case comprehensive cancer center stanton l. gerson, md ...€¦ · case comprehensive cancer center...
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CaseComprehensiveCancerCenterStantonL.Gerson,MD,DirectorCancerMoonshotInitiative
Observations,RecommendationsandSuggestedFocusAreas
March30,2016
DiscussionOverview
Background
I. RecommendationsA. ProvideSupportforAcademicCancerCenter-basedDrugDevelopmentPipelinesB. Support“BigData”IntegrationTools
II. Enhancing the quality and value of community based networks operated bymajor CancerCenters
A. CoordinatedApproachB. QualityReportingC. ClinicalTrials
III. FocusAreasA. RecommendedFocusAreastoProduceSubstantialResults
§ ScreeningandPreventionØ HPVVaccinationtoReduceCervicalandHead&NeckCancersØ LungandColonCancerScreeningØ EsophagealCancerScreeningØ AspirinforColorectalCancerPreventionØ Exercise,WeightReductionandDiet
§ TranslatingGenomicInsightstoReducedRiskandImprovedTreatmentØ AdolescentandYoungAdultCancerGenomicsØ UniqueGeneticCausesofCancerinAfricanAmericansØ HighCancerIncidenceinFamiliesØ CancerRecurrenceandMetastasis
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CaseComprehensiveCancerCenterExecutiveCommitteeStantonL.Gerson,MD,DirectorCancerMoonshotInitiative
Observations,RecommendationsandSuggestedFocusAreas
March30,2016Background:
TheCaseWesternReserveUniversity(CWRU)ComprehensiveCancerCenterExecutiveCommitteehas been working under the guidance of Director Stan Gerson to develop recommendations toinformandguidetheworkoftheOfficeoftheVicePresidenttoadvanceprogressoncancer.
The Executive Committee brings together the Case Comprehensive Cancer Center (Case CCC)consortium partners – including University Hospitals (UH), Cleveland Clinic (CC), Case WesternReserveUniversity (CWRU)andmemberMetroHealth System– in a collaborativeeffort todriveprogressincancerresearchandtreatmentforthebenefitoftheservicepopulationinnortheasternOhio.
SetforthbelowareourobservationsandrecommendationsregardingtheCancerMoonshotwhichincludes matters of national applicability, issues of particular impact in Northeastern Ohio, andopportunitiesrelatedtoparticularareasofconsortiumexpertise.
Manybarriersexistinpreventingexpeditedtreatmentsolutionsforcancercare.Includedinthosebarriersarebothinfrastructureandpoliticalchallenges.
Someofthekeybarriersinclude:§ TheVeteransAdministrationasanindependentsystem§ Lowscreeningrates§ LowHPVvaccinationrate§ Universalconsentneeds§ Povertyandaccess§ Environmentalexposures§ Hospitalcompetition§ Restricteddatasharing
InNortheastOhio,theCaseComprehensiveCancerCenter:§ Captures2outofevery3oncologypatients§ Enrollsalmost10%ofpatientsinclinicaltrials
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I. Recommendations:
A. ProvideSupportforAcademicCancerCenter-basedDrugDevelopmentPipelines.
CaseCCCinvestigatorsandtheirsponsor institutions(CWRU,UHandtheClevelandClinic)have developed robust pipelines of new anti-cancer drugs that are in various stages ofdevelopment--rangingfromchemistrytopreclinicalmodelstophase1and2clinicaltrialsbeingconductedatconsortiumhospitals.Wemodelnewtargets,mechanismsoftreatmentresistance,andnoveldrugcombinations.
The National Cancer Institute (NCI), the institutions themselves, or philanthropic sourcessupportfundingforthispipelineactivity.Currently,17drugsand5nano-therapeuticsareinsomestageofdevelopment.Thismodelofdevelopmentprovidesanenvironmentwheredrugdevelopmentcanproceedinacostefficientandobjectivemannerfocusedonscienceandnotonedrivenbycommercialconsiderations.
Federal fundingshouldbeprovidedfor this typeofdevelopmentmodel. Inparticularwehaveexperiencedaneedforinfrastructureresourcestosupportearlytestingandmodeling,andtosupportlicensingtopharmaceuticalandbiotechnologyentities.
B. Support“BigData”IntegrationTools.
The Consortium partners have developed and implemented a solution to the big datasharingchallenge. It is a singleplatform for secureclinicaldata fromallmajorClevelandhospitals – UH, CC, MetroHealth System, which together account for 70% of the 4.3Mnorthern Ohio population -- including but not limited to EHR data, genomics, clinicaloutcomesandriskassessments.
