Disrupve Technologies€¦ · 04/04/2019 · Paents and Methods: • 350,000 HMO-Henry Ford System...
Transcript of Disrupve Technologies€¦ · 04/04/2019 · Paents and Methods: • 350,000 HMO-Henry Ford System...
Disrup've Technologies Construc've or Destruc've ? Focus on Prostate Biopsies and what drives them and results
3DbiopsyClaricoreShearletMDxHealth
COI
A disrup've technology is one that displaces an established technology and shakes up the industry or a ground-breaking product that creates a completely new industry. Harvard Business School professor Clayton M. Christensen coined the term disrup've technology.
• Internet• Ar:ficialIntelligence• SpaceColoniza:on• 3DPrin:ng• MedicalInnova:onsgeneedi:ngDNAtes:ngCRISPRESWLRobotsCTMRINGIEMRs
• HighSpeedTravel• Robo:cs• BlockchainTechnology• AutonomousVehicles• AdvancedVirtualReality• RenewableEnergy
Disrup6ve
Construc6ve Destruc6ve
Moststartoutasconstruc:vebutsomeendupdestruc:ve
In my opinion the most disrup've technology in Urology /Medicine is EPIC & other EMRs-LATER
My focus will be primarily on Prostate as relates to or influences biopsies • PSA• ProstateBiopsy• ProstateImaging• ProstateGenomics• ProstateTreatmentModali:es• ProstateHealth
PSA Disrup've Technology Construc've to Disrup've and back to Construc've
• CONSTRUCTIVE:
• Breakthroughmarker• Heraldedasthemostimportanttumormarkerinoncology• UnprecedentedinMonitoringofDisease• Inexpensive,availableinminutes• Earlydetec:on–PrevalenceversusIncidence
PSA Destruc've
• Pa:entS:mulatedAnxiety• PhysicianStressAmplifier• Overdiagnosisleadingtoovertreatment• Isoforms• AQempttomakeitsignaloutwhomtobiopsy
History and Direc'on: PSA Based Screening
Flying High
Worlds shortest vaca'on: USPSTF
Drecommenda:on• DoNotOrder• SharedDecisionMaking
Crecommenda:on(May2018)
Can we make PSA Construc've in 2018
• YES
Familyprac:cephysiciansareconfusedbyourmessageTheyorder
90%ofPSA
• Cutoffsof2.5and4• PSAvelocity• PSAdensity• AgeSpecificPSA• %freePSA• ComplexPSA• phi• PCA3• SelectMDx• 4K• HELP!
Is there a simple cut-off andPSA level that is “safe?” YES
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19-foldIncreaseinriskforAfricanAmericans
12%
8%
6%
4%
2%
0%Percen
tdevelop
ingprostatecan
cer
0.51%
7.85%
15-foldIncreaseinrisk
Percen
tdevelop
ingprostatecan
cer10.39%
ROCCurveforAllPa:entsPSA<1.5ng/mLPSA1.5-4ng/mL
1.0
0.8
0.6
0.4
0.2
0
0 0.2 0.4 0.6 0.8 1.01-Specificity
Es:matedAreaC=0.87251
Maximumsensi:vityandspecificityatPSA1.5ng/mL
OverallStudyPopula:on(21,500)
10%
CrawfordED,etal.BJUInt.2011;108(11):1743-1749.
