ARE NON-DENSE METALS LIKE ALUMINUM CAN STOP BETA PARTICLES. SO WE HAVE MANY THERAPIES THAT USE BETA PARTICLES LIKE PROSTATE SEED IMPLANTS AND SO FORTH. AND THEN GAMMA RAYS ARE CLASSIC RADIATION WE USE THERAPEUTICALLY THESE ARE STOPPED BY CONCRETE. SO IN OUR VAULT WHERE WE DELIVER RADIATION THERAPY THERE'S TYPICALLY SIX FEET OF CONCRETE IN THE VAULT, AND THAT'S ENOUGH TO ACTUALLY MAKE SURE WE STOP ALL THE PENETRATION OF ANY PHOTONS OR POTENTIAL GAMMA RAYS. WHEN WE TALK ABILITY ELECTROMAGNETIC SPECTRUM RADIATION WE ARE OPERATING FROM THERAPEUTIC VIEWPOINT IS HERE AND GAMMA RAY AREA. SO JUST PUT THAT INTO PERSPECTIVE. HOW ARE X-RAYS GENERATED? ON THE LEFT IS GENERAL SCHEMATIC OF X-RAY TUBE WHICH OFTEN IS A VERY SIMPLISTIC VERSION OF HOW X-RAY MACHINE WORKS. SO YOU HAVE YOUR AN NODE AND CATHODE AND THIS OPERATEDS IN ASSUME AND YOU APPLY ELECTRICAL CURRENT ACROSS THIS TO DEVELOP THE X-RAY BEAM. THIS IN A MUCH MORE FANCY VERSION IS IN WHAT WE CALL HERE WHICH IS A LINEAR ACCELERATOR WE ABBREVIATE AS LINAC. THIS IS ONE OF THE GENERAL VENDORS USED IN OUR COUNTRY, THERE'S A COUPLE OF THOSE. AND SO WHAT HAPPENS IS THIS PART HERE IS CALLED THE GANTRY, HEAD OF THE MACHINE AND THIS IS WHERE THE PHOTON OR ELECTRONS COME OUT OF THE MACHINE HERE. THE PATIENT LIES ON THE BLACK TABLE TOP HERE AND THIS TABLE TOP ROTATES UP DOWN SIDE TO SIDE AND ROTATE IN A HELP CIRCLE WAY. AROUND THE MULLEN YARR ACCELERATOR. AND SOME OF THE NEW MODERN MACHINES CAN ALSO HAVE THIS TABLE HAVE A PITCH AND A YA SO THE TABLE CAN ROTATE SLIGHTLY ON TOP OF OR WITH THE PATIENT ON TOP OF IT. THIS PART HERO AT A TIME AROUND THE PATIENT IN A -- ROTATES AROUND THE PATIENT IN A 360 MOVEMENT TO GET ALL ANGLES AND A LOT OF ACTUAL MACHINERY THAT OPERATES THIS, BELIEVE IT NORTH IS NOT PICTURED HERE SO IT'S UNDER THE GROUND OR OFTEN TIMES THIS IS AT THE BACK OF A WALL AND BEHIND THAT WALL IS A LOT OF OTHER MACHINERY. BASICALLY THIS AND A MORE FANCY VERSION IS ALL LOCATED RIGHT HERE AT THE TOP OF THE MACHINE. AS I MENTIONED LINEAR ACCELERATORS CREATE HIGH ENERGY PHOTONS AS WELL AS ELECTRONS. IN GENERAL WHAT HAPPENS HERE IS THE -- THERE'S AN ELECTRON GUN THAT SHOOTS ELECTRONS INTO THE MACHINE, THEY THEN GO THROUGH THIS WAVE GUIDE HERE. THERE'S VENDING MAGNETS WHICH INVENTORY SLAM ELECTRONS INTO A PIECE OF METAL WHICH CREATES PHOTONS. SO THAT'S ACTUALLY HOW THAT HAPPENS. IF WE ARE IN AN ELECTRON MODE WE WILL MOVE THAT PIECE OF METAL SO PHOTONS ARE NOT CREATED. WHEN WE LOOK AT THE BEAM THAT COMES OUT OF A MACHINE WITH UNIFORM BEAM CHARACTERISTICS, SO WHAT THAT MEANS IS IF YOU ACTUALLY RADIATED A PIECE OF FILM AND YOU HAD A MEASURING DEVICE AS IT WENT ACROSS THAT FILM FROM LEFT TO RIGHT YOU WOULD MEASURE THE SAME DOSE OF RADIATION AT EACH OF THOSE POINTS. THERE'S A LOT OF THINGS THAT HELP SHAPE THE BEAM TO MAKE SURE WE HAVE UNIFORM BEAM CHARACTERISTICS. WE ARE ABLE TO SHAPE THE FIELD VERY PRECISELY. AND THEN DELIVER PRECISE TREATMENT THROUGH A LOT OF MOTIONS THAT I JUST MENTIONED, ROTATION COUCH ROTATION AND PATIENTS ARE ALSO IMMOBILIZED SO THEY DON'T MOVE DURING THERAPY AND WE HAVE A VARIETY OF DIFFERENT TYPES OF IMMOBILIZATION DEVICE I WILL TALK MORE ABOUT LATER. WHEN WE TALK ABOUT SOME OF THE BASICS OF RADIATION THERAPY, SOME OF THE GENERAL LYNN GO IF YOU WILL THAT WE USE ARE THINGS SUCH AS HERE, SO GTB STANDS FOR GROSS TUMOR VOLUME, CTV STANDS FOR CLINICAL TARGET VOLUME AND THIS IS TYPICALLY AN ISOTROPIC EXPANSION FOR WHAT WE CALL MICROSCOPIC EXTENSIONS OF DISEASE SO EVERYTHING WE DO IN RADIATION THERAPY IS BASED ON A CT SCAN, SOMETIMES AN MRI IN RARE INSTANCES. AND WHAT WE KNOW IS THAT WHAT WE SEE ON THAT CT SCAN IN TERMS OF THE TUMOR VOLUME THERE MAY STILL BE CANCER CELLS MILLIMETER AWAY FROM THAT FOR EXAMPLE. SO THIS CTB ACCOUNTS FOR THAT. WE THEN PERFORM WHAT'S CALLED A PTV OR PLANNING TARGET VOLUME AND THIS IS AN ISOTOPE EXPANSION FOR SET UP UNCERTAINTY SO THOUGH WE HAVE A PATIENT I WILL MOBILIZED SO THEY'RE PRECISE WITHIN A COUPLE OF MILLIMETERS EVERY DAY THINGS COULD BE OFF A MILLIMETER OR TWO MILLIMETERS SO THAT ACCOUNTS FOR THAT POTENTIAL ERROR. WE ALSO HAVE THE ABILITY TO CREATE AN INTERNAL TARGET OR TUMOR VOLUME. AND THIS IS BASICALLY A VOLUME DRAWN WHICH ACCOUNTS FOR ORGAN OR TUMOR MOTION. THINK ABOUT A LUNG TUMOR, IF IT'S IN THE MIDDLE OF THE LUNG AS YOU ARE BREATHE THAT TUMOR IS MOVING WHILE WE ARE BREATHING. SO WE ACTUALLY HAVE THE ABILITY TO DO A 4D CAT SCAN WHICH TRACES THE PATIENT'S BREATHING CYCLE AND WE CAN SEE HOW THAT TUMOR IS MOVING AND ALL THE PHASES OF THAT BREATHING CYCLE. WHEN WE THEN DRAW OUT AREA WE TARGET WE INCLUDE THAT ENTIRE AREA WITH ALL THE MOTION AND WE CALL THAT AN ITV. WHEN IT COMES TO PLANNING TECHNIQUES THERE'S A LOT WE CAN USE FOR RADIATION THERAPY. I'M STARTING TO EXPLAIN THESE IN THE SIMPLEST FORM TO MORE COMPLEX FORMS. SO IN GENERAL WHEN WE TALK ABOUT BASIC RADIATION, WHERE YOU ARE TALKING WHAT WE CALL 3-D UPON FORMAL RADIATION THERAPY OR 3-D CRT. BASIC TENANTS IS WE USE A CT SCAN TO PLAN FROM ANATOMY AND NOL FROM MULTIPLE ANGLES THAT WE CAN USE AND WE CREATE THIS VIRTUAL PATIENT FROM WHICH WE DELIVER THE HER PI. -- THERAPY. THIS TECHNIQUE IS WIDELY USED IN THE U.S. AND IN MANY OTHER COUNTRIES AS WELL. IT'S COMMONLY USED FOR EARLY STAGE BREAST CANCER PATIENTS, IF WE HAVE A BONE METASTASIS THAT BEARE TREATING, FOR SOE OF THE MORE SIMPLISTIC THINGS WHERE WE DON'T HAVE A LOT OF OTHER ORGANS AT RISK BUT WE NEED TO THINK ABOUT HEART, LUNG, BOWEL, SO FORTH. IMRT INTENSITY NOTED LATED RADIATION THERAPY. AND -- MODULATED RADIATION THERAPY. THIS IS WHAT I LIKE TO TEACH MY RESIDENTS, IS THINK ABOUT YOU HAVE A TARGET THEN YOU WILL LOOK AT THE TARGET FROM MULTIPLE ANGLES BUT FROM EACH DIFFERENT ANGLE YOU MAY HAVE DIFFERENT OTHER ORGANS IN THE WAY. SO FROM THIS ANGLE YOU MAY ONLY SEE THE TARGET FROM THE SIDES, ANOTHER ANGLE YOU MAY SEE IT IN THE FRONT, SO INTENSITY MODULATED RADIATION THERAPY TARGET IN A DIFFERENT WAY THAT WHEN YOU COMBINE THAT TOGETHER YOU'LL RECEIVE A HOMOGENOUS DOSE OF RADIATION. SO WHAT YOU CAN SEE IN THIS FIGURE HERE IS THIS IS AN EXAMPLE OF A PATIENT PROBABLY WHO HAS PROSTATE CANCER AND HAD SURGERY, THERE'S FIVE BEAMS THIS PICTURE IS DEPICTING. FROM EACH BEAM WHAT THIS MAP IS LOOKING AT WE CALL THIS AFFLUENCE MAP EACH PICTURE HAS A VERY DIFFERENT SHAPE TO IT. THOSE SHAPES ARE BASICALLY THE DIFFERENT VIEWS IS THE BEAM IS SEEING TO DELIVER RAID YEAR AGO THERAPY TO THAT AREA. THIS ALLOWS CUSTOMIZATION BASED ON A SPECIFIC PLANNING OBJECTIVE. SO WHAT IT ALLOWS US TO DO IS TELL THE SYSTEM TO TREAT TUMOR TO 50 GRAY, GRAY IS DOSE OF RADIATION BUT I WANT YOU TO KEEP THE BLADDER AT 20 GRAY THOUGH NEXT TO IT AND TOUCHING THAT ORGAN. THIS ALLOWS US TO DO THAT WITH A LOT OF EASE. THIS IS ANOTHER EXAMPLE OF THAT IN A PATIENT WITH A HEAD AND NECK CANCER. WHAT THESE PANELS HERE SIMULATE ARE MULTIPLE DIFFERENT BEAM ANGLES SO IN THIS SPECIFIC EXAMPLE IS THERE NINE OF THOSE. THIS IS A COMMON TECHNIQUE USED FOR HEAD AND NECK CANCER BECAUSE THEY HAVE A LOT OF ORGANS AT RISK ALL IN THE AREA ADJACENT TO THAT AND WE WANT TO DO ORGAN SPARING SO THIS IS A COMMON TECHNIQUE USED FOR OUR HEAD AND NECK CANCER PATIENTS AS WELL. ANOTHER FORM OF RADIATION THERAPY KIND OF INCREASING COMPLEXITY IS WHAT WE CALL VMAT OR VOLUME METRIC MODULATED ARC THERAPY, THIS IS WHAT I SHOWED YOU WITH IMRT EXCEPT MACHINE ROTATES AROUND THE PATIENT IN A 360-DEGREE ARC AND DELIVERS RADIATION THERAPY THE ENTIRE TIME THE TREE IS MOVING AROUND THE PATIENT. WHAT'S REALLY UNIQUE ABOUT THIS THERAPY IS IT ACTUALLY ALLOWS FOR QUICKER TREATMENT DELIVERY SO SOMETIMES IF WE HAVE A PATIENT WITH HARD TIME LYING ON THE TABLE OR WEARING THEIR MASK, WE MIGHT THINK ABOUT THIS THERAPY A LITTLE BIT MORE BECAUSE IT DELIVERS IT QUICKER. IT ALLOWS MORE CON FORMALITY OF THE MODERATE DOSE HOMOTHERAPY AND INCREASE HETEROGENEITY LOOKING ACROSS THE TARGET IT'S ESSENTIALLY THE SAME. BUT IT IS AT EXPENSE OF SURROUNDING MORE LOW DOSE TO SURROUNDING TISSUE SO THIS IS AN EXAMPLE OF AN IMRT PLAN ON THE LEFT AND VMT PLAN ON THE RIGHT, THIS IS A PATIENT WITH PROSTATE CANCER IN THE PAST ANDED THAT HAIR PROSTATE REMOVED. AND WHAT YOU CAN SEE HERE IS THAT THE RED AREAS ARE HIGH DOSE RADIATION THAT'S OUR TARGET. IF YOU LOOK RELATIVELY SIMILAR, ACROSS BOTH BUT WITH THE IMRT PLAN ON THE LEFT IS STREAKING MODERATE DOSE RADIATION OUT INTO THE OTHER ORGANS WHEREAS IN THE VMAT PLAN ON THE RIGHT YOU CAN SEE THAT'S HUGGING THE TARGET A LITTLE BIT BETTER. SO THAT IS THE DIFFERENCES IN THESE TWO TECHNOLOGIES. VMT NOW HAS REALLY I WOULD ARGUE REPLACED OUR IMRT THERAPIES BECAUSE IT'S QUICKER AND YOU GET KIND OF A MORE HOMOGENEITY OF DOSE. THIS IS WIDELY USED THROUGHOUT THE COUNTRY AND THE WORLD. BRACHYTHERAPY IS ANOTHER TECHNIQUE OF RADIATION THERAPY. PLACING A RADIATION SOURCE INSIDE OR ADJACENT TO A TUMOR, IT ALLOWS A RAPID DOSE FOLLOW-UP IN