All data is stored in a secure, HIPAA compliant CWRU managed database called theCLEvelandAreaResearchPlatformforAdvancingTranslationalHealthcare(CLEARPATH)and
3-yearreturn(atCaseCCCalone):
• 5newcanceragentsbeginclinical trialsafterpreclinicaldevelopmentandFDAreview
• 3newpathwaysoftreatmentresistance identifiedwithtreatmentalternativesdescribed
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is available to any CWRU affiliated investigator under an overarching approved protocol;investigatorsmayalsorequesttore-identifyindividualsusingtheirownindividualapprovedprotocol. CLEARPATH is scalable for all diseases and can easily include more hospitalsand/oradditionalresearchnetworks.
Inaddition,CaseCCCinvestigatorshavedevelopedbigdatainterrogationtoolsofelectronicmedicalrecordsthatevaluatedrugrepurposingbyfindingwhichcommonlyuseddrugsareassociatedwithimprovedoutcomesinpatientswithcancer.Afindinginovariancancersisnowbeingevaluatedinclinicaltrial.
II. Enhancing the quality and value of community based networks operated bymajor CancerCenters:
A recognized need of theMoonshot effort is facilitating collaborations with researchers,doctorsandpatientstoovercomeinconsistentcare,excesscost,andpooroutcomes.
TheAmericanAssociationofCancerInstitutes(AACI)andtheNationalCancerInstitute(NCI)DesignatedCancerCentersrepresentapproximately92CancerCentersnationally.Throughthesecentersandtheirregionalcommunitybasednetworks, includingcare inruralareas,care for anestimated700,000patientswith canceroccurs, representingover40%of theentirecountryburdeninnewlydiagnosedcancerpatients.
By focusing efforts on coordinating care and emphasizing rapid introduction of newdiscoveriestopatientbenefit,throughtheAACI/NCIcancercenters,wecouldsubstantiallyaffectthequalityofcareandoutcomesforthesepatients.
Thisapproachrequires3maininitiatives:
A. CoordinatedApproach.
Through theAACIandNCIdesignatedcancer centers,modelsof care (carepaths) canbeagreed upon with strategy, infrastructure and business implication support. Consistentcare will improve quality and outcomes, and reduce costs. While the National Cancer
3-yearreturn:
• Reviewofthestructureandimpactofthisbigdatainitiativeonresearch,patientcareandqualityassessmentswillbenefitothercentersandregions
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CenterNetwork(NCCN)guidelinesareaconsistentstartingpoint,allmajorcancercentersarelinkingNCCNtodiagnosticandtreatmentstandards.
B. QualityReporting.
Qualityreportingisessentialtounderstandtheeffectaswellasdrivecompliance.SharingEMRanddatabasesarenecessarytoachievethisgoal.
C. ClinicalTrials.
Clinicaltrialsprovideaccesstonoveldrugs.Toimproveaccessacrosscommunitynetworksweneedto:
§ Reducebarrierstoenrollment§ Increasegenomicandotherspecialtestingformarker-basedtreatment§ Develop clinical trials that are appropriate for regional sites to improve patient
outcomes.
Attention to these approaches would enhance coordinated care, reduce competition,improveoutcomesandmanagecosts.
III. FocusAreas
A. RecommendedFocusAreastoProduceSubstantialResults:
CaseCCCisinsupportofthefocusareasidentifiedintheNCIbudgetjustification,andtheletterofsupportprovidedbytheAssociationofAmericanCancerInstitutes.
Basedonourexpertise,wehaveidentifiedanumberoftopicsofopportunitythatpertaintotheMoonshot’sgoalofsignificantlyadvancingprogressoncancer.ThesetopicsfallundertwoareasofConsortiumcorecompetency–ScreeningandPreventionandGenomics.
Specifically,we identify topicswherewewouldpropose federal support for collaborativeprojects using coordinated clinical and research databases. These projects wouldaccelerate,within3years,transferofdiscoveriesintomeaningfulimpactonpopulationsinareas of cancer screening, prevention, early detection, integrated care, personalizedmedicineandinspecificareasofpediatriccancers,youngadultcancersanddrugdiscoverytoclinicalapprovalofmoreeffectivetreatmentsforcancer.
