sidney kimmel comprehensive cancer center (skccc) overview william g. nelson, m.d., ph.d. director
TRANSCRIPT
Sidney Kimmel Comprehensive Cancer Center (SKCCC)
Overview
William G. Nelson, M.D., Ph.D.
Director
11 colorectal cancers11 breast cancers24 pancreas cancers22 gliomas22 meduloblastomas
2 leukemias1 breast cancer
1 breast cancer4 granulosa cell tumors
1 lung cancer Sanger1 melanoma
*Vogelstein B AACR Annual Meeting (2010)
WashingtonUniversity
British ColumbiaCancer Research
Centre
Sanger InstituteScience, Feb 16, 2001
Whole Exome Sequences of 100 Human Cancers*
3142 mutated genes286 tumor suppressors33 oncogenes
SKCCC
Hypermethylation(versus normal
tissues)
Hypomethylation(versus normal
tissues)
Genome-Wide Epigenetic Alterations inMetastases from Men Dying of Prostate Cancer*
*Yegnasubramian S,Aryee MJ et al. (2012)
A Molecular Description of Lethal Prostate Cancer
Haffner MC, Yegnasubramanian S et al. (2012)
pretreatment biopsies from subjects (n = 30) with melanoma treated with an anti-PD-1 antibody
Heterogeneous Responses of Melanoma to Anti-PD-1*
0/14 responses
cytoplasmic or absentB7-H1 expression
(14 cases)
11/16 responses
membranousB7-H1 expression
(16 cases) *Brahmer JR et al. J Clin Oncol 28: 3167-75 (2010)
Translational Research in Hematology/Immunology has Revolutionized
Bone Marrow Transplantation*
Opportunity: Allogenic bone marrow transplantation (alloBMT) has proven benefit in the treatment of hematological malignancies and inherited bone marrow disorders.
Challenge: HLA-matched bone marrow donors are under-represented among African-American and other minority populations.
Solution: Innovative strategy for establishing immune tolerance in bone marrow allografts reduces graft-versus-host disease (GVHD) and making alloBMT more accessible to minority patients.
*Brunstein CG et al. Blood 118: 282-288 (2011)
*Ramos-Gomez M et al. Proc Natl Acad Sci USA 98: 3410-5 (2001);Yu X and Kensler TW Mutation Res 591: 93-102 (2005)
Nrf2-/-wild-type
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inInducers(oltipraz,
sulforaphane,others)
Keap1/Nrf2 Pathway for Cancer Chemoprevention*
Broccoli Sprouts Tea Intervention: HeZuo TownshipQidong, P.R.C. (2003-2004)*
*Kensler TW and Co-Workers
Age Specific Incidence Rate of Liver Cancer(Hepatocellular Cancer or HCC):
Qidong and Beijing
HC
C I
nci
den
ce (
per
105
/yea
r)
15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80-AGE
300
250
200
150
100
50
0
Qidong
Beijing
USA
HC
C I
nci
den
ce (
per
105
/yea
r)
15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80-AGE
300
250
200
150
100
50
0
Qidong
Beijing
USA
potentially preventableby attenuating carcinogenicity
of aflatoxin B1
Biomarker Discoveries
Biomarker Assay Platforms
Regulatory/Systems Considerations
Integration into Clinical PracticeTest Marke
rSpecimen Company Disease Indication
PCA3 RNA urine Dianon prostate cancer
predicts prostate biopsy outcome
MGMT methylation
DNA tissue MDxHealth glioblastoma predicts response to temozolomide
GSTP1 methylation
DNA urinetissue
LabCorpMDxHealth
prostate cancer
predicts prostate biopsy outcome
AMACR protein tissue many prostate cancer
diagnosis aid
DNA Beaming, PARE,MSP, nanoMSP, MOB, COMPARE, GEMINI
germline DNA variantssomatic DNA mutations, translocations, etc.somatic DNA somatic methylation changesRNA expression changes, splice variantsprotein expression changes
CLIA, biospecimen collection/archiving, HIPAA, health recordinformation technology
Translational Development of Molecular Biomarkers at SKCCC: What are the
Challenges?