MAXIMAL SPARING OF NORMAL TISSUE SO BECAUSE IT'S BEING INSERT INTO THE BODY WE DON'T HAVE TO GO THROUGH FROM THE OUTSIDE IN. SO THIS IS COMMONLY USED FOR TUMORS AND BODY CAVITIES GYN CANCER, CERVICAL CANCER, ENDOMETRIAL CANCER VAGINAL CANCER ALSO FOR SOME HEAD AND NECK CANCER NAY SOW FEIGN JOEL CANCER. AND ALSO TUMORS THAT ARE CLOSE TO THE SURFACE OF THE SKIN. SO PROSTATE, PEOPLE PROBABLY HEARD PROSTATE BEFORE THIS IS BRACHYTHERAPY INSERT SEES DIRECTLY TO PROSTATE, ALSO SARCOMA, THE TONGUE, THE LIP AND THEN THE BREAST AS WELL. SO SOME EXAMPLES EXAMPLES OF BRACHYTHERAPY, THIS IS A PATIENT WHO HAD AN OCULAR MELANOMA. SO A MELANOMA IN BACK OF THE EYE. AND WHAT WE CAN DO IN CONJUNCTION WITH THE OPHTHALMOLOGIST IS STITCH A LITTLE RADIO ACTIVE PLAQUE ON TOP OF TUMOR BEHIND THE EYE, REREMOVE THAT AND THE TUMOR IS TREATED. THIS IS AN EXAMPLE OF A PATIENT WHO HAS CERVICAL CANCER, AND WE HAVE DEVICES ON THIS PARTICULAR EXAMPLE CALLED A TIN RING SO WE INSERT THIS THROUGH THE CERVIX TO UTERUS. WE HAVE A WHITE DONUT THAT SITS OUTSIDE THE CERVIX AND VAGINAL WALL AND TOUCHING THE CERVIX. AND THROUGH BOTH CATHETERS WE DELIVER RADIATION TO THE CERVIX WITHOUT GETTING SIGNIFICANT RADIATION DOSE TO BLADDER OR THE RECTUM. THIS IS STILL VERY COMMONLY USED THROUGHOUT THE WORLD FOR CERVICAL CANCER TREATMENT AND VERY IMPORTANT PART OF THE CERVICAL CANCER. ANOTHER ONE IS SRS. THIS HAS BEEN USED TO TREAT BRAIN TUMORS AND KIND OF THE MACHINE THAT MOST PEOPLE HAVE HEARD ABOUT A LITTLE BIT MORE IS CALLED GAMMA KNIFE. THIS WAS GAMMA KNIFE WAS THE FIRST MACHINE THAT WAS DEVELOPED TO DELIVER STEREO AT THAT TIME TICK SURGERY, WE PLACE A FRAME TO PATIENT HEAD THAT HAS A THREE DIMENSIONAL COORDINATE SIMILAR. THEY UNDERGO MRI WITH THAT FRAME ON AND DO TREATMENT PLANNING AND DELIVERY WITH THAT FRAME AND BASICALLY WHAT HAPPENS IS YOU HAVE 101 BEAMS THAT ALL INTERSECT AT THAT ONE FOCAL POINT SO HIGH DOSE RADIATION AT TUMOR BUT ANY BEAM PATH THERE'S NEGLIGIBLE DOSE RADIATION THERAPY. THIS TECHNOLOGY DEVELOPED TO TREAT TUMORS IN OTHER SITES OF BODY JUICING SAME TYPE, THAT'S STEREO TAKE TICK BODY RADIATION THERAPY OR SBRT. AND THIS IS NOW COMMONLY USED IN LUNG CANCER, LIVER CANCER, BONE TUMORS, LOTS OF DIFFERENT TYPES OF THERAPY, AND ACTUALLY WHAT'S REALLY EXCITING ABOUT SBRT NOW IS IT'S SHOWING A HUGE IMPACT IN PATIENT WHOSE HAVE WHAT WE CALL OLIGOMETASTATIC CANCER, PATIENTS WITH METASTATIC DISEASE THAT MAYBE ONLY HAVE THREE TO UP TO SEVEN LESIONS, NOW WHEN WE GIVE PATIENTS STEREO TACTIC RADIATION TO THOSE LESIONS WE ARE IMPROVING THE OVERALL SURVIVAL RATES WHICH IS EXCITING SO THIS PER THINK IS SO SUCCESSFUL THAT IN LUNG CANCER IT'S BEEN COMPARED HEAD TO HEAD IN A RANDOMIZED STUDY WITH LUMPECTOMY, GOLD STANDARD SURGERY FOR EARLY STAGE LUNG CANCER AND OUTCOMES ARE THE SAME WITH SBRT COMPARED TO SURGERY, SO THIS IS STARTING TO REPLACE SURGERIES THAT WE ARE DOING. ONE THING I ALWAYS LIKE TO MENTION THE IS A BRAND OF MACHINE THAT DELIVERS STEREO TACTIC RADIOTHERAPY. GEORGETOWN HAS SEVERAL CYBER KNIVES, MANY OTHER RADIATION ONCOLOGY CENTERS IN THE AREA HAVE THIS AS WELL. BUT THEY HAVE DONE A LOT OF MARKET SO PEOPLE HEARD OF CYBER KNIFE BUT NOT SBRT. SO AGAIN KIND OF JUST THE BRAIN OF THE MACHINE THAT DELIVERS THAT. SO AGAIN HERE IS A PICTURE OF A TUMOR IN THE BRAIN, HERE IS A EXAMPLE OF EARLY STAGE LUNG CANCER TREATED WITH SBRT. SO COUPLE OF BASICS ON RADIATION BIOLOGY AND SOME OF THE PRINCIPLES OF THAT. SO ONE IS RADIATION SURVIVAL CURVE. THIS IS A CLASSIC FIGURE THAT WE LEARN ABOUT. SHOWING EFFECT OF DIFFERENT TYPES OF RADIATION, AND THEIR CELL KILL. SO ON THE Y AXIS WE HAVE SURVIVAL AND LOGARITHMIC FASHION ON X AXIS WE HAVE INCREASING DOSES OF RADIATION THERAPY. WHAT WE CAN SEE WITH THIS DEPICT, THIS SLIDE HERE THAT I'M USING A CURSOR ON IS EFFECT OF ALPHA RAYS. WHAT YOU CAN SEE IS ALPHA RAYS THIS IS THEY CAN LOGARITHMIC KILL. OVER HERE X-RAYS AS WELL AND YOU CAN SEE A BIG DIFFERENCE BETWEEN X-RAYS SIMILAR TO GAMMA RAYS, COMPARED TO ALPHA RAYS AS WELL. ONE OF THE THINGS WE DO IN RADIATION THERAPY IS TALK FRACTIONATION. SO IT'S VERY RARE WE GIVE A SINGLE DOSE RADIATION THE OTHER IS WE CAN HARM ORGANS NEAR THAT YARR SO WE FRACTIONATE RADIATION SO WE GIVE LITTLE DOSES OVER LONG TEAM PERIOD AND YOU EFFECTIVELY GET THE SAME NUMBER OF CELL KILL WITH USING FRACTIONATION. YET OUR NORMAL TISSUES ARE ABLE TO RESPOND TO THIS MUCH BETTER. SO CRASH NATURAL FOR FRACTIONATION IS TO -- RATIONAL IS STOW TAKE ADVANTAGE OF SURVIVAL OF NORMAL TISSUE TO SMALLER DOSES AND AMPLIFY THAT OVER MANY TREATMENTS. SO THIS IS ANOTHER PICTURE HERE, LOOKING AT THE DIFFERENCES BUT -- BETWEEN EARLY RESPONDING TISSUE AND TUMOR TISSUE AND LATE RESPONDING TISSUES. SO TUMOR AS WELL AS CELLS IN OUR BODY THAT HAVE RAPID TURN OVER HAIR, SKIN, LINING OF GI TRACK AND ESOPHAGUS AND MOUTH, THOSE ARE EARLY RESPONDING TISSUES SO THEY HAVE AN EFFECT EARLY ON IN THERAPY BUT THEY CAN HEAL OVER TIME. TAKING ADVANTAGE OF IMPROVED SURVIVAL OF NORMAL TISSUES. THE LATE RESPONDING TISSUES ARE NOT AFFECTED EARLY ON BUT CAN BE AFFECTED LATER ON SO THESE ARE THE THINGS THAT WE WORRY ABOUT MORE RAID YEAR AGO ONCOLOGY, WHAT ARE OUR LONG TERM EFFECTS ARE WE CAUSING LOCK TERM ORGAN DAMAGE FOR THESE PATIENTS. WITH TALK FOUR RES, REPAIR, REASSORTMENT OR SOME TEXTBOOKS CALL IT RADIO DISTRIBUTION. REOXYGENATION AND REPOPULATION. I WILL TOUCH ON EACH BRIEFLY HERE, IN TERMS OF REPAIR, THE HEALTHY CELLS ARE ABLE TO REPAIR THE DNA DAMAGE CAUSED BY RADIATION ON A DAILY BASIS. SO THAT OCCURS EVERY DAY BETWEEN TREATMENT FOR PATIENT. SOMETIMES THE TUMOR CELLS CAN UNDERGO REPAIR AS WELL THAT'S PART OF THE REASON WE HAVE TO FRACTIONATE OVER DAYS AND GET TO OVERALL HIGHER DOSE OF RADIATION THERAPY. REASSORTMENT -- REPAIR. THE DNA IS PRIMARY TARGET OF RADIATION. AND THERE IS REALLY TWO DIFFERENT AFFECTS OF RADIATION AT THE DNA LEVEL. THE EASIER ONE IS DIRECT EFFECT SO RADIATION CAN COME IN AND DAMAGE THE DNA DIRECTLY. AND CAUSE A DOUBLE STRAND BREAK. THESE ARE WHAT WE ARE LOOKING FOR IS DOUBLE STRAND BREAKS BECAUSE IF YOU INDUCE DOUBLE STRAND BREAK THAT WILL DIE THEN OR DIE WHEN IT GOES TO TRY TO DIVIDE INTO TWO NEW CELLS. IN ADDITION TO THAT THOUGH WE CAN HAVE WHAT'S CALLED SINGLE STRAND BREAKS, THESE ARE OFTEN DUE TO INDIRECT EFFECT OF THE RAID YEAR AGO. SO WHAT WE MEAN BY INDIRECT EFFECT OF RADIATION IS RADIATION WILL INTERACT WITH SOMETHING ELSE IN THE CELL IT WILL KICK OFF FREE RADICAL OR OXIDANT AND THAT OXIDANT WILL BE SITTING NEXT TO DNA AND GO AND DAMAGE PART OF THE DNA. THAT OFTEN CAUSE WHAT IS WE CALL SINGLE STRAND BREAKS. BUT WITH SINGLE STRAND BREAKS BECAUSE YOU HAVE THE OTHER COMPONENT THERE DNA STRAND THOSE CAN BE REPAIRED OVER TIME SO THAT'S TYPICALLY KIND OF WHAT HAPPENS. SO IN GENERAL WE ARE LOOKING FOR DOUBLE STRAND BREAKS WHAT IS KEY. WHEN YOU THINK ABOUT WHAT IS MORE LIKELY TO HAPPEN SINGLE STRAND BREAKS OR DOUBLE STRAND BREAKS, DOUBLE STRAND BREAKS ARE MORE RARE AND THE REASON IS AGAIN OUR DNA HAS THINGS LIKE HISTONES AND PROTECTIVE PROTEINS AND ALL THESE THINGS THAT TRY TO MAKE IT MORE PROTECTED BUT AGAIN THEY DO HAPPEN CUMULATIVELY OVER THE COURSE OF RADIATION THERAPY. ANOTHER THING TO NOTE, THERE IS A DIFFERENCE BETWEEN EFFECT OF PHOTON THERAPY WHICH AGAIN IS OUR REGULAR RADIATION AND ON PARTICLE THERAPY. PARTICLE THERAPY ARE THINGS LIKE PER TON RADIATION CARBON IONS, COUPLE OF OTHER ONES OUT THERE AS WELL. PHOTONS MORE OFTEN CAUSE SINGLE STRAND BREAKS, PARTICLE THERAPY BECAUSE THEY ARE BIGGER THEY ACTUALLY MORE OFTEN CAUSE DOUBLE STRAND BREAKS. CELLS THAT CORRECT -- CELLS THAT CAN CORRECT DNA DOUBLE STRAND BREAK CAN GO ON TO DIVIDE ANOTHER DAY AND ULTIMATELY REPAIR THEMSELVES. WHEN WE TALK ABOUT REDISTRIBUTION, ONE THING THAT HAPPENS IS RADIATION CAN OFTEN INDUCE THE CELL CYCLE TO ARREST AND THEN BILL IN A PHASE WHERE IT CAN REPAIR ADDITIONAL DAMAGE OR WHERE NOT SUSCEPTIBLE TO THAT DAMAGE. SO AGAIN HERE IS ONE OF THE PATHWAYS OF HOW ALL THAT WORKS. SO YOU CAN HAVE IONIZING RADIATION, AND THEN IT CAN GO THROUGH THE ATM AND P53 PATHWAYS AND ULTIMATELY CAUSE CELL CYCLE ARREST OR APOPTOSIS. THE PHASES MOST SENSITIVE TO RADIATION THERAPY ARE THE G2 PHASE AND MITOTIC PHASE. THE G1 PHASE OFTEN TIMES IS LESS SENSITIVE TO RADIATION THERAPY AS WELL AS G 0. SO ONE OF THE THERAPIES THAT'S OUT THERE, PEOPLE MAY HAVE HEARD OF CHECK POINT INHIBITORS SO CHECK POINT INHIBITORS WHAT THEY DO IS BASICALLY BREAK DOWN THESE CHECK POINTS HERE ALLOW THE CELL TO CONTINUE IN THE CELL CYCLE SO THAT IT DOES ULTIMATELY GET INTO A PHASE, WHERE THINGS ARE MORE SUSCEPTIBLE TO RAID CONGRATULATION DAMAGE OR DAMAGE TO CHEMOTHERAPY AGENTS AS WELL. SO CHECK POINT INHIBITORS HAVE PROVEN VERY EFFECTIVE IN MANY CANCERS AND THERE'S A LOT OF WORK BEING DONE ON THESE AS WELL. AGAIN AS I JUST MENTIONED THE M PHASE AND G2 PHASE ARE THE MORE RADIO SENSITIVE. HERE ARE THE RIGHT