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§ ScreeningandPrevention
TheCancerMoonshotshouldnotsolelyfocusonresearchanddevelopmentrelatedtotreatments and cures, but also embrace the areas where immense progress can bemadeinreducingcancerincidence,includingscreeningandprevention.
Ø HPVVaccinationtoReduceCervicalandHead&NeckCancers: Currently,onlyabout30%ofboysandgirls intheagerangeof11-15yearsoldarebeing vaccinated for HPV. In Northeast Ohio, the Consortium partners havecommittedtodevelopingprogramstoacceleratethatvaccinationratetowardagoalof70%orhigher.What will be needed to drive this level of improvement (both here and in othercommunities)issupportfor:
§ Populationstudies§ DevelopmentofmessagingandpubliceducationprogramsthattheHPV
vaccineisacancervaccine(withdisseminationofthatmessagethroughprimarycareandpediatricofficesandschool-basededucationprograms)
§ Vaccinationratemonitoringprograms.
Case CCC’s region-wide Pediatric Practice Based Research Network is ideallypositionedtorapidlyimplementsuchaninitiativewithappropriatefundingsupport.Community interest encouraging vaccination for all school-aged children shouldfacilitateimprovementinvaccinationrates.
Ø LungandColonCancerScreening:
The Cleveland area has high death rates from colon cancer and lung cancer, aproblemthat ismostpronouncedinourunderservedAfrican-Americancommunitywhere screening rates are low and smoking rates are 40% above the nationalaverage.Nationally,ratesoflungcancerscreeningforhigh-riskpopulations(thoseover50yearsofagewithahistoryofsmokingfor30yearsormore)arequite low(lessthan30%).Thissignificantlyraisesmortalityratesresultingfromlatediagnosisofthesecancers.Similarly,greatgains inpreventionandtreatmentofcoloncancercanbeachievedthrough improvements in screening. Better deployment of low-cost lung cancerscreeningaswellaspotentiallycoloncancerDNAtesting(atechniquedevelopedat
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CWRU)asanalternativetocolonoscopycanhelpwiththisimprovement.UHandCCadminister inexpensive CT screening programs for at-risk smokers and patientregistriesthatallowformonitoringoffollow-up.Significantadvancesinpreventionthroughscreeningcouldbepromotedbyfederalsupportto:
§ EvaluatewhetheraDNA test for colon cancerhasbetter acceptance inthepopulationthancolonoscopy
§ Offsetcostsofscreening,databasemaintenanceandfollow-up§ Developandevaluatenewsmokingcessationprograms
Additionally, support for novel imaging techniques (e.g., MRI fingerprinting), andscreening tests (e.g., DNA based blood and saliva testing) hold the promise ofbringingnoveltechnologiesintobroaderuse.
Ø EsophagealCancerScreening:
ObesityandBarrett’sEsophagusareassociatedwith increasedratesofesophagealcarcinoma (EC). Given that there has not been a great deal of improvement intreatment,earlydetectionofbothBarrett’s(topreventtheonsetofcancer)andofEC(whenstillcurable)isanimportantmedicalobjective.Case Comprehensive Cancer Center members have identified DNA changesdetectable fromabrushingof theesophaguswitha very simple self-administeredballoonswabthatcancollectasampleforDNAanalysisfromtheloweresophagusinamatterofminutes.Funding to support evaluation of this balloon brush as a tool for prevention andearlydetectioninpatientsthoughttohaveBarrett’sassociatedrefluxcouldrapidlyestablishanewmethodtoreducetherisksanddeathsofesophagealcarcinoma.
Ø AspirinforColorectalCancerPrevention:
CaseCCC,withcollaboratorsatHarvard,demonstratedthemolecularbasis forthedailyuseofaspirintoprotectagainstcoloncancer.WedemonstratedthatPGDH-15isariskstratificationbiomarkerthatpredictswhowillandwhowillnotbenefitfromaspirinchemoprevention.
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Population screening forPGDH-15 identify those (~50%)whobenefit fromaspirin,reducing the use for those without benefit, and is an example of personalizedprecisionpreventivemedicine.To capitalize on this advancement, funding is needed to initiate a multi-sitepopulation-based assessment screening and intervention trial that identifies whobenefitsfromaspirinusewithreducedincidenceofcoloncancer.