5-yearDiagnosisRate
>1.5to4isa“dangerzone”
Pa:entsandMethods:• 350,000HMO-HenryFord
System• Meninsystem1997-2008• Ini:alPSAbetween1-5ng/ml• Minimum5yearsfollow-up• No5ARIs
Results:• Meanage55years• MeanPSA1.0• AfricanAmerican:29%• DetectedCancer:2%
Surrogatefor:1. BPH-mostcommon
2. ProstateCancer ProstateHealth3. LongtermPCarisk
4. Evaluate-Don’tBiopsyeveryonewith>1.5ng/ml!!!!5. UsePCMstohelpdeterminewhomtobiopsy
AWayForward:PSA>1.5-4ng/mL
73%<1.5NG/ML
PSA alone to guide prostate biopsy decisions: END Risk Stratification for Clinically Significant Pca ANOTHER DISRUPTIVE TECHNOLOGY
PCP/Urologist PSA>1.5
Urologist Repeat PSA,
Genomic Test
Very Low Risk
for GS ≥ 7 PCa
Consider Biopsy
Increased Risk
for GS ≥ 7 PCa
Avoid Biopsy
For patients being considered for prostate biopsy
Genomic Tests: SelectMDx, phi and 4K score
FamilyPrac::oner Urologist
Rou6neLab/PSA
PSA<1.5RepeatPSA5years
PSA>1.5
phi4K
SELECTMDx
LowRisk
HighRisk
TRUSBx
ConsiderreferraltoUrologist
Copyright:E.D.Crawford,2017
Sharedcare
Pa'ent/Physician Website
www.pcmarkers.com
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Guidingyouthroughtheneweststateoftheartprostatecancerdiagnos:candprognos:ctests
Make Genomics/PSA Great Again
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Focus will be primarily on Prostate
• PSA• ProstateBiopsy• ProstateImaging• ProstateGenomics• ProstateTreatmentModalites• Prostate
Prostate Biopsies: Long History
• VimSilvermanJAMA,1954• Menghini’sAspira:onNeedle• Tru-cut• FineNeedleAspira:on-justwhenpeaking• Ultrasound• AandBmodes• BK–introduc:on• BillCoonerandFredLee• Themostdangerousweapontoday:AUrologistandBiop6cGun
US Guided Prostate Biopsy-Disrup've Technology • “Transrectalultrasoundinthediagnosis,staging,guidedneedlebiopsy,andscreeningforprostatecancer”.LeeF.ProgClinBiolRes.1987;237:73-109
• “Transperinealprosta:cbiopsyguidedbytransrectalultrasonography”.VallancienG,LeoJP,BrissetJM.ProgClinBiolRes.1987;243B:25-7
30 year old technology
Prostate Biopsy- Destruc've
• 1.2M:mesperyear(3.4Mworldwide)• 180,000newcasesprostatecancer• TRUS:95%
• Officeprocedure
• TPMB5%• ORprocedure
Biopsy Procedures Outlook to 2020, Global Data, July 2014.
End-fire be[er than side-fire: Construc've Technology
Bjurlin et al. Urol Clin North Am 14: 299, 2014.
20-60%increaseddetec:onrate
3D Biopsy Mapping is this Disrup've Technology ?
Transperineal Mapping Prostate Biopsy
Avariableneedle15-60mmcores-IsthisDisrup6ve?
-----------------
3DBiopsy™ - The Next Dimension
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§ A large number of biopsy cores are taken during mapping biopsy
– 80-120 biopsy cores
§ Biopsy needle deflection errors
– Inaccurate localization of lesions
– Some cancer lesions may be outside of the treatment zone
§ Lack necessary software for needle tracking and targeted focal therapy
3DBiopsy: Disrup've Technology
1. Variable Length Actuator and Needle:
Ø to replace existing biopsy devices-20M procedures/yr.
Ø First target market-prostate cancer (3.4M proc./yr.)
2. Integrated 4 Component System:
Ø To become the new standard of care for prostate cancer diagnosis and management
Ø Applicable to other organs such as breast, lung, liver
3. Integrated Pathology System:
Ø Revolutionary specimen management system
Ø Can be used for all tissue biopsies (>50M proc./yr.)