IS JUST AGAIN, A CELL SURVIVAL CURVE LOOKING AT THE CELL KILL AND THESE DIFFERENT PHASES WITH THE MOST CELL KILL SEEN AGAIN IN THE M AND G2 PHASE THAT YOU CAN SEE HERE. SOMETHING WE DOLL IS COMBINE RADIATION THERAPY WITH OTHER MODALITIES THAT CAN CHANGE WHICH PART OF THE CELL CYCLE CANCER CELLS ARE IN, THIS IS ONE OF THE REASONS WE OFTEN TIMES COMBINE CHEMOTHERAPY WITH RADIATION BECAUSE THE CHEMOTHERAPY SENSITIZE IT IS CELLS TO RADIATION MORE AND THE WAY THEY DO IT OFTEN TIMES IS PUSHING THAT CELL INTO A DIFFERENT MORE SENSITIVE PHASE OF THE CELL CYCLE. REOXYGENATION, FOLLOWING RADIATION THERAPY, TUMORS CAN REOXYGENATE. WHAT WE KNOW IS THAT TUMORS WITH A MORE OXYGENATED ENVIRONMENT, RADIATION THERAPY IS MORE EFFECTIVE AND THOSE ENVIRONMENTS THAN IN A HYPOXIC ENVIRONMENT. THERE'S A LOT OF REASONS FOR THAT. THE MAIN ONE I SHOWED YOU A COUPLE OF SLIDES AGO IS RADIATION INDUCES FREE RADICALS, THE MOST COMMON FREE RADICAL IN OUR BODY COMES FROM WATER. IN GENERAL OXYGENATED AREAS ARE MUCH MORE SUSCEPTIBLE TO RADIATION THERAPY DAMAGE. SO AGAIN YOU CAN SEE THAT HERE DEPICTED ON THESE CURVES, HYPOXIC ENVIRONMENT TENDS TO BE MORE RADIO RESISTANT WHEREAS AIR RATED ENVIRONMENT TENDS TO HAVE MORE CELL KILL. THE OTHER AREA THIS IS PERTINENT IS WITH TUMORS AND THEIR BLOOD SUPPLY. SO TUMORS AS THEY GROW BIGGER OFTEN TIMES OUTGROW BLOOD SUPPLY SO YOU WILL DEVELOP NECROTIC OR HYPOXIC AREAS INSIDE THE TUMOR. YOU HAVE BEEN TIMES THOSE AREAS CAN BE MORE DIFFICULT TO ACTUALLY KILL THAN THE PARTS OF THE CELL OTHER PARTS OF THE TUMOR THAT ARE WELL OXYGENATED. SO THIS IS SOMETHING ELSE WE THINK ABOUT IS HOW TO MODULATE THAT A LITTLE BIT, HOW TO IMPROVE BLOOD FLOW TO AREAS TO MAKE RADIATION THERAPY MORE EFFECTIVE. ANOTHER THING THAT'S OUT THERE ARE DIFFERENT THINGS, I HAVE ALLUDED TO THIS ALL RIGHT, RADIATION MODIFIERS. SO THESE'S A COUPLE OF WAYS TO MODIFY THINGS OR INDUCE A MODIFICATION ARE THE RADIATION. AS MENTIONED BEFORE THERE'S THINGS WE CAN DO TO SENSITIZE THE TUMOR TO RADIATION. SO THESE ARE SOME CLASSIC CURVES HERE IN RADIATION WHERE YOU LOOK AT TUMOR CONTROL OVER DOSE SO HIGHER THE DOSE OF REDIATION WE GIVE THE LESS OR THE MORE CELL KILL OR TUMOR CONTROL MEANING MORE EFFECTIVE THE RADIATION. THIS GRAPH IS COUNTER INTUITIVE WITH THAT. WE ALSO HAVE A CURVE HERE FOR OUR NORMAL TISSUES SO WHAT YOU CAN OFTEN SEE IS THAT IF WE INCREASE DOSE OF RADIATION WE ALSO GET MORE NORMAL TISSUE CELL KILL. SO OFTEN TIMES WHAT WE ARE LOOKING AT IS HOW TO GIVE SAME DOSE RADIATION AND GET BETTER TUMOR CONTROL WITH THE SAME OR LESS TISSUE DAMAGE. THAT'S DEPICTED HERE IN THIS GRAPH HERE. ALTERNATIVELY CAN WE GET RADIATION MODIFIER THAT CAUSES RADIO PROTECTION OF NORMAL TISSUE SO INSTEAD OF MOVING THAT SHIFTING THAT TO THE LEFT CAN WE SHIFT IT TO THE RIGHT. SO THERE'S BEEN A LOT OF WORK DONE ON RADIO PROTECTION MODIFIERS. A LOT OF THESE STUDIES HAVEN'T PANNED OUT SO WELL WHEN THEY PROTECT THE NORMAL TISSUES THEY PROTECT THE TUMOR A LITTLE BIT. THERE'S A BIG ONE WE USED TO USE IN HEAD AND NECK CANCER, TO HELP PROTECT FROM MUCOUSITIS, IT'S FALLEN FROM FAVOR FOR VARIETY OF REASONS IT WASN'T WELL TOLERATED EITHER. BUT AGAIN SO THIS IS SOMETHING THAT PEOPLE ARE ALWAYS LOOKING AT AND THERE'S A LOT OF WORK BEING DONE IN THIS ARENA BUT FROM A NUCLEAR DISASTER TYPE OF VIEWPOINT. SO WHAT ABOUT SOME OF THE DIFFERENT RADIATION TARGETS THAT WE CAN USE. TO HELP MODIFY RADIO SENSITIZE, SO THESE ARE SOME OF THE DIFFERENT TARGETS THAT ARE OFTEN LOOKED AT AND IN TARGETS HAVE ALSO ALREADY BECOME ACTIVE DRUGS WE USE IN COMBINATION WITH RADIATION. SO GROWTH FACTOR RECEPTORS LIKE EGFR RECEPTORS, THE VEGF RECEPTOR, SO THIS IS ONE OF THE DRUGS THAT TARGETS THIS IS CALLED CITY TUX HAS BEEN, ONE DRUG THAT TARGETS THIS IS B EBSISMAB DNA REPAIR PROTEINS, TRANSCRIPTION FACTORS SIGNAL TRANSDUCTIONS PROTEINS, THERE'S A NEW DRUG TARGETING PI 3 KINASE PATHWAY WHICH IS BEING USED NOW IN PATIENTS IN ADDITION TO THAT WE CAN LOOK AT MULTI-TARGET INHIBITION, CHAPERONE PROTEINS, MICROENVIRONMENT ANGIOGENESIS AND VASCULATURE, A BIG AREA PEOPLE ARE WORKING ON IS EPIGENETIC MODIFICATION (INDISCERNIBLE) COMMONLY USED IN GLEE BLASTOMA HARNESSES THIS AND IN ADDITION TO THAT THERE'S OTHER RADIATION INDUCIBLE TARGETS WHICH HAVE BEEN LOOKED AT AS WELL. SO THIS IS JUST ONE VERY SMALL EXAMPLE AND THIS IS AN OLDER SLIDE, SO TO BE HONEST THIS IS MUCH BIGGER NOW BUT LOOKING AT THE DIFFERENT TARGET THE EGFR FAMILY SO EGFR AT NORMAL GROWTH FACTOR, THERE'S MANY TARGETS THAT ARE IN CLINICAL USE AS I MENTION BEBZIZMAB TARSEVA AND MANY MORE THAT AREN'T DEPICTED HERE AS WELL. SO WHEN WE LOOK AT WHAT ARE SOME OF THE ISSUES FOR TARGET OR AGENT DEVELOPMENT, ONE OF THE BIG THINGS IS MECHANISM SO WE LOOK AT SPECIFIC CELL TYPES, OR IS IT DUE TO A SPECIFIC CONDITION, THE CANCER. WE HAVE TO LOOK AT METHOD OF TARGETING SO LOOKING AT ANTIBODY THERAPY VERSUS SMALL MOLECULES VERSUS GENE THERAPY, AGAIN, THERE'S CHALLENGES WITH EACH OF THESE DIFFERENT APPROACHES, ANTIBODIES DON'T PENETRATE THE BLOOD BRAIN BARRIER, THEY MAY GIVE THERAPIES WE ARE NOT PROTECTING THE BRAIN FOR EXAMPLE. WE CERTAINLY HAVE THE LOOK AT THE THERAPEUTIC RATIO. SO WHAT WE WANTING TO KILL MORE TUMOR OPPOSED TO MORE NORMAL CELLS AS WELL? ONE EXCITING AREA WHICH PEOPLE ARE WELL AWARE OF NOW ARE SOME OF THE IMMUNOMODULATORY AGENTS OR IMMUNOTHERAPY, THESE ARE FINED WITH RAID YEAR, WE CAN DEVELOP THE SCOPAL EFFECT WHICH I WILL SHOW A SLIDE OF IN A MINUTE HERE. THERE'S A VARIETY OF DIFFERENT TYPES OF AGENTS SO PDL 1 INHIBITORS AND MANY OTHERS. SO ONE -- THERE'S A LOT OF DRUGS ON COMMERCIALS NOW AND IT'S A REALLY EXCITING TIME BECAUSE WE ARE SEEING SOME NICE OUTCOMES IN PATIENTS WITH THESE AGENTS. SO WHAT THE SCOPAL EFFECT IS, THIS IS KIND OF THE SEMINOLE CASE REPORT, FROM NEW ENGLAND JOURNAL OF MEDICINE, THIS WAS A PATIENT WITH METASTATIC MELANOMA. THEY WERE RECEIVING IMMUNOTHERAPY, AND WHAT HAPPENED IS THEY DEVELOPED THIS METASTASIS HERE KIND OF IN THE PERISOMETIME AREA THAT WAS TREATED WITH RADIATION USING THAT SBRT APPROACH I MENTIONED EARLIER. WHAT WAS SURPRISING IS WHEN THEY GAVE RADIATION WHILE PATIENT WAS ON IMMUNOTHERAPY, THOUGH THEY ONLY TARGET THIRD DEGREE AREA, OTHER PATIENTS OF OF KNOWN DISEASE GOT SMALLER SO THIS IS WHAT'S CALLED THE SCOPAL EFFECT YOU GET THIS EFFECT OF CANCER SHRINKAGE AND OTHER PARTS OF THE BODY THAT NEVER HAD RADIATION THERAPY. SO THIS WAS REALLY EXCITING AND PEOPLE ARE DOING WORK IN THIS ARENA AS WELL SO MOVING TO RADIATION THERAPY IN THE CLINICAL PRACTICE JUST TO GIVE EVERYONE A FLAVOR OF WHAT IT ENTAILS. AGAIN, OUR GENERAL TWO GOALS IN RADIATION THERAPY ARE TO CURE CANCER, CERTAINLY IF LOCALIZED, OR METASTATIC WE HAVE A RUNNEL ROLE IN PATE LATING SYMPTOMS SO HALF THE SYMPTOMS ARE PAILIATION. SO THIS CAN BE ONE CANCER TO MULTIPLE ORGANS THAT ARE CAUSING ANY BOTHER SOME SYMPTOMS FOR THE PATIENT SO THAT'S CLASSIC EXAMPLES ARE BONE METASTASIS WHERE PAIN LUNG LESION CAUSING COLLAPSE OF LUNG TISSUE SO WE MAY TREAT THAT AREAS THAT ARE BLEEDING FROM TUMOR AS WELL OR CLASSIC INDICATIONS. SO AGAIN, WHEN WE TALK ABOUT TYPE OF CANCER ANY SOLID TUMOR IS TREATED WITH RADIATION THERAPY. IN GENERAL RADIATION DOESN'T HAVE LARGE ROLE AND SOME OF THE TUMORS ARE OR CANCERS LIKE LEUKEMIAS, THERE'S STILL A ROLE IN SOME LYMPHOMAS BUT NOT ALL. BUT MOST SOLID TUMORS AT SOME POINT DO HAVE RADIATION THERAPY AS PARTS OF THEIR CARE. SO THE ONCOLOGY TEAM RADIATION ONCOLOGY REALLY FITS IN WITH A WHOLE ONCOLOGY TEAM. CANCER AS MANY PEOPLE PROBABLY KNOW IS REALLY A MULTI-DISCIPLINARY DISEASE, COME TOGETHER TO TREAT A SINGLE CANCER PATIENT. THAT ALSO INCLUDES DIFFERENT THINGS LIKE SOCIAL WORKERS, NUTRITIONISTS, SURVIVORSHIP, A LOT OF SPECIALTIES THAT COME IN TOGETHER FROM -- TO TREAT ONCOLOGY PATIENT. WHEN WE SEE A PATIENT WHETHER THEY ARE CURATIVE OR PALLIATIVE BUT CERTAINLY SEEING A PATIENT THE GENERAL IDEA IS DEVELOP MULTI-MODALITY PLAN. OFTEN TIMES THIS MAIN INCLUDE SURGERY RADIATION SOME SYSTEMIC THERAPY, BUT THERE'S ALSO SOMETIMES OTHER LOCAL THERAPIES THAT WE MAY INCORPORATE AS WELL. LIKE FOCAL ABLATION TECHNIQUES, LIKE ULTRASOUND OR DIFFERENT WAYS OF DRUG DELIVERY. RADIATION THERAPY TREATMENT IS A PROCESS AND SO I'LL WALK YOU THROUGH THAT BRIEFLY HERE. IT STARTS OFF WITH A CONSULTATION WITH RADIATION ONCOLOGIST, IF THE RADIATION ONCOLOGIST DEEMS A PATIENT TO BE CANDIDATE FOR RADIATION THERAPY, THE NEXT STEP IS UNDERGO A CT SIMULATION OR PLANNING SESSION. ONCE PERFORMED WE TAKE THE CT IMAGES AND THAT'S HOW WE CREATE THE RADIATION PLAN AND TRANSFER THOSE IMAGES TO A TREATMENT PLANNING SYSTEM. WE HAVE THE ABILITY AT THAT TIME TO FUSE OUTSIDE IMAGES LIKE A PET SCAN OR MRI SCAN TO HELP DO OUR DELINEATION OF THE TARGETS. WE THEN UNDERGO CONTOURING, I WILL SHOW YOU COUPLE OF PICTURES OF THESE STEPS, WHERE AS A PHYSICIAN YOU HAVE TO WITHDRAW THE AREAS YOU WANT TO TARGET, WHAT I