Improving Cancer Health at a Population Scale:Covered Lives in the
Johns Hopkins Health SystemOrganization
(Characteristics)Population Size
Johns Hopkins Community Physicians (Primary Care Provider Network)
>260,000
Johns Hopkins Priority Partners
(Medicaid Health Maintenance Organization)
>185,000
Johns Hopkins Employee Health Program
(Health Insurance Plan)
>50,000
Johns Hopkins US Family Health Plan
(Provider to US Government and Military Employees and Families)
Enrolling
Cancer Prevention and Control Program members already working with these entities to establish cancer screening guidelines and improve screening performance- first project focuses on reducing over-screening for prostate cancer among elderly men
Individualized Health/Personalized Medicineat SKCCC and at Johns Hopkins Medicine
Individualized Health Initiative (IHI) planning led by Provost, Dean of Engineering, and SKCCC Director- launched with Scott Zeger as leader in July 2012
Envisioned $1.5B project (>$0.5B for Epic health record/management system-investment in research information technology needed)
Brings together Schools of Medicine, Public Health, Engineering, Nursing, Arts & Sciences, Business, Applied Physics Laboratory
$30M Malone gift to Engineering
$30M Commonwealth Foundation gift to SKCCC for Personalized Cancer Medicine
Informationfor Health
LearningCommunities
for Health
Laboratory forAdvanced
Biotechnologiesfor Health
OrganizationalModel for
Affordable Health
Design andDeploy NewResearch
Information System
Develop BioethicsFramework
Design New Approach for Clinical Trials
Build NetworkThroughout
Johns HopkinsHealth System
Develop BetterMeasurements,
Diagnostics,and Treatments
• Epigenome/Genome Core
• High PerformanceComputing Core
• Statistics Core• Biorepository
Apply IHIPrinciples,
Methods, and Tools to
Population Health at
Significantly Lower Cost
IHIDirector’s Office
AppliedPhysics
Laboratory
JohnsHopkins
UniversityJohns
HopkinsMedicine
SKCCC Membership(who we are)
• 254 SKCCC members from 28 Johns Hopkins Departments
– 95 additions/36 departures over 6 years
• Membership requires Program nomination and Executive Committee approval
• Increasing diversity: 39% of new SKCCC members now non-white or female
Oncology33%
Other Med Depts33%
Surgical Depts17%
Sch Public Health9%
Basic Sciences6%
Sch Engineering2%
• Membership Criteria: ̶Q Principal Investigator (PI)/Project Leader of a peer-reviewed,
cancer-relevant grant̶Q Co-PI of a peer-reviewed, cancer-relevant grant ̶Q Contributor to cancer clinical protocol development̶Q New faculty investigator with promise of meeting criteria for full
membership within 3 years
SKCCC Programs
PROGRAM # MEMBERS FUNDINGPEER-REVIEWED (TOTAL)
ACCRUALS/ NEW PTS
(2011)Cancer Biology 29 $10.0M ($15.5M)
Hematologic Malignancies/BMT 29 $10.1M ($14.9M) 53.3%
Cancer Immunology 29 $11.2M ($12.3M)
Viral Oncology 17 $6.0M ($6.4M)
Cancer Prevention & Control 31 $8.6M ($9.9M)
Chemical Therapeutics 26 $13.4M ($17.0M)
Prostate Cancer 32 $10.2M ($14.6M) 17.6%
Breast Cancer 28 $6.6M ($10.5M) 16.1%
Gastrointestinal Cancer 29 $9.0M ($14.8M) 33.8%
Upper Aerodigestive Cancer 26 $5.2M ($11.0M) 22.1%
Brain Cancer 17 $7.5M ($10.6M) 17.1%
Cancer Molecular & Functional Imaging
25 $13.3M ($14.0M)
SKCCC Facilities
Current Space: 621,160 ft2
• Clinical: 323,300 ft2
• Research: 222,000 ft 2
• Other: 75,860 ft2
Research Programmembers are co-locatedto maximize collaborationinteractions
SKCCC Cancer Care Delivery SitesBayview Campus:
25,000 ft2
Suburban Hospital: 7,000 ft2
Sibley Hospital: 30,000 ft2
