NCI Current/Planned

Initiatives and Resources:

Imaging as a Biomarker

Robert J. Nordstrom, Ph.D.

Program Director
Cancer Imaging Program
NCI

May 14,2010
 Presentation Outline

Ø Introduction
Ø Cancer Imaging Program Initiatives
Ø Quantitative Imaging Network
Ø Translational Research
 The Value of Imaging

Reliable image data could lead to:



Ø Earlier go/no-go decisions on

compounds
Ø Smaller clinical trials with fewer
patients
Ø Faster regulatory approval


Cost Savings
Reduced Time to Market
 Imaging as a Biomarker

Ø Definition: Biomarkers are

characteristics that are objectively
measured and evaluated as indicators of
normal biological processes, pathogenic
processes, or pharmacologic responses
to therapeutic intervention.

- The Biomarker Consortium
 Imaging as a Biomarker
Ø Multi-step process:
o Engage stakeholders
§ Academia, industry, pharma, federal
agencies
o Create consensus on quantitative
imaging concerns and solutions
o Encourage adoption of more
standardized methods
§ Data collection
§ QA/QC
 Imaging Biomarkers

Ø To meet the clinical practice and

research biomarker needs, image
data must be trustworthy:
o Quantitative
o Accurate
o Reproducible

 Imaging Biomarker Challenges

Ø Need rigorous assessment, validation

and comparison of imaging
methods.
o Clinical trials at different levels.
o Consensus of validation methods.
Ø Need quantitative markers
o RECIST is good. What’s better?
o Functional response indicators

Imaging Biomarker Challenges

Ø Change radiology culture toward

more quantification,
standardization.
Ø Dissolve oncologists concerns over
imaging.
Ø Exploit related data from multiple
sources.
The Cancer Imaging Program

Cancer Imaging

Mission: Promote and support cancer-related basic, translational,

and clinical research in the imaging sciences and technologies, and
the integration and application of these imaging discoveries and
developments to the understanding of cancer biology and to the
clinical management of cancer and cancer risk.
 The Cancer Imaging Program

Cancer Imaging

Clinical Trials Branch Image-Guided Interventions Branch

Imaging Technology Development Branch

CIP Initiatives
 Unsolicited Applications

Ø PA-10-067 for R01 investigator-

initiated applications.
 http://grants.nih.gov/grants/guides/pa-files/PA-10-067.html
Ø Circumscribed, basic or clinical
research.
Ø 5 years or less
Ø <$500k direct costs
 CIP/NCI Initiatives

Ø American College of Radiology Imaging Network

(ACRIN)
o RFA-CA-07-505

o Primary Scientific Aims

§ Strategies for imaging surveillance of
populations at high risk for cancer.
§ Imaging approaches to the characterization of
disease in order to guide targeted therapy.
§ Biomarkers of therapeutic response for
implementation in clinical trials and clinical
care.
§

o http://www.acrin.org

 CIP/NCI Initiatives

Ø Reference Image Database to Evaluate Response

(RIDER)
o Development of web-accessible public resource of
image data
o Permit comparison of different imaging and analysis
methods for measurement of therapy response
o NCI image archive
o Consensus papers published
§ Translational Oncology, Vol. 2, No. 4 195 – 197, 198 – 210,
211 – 215, 216 – 222, and 223 – 230, (2009).


 RIDER Web Site
https://wiki.nci.nih.gov/display/CIP/RIDER
 CIP/NCI Initiatives

Ø Academic – Industrial Partnership R01:

o PAR-10-169
o Accelerate translational research in in vivo animal or
human subject imaging to solve a targeted cancer
problem by creating multidisciplinary teams of
academic and industrial researchers.
o Encourage more rigorous methods of translation and
imaging validation.
o Expiration date: May 2013
 http://grants.nih.gov/grants/guide/pa-files/PAR-10-
169.html
o
 CIP/NCI Initiatives

Ø Network for Translational Research (NTR):

Optical Imaging in Multimodal Platforms U54:
o Develop, optimize and validate next-generation
multimodal imaging platforms for targeted cancer
problems.
o Molecular imaging and probe development.
o Optical imaging methods coupled with more traditional
imaging methods
§ Increased sensitivity & specificity
§ Comparison of imaging methods for methods validation.
o http://imaging.cancer.gov/programsandresources/speciai
zedinitiatives/ntroi
o
 CIP/NCI Initiatives

Ø Quantitative Imaging for Evaluation of Response

to Cancer Therapies U01:
o Quantitative Imaging Network (QIN)
§ Support multi-disciplinary research teams to develop
quantitative imaging methods to measure response to
therapy.
§ Commercial imaging platforms.
§ Optimization and validation of software tools in ongoing
clinical trials
§ Provide image meta-data, clinical outcome data, and
measurement results as a public resource.
§ Phantoms.
§ http://grants.nih.gov/grants/guide/pa-files/PAR-08-225.html
§
 The Quantitative Imaging
Network (QIN)
Ø PAR-08-225; a U01 Mechanism
Ø Submission dates:
o February 5, June 5, and October 5
Ø Four rounds have been reviewed
Ø Next round will be reviewed in June
Ø Four more rounds
Ø Expiration: September 2011