MENTION BEFORE, GTB CTB PTB, WE CONTOUR OUT NORMAL STRUCTURE SO WHAT ARE THE AREAS TO AVOID WITH RADIATION, HEART, LUNG, GLANDS, THEN THAT RADIATION PLAN IS CREATED AND IT'S CUSTOMIZED FOR THAT PATIENT. THERE'S A FIELD OF PEOPLE CALLED DOSIMETRIESES THAT HELP DO THIS. AS A PHYSICIAN WE L INVESTIGATE WHAT THAT PLAN, THAT PLAN IS EVALUATED BY MEDICAL PHYSICIST. ONCE APPROVED THE PLANS TRANSFER TO OUR TREATMENT MACHINES AND THEN THE PATIENT UNDERGOES THE ACTUAL TREATMENT DELIVERY. THIS IS AN EXAMPLE OF A CT SCAN OF ONE OF OUR HEAD AND NECK PATIENTS SO THIS IS A SNAP SHOT OF WHAT OUR PLANNING SOFTWARE LOOKS LIKE SO THIS WAS A PATIENT WHO HAD A MOUTH CANCER WHO HAD SURGERY AND WHAT YOU CAN SEE IS WHAT'S IN THIS RED AREA HERE IS OUR TARGET OR OUR GTB. THEN YOU CAN EASILY APPRECIATE HERE ARE ALL THE OTHER THINGS CONTOURED OUT HERE, THE MANDIBLE THE CAROTID GRANDS BRAIN STEM SPINAL CORD ALL THIS WORK IS& DONE FOR EVERY SINGLE PATIENT. DEPENDING ON DISEASE WE ARE TREATING CAN SOMETIMES TAKE 15 MINUTES OR SOMETIMES TAKE AN HOUR EVEN. SO MOVING FORWARD NOW I THOUGHT I WOULD GO THROUGH A LITTLE BIT OF THE -- AM I MISSING A SLIDE? GOOD? OKAY. SO WE WOULD -- THOUGHT I WOULD GO THROUGH COUPLE OF PATIENT PRESENTATIONS FROM OUR MOST COMMON DISEASES THAT WE TREAT. SO AGAIN THIS FIRST PATIENT HERE, IS A 55-YEAR-OLD FEMALE WITH A NEW LUMP IN HER LEFT BREAST. SHE UNDERWENT A MAMMOGRAM PART OF HER WORK UP SUSPICIOUS ABNORMALITY THAT WAS SEEN, SHE HAD A BIOPSY CONSISTENT WITH INFILTRATING DUCTILE CARCINOMA WHICH IS COMMON TAKE OF BREAST CANCER AND NO FAMILY HISTORY OF BREAST CANCER AT THE TIME OF DIAGNOSIS SO THE FIRST THING WE HAVE TO DEVELOP IS A TREATMENT PLAN. FOR BREAST CANCER ONE STEP IS TO UNDERGO SURGERY SO PATIENTS CAN CHOOSE A MASTECTOMY OR BREAST CONSERVING THERAPY WHICH CONSIST OF LUMPECTOMY PLUS RADIATION. MASSECTOMY IS A MUCH BIGGER SURGERY FOR PATIENTS. BUT THERE ARE RANDOMIZE STUDIES DONE FOR APPROPRIATE PATIENTS COMPARING A MASTECTOMY VERSUS LUMPECTOMY PLUS RADIATION AND THE CURE RATE FOR BOTH THERAPIES ARE THE SAME AND THE WOMAN HAS ADVANTAGE OF MAINTAINING BREAST OR COSMESIS SO THE PATIENT IN THIS SCENARIO SUGGESTS -- SHE UNDERGOES A LUMPECTOMY AND LYMPH NODE BIOPSY, THEY INJECT A DIE INTO THE BREAST. THEY THEN WAIT FOR A BRIEF PERIOD OF TIME AND THAT WILL TRACK TO THE LYMPH NODES AND AXILLA OR ARMPIT. THEY DO THAT WITH A BLUE DYE AND RADIO TRACER AND THEN AT THE TIME OF THE SURGERY THEY FIND THE LYMPH NODE AREAS AND THIS REMOVE THE LYMPH NODES THAT LIGHT ONE THE RADIO TRACER AND THE DYE. AT TIME OF SURGERY PATHOLOGY REVEAL AD THREE CENTIMETER TUMOR AND FOUR AXILLARY LYMPH NODES POISE POSITIVE FOR CANCER, THE PATIENT RECEIVES CHEMOTHERAPY AND RETURNS TO RADIATION ONCOLOGY TO START RADIATION PROCESS. SO THE FIRST THING WE HAVE TO DO IS DETERMINE WHAT TYPE OF RADIATION SHOULD WE GIVE HER. SO IN THIS CASE IT WOULD BE EXTERNAL BEAM RADIATION AND WE HAVE THREE DIFFERENT TECHNIQUES WE CAN USE, PART TIME RADIATION PHOTON THERAPY, OR ELECTRON THERAPY FOR SOME PARENTS THEY USE BRACHYTHERAPY WHICH I MENTION SOD THERE'S A DIFFERENCE BETWEEN SEALED AND UNSEALED SOURCES THIS IS A BRACHYTHERAPY PLAN FOR BREAST CANCER PATIENT. WHAT HAPPENS IS CATHETERS GO THROUGH THE BREAST AND THROUGH THIS WHITE TAIL YOU CAN SEE HERE WE ARE ABLE TO CONNECT THAT TO A SMALL RADIATION MACHINE. WHICH THEN DELIVERS RADIATION THROUGH THERE. THIS TECHNIQUE ISN'T DONE IN OUR COUNTRY AT ALL BUT I THOUGHT I WOULD MENTION IT HERE. IT'S DONE A LITTLE MORE IN EUROPE. SO IN THIS CASE WE CHOOSE PROTON THERAPY FOR THIS PATIENT SO THE PATIENT UNDERGOES CT SIMULATION, SO YOU CAN SEE AN EXAMPLE OF THE BREAST TISSUE HERE. THEN WE HAVE TO DRAW OR DELIVER RADIATION AS WELL AS SET WHAT WE CALL OUR RADIATION FIELD. SO WHAT MAYBE A LITTLE BIT DIFFICULT TO SEE IS THERE'S PURPLE LINES HERE WHICH INDICATE WHAT WE CALL OUR TANGENT FIELD FROM RADIATION. SO ONE COMES FROM MEDIAL SIDE, ONE FROM THE LATERAL SIDE AND WE ESSENTIALLY SANDWICH ALL THE BREAST TISSUE INTO THAT AREA. ONE THING YOU CONNOTE THOUGH IS THIS IS THE HEART, YOU CAN SEE PART OF THE HEART IS IN THIS FIELD HERE SO THAT'S SOMETHING WE WORK THROUGH IN THE PLANNING PROCESS TO MINIMIZE ANY RADIATION DOSE TO THE HEART. THIS SPECIFIC SCENARIO, THIS WOMAN HAD POSITIVE LYMPH NODES IN HER ARM PITTED WE INCLUDE SUPER CLAVICULAR FIELD TREATING THE SUPER CLAVICULAR LYMPH NODES, KNOWN DRAINING LYMPH NODES IN THE BREAST TISSUE. THAT FITS TOGETHER WHERE WE DON'T HAVE ANY OVERLAP OF WHAT WE CALL SUPER CLAVICULAR FIELD AND TANGENT FIELD. ONCE WHICH SET THE FIELD AND DRAWN CONTOURS WE DRAW A RADIATION PLAN. THIS IS AN EXAMPLE OF ONE OF THOSE PLANS SO THE RED SQUIGGLE LINE HERE IS WHAT WE CALL HUNDRED PERCENT DOSE LINES, THAT'S THE AMOUNT WE WANT IN OUR TARGET. AND THEN AS YOU GO DOWN HERE YOU SEE LOWERING DOSES OF RADIATION THERAPY. THERE'S VARIOUS WAYS WE CAN MODULATE THIS TO MAKE SURE WE GET THE HIGHEST DOSE IN THE APPROPRIATE AREA. ONCE THAT'S DONE WE ARE ABLE TO DELIVER THE TREATMENT. SO ONE OF THE THINGS THAT WE DO WHEN WE'RE DELIVERING RADIATION THERAPY IS WE WILL TAKE AN IMAGE ON THE TREATMENT MACHINE, TO MAKE SURE WE ARE LINING EVERYTHING UP CORRECTLY ON THAT DAY. SO THIS IS AN EXAMPLE HERE WHAT WE CALL PORT IMAGE WHERE WE TAKE AN X-RAY WHEN PATIENTS LAY ON THE TREATMENT TABLE AND THE POSITION AND WE ARE SHOWING THAT THE BOX HERE IS THE FIELD AND THEN WE HAVE THESE -- THIS BLUE LINE HERE WHICH SHOWS SO THIS IS ACTUALLY THE FIELD BEING DELIVERED. SO THIS IS ACTUALLY THE PORTAL IMAGE OF THAT PATIENT. AND WE ARE ACTUALLY SHOWING THAT THIS SHAPE IS EXACTLY THE WAY WE PLANNED IT FOR RAID YEAR AGO THERAPY. WE DO THAT TO MAKE SURE THAT WE ARE IN THE RIGHT AREA. FOR BREAST CANCER IT'S EASIER BUT OTHER PARTS OF THE BODY TREATING THE SPINE AREA FOR EXAMPLE WE NEED TO KNOW EXACTLY WHICH VERTEBRAL BODIES WE ARE TREATING EACH DAY SO WE TAKE THESE IMAGES ON THE TREATMENT MACHINE TO ENSURE EXACT LOCATION. ANOTHER EXAMPLE IS A PATIENT WITH PROSTATE CANCER. SO THIS IS A 54-YEAR-OLD MALE ELEVATED PSA ON PROSTATE ANTIGEN ON ROUTINE EXAM NO MEDICAL PROBLEMS AND BIOPSY PERFORMED WHICH SHOWS PROSTATE CANCER WITH WHAT'S CALLED THE GLEASON SCORE OF SIX, A LOWER RISK PROSTATE CANCER. SO AGAIN WHEN WE THINK ABOUT DEVELOPING A TREATMENT PLAN FOR THIS PATIENT, THIS HAS A LOT OF DIFFERENT OPTIONS ACTUALLY SO THEY CAN UNDERGO SURGERY WITH UPROUSEECTOMY. THEY CAN UNDERGO SURGERY AND RADIATION IF THEY HAVE HIGHS RISK FEATURES SEEN AT TIME OF SURGERY OR UNDERGO RADIATION THERAPY ALONE, AND IN THIS PARTICULAR PATIENT THEY MAY BE A CANDIDATE FOR BRACHYTHERAPY OR PROSTATE SEEDS, EXTERNAL RADIATION OR COMBINATION, OR THEY CAN GET RADIATION HORMONAL THERAPY, SO THERE'S OPTIONS FOR THIS PATIENT AND WE HAVE TO WEIGH THESE OPTIONS IN TERMS OF PROS AND CONS IN TERMS OF CANCER AS WELL AS PATIENT'S OWN DESIZER AND WHAT THEY WANT. SO THIS IS AN EXAMPLE OF A PROSTATE PLANT FOR ONE OUR PATIENTS SO IT'S LITTLE DIFFICULT, THIS IS AN ULTRASOUND IMAGE, THE ULTRASOUND PROBE IS IT IS IN THE RECTUM SO IT'S A TRANSRECTAL ULTRASOUND WHAT IS IN GRAY HERE I'M CIRCLING IS THE PROSTATE GLAND AND THEN THE WIDER TISSUE AROUND THAT ARE SOME OF THE SUPPORTING TISSUES AND SO FORTH. WHAT HAPPENS IS ALL UNDER ULTRASOUND GUIDANCE, WE PUT CATHETERS INTO THE PROSTATE THROUGH THE PERITONEUM THROUGH THE SKIN. THOSE CATHETERS ARE HOLLOW ON THE INSIDE AND THROUGH THOSE WE CAN ACTUALLY PUT SEEDS DIRECTLY INTO THE PROSTATE. EACH GREEN DOT SIMULATES A SEED. WHAT YOU CAN NOTICE IS THAT THERE'S THIS AREA HERE IN THE MIDDLE THAT WE DON'T SEE ANY OF THOSE. THE REASON FOR THAT THIS IS WHERE THE YOUR RETHAT SITS FROM TUBE TO BLADDER TO THE OUTSIDE. WE WANT TO AVOID THAT AREA WITH THE SEEDS SO YOU CAN SEE WE CAN GET A NICE DOSE OF RADIATION TO THE ENTIRE GLAND WE ARE ABLE TO AVOID AND SPARE THAT. THIS IS AN EXAMPLE OF A PATIENT WHO GETS EXTERNAL BEAM RADIATION WITH THAT VMAT TECHNIQUE THAT I MENTIONED BEFORE. WHAT IS IN RED AND BLUE HERE IS THE PROSTATE AND THAT PTV I TALKED ABOUT, AND THEN YOU CAN SEE THE LINES THAT ARE REALLY TIGHT AROUND THE PROSTATE, WITH THE LOWER VERY LOW DOSE THAT STREAKS OUT INTO THE TEMPORAL -- IT'S TIGHT SO WHAT'S DILLONIATEED IN YELLOW IS BLADDER, IT'S TIED AROUND THAT AND WHAT IS IN BROWN HERE IS THE RECTUM AND YOU CAN SEE WE ARE GETTING -- KEEPING HIGH DOSE AWAY FROM THE RECTUM AS WELL. WITH PROSTATE CANCER WE HAVE ABILITY TO DO IMAGE GUIDED RADIATION THERAPY. SO WHAT WE CAN DO IS IMPLANT THREE GOLD MARKERS TO THE PROSTATE WHICH THEN WE CAN USE TO TRIANGULATE EXACT LOCATION OF PROSTATE ON A DAILY BASIS. BELIEVE OR NOT FOR THE PROSTATE DEPENDING HOW THE BLADDER IS IN THE FRONT AND HOW FULL RECTUM IN THE BACK THE PROCESS IS SHOWN TO MOVE TWO CENTIMETERS IN GIVEN DIRECTION SO WE HAVE TO ACCOUNT FOR THAT SO HOW TO TRIANGULATE THAT LOCATION. IS CLASSIC WAY TO DO THIS IS IMPLANTING THE MARKERS INTO THE PROSTATE