All Children’s Hospital: 46,800 ft2
• New Faculty (8 positions)
• Radiation Oncology ($17.1 million)
• Medical Oncology ($10.5 million)
• Pulmonary ($2.8 million)
• Other Commitments ($6.6 million)
• Clinical space- 20,000 ft2; Laboratory/support space- 5,000 ft2
Johns Hopkins Singapore: 50,000 ft2
Trans-Disciplinary Cancer Researchat SKCCC
• Multiple collaborative trans-disciplinary Research• Programs
• Collaborative grants rose from 18 to 30 over the past 5 including 6 SPOREs, 7 P01s, 8 U01s, 5 U54s,1 U24, 1 P30, 2 P50s
• Meetings, seminars, retreats
• Many points of interactions between Research Programs
Cancer Molecular and Functional Imaging
Non-ProgrammaticallyAligned
Cancer Biology
Hematological Malignancies
Viral Oncology
Cancer Prevention and Control
Chemical Therapeutics
Breast Cancer GI Cancer
Upper AerodigestiveCancer
Brain Cancer
Cancer Immunology
Prostate Cancer
2006-2011263 researchers2032 collborations643 intra-Programmatic1389 inter-Programmatic
Program Interactions Promote Team Science
Cancer Molecular and Functional Imaging
Non-ProgrammaticallyAligned
Cancer Biology
Hematological Malignancies
Viral Oncology
Cancer Prevention and Control
Chemical Therapeutics
Breast Cancer GI Cancer
Upper AerodigestiveCancer
Brain Cancer
Cancer Immunology
Prostate Cancer
2006-2011263 researchers2032 collborations643 intra-Programmatic1389 inter-Programmatic
Program Interactions Promote Team Science
SKCCC Grant Funding
2000 2005 2010$0
$10$20$30$40$50$60$70$80$90
$100
$41.4
$75.6
$93.8
NCI Funding Base
Mil
lio
n
• $203.6M in cancer-relevant grants
• $93.8M in NCI grants
• $59.8M in other NIH grants
SKCCC Clinical Research Accrual
• >2-fold increase from 2004 to 2010– 2261 5036
• 44% extern. peer reviewed• 54% institutional
20042005
20062007
20082009
20100
200
400
600
800
1000
1200
1400
Industry
National
Institutional
Extern. Peer Reviewed
Interventional studies
Inte
rven
tiona
l acc
rual
s
Non-interventional studies
Since 2004: 61% increase in accruals to investigator-initiated solid tumor trials (401 to 665); 56% increase in overall accruals to solid
tumor trials (634 to 991)
Emphasis on early phase (26%) and investigator-initiated (66%) intervention trials
Training at SKCCC: A Pipeline of Talent
Career Path Since 1973# (%)
Last 20 Yrs# (%)
Last 10 Yrs# (%)
Academia 156 (64%) 105 (76%) 50 (81%)
Private Practice 67 (28%) 26 (19%) 9 (15%)
Industry 14 (6%) 5 (4%) 0 (0%)
Other 6 (3%) 3 (2%) 3 (5%)
Total 243 (100%) 139 (100%) 62 (100%)
Trainees Number
Pre-doctoral 122
Post-doctoral 183
Yearly Census of TraineesCareer Choices of Hem/Onc Fellows
48%
26%20%19%
SKCCC
NCI Centers
MD
US
years from diagnosis
2 3 4 51
frac
tio
n r
emai
nin
g a
live
1
0.8
0.6
0.4
0.2
0
Quality of Cancer Care at SKCCC and Other NCI-Designated Cancer Centers
Example: AJCC Stage I Pancreatic Cancer
SKCCC as a Global Asset for Cancer:Interactions/Collaborations for Key Missions
Clinical Care• Diagnosis/treatment planning to ensure accuracy of tumor stage/grade
guiding treatment planning• Founding member of National Cooperative Cancer Network (NCCN)• Evolving strategies for improving care quality
Research• Key strengths in cancer genetics/epigenetic likely scalable• Clinical trials infrastructure/oversight expertise• Biobanking experience• Cancer prevention interventions active even in resource-poor regions
Education• Strong pipeline for academically-oriented trainees• Already significant international reach of education and training
experiences
Sidney Kimmel Comprehensive Cancer Center (SKCCC)
Overview
William G. Nelson, M.D., Ph.D.