Ø Exercise,WeightReductionandDiet:
It is well known that obesity is a major cause of heart disease, diabetes andmetabolic syndrome. Less recognized is its profound effect on increasing risks ofcolon,endometrial,breastandovariancancers. Conversely,exercisereducesrisksofrecurrenceforthesecancers.Programs to reduce obesity through exercise in children and young adults, andprogramsthatincreaseexerciseafterthediagnosisofcancercanhaveasignificantimpact. The link between healthy foods and lower cancer incidence is also wellestablished,andimprovingdietaryhealthbyattackingtheproblemofhealthyfooddesertsinurbanareasneedstoberecognizedaspartofananti-cancerstrategy.CaseCCChasfundedinvestigatorsevaluatingobesityandcancer;studyingexercise--bothinschoolagechildrenasaprimarycancerpreventionmethod,andincancersurvivors(includingtheelderly)asitpertainstoreoccurrence;withinterventionstocorrecteachoftheserisksforcancer.Anadditionalfocusareahasinvolvedstudyingandremovinghealthyfooddesertsinourcommunity,analyzingtheinterventionforimprovedhealthoutcomes.Fundingisneededforeducationprograms,skilledfitnesstrainerstoimplementandevaluateexerciseinterventions,andbiomarkermonitoringoftheimpactofexerciseoncancerrisk.
§ TranslatingGenomicInsightstoReduceRiskandImproveTreatment:
Ø AdolescentandYoungAdultCancerGenomics:
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Advances inoutcomes forpatientswithcanceraged15-30years lagsbehindbotholder and younger individuals and there is a lack of ongoing focus on research incancers in this age group. Further understanding of the etiology and biology ofAdolescentandYoungAdult(AYA)cancerisnecessarytomakesignificantadvancesinthispopulation.Through philanthropic support, Case CCC has developed a scientific focus on theetiology and biology of AYA cancers -- with special attention from these youngpatients.Federalfundingshouldbedirectedtosupportgeneticanalysisandinterpretationtoidentifybothknownandnovelpathwaysleadingtocancerinthisagegroup.
Ø UniqueGeneticCausesofCancerinAfricanAmericans:
For the first time, Case CCC investigators have identified unique genetic changesresponsible for colon cancers and for myelodysplastic syndrome and acutemyelogenous leukemia in African Americans living in northern Ohio, includingCleveland.Thisfindingprovidesdirectevidencethatcancertreatmentsareinadequateforthispopulation,sincecurrentFDA-approvedtreatmentsareorientedtowardadifferentsetofgeneticchangesseeninCaucasians.Fundingshouldbedirectedtovalidatetheseuniquegeneticandpotentialepigeneticchanges inminoritypopulationsacrosstheUS,andtoevaluatenewscreeningandtreatment paradigms for African Americans carrying these mutations in theirtumors.
Ø HighCancerIncidenceinFamilies:
Therearemanyfamilieswithaveryhighincidenceofcancerthatcannotbetiedtoanycommonlyknowngeneticindicators(astheBRCA1,2genesandbreastcancer).CaseCCC,workingthroughbothUHandCCF,supporthigh-riskcancerfamilyclinicsthatareservingfamilieswithhighratesofcancer,includingbysupportingextensivescreeningandgenetictesting.Thistypeofselectionandextensivegenomicanalysisof complex cancer families is critical to determine risk and treatment options forthesefamilies.
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Fundingtocontinuetocollectthesefamilymembersacrossthetwohealthsystemsand select complex cancer families for complete and extensive genomic anddatabase analysis to uncover the genetic cause of cancer in that family is badlyneeded.
Ø CancerRecurrenceandMetastasis:
Thegreatestfearforanycancerpatientisthewordrecurrence.Understandingthebiology behind tumor metastasis, and spread to other organs remains critical todevelopingnewmethodsofearlydetectionandtreatments.In Cleveland, investigators are evaluating metastasis samples to understand theirgeneticabnormalities,inordertoimprovedetectionandtreatmentstrategies.Fundingisneededtoexpandresearchinthisareausingpatientderivedsamplesthatwillrepresentamajoradvancewhenthecausesandtriggersareidentified.
ContactStantonL.Gerson,MD
DirectorCaseComprehensiveCancerCenter
Cleveland,Ohio216-844-8562
[email protected]://cancer.case.edu/
3-yearreturn:
• ImprovedratesofcancerscreeningandHPVvaccination• Identificationof newgenesassociatedwithAYAcancersandcancers in
families• ValidationofcancerriskgenesinAfricanAmericanswithcoloncanceror
AML/MDSwith newdiagnostic approaches and new therapies directedtowardsthesegeneticchanges
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