WHICH THEN STAY WITH THE PATIENT FOR THE REST OF THEIR LIFE. ANOTHER COOL TECHNOLOGY THAT'S AVAILABLE IS CALLED CALYPSO AND WHAT THESE ARE ARE RATED OWE FREQUENCY BEACONS. WE CAN IMPLANT THOSE INTO THE PROSTATE AND WHILE THE PATIENT IS GETTING TREATED WE HAVE A RADIO FREQUENCY DETECTOR THAT SITS OVERTOP OF PROSTATE OR OVER PATIENT KIND OF LIKE A LITTLE SHEET HERE. THAT CAN TELL US AND TRACK WHERE THE PROSTATE IS DURING THE ENTIRE THERAPY. IF FOR EXAMPLE A PATIENT PASSES GAS ON THE TABLE AND THE PROSTATE MOVES WE CAN STOP THE TREATMENT, REALIGN THE PATIENT AND CONTINUE WITH THERAPY. SO THIS IS A PICTURE OF THESE GOLDFISH DURABLE MARKERS SO THIS IS A IMAGE ON THE TREATMENT MACHINE EACH DAY BEFORE PATIENT GETS TREATED. SO WHAT'S ON THE LEFT HERE AND HERE ARE THE IMAGES THAT ARE ACQUIRED AT THE TIME OF THE PLANNING SESSION. AND THEN WHAT IS ON THE RIGHT HERE AND HERE ARE IMAGES THAT WE TOOK THAT DAY BEFORE TREATMENT. SO WHAT WE DO IS TRY TO MAKE SURE THAT THESE -- THAT ARE IN GREEN HERE ARE EXACT SAME SHAPE AS WHAT WE SEE THAT DAY FOR THE TREATMENT. ANOTHER COOL THING WE ARE ABLE TO DO ON THE TREATMENT MACHINES IS ALSO DO A MINI CAT SCAN, SO HOW THAT CAN BE BENEFICIAL FOR OUR PROSTATE PATIENTS IS WE CAN TRACK A PATIENT BLADDER FILLING TO SEE IF IT'S COOL ENOUGH SO IN THE CASE OF PROSTATE CANCER SOMETIMES A PIECE OF BOWEL MAYBE SITTING ON TOP OF THE PROSTATE, IT PUSHES THAT PIECE OUT OF THE WAY SO IT DOESN'T RECEIVE RADIATION. THIS IS A PICTURE OF A PATIENT WHO HAD THEIR CT, WHAT YOU SEE IN THE BIGGER PICTURE HERE IS AGAIN THIS IS IS THE PATIENT AT TIME OF PLANNING SESSION AND WHAT'S IN YELLOW IS THE BLADDER. WHAT'S HARDER TO SEE IS WHERE INSIDE KIND OF IN THIS AREA DOING THIS WITH IS THIS IS HOW THE PATIENT LOOKS TODAY. WHAT YOU CAN SEE ON THE ADVANTAGE TALL IMAGE HERE IS THE BLADDER SHOULD BE THIS YELLOW BUT WHAT YOU SEE IS MUCH, MUCH SMALLER TODAY THAN IT WAS THE DAY OF THE PLANNING SESSION. SO IN THIS EXAMPLE WE CAN HAVE THE PATIENT GET OFF THE TREATMENT TABLE, DRINK A LITTLE BIT MORE WATER, FILL THEIR BLADDER AND WE WOULD GO ON TO TREAT THEM ONCE BLADDER IS FULL. SO PART OF THESE TYPES OF ADVANCES ARE REALLY THE REASON WE HAVE BETTER OUTCOMETS NOW COMPARED TO WHAT WE USED TO DO IN THE PAST. SO DELIVERING THERAPY PI, SO THE QUESTION IS RADIATION WORK EVERY TIME? SO AGAIN WE DO KNOW THERE ARE SIDE EFFECTS FROM RADIATION THIS IS ESSENTIALLY NORMAL TISSUE TOXICITY. AND AS I BRIEFLY MENTION WE CAN HAVE ACUTE EFFECTS AND LATE EFFECTS AND I WILL GIVE A COUPLE OF EXAMPLES OF THOSE IN A SECOND. WE DO KNOW CANCER CELLS SOMETIMES HAVE STEM CELLS DEPLETION AS WELL AS BODY CAN, WE CAN ALSO INDUCE CHRONIC OX DAYTIVE DAMAGE, SOMETIMES VASCULAR DESTRUCTION FIBROSIS AND MORE. BUT AGAIN RADIATION IS REALLY DOSED TO NORMAL TISSUE AND NOT THE TUMOR. SO WE ARE OFTEN TIMES LIMITED IN THE DOSE WE CAN DELIVER SAFELY BY OUR NORMAL TISSUE. THAT OFTEN TIMES IS REALLY WHAT DEFIANCE THE TOTAL DOSE THAT WE ARE DELIVERING. SO A GOOD EXAMPLE OF THIS IS PULMONARY FIBROSIS. SO THIS IS A VERY OLD EXAMPLE, THIS IS NOT WHAT WE WOULD DO ANY MORE, HARD TO SEE HERE BUT THIS IS FROM 1992. THIS IS A PATIENT WHO HAD A LUNG CANCER AND WE TREATED THIS HUGE AREA WITH RADIATION WHICH WE WOULD NEVER DO TODAY. WHAT YOU CAN SEE IS OVER TEN YEARS LATER THE PATIENT HAS DAMAGE TO THE LUNGS U PULMONARY FIBROSIS IN THIS SHAPE AS IT WAS DELIVERED AT THAT TIME. SO NOW WE KNOW A LOT MORE ABOUT THE PATHWAYS OF -- IN THE BODY THAT ACTUALLY RESULT IN EITHER RADIATION NEWSPAPER NIGHTIS OR LEAD TO PULL MOLL FIBROSIS, WE LOOK AT -- PULMONARY FIBROSIS TGF BETA WHICH CULMINATES WITH THIS RISK AND SO FORTH. ANOTHER EXAMPLE OF LONG TERM SIDE EFFECT PATIENTS WE HAVE ARE LYMPHEDEMA, THIS IS DUE TO VESSEL DAMAGE, BASICALLY WHAT HAPPENS AFTER RADIATION THERAPY IS DEVELOP SCLEROSIS OF LYMPHATIC CHANNELS WHICH CAN RESULT IN SLOWING OF HOW THE FLUID IS MOVING THROUGHOUT THE BODY. AND PATIENTS CAN ULTIMATELY DEVELOP CHRONICALLY FA DEE MA OF EXTREMITIES FROM RADIATION THERAPY. WE THINK ABOUT THIS A LOT O IN BREAST CANCER, IT OFTEN TIMES IS MORE RELATED TO ACTS LAYER RADIATION BUT WE KNOW RADIATION CONTRIBUTES AS WELL. AN EXAMPLE OF A SHORT TERM SIDE EFFECT IS WHAT WE CALMIOUS SIGHTIS OR INFLAMMATION OF THE MUCOSA. WE SEE THIS IN HEAD AND NECK CANCER PATIENTS CAUSING THEM PAIN AND DIFFICULTIES WITH EATING. THIS IS A SIDE EFFECT WE HAVE TO MANAGE IN OUR HEAD AND NECK CANCER PATIENTS SO SOMETIMES WHAT YOU CAN SEE IS THAT YOU CAN DEVELOP STEM CELL DEPLETION OF THE MUCOSAL LINING THAT CAN TAKE SEVERAL WEEKS TO IMPROVE. SO WHAT ARE SOME OF THE ADVANCES IN RADIATION ONCOLOGY, WHAT ARE SOME OF THE FUTURE, SO THERE IS A BIOLOGY COMPONENT, SO HOW CAN WE USE RADIATION TO INDUCE TARGETS FOR OTHER AGENTS. WE NEED TO DEVELOP BETTER RADIATION SENSITIZERS AND PROTECTORS. AND WE STILL NEED TO DO MORE WORK COMBINING RADIATION WITH OTHER TARGETED DRUGS AND DEVELOP SYNERGIST I CAN EFFECTS. FROM A PHYSICS VIEWPOINT THOUGH WE HAVE DONE WORK IMPROVING TARGETING WITH IMAGING WE ARE LOOKING TO IMPROVE THIS AND IMPROVING DELIVERY METHODS, SOMETHING ELSE WORKED ON TO MAKE OUR TREATMENTS QUICKER FOR PATIENTS. THE LAST TIME THEY HAVE TO LAY ON THE TABLE THE LESS LIKELY THEY ARE TO MOVE. SOME OF THE CLINICAL THINGS TRANSLATING SOME OF THE EXCITING LABORATORY FINDINGS THAT PEOPLE ARE WORKING ON INTO CLINIC AND DEVELOPING MORE CLINICIAN SCIENTISTS AND ALSO ADDED HERE, WE USUALLY GET QUESTIONS ABOUT THIS BUT HOW WE CAN SYNERGIZE RADIATION WITH SOME OF THE IMMUNOTHERAPY AGENTS AS WELL, WE KNOW RADIATION THERAPY STIMULATES THE IMMUNE SYSTEM. ONE OF THE NEW TYPES OF RADIATION AVAILABLE IN THE AREA BOTH IN BALTIMORE AND THEN ALSO DOWN IN DC PART OF THE RADIATION SO I WANT TO TALK A BRIEF TALK WHY PROTON RADIATION IS DIFFERENT THAN ELECTRON RADIATION, THIS IS AN ADVANCEMENT SO OUR REGULAR RADIATION IS DEPICTED HERE IN THE BLUE. SO IT STARTS OFF IN THE BODY A LITTLE WEAKER. GETS STRONG COUPLE OF CENTIMETERS IN AND GETS WEAKER AND WEAKER AS IT PASSES THROUGH THE BODY. PROTON THERAPY IS DIFFERENT IN THAT IT STARTS IN THE BODY WEAKER. IT GETS STRONG WHERE WE TELL IT TO AND THEN IT STOPS. SO ONE OF THE MAIN BENEFITS OF PROTON RADIATION WHEN THEY STOP WE CAN AVOID EXCESS DOSE RADIATION WE CAN'T MODULATE WITH OUR REGULAR THERAPY. SO AN EXAMPLE OF WHAT THIS MEANS FOR PATIENTS IS BREAST CANCER PATIENTS SO ON THE RIGHT IS REGULAR RADIATION, AND SO YOU CAN SEE THE BREAST TISSUES OUTLINED HERE IN ORANGE, THE RED AREA WHICH IS THE HIGH DOSE RADIATION, LOWER DOSE AS WE GO INTO THE GREENS. ON THE LEFT IS PROTON THERAPY PLAN ASK WHAT IS EASY TO SEE IN THIS EXAMPLE IS WE ARE AVOIDING BUNCH LOW DOSE RADIATION TO HEART WITH PROTON RADIATION THAN COMPARED TO OUR PHOTON THERAPY. THE OTHER THING HARD TO SEE IS THERE'S TINY GRAY CIRCLES HERE AND THESE ARE CORENARY VESSELS SO WHAT WE CAN SEE IS WHEN HE ARE SPARING THREE OF FOUR CORONARY VESSELS WITH PROTON THERAPY WHICH WE ARE NOT DOING WITH REGULAR RADIATION. WE KNOW IN THIS PARTICULAR EXAMPLE THAT RADIATION IS A RISK FACTOR FOR HEART DISEASE JUST LIKE HIGH BLOOD PRESSURE DIABETES, HIGH CHOLESTEROL, BUT IT'S SOMETHING WE CAN'T TAKE IN THE FUTURE SO HERE IS JUST KIND OF THAT SUBTRACTION PLAN AS WELL. SO AGAIN WE HAVE UP IN BALTIMORE, A REGIONAL RESOURCE TO A LOT OF OTHER PROVIDERS IN THE AREA SO WE ARE USED TO BE PARTNER WITH GEORGETOWN, NORTHERN VIRGINIA, AND MANY OTHER CENTERS AND THEY ALL COME TOGETHER TO TREAT PATIENTS FROM THEIR PRACTICES, AT OUR PROTON SENSOR AS WELL. TAKE HOME MESSAGES, RADIATION IS A TOOL USED IN CANCER THERAPY. IT STILL HAS A HUGE PLACE IN CANCER THERAPY. IT WORKS PI BICAUSING DNA DAMAGE WHICH CAN LEAD TO CELL DEATH. BUT AGAIN OUR TUMOR CELLS AREN'T ABLE TO REPAIR TA DAMAGE, WHEREAS OUR REGULAR CELLS ARE. THE AFFECTS CAN BE ALTERED BY A LOT OF THINGS INCLUDING PHYSICAL FACTORS PHYSIOLOGIC FACTOR, FRACTIONATION DRUGS AND MANY OTHER VARIABLES. RADIATION CAN ALSO CAUSE COMPLICATIONS AND A LITTLE PLUG THAT RADIATION IS ALSO INTERESTING STILL. SO ANY QUESTIONS? [APPLAUSE] NEW PROCEDURE FOR BREAST CANCER- PATIENTS? SURE. SO AFTER WE RECENTLY DEVELOPED, IT'S GONE THROUGH FDA CLEARANCE AND TESTING NEW RADIATION MACHINE CALLED THE GAMMA POD WHICH IS ALSO SPECIFICALLY DESIGNED AROUND BREAST CANCER. SO WHAT IS UNIQUE ABOUT THE GAMMA POD IS IT ACTUALLY ENABLES US TO DELIVER THAT TYPE OF RADIATION THAT I CALLED STEREO TACTIC BODY RADIATION TO THE BREAST. IT MOVES WITH BREATHING, AS WE BREATHE OUR CHEST MOVES UP AND DOWN SO THERE'S BARRIERS TO DELIVERING THAT RAID YEAR AGO BEFORE THE GAMMA POD WAS DEVELOPED. SO WHAT'S REALLY EXCITING IS IT'S A REALLY ALLOWING US TO DELIVER HIGHER DOSES OF RADIATION IN A SHORTER TIME FRAME. SO MAKING THERAPY MORE CONVENIENT, SO INSTEAD OF FOUR WEEKS TO DELIVER RADIATION WE ARE ABLE TO DELIVER IT IN FIVE TREATMENTS FOR APPROPRIATE PATIENTS. THEN WE WILL HAVE CLINICAL TRIALS OPEN