Director
The Wilmer Ophthalmological Institute The Johns Hopkins University School of Medicine
The Johns Hopkins Hospital
Research in the Middle East
The Experience at King Khaled Eye Specialist Hospital, Saudi Arabia
Deepak P Edward, MDDirector of Research, KKESH, Riyadh KSAProfessor of Ophthalmology
What is the MISSION of the KKESH – WEI Affiliation?
To contribute to ophthalmic knowledge and reduce suffering through preventions and cures of medical conditions leading to blindness and vision loss within the Kingdom of Saudi Arabia and around the world, through leadership and excellence in research, education, and patient care
Overview of KKESH
• 200 bed eye hospital• Operational since
1982• ~120,000 patient
visits a year• Joint Commission
International accredited
Overview of Research at KKESH
• Personnel
• Clinical Research
• Basic Research
Overview of Research at KKESH
• Structure to Clinical Research
• IRB
• Research Council
• Laboratory
Strategic Plan
• Local faculty feedback
• Administration alignment
• Anonymous survey
• Create strategic plan
• NEED MANY PARTIES TO BUY INTO YOUR PLAN
Research Strategic Plan
• Plan presentation
• Revisions and approval
• Plan budgeting
• Job revisions/creation
• Space allocation
What is the MISSION of the KKESH – WEI Affiliation?
Challenges, successes and lessons learned in establishing the research program
Implementation of Plan
• Reorganize the structure of the Department of Research
Small Steps Forward
• ROBUST IRB
• COLLABORATIVE AGREEMENT WITH JHU IRB
• SHORTEN REVIEW CYCLE FOR RESEARCH PROPOSALS
• HIRE PERSONNEL
Biostats
Clinical Coordinators
Basic scientists
IRB Manager
Epidemiologist
Medical Editor
• LAB EQUIPMENT
Enhance Visibility
• Enhance the visibility of KKESH as a center of research excellence in the Middle East
• Invite internationally renowned research Visiting Professors to assist building research programs at KKESH
PROMOTE VISIBILITYhttp://rd:kkesh.med.sa
JHU-KKESH COLLABORATION FUNDING• First Cycle of funding for collaborative research
between JHU faculty and KKESH faculty in process
• 8 studies fundedDiabetesSurgical SimulationOncologyEpidemiologyGenetics
• Second cycle 17 applications: Review process under way
Innovations/ Training Programs
• Medical student research training program
• Mentorship to young faculty and fellows
• Clinical coordinator research training program
Innovations/ Training Programs• Other training programs
How to do clinical researchHow to write a paper
• Courses plannedHow to make an effective oral research
presentationClinical trials/Ethics
Challenges/ Opportunities
•“IBM POLICY”
•HR
•FINANCE
•PURCHASING
International Collaborations/ Opportunities
•JHU collaborations
•Singapore collaboration
•Genetics
•Ocular Oncology
Identify Additional Funding Sources
• Leverage KACST funding to accomplish goals
• Ministry of Health
Research Strategic PlanTimelines
Year 1 Year 2 Year 3 Year 4 Plan Execute Results Plan Execute Results Plan Execute Results Plan Execute Results Investigator Initiated Clinical Trials/Projects Unit
x x x x x x x x
Oncology/Pathology x x x x x x x x Stem Cell Unit x x x x x Retinal Diseases Program
x x x x x x x x
Epidemiology x x x x x x x Genetics x x x x x x x Inflammatory eye disease
x x x x
Develop educational initiatives in research
x x x x x x x x x
Inter-specialty based research programs
x x x x x x x x x
Research website and news letter
x x x x x x x x
Research Strategic PlanChallenges
•Personnel
•Purchase
•Participation
Measures of Success
• Number of High impact publications with KKESH authors
• Number of invited presentations globally by KKESH staff
• Number of grants: by KKESH staff
• Number of local trainees in research
Lessons Learned
•PATIENCE
•BUY IN AND TRUST
•LOCAL CULTURE
•POSITIVE ATTITUDE
•CELEBRATE SUCCESS
Thank you!