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ClariCore™ Op'cal Biopsy System
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§ Shortcomings of Prostate biopsies
§ Over 90% of the biopsy cores are normal or negative cores
§ Some high risk cancers are missed
§ Pressure on pathology reimbursement
§ Increasing trend toward placing more patients under watchful-waiting or active surveillance in case of low grade disease
• Started December 2015 at University of Colorado Hospital, Aurora, CO (PI: Dr. Crawford)
• Other Participating Centers: • Johns Hopkins University, Baltimore, MD (PI: Dr. Partin) • Memorial Sloan-Kettering Cancer Center, New York, NY (PI: Dr. Eastham) • The Urology Center of Colorado (TUCC), Denver, CO (PI: Dr. Karsh) • Grand Strand Urology, Myrtle Beach, SC (PI: Dr. Shore)
• Phase I study completed in April 2017
• Number of patients enrolled: 200
Mul'center Phase I Clinical Trial for ClariCore™ System
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Update TRUS Data
AlgorithmPerformanceMeasures %(95%ConfidenceInterval)
Sensi6vity 85.95%(80.09–90.61%)
Specificity 87.98%(85.76–89.95%)
Nega6vePredic6veValue 97.05%(95.84–97.92%)
Posi6vePredic6veValue 57.61%(53.15–61.93%)
AreaUnderCurve 0.87(0.85–0.89)
Table 1. Diagnostic performance of the developed classification algorithm.
LUMEA Disrup've Technology
• Transformingpathologyfordigitalage• Integratedmachinelearningtools• Lowerlabcostandimprovequality
LUMEA Specimen Handling
• BxBoard• GrossExamAI• BxChip
LUMEA AI Diagnos'cs: 6 cores in seconds
• BxLink(LIS)
AI
Focus will be primarily on Prostate
• PSA• ProstateBiopsy• ProstateImaging• ProstateGenomics• ProstateTreatmentModalites• Prostate
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MRI Definitely Disrup've But
§ Some potentially important cancers (15%-30%) conceal to MRI
– 1 out 5 patients with Gleason Score ≥ 7 cancer missed
§ Cost-effectiveness yet to be resolved
§ Technology remain in evolution
§ Interobserver variability between radiologists
§ Do you really need fusion biopsies or are cognitive just as good
Kasivisvanathan V et al. N Engl J Med 2018;378:1767-1777
Summary of Key Results in 612 Patients – Predictors of Detection
Significantpredictorsofdetec:on(univariate)• Largersize• HigherGS• Indexlesionstatus• Solitarytumor
RobReiter,MDFDUS8.18
PROMIS Trial: Challenges
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1. UK cohort is “symptomatic” - May harbor large lesions (≥ 0.5cc) easily visible on mpMRI whereas US cohort is largely “asymptomatic” and may harbor smaller clinically significant (CS) lesions (≤ 0.5cc)
2. Success/Failure based on a single PIRADS Lesion per Patient – Disease is multifocal and there can be more than one clinically significant (CS) lesion based on histopathology data
3. Absence of Lesion-Level Analysis – Unclear whether mpMRI diagnosed all of the CS significant lesions based on histopathology as opposed one CS lesion per patient
4. Anterior versus Posterior Lesions – TRUS biopsies miss anterior lesions. Need a comparison (sensitivity) of mpMRI and TRUS biopsy for posterior lesions
5. Lack “concordance” and “discordance” information of PIRADS lesions and Histopathology – Unclear how this was done unless PIRADS lesions and corresponding cancer lesions are large (“symptomatic”) and quite obvious
ShearletAlgorithm
LesionSegmenta:onROIRadiologist
We Can Improve MRI Using Shearlets
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§ Reduceinterobservervariabili:es§ Diagnoseallimportantcancers§ Cost-effec:ve(reduce:me)