IN THE NEXT MONTH OR TWO, WE WILL CHANGE PARADIGM HOW BREAST CANCER TREATMENT IS DONE AND DELIVER RADIATION FIRST FOLLOWED BY THE SURGERY, WHAT WE HAVE DONE IN PRELIMINARY WORK IS SHOWN WE ARE ABLE TO GET RID OF BREAST TUMORS WITH RADIATION ALONE, THAT IS AN EXCITING CLINICAL TRIAL THAT WE WILL HAVE IN THE NEAR FUTURE. >> I THINK I'M WONDERING IF RADIATION HAS SOME EFFECTS OF PROTEIN CELL OR SOME OTHER EFFECTS ONLY DNA DAMAGE IS SOLE EFFECT OF RADIATION AND THERE ARE -- OTHER -- WONDERING IF THERE ARE OTHER SOME RESEARCH ABOUT THAT. >> YEAH. SO IN GENERAL THERE'S NOT THOUGHT TO BE ANY EFFECT TO SAY THE OTHER ORGANELLES IN THE CELL FROM RADIATION. IT DOESN'T DISRUPT THE CELL MEMBRANE PER SE. IT DOESN'T EFFECT ENDOPLASMIC RETICULUM, THERE'S SOME DEGREE OF EFFECT IN MITOCHONDRIA, BECAUSE THEY HAVE SOME DNA AS WELL. BUT AGAIN WHEN WE THEN COMBINE RADIATION WITH SOME OF THESE OTHER DRUGS, THERE IS SYNERGY WHERE THERE CAN BE EFFECT SO IF YOU HAVE A RECEPTOR INHIBITOR THAT THEN COULD HAVE AN EFFECT WHEN YOU COMBINE THOSE THERAPIES TOGETHER. >> THANK YOU, INTERESTING TALK. I HEARD ABOUT PROTEIN THERAPIES EVERY DAY ONE DRIVING HERE A LOT OF TIDESMENT IN THE RADIO APPARENTLY. TIDESMENT. SO CAN YOU BREEZE (INDISCERNIBLE) WITH PROTON THERAPY COMBINED WITH THE OTHER THERAPY LIKE THE CISPLATIN TREATMENT, COUPLE OF TREATMENT AND ALSO ADS WELL AS THE CANCER TARGET DRUGS ESPECIALLY FOR BREAST CANCER. >> PROTON THERAPY CAN BE COMBINED WITH CHEMOTHERAPY DRUGS AND CAN BE COMBINE WITH HYPOTHERMIA WHICH IS A HEAT THERAPY THAT IMPROVES BLOOD FLOW. IT'S SAFE TO COMBINE WITH NOT AWARE OF ANY CHEMOTHERAPY OR IMMUNOTHERAPY DRUG THAT IT'S NOT SAFE TO COMBINE WITH. WE HAVE DONE, I HAVE PERSONALLY TREATED MANY PATIENTS WITH CONCURRENT CHEMOTHERAPY AND PROTONS OR CONCURRENT HYPOTHERMIA, AGAIN, THE IDEA IS ABOUT SEI ENERGIZING THESE EFFECTS TO GET THE BEST TUMOR CELL KILL WHILE MINIMIZING DAMAGE TO HEALTHY TISSUE. SO WE ARE SEEING EXCITING OUTCOMES WHEN WE ARE COMBINING PROTON THERAPY WITH OTHER AGENTS FOR CERTAIN TUMORS, WE DO KNOW PROTON THERAPY SLIGHTLY IMPROVE CURE RATE SO THE CLASSIC EXAMPLE IS A CORDOMA, A BONE TUMOR OF THE BASE OF THE SKULL. SO I THINK THERE'S GOING TO BE SOME EXCITING OUTCOMES SEEN IN THE NEAR FUTURE ESPECIALLY AS PROTON CENTERS BECOME A LITTLE BIT MORE COMMON IN OUR COUNTRY. YEAH. SO IT CAN BE USED IN BRAIN TUMORS, WE USE BREAST TUMORS, PROSTATE -- SO ESSENTIALLY ANY CANCER WE TREAT WITH RADIATION WE HAVE THE ABILITY TO CHOOSE PART TIME THERAPY AS WELL. >> WE WILL BE MOVING ON. THANK YOU. >> THANK YOU. [APPLAUSE] ANNOUNCEMENTS. OUR NEXT SPEAKER IS DR. OLAPU. HE WAS EDUCATED IN ENGLAND, HE'S A MEMBER OF THE ROYAL COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS. HE THEN CAME TO THE U.S. AND GOT MASTERS DEGREE IN PUBLIC HEALTH AT OREGON STATE UNIVERSITY. CURRENTLY HE'S IN THE DIVISION OF CANCER TREATMENT AND DIAGNOSIS IN THE OFFICE OF CANCER COMPLIMENTARY AND ALTERNATIVE MEDICINE. SO WE HAVE HAD SEVERAL PEOPLE SIGN UP AND SEE TUMOR BOARDS AND CASE REPORTS AND TODAY HE IS BRINGING YOU THE CASE REPORTS. >> THANK YOU, DR. MOODY. GOOD AFTERNOON, EVERYBODY. JUST GO BRIEFLY ABOUT CASE REPORTS, WE WILL BE OUT OF HERE VERY QUICKLY. SO WHAT ARE OBJECTIVES? GIVE YOU A BRIEF BACKGROUND OF CASE REPORTS. HOW CAN CASE REPORTS BE USED OR IN WHAT WAYS ARE THEY USED? DESCRIBE SEVERAL CASE REPORTS SO THAT YOU HAVE AN IDEA WHAT THEY LOOK LIKE. WHAT OUTLINES IMPORTANT INFORMATION WHAT HAVE A GOOD CASE REPORT SHOULD LOOK LIKE. THIS IS ONE DEFINITION OF CASE REPORT. A CASE REPORT IS A FORMAL SUMMARY OF UNIQUE PATIENT AND CASE OF ILLNESS INCLUDING REPRESENTING SIGNS AND SYMPTOMS, DIAGNOSTIC STUDIES TREATMENT CAUSE AND OUTCOME. SOME HISTORICAL BACKGROUND, PROBABLY THE OLDEST EXAMPLE OF MEDICAL LITERATURE CONTAINING CLINICAL CASES IS A TEXT FROM (INDISCERNIBLE) THIS WAS AROUND 600 BC SOME PEOPLE BELIEVE THIS WAS REWRITTEN FROM TEXT SOME CENTURIES BEFORE THAT TIME. AMONG THESE WERE 48 CASES DISCUSSING INJURIES OF ALL DISORDERS OF THE HEAD AND UPPER TORSO. CASE REPORTS USUALLY ARE HOW INDIVIDUAL WHOSE PLAY SIGNIFICANT ROLE IN THE HISTORY OF CASE REPORTS, SO THIS CASE REPORT NAMED AFTER -- FOR EXAMPLE WE HAVE WHAT WE CALL THE HIPPOCRATIC CASE HISTORIES. THESE ARE USUALLY RETROSPECTIVE ACCOUNTS THAT DESCRIBE ONLY CLINICAL RELEVANT FINDINGS. THIS CASE REPORT CONTAIN MENTAL AND PHYSICAL FINDINGS ABOUT THE PATIENTS AND RARELY DO THEY INCLUDE THE COMPLAINTS OF THE PATIENT, THE PATIENT BACKGROUNDS ARE USUALLY ABSENT. WE HAVE WHAT WE CALL THE CASE REPORT. WHAT GALLON INTRODUCED WAS A CONVERSATIONAL TOOL INTO THE CASE REPORTS AND USUALLY PLACES HIMSELF, HE PLACES HIMSELF IN THE FIRST PERSON BEING AN ACTIVE AGENT IN THE CASE DESCRIPTION, HE DESCRIBE HIS WORKING DAY, HIS DOUBTS, HIS TENTATIVE DIAGNOSIS AND HIS INTERACTIONS WITH OTHER PHYSICIANS AS THE DISEASE UNFOLDEDS. IN THE MIDDLE OF -- APPEARED A SAFE WESTERN MEDICINE WAS DORMANT. AROUND THE SAME TIME THERE WAS A FLOURISH OF MEDICAL LITERATURE FROM THE ISLAMIC WORLD. THIS CASE REPORT WAS SIMILAR TO WHAT GALLON THE STYLE IN WHICH HE WAS USED. IN 17 AND 18TH CENTURY CASE REPORTS STILL AHEAD TO CONVERSATION TUNE OF GALON BUT THERE WAS MORE EMPHASIS TN PATIENT SUBJECTIVE EXPERIENCE. AROUND THE SAME TIME PHYSICIAN WERE DRAMATIC IN THE WAY THEY WROTE CASE REPORTS BECAUSE THEY WANTED TO HEIGHTEN THE NARRATIVE TENSION AND DEGREES OF PHYSICIAN INVOLVEMENT WITH SUFFERING SUBJECTS. MORE APPEALING FOR EXAMPLE A GIRL THREE YEARS OLD WHO REMAINED A QUARTER OF HOUR UNDER WATER WITHOUT DROWNING APPEARED IN A CASE REPORT IN PHILOSOPHICAL TRANSACTIONS IN 1739. IN THE 19TH CENTURY CASE REPORTS DEALT LESS WITH PATIENT SUBJECTIVE ACCOUNTS OF THE ILLNESSES. THERE WAS A MORE FOCUS ON TECHNICAL TERM SO MORE MEDICAL TERMINOLOGY WAS USED. AND THE TEXT WERE ORGANIED TO SECTIONS FOR EXAMPLE DEMOGRAPHIC DETAILS OF THE PATIENT AND OUTLINE OF THE THE CLINICAL COURSE OF EVENTS. IN THE AREA OF CANCER HISTORY IS SIMILAR TO WHAT WE HAVE IN CASE REPORTS IN GENERAL. AND DESCRIBES CASE REPORTS ADS FOURTH LINE OF EVIDENCE WHERE EVERYTHING BEGINS. LIKE I SAID EARLIER, THE CONCEPT CASE REPORT ARE SIMILAR HISTORICAL BACKGROUND LIKE OTHER CASE REPORTS BUT HOWEVER THESE CASE REPORTS WERE FIRST RECORDED IN TUMORS OF THE BREAST. CASE REPORTS COMPLETE SEVERAL ROLES. FOR EXAMPLE RECOGNITION AND DESCRIPTION OF NEW DISEASE. IN 1999 IN NEW YORK WEST NILE ENCEPHLITIS WAS DESCRIBED FROM CASE REPORTS. CASE REPORTS PLAY IMPORTANT ROLE IS DETECTION OF DRUG SIDE EFFECTS. THIS WOULD BE ADVERSE OR BENEFICIAL. IT'S SIGNIFICANT PERCENTAGE OF DRUG RETRACTIONS ARE USUALLY DUE TO CASE REPORTS. SUDDEN -- BECAUSE OF THE STUDIES SIDE EFFECTINGS ALLOW THE SHOWED THAT THE DRUG COMPANY USED TO TREAT ERECTILE DYSFUNCTION WHICH IS WHAT IS LICENSED TO TREAT TODAY. THERE WAS ASSOCIATION BETWEEN DEPRESSION AND SMOKING CESSATION. AS A RESULT OF THAT ASSOCIATION ANTIDEPRESSANT USED TO TREAT NICOTINE -- TO TREAT NICOTINE WITHDRAWAL SYMPTOMS. CASE REPORT WOULD BE USEFUL IN THE STUDY OF MECHANISM OF DISEASE. FOR EXAMPLE, LOOKING AT A FAMILY HISTORY LEFT TO THE DETECTION OF INHERITED DIABETES ASSOCIATED WITH DEAFNESS. CASE REPORTS ARE VERY IMPORTANT IN MEDICAL EDUCATION AND AUDIT, FOR EXAMPLE THE NEW ENGLAND JOURNAL OF MEDICINE HEALTH CASE REPORTS IN THE JOURNAL EVERY WEEK. IT CAN BE ALSO IN RECOGNITION OF REAL MANIFESTATION OF DISEASE. DEFINITELY HAS IMPACT ON HEALTH POLICY. THE LATEST IS THE E CIGARETTES AND ASSOCIATION WITH IT LED TO SOME STATES IN THIS COUNTRY AND AROUND THE WORLD CHANGING POLICY AROUND E CIGARETTES. SO CASE REPORTS USED TO DESCRIBE KNEW DISEASE INITIALLY STARTED CONVERSATION BETWEEN MEDICAL COLLEAGUES THAT ULTIMATELY BECAME THE ORIGINAL JOURNALS. CASE REPORTS OF MELANOMA DESCRIBED BY (INDISCERNIBLE) IN GENERAL 18372 HODGE KIN REPORT CASES IN LONDON WHICH TWO OF WHICH WHAT WE KNEW TODAY AS HODGKINS LYMPHOMA. 