Brian R. Matlaga, M.D., M.P.H.James Buchanan Brady Urological Institute
Johns Hopkins Medical InstitutionsBaltimore, Maryland
Advancing Kidney Stone ManagementA Collaborative Approach
Background
• Introduction of an advanced surgical technique for kidney stone management
• Required education of:– Physicians– Nurses– Equipment specialists
• Unique process• Tracked the effectiveness of our program
The Surgical Management of Kidney Stones
How are kidney stones managed?
Historically, shock wave lithotripsy
was most common approach
Shock Wave Lithotripsyin vitro
However, this is becoming less effective…
• Inferior outcomes associated with– Large stone size– Multiple stones– Stones of certain composition
• Cystine, brushite, calcium oxalate monohydrate
– Stones in lower pole of the kidney– Obese patients (large skin-to-stone distance)
Other effects of SWL have been described
Endoscopic therapies becoming more commonly applied
The Landscape is ChangingThe Rise of Ureteroscopy
• Study of practice logs submitted to ABU– Authoritative snapshot of clinical practice
• Initial certification (1 year practice)• 1st recertification (10 years practice)• 2nd recertification (20 years practice)
Journal of Urology, 181:2152, 2009
The Landscape is ChangingThe Rise of Ureteroscopy
• Found increased utilization of URS in younger cohorts– Initial certification – 52% of all cases– 1st recertification – 38% of all cases– 2nd recertification – 36% of all cases
Journal of Urology, 181:2152, 2009
Why is this?
• Our collective experience with URS– Superior for distal ureteral stones
Journal of Urology, 188:130, 2012
• Our collective experience with URS– Superior for proximal ureteral stones
Journal of Urology, 188:130, 2012
Journal of Urology, 188:449, 2012
What are barriers to more widespread adoption of
ureteroscopy?
How to flatten the learning curve?
• This is what we have to address…– Access to the stone– Manipulation of the stone– Fragmentation of the stone– Drainage of the kidney– Equipment maintenance
Access to the Stone
• Guidewire access– Sometimes this is
difficult• Impacted stone,
tortuous ureter– What can help?
• Combo wire• Glidewire• Angled tip wire
Access to the Stone
• Challenging cases may benefit from pre-formed catheters
Relocation of Lower Pole Stones
How can institutional partnerships help with this process?
• At Johns Hopkins we have…– Robust clinical experience– Familiarity with educational initiatives
• Resident / Fellow training• Invited faculty at national / international courses
– Infrastructure to track outcome metrics
Implementing the Program
• Focused didactic curriculum– 5 days’ duration– Lectures focused on details for
• Physician staff– Surgical techniques– Equipment utilization
• Nursing staff– Preparation of required equipment – Techniques of assistance
• Equipment management– Proper equipment care techniques– Minimizing ureteroscope damage during processing
Implementing the Program
• Didactic materials– Review of ureteroscope and laser attributes– Discuss utility of instrumentation
• Wires, baskets, graspers, etc.
– Review of unedited surgical videos• Fundamental techniques• Advanced surgical maneuvers
Implementing the Program
• Surgical preceptoring– “Shoulder-to-shoulder”I nstruction– Initial demonstration of surgical technique
• Local physicians as assistants
– Transition of roles– Ultimately with local physicians completing
entire case
Tracking Effectiveness
• Rationale– First effort of its kind– Quality improvement
• Define what is important to us– Clinical outcomes– Goals were safety and efficacy
Outcomes
• Our experience– 12 months following introduction of URS / Laser
• 32 URS / laser lithotripsy procedures– 24 renal stones / 5 ureteral stones treated– 1.1 cm mean stone size
• No intra- or post-operative complications– Likely in part related to emphasis on safe approaches
Ruiz et al. Clinical Nephrology (in press)
Lessons Learned
• With a well-thought out curriculum, complex procedures can be effectively introduced
• Tracking clinical outcomes enables a better understanding of success
• Puts in place an infrastructure for academic productivity