GleasonScore7and8tumors>0.5cc
UCH Study: mpMRI miss CS tumors
47pa:entshadmappingbiopsyaqerMRI34hadclinicallysignificantcancer
MRImissed6/34(18%)pa:entswithCScancer(table)
MRImissed10/25(40%)tumorswithGleasonScore≥7and27/60(45%)CScancer(table)
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• Some potentially important cancers are MRI-invisible
• Cost-effectiveness is yet to be resolved
• High “interobserver variability” between radiologists
Indication to Biopsy by PIRADSv2 ≥ 3 Patient Level Lesion Level N = 47 (CS=34) N =122 (CS=60)
Sensitivity 82% 55% Specificity 54% 74% PPV 82% 67% NPV 54% (87%*) 63%
Somepa:entsmayharbormorethanoneCSlesion(figure)
Promising Preliminary Results Disrup've Technology
Classification Results for Malignant vs Benign ROIs Patient # Parameter Sensitivity Specificity Classification
Rate
1 ADC 100% 100% 100% DCE 100% 100% 100% T2W 60% 100% 80%
2 ADC 100% 100% 100% DCE 100% 100% 100% T2W 80% 60% 70%
3 ADC 100% 100% 100% DCE 100% 100% 100% T2W 100% 60% 80%
4 ADC 80% 100% 90% DCE 100% 100% 100% T2W 100% 100% 100%
Overall ADC 89% 100% 97% DCE 100% 100% 100% T2W 92% 83% 94%
§ Overallhighsensi:vityandspecificity§ Iden:fymalignantregionswithhighdegreeofaccuracy
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MRI and US image fusion
• Defini:onoffusion“Imagefusionistheprocessofcombiningrelevantinforma:onfromtwoormoreimagestoprovideamoreinforma:veimagethanthe
originalinputimages”1
Haghighat, MA et al Comp and electrical engineering 2011
Theore'cal Advantages/disadvantages of MR/TRUS Fusion Advantages• ImprovedYield• FewerTotalbiopsies• BeQeraccuracy• Addconfidencetodiagnosis(espforac:vesurveillance)
Disadvantages• Increasedcost• Maydiagnosemoreirrelevantcancers• Maytaketheimageguidanceofprostatecanceroutofthespecialist’shands
Available Plaborms approved by FDA
• UroNav• Invivo
• Gainsville,FL
• Urosta:on• Koelis
• LaTronche,France
• ArtemiswithProfusetm
• Eigen• GrassValley,CA
mpMRI is clearly disrup've-
• 1.Thejuryiss:llout• 2.Noques:onthatdetectshighgradelesions,Butatwhatcostbothfinanciallyandclinically
• 3.Genomicsmarkersareimportanthavenotbeenevaluated• 4.InhandsoflessexperiencedfusionbiopsiesbeQer,butnotinthehandsofaseasonedultrasonograher
• MpMRIwillbedisrup:veandbacktoconstruc:ve
Next Disruptive Technology: Micro-Ultrasound?
• Systematic biopsies do not find enough cancer; false negative rates are too high
• Some looking to dramatic shifts in care such as MRI/US-Fusion which requires multiple specialists, expensive equipment and much longer procedure times
• Need a better ultrasound-based system to: • Better visualize cancer -- and target suspicious regions during the biopsy procedure • Improve the accuracy of ultrasound’s systematic sampling • Maintain the benefits of ultrasound – affordable, real-time,
known modality, standard of care
Micro-Ultrasound vs. Conventional Ultrasound • Novel micro-ultrasound system
operating at 29 MHz • Much higher than conventional 6-9MHz systems
• 300% improvement in resolution – both axial and lateral – down to 70 microns
• Enables real-time targeting of biopsies
• Commercial version with clinical approvals (CE, FDA, Health Canada) is available now
Exact Imaging’s ExactVu™ 29 MHz Micro-Ultrasound System
Micro-Ultrasound: When it makes a difference Hard to see Isoechoic lesions
Pathology results: Gleason 7
Pathology results: Gleason 7
Pathology results: Gleason 7
Tissues with slightly different echogenicities that have
