Transcript SKCCC - Johns Hopkins Medicine

Sidney Kimmel Comprehensive
Cancer Center (SKCCC)
Overview
William G. Nelson, M.D., Ph.D.
Director
Whole Exome Sequences
of 100 Human Cancers*
11 colorectal cancers
11 breast cancers
24 pancreas cancers
22 gliomas
22 meduloblastomas
SKCCC
Washington
University
British Columbia
Cancer Research
Centre
2 leukemias
1 breast cancer
1 breast cancer
4 granulosa cell tumors
3142 mutated genes
286 tumor suppressors
33 oncogenes
1 lung cancer Sanger
1 melanoma
Sanger Institute
Science, Feb 16, 2001
*Vogelstein B AACR Annual Meeting (2010)
Genome-Wide Epigenetic Alterations in
Metastases from Men Dying of Prostate Cancer*
Hypermethylation
(versus normal
tissues)
Hypomethylation
(versus normal
tissues)
*Yegnasubramian S,
Aryee MJ et al. (2012)
A Molecular Description of
Lethal Prostate Cancer
Haffner MC, Yegnasubramanian S et al. (2012)
Heterogeneous Responses of Melanoma to Anti-PD-1*
cytoplasmic or absent
B7-H1 expression
(14 cases)
0/14
responses
membranous
B7-H1 expression
(16 cases)
11/16
responses
pretreatment biopsies
from subjects (n = 30) with
melanoma treated with an
anti-PD-1 antibody
*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 AfricanAmerican 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)
+ oltipraz
- oltipraz
gastric tumors/mouse
after benzo[a]pyrene exposure
Inducers in
(oltipraz,
sulforaphane,
others)
Keap1/Nrf2 Pathway for
Cancer Chemoprevention*
wild-type
Nrf2-/-
*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)
Broccoli Sprouts Tea Intervention: HeZuo Township
Qidong, P.R.C. (2003-2004)*
*Kensler TW and Co-Workers
HCC Incidence (per 105/year)
Age Specific Incidence Rate of Liver Cancer
(Hepatocellular Cancer or HCC):
Qidong and Beijing
300
Qidong
250
Beijing
USA
200
potentially preventable
by attenuating carcinogenicity
of aflatoxin B1
150
100
50
0
15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80-
AGE
Biomarker Discoveries
germline DNA variants
somatic DNA mutations, translocations, etc.
somatic DNA somatic methylation changes
RNA expression changes, splice variants
protein expression changes
Translational Development
of Molecular Biomarkers
at SKCCC: What are the
Challenges?
Regulatory/Systems Considerations
CLIA, biospecimen collection/
archiving, HIPAA, health record
information technology
Biomarker Assay Platforms
DNA Beaming, PARE,
MSP, nanoMSP, MOB,
COMPARE, GEMINI
Integration into Clinical Practice
Test
Marker
Specimen
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
urine
tissue
LabCorp
MDxHealth
prostate
cancer
predicts prostate
biopsy outcome
AMACR
protein
tissue
many
prostate
cancer
diagnosis aid
Improving Cancer Health at a Population Scale:
Covered Lives in the
Johns Hopkins Health System
Organization
(Characteristics)
Population Size
Johns Hopkins Community Physicians
(Primary Care Provider Network)
>260,000
Johns Hopkins Priority Partners
>185,000
(Medicaid Health Maintenance Organization)
Johns Hopkins Employee Health Program
>50,000
(Health Insurance Plan)
Johns Hopkins US Family Health Plan
Enrolling
(Provider to US Government and Military
Employees and Families)
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 Medicine
at SKCCC and at Johns Hopkins Medicine
 Individualized Health Initiative (IHI)
planning led by Provost, Dean of
Engineering, and SKCCC Directorlaunched 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
Johns
Hopkins
University
Applied
Physics
Laboratory
IHI
Johns
Hopkins
Medicine
Director’s Office
Information
for Health
Learning
Communities
for Health
Laboratory for
Advanced
Biotechnologies
for Health
Organizational
Model for
Affordable
Health
Design and
Deploy New
Research
Information
System
Develop Bioethics
Framework
Develop Better
Measurements,
Diagnostics,
and Treatments
Apply IHI
Principles,
Methods, and
Tools to
Population
Health at
Significantly
Lower Cost
Design New
Approach for
Clinical Trials
Build Network
Throughout
Johns Hopkins
Health System
• Epigenome/
Genome Core
• High Performance
Computing Core
• Statistics Core
• Biorepository
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
Basic Sciences
6%
Sch Engineering
2%
Sch Public Health
9%
Oncology
33%
Surgical Depts
17%
•
Increasing diversity: 39% of new
SKCCC members now non-white or
female
•
Membership Criteria:
̶
Principal Investigator (PI)/Project Leader of a peer-reviewed,
cancer-relevant grant
̶
Co-PI of a peer-reviewed, cancer-relevant grant
̶
Contributor to cancer clinical protocol development
̶