 QIN Application Timeline

Oct 08 Feb 09 Jun 09 Oct 09 Feb 10

12/1 10/3 11/2 9/(2) 12/(?) Jun 10 Oct 10 Feb 11 Jun 11

Release Date Expires

August 2008 Sept 2011

More Opportunities

Success Rate: 6/33 = 18%

 Purpose of the QIN Program

Ø Promote research on quantitative imaging

of cancer tumor response to therapies.
Ø Goal: Facilitate clinical decision making.
Ø Our hypothesis: Optimized and validated
quantitative imaging techniques are
needed on commercial platforms for
large scale multi-center multi-platform
clinical trials.
Ø
 The Ideal “Model” Program

Ø Investigator wishes to develop quantitative tools

for a clinical imaging problem.
Ø Builds algorithms and processes by using validated
database images (retrospective).
Ø When tools appear to be working, investigator will
couple to an ongoing and appropriate clinical
trial to validate the tools prospectively.

Of course, there are countless variations on this theme.

Current & Planned QIN Status

Ø Currently, 6 charter members

o 1 Face-to-face (kick-off) meeting
Ø Planned, over 12 members by 2011
Ø Broad range of imaging modalities
o CT and PET/CT
o SPECT
o MRI, DCE-MRI, DW-MRI
Ø Phantom studies
Ø Longitudinal studies
Ø Database development and sharing
 Clinical Trials

Ø Phase I,II, and/or III

Ø Ongoing or planned trials must be
identified: Trials not supported by
QIN
Ø QIN will support additional images
beyond trial protocol (IRB
approval)
The Charter Members of QIN
 Organ Sites Being Studied in
QIN
Ø Lung
Ø Breast
Ø Prostate
Ø Head & Neck
Ø Colon
 Network Organization
Technical
Advisory
Steering Committee

Technical
Teams
….
Working Groups
 Steering Committee
Organization
Ø Rotating annual chair
Ø Monthly teleconference meetings
Ø Organization
o Two representatives from each team
§ PI plus an alternate

§ Only 1 vote for team

o Two program staff

§ Only 1 vote

o Lead Program Director

§ No vote

o Others (non-voting) may be invited to participate, depending on

the subject of the meeting.
Ø Two yearly face-to-face meetings
 Working Groups

Ø Provide “open science” means to address common

issues.
o Data sharing, QC issues
o Software tools, clinical involvement
Ø Network-wide groups.
o Each team contributes members to each
working group. A chair is chosen annually.
o Consensus-building groups.
o Will hold separate monthly meetings
(autonomous).
o Avoid placing PI on working groups.
 Communication Within QIN

Ø Steering Committee meetings provide

team-to-team communication.
Ø Regular meetings within each team
provides team-to-working group
communication.
Ø Chairs of working groups can participate
(non-voting) in steering committee
meetings.
 Working Groups

Ø Data Collection
Ø Image Analysis & Performance
Metrics
Ø Bioinformatics/IT & Data Sharing
Ø Clinical Trial Design & Development
Ø Outreach & Collaboration
 External Advisory Committee

Ø Not yet implemented in QIN

Ø Chosen by the Steering Committee
Ø 4 – 6 members; multi-year term
Ø Representatives from:
o RSNA (QIBA), SNM, AAPM, ISMRM, etc.
o FDA, NIST
o Industry, Pharma
o Clinical Trial Groups
 Where These Programs Fit
Within Translational Research
Ø Definition
o Research that transforms scientific discoveries
arising in the lab, clinic, or population into
new clinical tools and applications that
reduce cancer incidence, morbidity, and
mortality.
Ø Need translational research milestones and
metrics.
 The Translational Pipeline
15 – 20 years

IND / IDE
Feasibility Testing Submission FDA Submission
Concept & Design Validation

Basic Research Standardization Standard of Care

Prototyping Clinical Studies

$ Millions to 100’s of millions

 The Translational Pipeline

IND / IDE
Feasibility Testing Submission FDA Submission
Concept & Design Validation

Basic Research Standardization Standard of Care

Prototyping Clinical Studies

Research
Development
Clinical
 The Translational Pipeline

NTR U54

Academic/Industrial R01 ACRIN

R01 Research Quick Trials

QIN U01

Research
Development
Clinical
 Future Initiatives

Ø Uncertain, at best
o Funding uncertainties
o Search for new NCI director
Ø Best advice: Stick with status quo
Ø Good grantsmanship will be required
even more
o Talk to Program Staff often
Time for Questions?