sidney kimmel comprehensive cancer center (skccc) overview william g. nelson, m.d., ph.d. director

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)

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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

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


Why is this?

• Our collective experience with URS– Superior for distal ureteral stones


• Our collective experience with URS– Superior for proximal ureteral stones


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


• 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


• 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

sidney kimmel comprehensive cancer center (skccc) overview william g. nelson, m.d., ph.d. director

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