New faculty investigator with promise of meeting criteria for full
membership within 3 years
Other Med Depts
33%
SKCCC Programs
ACCRUALS/
NEW PTS
(2011)
# MEMBERS
FUNDING
PEER-REVIEWED (TOTAL)
Cancer Biology
29
$10.0M ($15.5M)
Hematologic Malignancies/BMT
29
$10.1M ($14.9M)
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)
PROGRAM
53.3%
SKCCC Facilities
Current Space: 621,160 ft2
• Clinical: 323,300 ft2
• Research: 222,000 ft 2
• Other: 75,860 ft2
Research Program
members are
co-located
to maximize
collaboration
interactions
SKCCC Cancer Care Delivery Sites
Bayview Campus:
25,000 ft2
Suburban Hospital:
7,000 ft2
Sibley Hospital:
30,000 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
All Children’s Hospital:
Johns Hopkins
46,800 ft2
Singapore: 50,000 ft2
Trans-Disciplinary Cancer Research
at 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
Program Interactions Promote Team Science
Hematological Malignancies
Cancer Immunology
Cancer Biology
Viral Oncology
Non-Programmatically
Aligned
Cancer Prevention
and Control
Cancer Molecular and
Functional Imaging
Chemical
Therapeutics
Brain Cancer
Prostate Cancer
Upper Aerodigestive
Cancer
2006-2011
263 researchers
2032 collborations
643 intra-Programmatic
1389 inter-Programmatic
Breast Cancer
GI Cancer
Program Interactions Promote Team Science
Hematological Malignancies
Cancer Immunology
Cancer Biology
Viral Oncology
Non-Programmatically
Aligned
Cancer Prevention
and Control
Cancer Molecular and
Functional Imaging
Chemical
Therapeutics
Brain Cancer
Prostate Cancer
Upper Aerodigestive
Cancer
2006-2011
263 researchers
2032 collborations
643 intra-Programmatic
1389 inter-Programmatic
Breast Cancer
GI Cancer
SKCCC Grant Funding
NCI Funding Base
• $93.8M in NCI grants
• $59.8M in other NIH
grants
Million
• $203.6M in cancerrelevant grants
$100
$90
$80
$70
$60
$50
$40
$30
$20
$10
$0
$93.8
$75.6
$41.4
2000
2005
2010
SKCCC Clinical Research Accrual
Interventional studies
Non-interventional studies
Interventional accruals
1400
1200
Industry
1000
National
800
Institutional
600
Extern. Peer
Reviewed
400
200
0
• >2-fold increase from 2004
to 2010
– 2261  5036
• 44% extern. peer reviewed
• 54% institutional
Emphasis on early
phase (26%) and
investigator-initiated
(66%) intervention trials
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)
Training at SKCCC: A Pipeline of Talent
Yearly Census of Trainees
Trainees
Career Choices of Hem/Onc Fellows
Number
Pre-doctoral
122
Post-doctoral
183
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%)
Quality of Cancer Care at SKCCC
and Other NCI-Designated Cancer Centers
Example: AJCC Stage I Pancreatic Cancer
fraction remaining alive
1
0.8
SKCCC
0.6
NCI Centers
MD
0.4
26%
20%
19%
US
0.2
0
48%
1
2
3
years from diagnosis
4
5
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
Research in the Middle East
The Experience at
King Khaled Eye Specialist Hospital, Saudi Arabia
Deepak P Edward, MD
Director of Research, KKESH, Riyadh KSA
Professor of Ophthalmology
The Wilmer Ophthalmological Institute
The Johns Hopkins University School of Medicine
The Johns Hopkins Hospital
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 VISIBILITY
http://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 funded
Diabetes
Surgical Simulation
Oncology
Epidemiology
Genetics
• 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 research
How to write a paper
• Courses planned
How to make an effective oral research
presentation
Clinical 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 Plan
Timelines
Investigator Initiated
Clinical Trials/Projects
Unit
Oncology/Pathology
Stem Cell Unit
Retinal Diseases
Program
Epidemiology
Genetics
Inflammatory eye
disease
Develop educational
initiatives in research
Inter-specialty based
research programs
Research website and
news letter
Year 1
Year 2
Year 3
Year 4
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Research Strategic Plan
Challenges
•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!
Advancing Kidney Stone Management
A Collaborative Approach
Brian R. Matlaga, M.D., M.P.H.
James Buchanan Brady Urological Institute
Johns Hopkins Medical Institutions
Baltimore, Maryland
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 Lithotripsy
in 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 Changing
The 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 Changing
The 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 preformed 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