distinct and irregular borders
Normal inflammation around capsule causing hypoechoic
area? No, scalloped edges are suspicious
Micro-Ultrasound vs. MRI/Ultrasound Fusion
Micro-Ultrasound • Real-time visualization,
real-time targeting • Its ultrasound - - just much higher-
resolution (300%) ultrasound • Just a few more minutes to perform
evidence-based PRI-MUS™ to identify and target suspicious regions
• One urology-based visit
MRI/US Fusion • Significant learning curve
(for urologists and for radiologists) • ~40 minutes for MR scan
+ Read and score MR image with PI-RADS + fuse image with u/s + perform targeted biopsy + re-configure if any patient movement
• Complex workflow • Multiple patient visits • Costly without additional
reimbursement codes • High variability of results (expertise @ site,
radiologist, MR instrument, sequences)
Over 100 years old Infections
Disruptive Technology. NGS
Focus will be primarily on Prostate
• PSA• ProstateBiopsy• ProstateImaging
• ProstateGenomics• ProstateTreatmentModali:es• Prostate
Fox Hunt
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PCM Buckets
Ini6alBiopsy:Iden6fy
SignificantPCa
SelectMDx
phi
4kscore
Nega6veBiopsy:WhomtoRebiopsy
ConfirmMDx
SelectMDx
phi
4kscore
WhomtoofferGene6cTes6ng:
AmbryGene:cs
MyriadGene:cs
GeneDx
Invitae
WhotoofferInterven6onal
TherapyvsAc6veSurveillance
OncotypeDx
Prolaris
Decipher
Promark
Whomtotreatornottreatpost-prostatectomy:
Prolaris
Decipher
Focus will be primarily on Prostate
• PSA• ProstateBiopsy• ProstateImaging• ProstateGenomics• ProstateTreatmentModali6es• Prostate
Willet Whitmore, MSKCC 1963-1986
• Istreatmentsufficientforthoseinwhomitisnecessary,andnecessaryforthoseinwhomitissufficient?
• Morepeoplemakealivingfromprostatecancerthandieofprostatecancer
• 20thcentury‘seekanddestroy’• 21stcentury‘targetandcontrol’
• A.VonEschenbach• Director,NCI
Goals for targeted abla'on
• Iden:fythelesion–specificityandsensi:vity?• US,MRI,3Dmapping,targetedbiopsy
• AccurateStaging–whatishappingoutsidetheprostate?
• BonescanandCATscan.roleforisotopes• Guidance
• localiza:on-canwegetthere?• Precision• Reproducibility–canwegothereagain
• Monitoring–weneedtoablateonlythetargetandminimizecollateraldamage
TFT Abla'on techniques: Disrup've Technology
• Photodynamictherapy• HIFU• Focallaser• FocalCryotherapy• Electropora:on• ACabla:on
My Opinion
• Idon’tbelieveinfocaltherapywhichascurrentlyprac:cedisrandomanddangerous.
• IdobelieveinTargetedFocalTherapyformenwithhigherriskcancerbasedon3Dmappingbiopsies,notsatura:onormpMRI
• IdobelievethatmostcasesofFTareperformedinlowriskpa6entswhoshouldbeofferedASorbeQeryetnotdiagnosed
• IdobelievethatweshouldeliminateASandfindingmostGS6cancers
In my opinion the most disrup've technology in Urology /Medicine is EPIC & other EMRs-LATER
EMRs construc(ve becomes destruc(ve
• Whodotheyserve?• pa:ents• Hospitals• Payers• Lookatyourparagraphnotesofadecadeagoandcompareto4pagesofcutandpaste,templatesandworthlessinforma:onforurologists!
• ButTherearelotsofadvantages:medsreview,druginterac:onandtripstoradiologytofindfilms
• Likemanythingsagoodthingbecomesencumberedandsteepedinbureaucracyandhiddenagendas.Weneedtotakecontrolandreturnbalance
Who is benefi'ng ? 76% hike in prices , 7 years
An'trust lawsuit!
And finally the most Disrup've Technology
• Thishascreateda“gene:c”muta:oninhumans• Changinghowwecommunicate,learn,andbehave• Thisandcomputershaveputusoncall24/7• PhysicianBurnout-EMR-Mobilephones
Mobile phones
The way we communicate !