1957, DESCRIBE TUMOR PRESENT ADS GROWTH IN ANGLE OF JOURNAL OF AFRICAN CHILDREN. IN 1990 FOSSETT AND COLLEAGUES DESCRIBE A NEW TYPE OF CANCER CALLED HEPATIC LYMPHOMA. BREAST REPORTS. THIS IS FROM -- (INDISCERNIBLE) NON-SMOKING, WHO PRESENTED WITH THREE WEEK HISTORY OF -- TO THE HOSPITAL. CT SCAN AN H X-RAY REVEALED COLLAPSE IN THE RIGHT BLOB OF THE LUNG, ON THE RIGHT SIDE AND LYMPH NODES AND MEDIA STINUM. THAT'S THE COLLAPSE, THE FLUID, AND YOU HAVE THE LYMPH NODES. PHYSICAL EXAMINATION IS SMALL MUSCLE IN UPPER OUTER QUADRANT OF RIGHT BREAST, HOWEVER THERE ARE NO NODES IN THE LINE IN THE CHAIN LYMPH NODES. MAMMOGRAM DIDN'T REVEAL SUSPICIOUS IMAGES HOWEVER IT PICKED UP HIGH -- SOLID NODAL 11.6 BY 6.6 BY 8.9-MILLIMETERS IN THE RIGHT BREAST, THIS WAS SUBSEQUENTLY BIOPSIED. YOU CAN SEE HERE (INDISCERNIBLE) ABOUT 50% OBSTRUCTION OF RIGHT MIDDLE LOBE. BRONCHOSCOPY THE BIOPSY WAS TAKEN THESE ARE ALL THE INFORMATION WE GATHERED AT THE TIME MAYBE THAT WAS THE PRIMARY BREAST TUMOR WITH LUNG METASTASIS FROM INDIANA PENDENT PRIMARY TUMORS. PSYCHOLOGICAL STAINED THAT SUGGESTED ADENOCARCINOMA. TISSUES FROM THE BREAST AND FROM THE FROM THE LUNG. BIOPSIES AFTER STAINING REVEAL INFILTRATION BY ADENOCARCINOMA. HOWEVER, THERE WAS NO EVIDENCE OF IN SITU CARCINOMA IN THE BREAST SPECIMEN. IMMUNOHISTOCHEMICAL STAINING OF THE LUNG AND BREAST REVEALED REACTIVITY WITH AI 1A 367 AND TTF 1. BUT HOWEVER LACK EXPRESSION OF CYTOKINE 20, P 63 PROGESTERONE RECEPTOR AND GADA 3. THIS IS THE BREAST. THIS IS FROM THE LUNGS SO THERE WAS NO INFILTRATION OF THE -- THE BREAST. THIS IS ALSO THE BREAST, THIS IS THE LUNGS, THIS IS THIS IS ALSO FROM THE BREAST ON THE LUNG THIS IS THE GABA 3 MOST NEGATIVE. SO RECEPTOR MUTATIONS WERE ALSO NEGATIVE HOW THEY LOOKED ALL ALL THE EVIDENCE HITS LOGICAL HISTOCHEMICAL STAINING WAS CONSISTENT WITH METASTASIS TO THE BREAST FROM PRIMARY LUNG ADENOCARCINOMA. STARTING TREATMENT WITH CISPLATIN AND AFTER INITIAL RESPONSE THE DISEASE PROGRESS AND SECOND LINE THERAPY DOCETAXEL WAS USED. HOWEVER DUE TO CLINICAL CONDITION, THE THIRD LINE WAS VISIBLE. CONTINUE PALLIATIVE SUPPORT PASSED AWAY AT 21. THIS IS A CASE, EXCELLENT RESPONSE TO I WERE LIMB HAS BEEN IN IN META TA STATIC CARCINOMA. -- METASTATIC CARCINOMA. HISTORY OF WEIGHT LOSS, 50-POUND WEIGHT LOSS DIFFICULTY SWALLOWING SOLID FOODS. INITIAL IMAGING SHOWED PASS HE CAN TENDING FROM GASTRIC FOLD TO BODY OF STOMA WITH MULTIPLE LYMPH NODES NEARBY FIVE CENTIMETERS IN SIZE. THIS IS THE MASS THERE, THIS IS OPPOSITE VIEW OF THE SAME MASS. MASS REVEAL HIGH GRADE CARCINOMA WITH NEUROENDOCRINE AND SQUAMOUS DIFFERENTIATION, THERE WAS STAIN FOR TUMOR MARKERS EXPRESS A 3 SYNAPTO(INDISCERNIBLE) DID NOT EXPRESS HER 2. HE ALSO HAD A NINE MILLIMETER METASTASIS MRI. TREATMENT BEGAN WITH MODIFIED DOCETAXEL CISPLATIN YOUR SILL. GENOMIC ALTERATIONS, GENE LOCATIONS WHICH ARE NOT ACTION ABLE. MOLECULAR PDL 1, TUMOR MUTATION WAS LOW. THESE CYCLES OF DCF AND WAS SWITCHED TO -- BECAUSE DISEASE PROGRESSED, PATIENT ALSO HAD EXTREME FATIGUE FROM THE INITIAL RESPONSE THEORY IMAGING, WAS HELD AFTER SIX CYCLES DUE TO SEVERE NAUSEA, VOMITING AND DEHYDRATION. WE HAD MULTIPLE ENDOSCOPIES INCLUDING WHICH THEY ALSO HAD LIQUID NITROGEN CRYOTHERAPY FOR ANY COMPLETE JUNCTION OBSTRUCTION. EVENTUALLY AS DISEASE PROGRESSED (INDISCERNIBLE) STAY IN PLACE. HE ALSO HAD ENDOSCOPIC GASTROSTOMY, COULD NOT TOLERATE ANY EATING BY MOUTH. CT WAS METASTATIC DISEASE TO THE LIVER. HOWEVER RESULT OF THE TRIAL UNIQUE SCREEN HISTOLOGY OF THIS CANCER AND RECENT SUBSIDIES OF ED 1 INHIBITION, THE SKIN AND HEAD AND NECK. TREATMENT WAS SWITCH OFF TO -- (INDISCERNIBLE) IN DECEMBER OF 2017. BECAUSE -- (INDISCERNIBLE) GIVE TWO CYCLES OF REDUCE DOSE OF CHECK POINT INHIBITORS. THEN DEMONSTRATE INCREASE DOSE SLIGHTLY. AT THE SAME TIME RECEIVE 14 RADIATION TREATMENTS TO GEG JUNCTION OBSTRUCTION BUT (INDISCERNIBLE) BEGAN TO FEEL BETTER, STINT WAS REMOVED, SCAN SHOW IMPROVEMENTS AND THE G MASS HEPATIC LESIONS IMPROVED SUBSEQUENT TREATMENT WAS MODIFIED TO MONTHLY MAINTENANCE AT FIXED DOSE STARTING IN MAY 2018. BY JUNE HE WAS ABLE TO RETURN BACK TO FULL TIME WORK. HIS TUBE WAS REMOVED IN IN JULY AND THE SCAN THAT MONTH SHOWED RES RIGHT. -- RESOLUTION IN THE GEG LYMPH NODE AND RESOLUTION OF HEPATIC METASTASIS. HE SHOWED INCREDIBLE IMPROVEMENT ON THE TREATMENT, THE MAIN SIDE EFFECT WAS MILD THYROIDITIS. IT SHOWED RESOLUTION OF VIABLE -- DISEASE, PET SCAN WAS NEGATIVE FOR OPTIC FDG ISOTOPE ALL SITES OF DISEASE. -- WILL BE MAINTAINED ON -- UNTIL THE END OF 2019. SO THIS WAS THE PET CT BEFORE. SOME OF THE METASTASIS IN LIVER, THIS IS THE STOMA DISEASE YOU CAN SEE ON THE OTHER SIDE. THIS IS SOLID TUMOR BRAIN METASTASIS OF PROSTATES CANCER, ER WITH HEADACHE FOLLOWING A FALL, COMPLAINED OF DECREASE VISION LACK OF WALKING AND DIFFICULTY CONCENTRATING FOR A MONTH. EVE FOLLOWED UP AT THE HOSPITAL FOR LOW URINARY TRACK SYMPTOMS AND FOR SIX MONTHS, HE HAD PAST HISTORY OF HYPERTENSION AND ISCHEMIC DISEASE CONTROLLED ON MEDICATION. MEDICAL EXAMINATION WAS (INAUDIBLE) REVEALED LESS SIDE (INDISCERNIBLE) WHICH IS LOSS OF VISION ON THE SAME SIDE -- LOSS OF VISION FIELD SAME SIDE BOTH EYES. FOR EXAMPLE IF (INAUDIBLE) ON THE LEFT SIDE, ON THE LEFT SIDE THERE'S ALSO LOSS OF VISION ON THE LEFT SIDE OF THE RIGHT EYE. HE ALSO HAD EXAMINATION REVEAL LARGE PROSTATE WITH NO (INAUDIBLE). MRI OF THE BRAIN FOCAL WELL DEFINED INTENTION LESION WITH FOUR CONTRAST ENHANCEMENT AND SIGNIFICANT PERILESION DEMAND LIGHT IN THE RIGHT POSE STEERIAL REGION. WE CAN SEE MASS THERE RIGHT HAND SIDE. REVEAL GLAND SHOWING ABNORMAL SIGNALS ON THE LEFT LOBE WITH FOCAL BREECH AREA PROSTHETIC LYMPH NODES. THOSE DEFINITELY INVOLVEMENT OF SENTINEL VESICALES. 5 NANOGRAMS. (INDISCERNIBLE) HAVING BONE SCANS CT SCAN OF THE CHEST, DID NOT SHOW ANY METASTATIC DISEASE. UNDERWENT GUIDED -- (INDISCERNIBLE) OCCIPITAL SPACE OF BINDING LESION AND HIGHLY VASCULAR FIRM DROSOPHILA LESION WAS FOUND IN THE OCCIPITAL REGION THE MRI DONE POST-OPERATIVELY WAS FINE, HISTOLOGICAL EXAMINATION REVEALED GLAND LESION COMPOSED OF GLANDULAR PATTERN WITH A BRIEF FORMATION. THIS GLAND TO COLUMN FAR CELLS HYPERCHROMATIC NUCLEOLIE, AND CYTOPLASM. THE LIEU MINUTE OF THE THE GLAND SHOW NECROSIS. THE BIOMARKERS SHOW AE 1 A 3 POSITIVE CKA 720 AND 20 NEGATIVE, PSA POSITIVE SYNAPTOAND NEGATIVE. CONSIDER THE STAINING OF THE HLE AND THE IHC IT WAS REPORTED METASTATIC ADENOCARCINOMA WITH PROSTATE ORIGIN. THIS IS -- (INDISCERNIBLE) GLIAL TISSUE ON HLA STAIN. POSITIVITY. PSA POSITIVITY. PATIENT SUBSEQUENTLY UNDERWENT TRANSRECTAL ULTRASOUND AND HAD 12 CORE BREAST BIOPSY ADENOCARCINOMA GLEASON SCORE FOUR AND FOUR. THEY DECIDED AFTER DISCUSSION TO TREAT WITH RADIATION AND HORMONAL THERAPY. THEY RECEIVE RADIATION DOSE OF 3,000 CENTIGRADE IN TEN FRACTIONS FOR THE WHOLE BRAIN. AFTER -- HE OPTED TO HAVE (INDISCERNIBLE). PRESENTLY -- HE WAS PUBLISH, FOLLOW-UP, 3.31, CASTRATION LEVEL. MRI DID NOT REVEAL EVIDENCE OF RECURRENCE, BONE SCAN WAS ALSO NEGATIVE. FOR METASTASIS. 12 MONTHS POST SURGERY DID NOT SHOW EVIDENCE OF RECURRENCE. THIS IS THE (INDISCERNIBLE) WITH ADVANCED MELANOMA METASTATIC TO THE LUNG AND LIVER. IT WAS THE REF NEGATIVE FOR DREF MUTATION. PATIENT WAS ELIGIBLE FOR IMMUNOTHERAPY. FIRST CYCLE HAD I WERE LIMB HAS BEEN, TWO WEEKS AFTER HE DEVELOPED BLOODY STOOLS. HE WAS THEN TREATED WITH IV PREDNISONE AND IV FLUIDS, STOOL STUDIES NEGATIVE FOR BACTERIAL LISTED THERE, THERE WAS NO PAIR SITES. PARASITES. BECAUSE SYMPTOMS IMPROVE THEY CAN'T TO TREAT WITH ORAL PREDNISONE TAPERING OFF SEVERAL WEEKS. AFTER DISCHARGE HE WASN'T PUT ON CTLE FOR INHIBITOR BECAUSE THEY FOUND THEY COULD BE INCREASE RISK OF RECURRENT COLITIS. IT WAS PLAN TO RESUME IMMUNOTHERAPY WITH (INDISCERNIBLE) EVERY THREE WEEKS HOWEVER PRIOR TO THE TREATMENT HE DEVELOPED FOUR EPISODES OF DIARRHEA AND NOW CLASSIFIED AS GRADE 2 TOXICITY. IT WAS ADMINISTERED IV DOSE OF PREDNISONE AS OUTPATIENT AND ASKED TO CONTINUE PREDNISONE AT HIGHER DOSE. AND PUT BACK ON (INDISCERNIBLE). SYMPTOMS WERE REST BREAST AND BLOODY STOOLS AND HAS BEEN NO, MA'AM MALL -- HAS BEEN NOMINAL PAIN. CT SCAN REVEALED (INDISCERNIBLE) BOWEL SUGGESTIVE OF PANCOLITIS. THAT'S I WILL THERE. -- THAT'S IT THERE. THERE WAS EVIDENCE (INAUDIBLE) UPPER ABDOMEN, FOCAL DI CORRUPTION. YOU CAN SEE HERE. WHICH WAS FELT TO BE SITE OF PERFORATION. WHILE THIS WAS GOING ON THEY FOUND THAT HEAR RESPONDED TO IMMUNOTHERAPY WITH DECREASE IN SIZE OF LIVER METASTASIS BY UP TO 70%. AND -- WAS DONE TO WITH (INDISCERNIBLE) AND AFTER -- IDENTIFIED ALONG TRANSVAS QUEUE LOAM, HE CONTINUED HIS STEROID TREATMENT. HOWEVER THE FIRST POST-OPERATIVE DAY HE HAD LARGE BLOODY BOWEL MOVEMENT WITH -- WITHOUT EVIDENCE OF BLOOD IN THE ILIOSTOMY, THE BLOODY SCHOOL CONTINUED TO THE SECOND POST-OPERATIVE DAY. SO THINK IT MIGHT BE ANOTHER PERFORATION. AFTER DISCUSSION DECIDED TO TREAT WITH INFLEXIMAB AND THIS WAS ADMINISTERED, SYMPTOMS IMPROVE WITHOUT FURTHER EPISODES OF RECTAL BLEEDING. ENDOSCOPY EVALUATION WAS DEFINED BECAUSE OF RISK OF BOWEL PERFORATION. CERTAINLY AFTER -- LOW FIBER DIET. CONTINUE TO IMPROVE EVENTUALLY WITH REHAB FACILITY WITH INSTRUCTIONS TO COMPLETE PREDNISONE. BECAUSE OF THE SEVERITY OF IMMUNE CHECK POINT INHIBITOR TOXICITY HE WAS NO LONGER CAN DADE FOR FURTHER THERAPY T. REMAIN INHIBIT THERAPY AND SUBJECT REST RATION OF INTESTINAL CONTINUITY WAS NEVER PERFORMED. SO WE HAVE CASES WHERE IT'S VERY DIFFICULT TO DO STUDIES CLINICAL STUDIES OBVIOUSLY NOT POSSIBLE. YOU KNOW YOU HAVE TOO MANY CASE REPORTS SO WHAT IS DIFFICULT FOR CLINICIANS IS FEW DAYSES REPORTED IN THE LITERATURE INFLAMMATION FROM THOSE CASES BECOMES WHERE THE -- THEY USE THE INFORMATION TO PLAN TO TREAT THEIR PATIENTS IF THEY COME IN ACROSS A CASE LIKE THAT. THIS IS CCL -- 60-YEAR-OLD LADY ON THE RIGHT HERE. HAD SEVERAL CHRONIC DISEASES. NO FAMILY HISTORY. MENOPAUSAL AGE 42. BUT WITHIN THE LAST YEAR NEGATIVE AND RECENT, GASTRIC ENDOSCOPY WAS INCONSISTENT WITH MALIGNANCY. TWO MONTHS PRIOR TO RECURRENT PRESENTATION SHE HAD AN ULTRASOUND MAMMOGRAPHY, THERE'S NOT IDENTIFY ANY ABNORMALITIES. NO LYMPH NODES IN AXILLA, SUPER CLAVICULAR OR -- AREAS HOWEVER EXAMINATION REVEALED THE BULKY CERVIX ITCHING WITH SIZE NORMAL ADNEXIA. THE VITALE SIGNS ABOVE ABNORMAL LIMITS. THE BLOOD WORK WAS FINE. CT SCAN SHOW DIFFUSED METASTATIC DISEASE WITH LYTIC BONE LESIONS, OUTUS WAS ENLARGED, BIG CENTRAL HYPODENSITY 1.8-CENTIMETER HYPODENSITY CLASSIFICATION LEFT PET CT SHOWED SIGNIFICANT HYPERMETABOLIC ACTIVITY OF THE CERVIX AND UTERO SKELETAL MET TA STATIC DISEASE AND -- METASTATIC DISEASE,. THERE WAS NO ACTIVITY IN THE BREAST. EXAMINATION OF ANESTHESIA CONFOUND WHAT THEY FELT CLINICALLY INITIALLY. SO THE GREEN ARROWS EVIDENCE OF DISEASE IN THE BONE, RED ARROW UTERUS AND BLUE ARROW IS CERVIX. YELLOW AXILLARY LYMPH NODE AGAIN YOU CAN SEE ISLET BONES HERE. SHOWING EVIDENCE OF DISEASE. METASTASIS. BIOPSY SHOWED THE CELL STROMA INFILTRATED BY A -- PLASMA SIDE CELLS ARRANGED IN SINGLE FILE WITH CYTOPLASMIC O (INDISCERNIBLE) PLEA OWE MORPHISM. MALIGNANT TESTED POSITIVE FOR CK 7 DATA 3 AND 91 TO 100% POSITIVE FOR ESTROGEN RECEPTOR SUPPORTING THE MAMMARY ORIGIN. THEY HAD TUMORS NEGATIVE. THIS IS HISTOLOGY. ON THE RIGHT LYMPH NODE SHOWED TUMOR CELLS OF MORPHOLOGICAL 31ST 10 TO 15%. PATIENT WAS TREATED WITH (INDISCERNIBLE) AND -- ACID. CLINICAL -- WAS SEEN PATIENT REPORTED RESERVATION OF THE PAIN. THIS IS 14-YEAR-OLD GIRL NOT SEXUALLY ACTIVE, HAD 10 REGULAR MENSTRUAL CYCLE WAS IN -- NO FAMILY HISTORY OF INDIVIDUAL CANCER. REPORTED TO GYNECOLOGY CLINIC BECAUSE OF ABNORMALITY IN ENDOMETRY YUM. SHE WAS SEVERELY ANEMIC BECAUSE OF RETINAL BLEEDING, WAS ADMITTED MRI ENDOMETRY YUM. CONTRAST WAS FOUND IN THE ENDOMETRIAL. ENDOMETRIAL HYPERPLASIA MALIGNANCY WERE DIAGNOSE BECAUSE OF THE DEFICIENT LIMIT SHOWED HIGH SIGNAL AND DECREETS UPPER END CO-EFFICIENT. SHE UNDERWENT DIAGNOSE NOTES ENDOMETRIAL ANESTHESIA, PATHOLOGY SHOWED MOST OF THE TISSUES SOME OF THEM BACK TO BACK HIGH LINEAR DENSITY, VERY NARROW INTERCITYIONAL, IT WAS DIAGNOSED AS ENDOMETRIAL -- YOU CAN SEE THICKENING ENDOMETRIAL, THAT'S MUSCLE OF UTERUS, THE MYOWEMETRIUM. IMMUNOSTAINING (INDISCERNIBLE) DID NOT INDICATE GERM LINE MUTATIONS. THERE WAS NO ACCUMULATION SUGGESTIVE OF METASTASIS. ON PET CT. >> ADENOCARCINOMA GRADE ONE. STAGE 1A STANDARD. IDEALLY THERE WILL HAVE BEEN HISTOECTOMY BILATERAL NEFF RECKTOMY BUT BECAUSE OF AGE AND PRESERVE FERTILITY, HORMONAL THERAPY WAS DECIDED, SHE WAS TREATED WITH PROGESTERONE FOR 26 WEEKS. SHE HAD (INDISCERNIBLE) WHILE ON HORMONAL THERAPY. HISTOLOGY BIOPSY AT SEVERAL WEEKS AFTER HYPOPLASIA, HORMONAL THERAPY WAS EFFECTIVE. AFTER 15 WEEKS IT WAS BENIGN ENDOMETRIAL AND HISTOECTOMY PERFORM BID END OF MPA -- PERFORMED BY MPA (INDISCERNIBLE) PROLIFERATIVE INHIBITION FOUND IN THE LESION. BECAUSE OF TREATMENT SHE DEVELOP A PELVIC INFLAMMATORY DISEASE THAT WAS TREATED WITH ANTIBIOTICS. AFTER TREATING THE PELVIC INFLAMMATORY DISEASE SHE WAS PRESCRIBED A LOW DOSE PROGESTERONE PILL. HAD PERIODIC ULTRASOUND TO ESTIMATE THE ENDOMETRIAL. SHE HAD EVERY FOUR MONTHS ON ANESTHESIA AND AFTER SEVERAL WEEKS PATHOLOGY -- HAVE NOT SHOWN DISEASE RECURRENCE. SO THIS IS WHAT IT LOOK LIKE ON HISTOLOGY. THIS IS THE HISTOOSSCOPY SHOWING NO EVIDENCE OF DISEASE. SOME 70-YEAR-OLD MAN RIGHT UPPER CHEST IN ONE MONTH NON-SMOKER DID NOT HAVE ANY COUGH, NO DISKNEEIA, NO COUGHING UP BLOOD, PAST MEDICAL HISTORY WASN'T SIGNIFICANT BUT HE HAD REDUCED -- CLINICAL EXAM ON THE RIGHT UP PER ZONE CHEST -- SUBSEQUENT CT SCAN OF THE RIGHT LIVER REVEAL 5.8 BY 5 MASS IN THE ANTERIOR SEGMENT OF THE UP PER LOBE OF THE RIGHT LUNG. BUT IN THE TRANSVERSE -- IN THE LATERAL CHEST WALL WITH ORIGINAL PREFER (INDISCERNIBLE) THERE WAS ALSO A LARGE HIGH NODE. SO THAT'S THE MASS THERE. INVOLVING THE LYMPH NODE. BRONCHOSCOPY -- HISTOLOGY REVEALED DIAGNOSIS OF NON-SMALL CELL LUNG CELL CARCINOMA. WITH NUCLEAR POLYMORPHISM WITH NO TARGET INHIBITIONS FOUND. THAT'S HISTOLOGY SEE 3A RECOMMENDED RAID CONGRATULATION THERAPY PATIENT DECLINED HE ALSO DECLINED PALLIATIVE RADIATION THERAPY. OPTIMIZE DIET INCREASE INTAKE OF FOOD AND VEGETABLES AN PICK UP EXERCISE. THREE MONTHS AFTER DIAGNOSIS HE REPORTED RESOLUTION OF CHEST PAIN, REPEAT SCAN SHOWED SIGNIFICANT REDUCTION IN SIZE OF THE YOU WANTER LOBE MASS MEASURING 3.8 BY 2.7-CENTIMETERS STILL INVADING THE RIGHT ANTERIOR CHEST WALL WITH ASSOCIATED -- THE LIMB RIGHT ALSO REDUCED IN SIZE SO WE CAN SEE COMPARED TO THE PREVIOUS ONE SIZE OF THE MASS. STILL HAD SOME -- NOT AS BAD AS LYMPH NODE REDUCED IN SIZE SO IN THE SCAN 6, 9, 12 AND 18 MONTHS AND SIZE OF TUMOR REDUCE DURING THE PERIOD OF TIME. MOST SCAN AT TIME THIS WAS PUBLISHED IT WAS 24 MONTHS AFTER DIAGNOSIS SHOWED STABLE FOCUS OF SOFT TISSUE DENSITY,N'T AT SIDE OF PRIMARY TUMOR WITH ASSOCIATED SCARRING OF ADJACENT LUNG (INDISCERNIBLE) AT THE RIGHT AN TIERIAL THERE WAS NO HIGH NODES, METASTASIS. SO THIS IS THE -- JUST SCARRING AGAIN SCARRING HERE ON THE LYMPH NODE COMPLETELY RESOLVED. CASE REPORTS IMPORTANT IN THE ERA OF EVIDENCE MEDICINE SOME PEOPLE BELIEVE CASE REPORTS ARE NOT IMPORTANT. IT DOESN'T CONTRIBUTE TO EVIDENCE BASED MEDICINE. BECAUSE IT CANNOT PROVIDE ANY EVIDENCE OF EFFICACY AND SAFETY, DIAGNOSIS AND TREATMENT OF DISORDER. ALBERT AND COLLEAGUES LOOK AT -- CASE REPORT (INDISCERNIBLE) AND THEY HAD SEVERAL CONSENT INCLUDING PUBLICATION BIAS SUPPORT OF POSITIVE RESULTS, CLAIMS OF EFFICACY AND SAFETY, INFORM CONSENT REPORTS AND UNDERREPORTING OF PATIENTS AND OUTCOMES. CASE REPORTS BUSINESS PERSPECTIVE, CASE REPORTS ARE RARELY CITED AND THEY CREATE A VALLEY FOR GENERAL EDITORS BECAUSE THEY NEGATIVELY AFFECT THE IMPACT FACTOR. THE HIGH IMPACT FACTOR AS WE KNOW CAN BE A FACTOR FOR THOSE WHO -- SUB THEIR WORK. FOR COMPANIES WHO WANT ALLOCATION OF THE ADVERTISING BUDGETS. ANALYZE BUSINESS IS EXCLUSIVELY WITH FINING BEST EVIDENCE FOR CLINICAL DECISIONS. AND FROM THE HIERARCHY OF EVIDENCE RANDOMIZE TRIALS FINAL EVALUATION OF THERAPIES OR TESTS ESPECIALLY WHEN THE CLINICAL IS NOT IMMEDIATELY -- OUR CASE REPORTS HAS BEEN CASE SERIES, HAVE -- ACTUALLY IMPORTANT, EQUALLY IMPORTANT PROGRESS OF MEDICAL SCIENCE AND EDUCATION. THIS IS MODIFIED PYRAMID OF STUDY DESIGN BY -- SO WE CAN SEE CASE REPORT ON SERIES HERE RANDOMIZE TRIAL IS THERE, THEN SOME BELIEVE SYSTEMATIC REVIEWS ARE -- SOME BELIEVE THAT WELL, THERE ARE ISSUES ALSO. RETRIEVED LOOK AT ANY ONE CASE OF TAMOXIFEN RELATED TOXICITY AS A RESULT OF THAT (INDISCERNIBLE) A CLEAR PICTURE OF THE NATURE AN DISTRIBUTION OF THE TOXICITY. AS WELL AS SEVERITY OF OCULAR AND ALSO RECOGNIZE THE DIFFICULTY IN -- TO TAMOXIFEN AN COMPETING CASES OF RETINAL AND CORNEAL ABNORMALITY. ALSO IN 20 YEAR REVIEW OF CASE REPORTS AND SERIES OF PRIMARY FA LOPIAN TUBE. AS A RESULT OF THIS REVIEW, OUTLINE CHARACTERISTICS TREATMENT FAILURE. AT THE TIME THERE WERE LACK OF CONTROL TRIALS AND USEFULNESS OF SECOND LAPAROTOMY FOR MONITORING DISEASE RESPONSE TO TREATMENT GIVEN. WE LOOK AT CARBO THERAPY USED BY CANCER PATIENTS, HAD TOXIC EFFECT. AND AT THE TIME THERE ARE CLINICAL TRIALS IDENTIFY FOR BRAIN -- SO ON. ALSO SOME PERSPECTIVE STUDIES FOR BUSINESS -- CONCLUSION WAS MANY WITH PROMISING CASE REPORTS NOT YET BEEN EXPLORED, RESULTS NOT REPORTED IN ENGLISH. ANALYSIS OF CASE REPORTS GIVE US? IT WAS CHARACTERISTIC AND CASE OUTCOMES CAN BE ASSESSED AT THIS LEVEL OF CLINICAL RESEARCH. HOWEVER WE KNOW WHERE THERE'S NO OTHER EVIDENCE THE BEST OF FIRST LINE OF EVIDENCE MUST BE TAKEN INTO ACCOUNT. (INDISCERNIBLE) FOCUS PUBLISHING CASE REPORTS AND MOSTLY OPEN ACCESS WITH HIGH ACCEPTANCE RATES. IN CONTRAST PEER REVIEW E JOURNALS MANY NEW CASE REPORTS GENERALS ARE NOT ADEQUATELY REVIEWED. SO PART OF CASE REPORT MEDICAL LITERATURE IS A SLIDE LOOKING AT CASE REPORTS THAT GO FROM CASE REPORTS TO CLINICAL TRIAL, (INDISCERNIBLE) REPRESENTED NOT GO AND GOING TO CASE SERIES SLIGHT IMPROVEMENT WE HAD 31% AND THEIR 69 DID NOT GO TO CLINICAL OR DID NOT GO TO CLINICAL TRIAL. SO HOW DO YOU WRITE GOOD CASE REPORT? TITLE GOOD INSTRUCTION PATIENT INFORMATION CLINICAL FINDINGS TIME LINE, DIAGNOSTIC ASSESSMENT THRAPEUTIC INTERVENTION. FOLLOW-UP OUTCOMES DISCUSSIONER, THIS WAS BY CARE GROUP WRITTEN A FEW YEARS AGO. CASE REPORTS SHOULD BE WRITTEN ORGANIZED AND STRUCTURED. IT IS RELEVANT IN MEDICINE TODAY AND IN RARE INSTANCES WE KNOW TRIALS ARE NOT POSSIBLE FOR REASONS, MAYBE THE ONLY EVIDENCE OF THE LABEL TO RECOMMEND TREATMENT. THANK YOU. AND I THANK MY COLLEAGUES. [APPLAUSE] >> ANY QUESTIONS? >> SO ON MY, MAILS NOW, ALMOST EVERY DAY I GET NEW JOURNALS ONLINE JOURNALS AND ASK YOU THE WRITE AN ARTICLE AND PLEASE HAVE IT READY TO TWO WEEKS. YOU SEE THIS WITH CASE REPORTS AS WELL? >> YES. >> THAT WILL DO IT THANK YOU. >> THANK YOU VERY MUCH.