In 2005, an estimated 172,570 Americans will be diagnosed with lung cancer, and
there will be an estimated 163,510 deaths, representing 13 percent of all
incident cancers annually and 29 percent of all cancer deaths. Lung cancer
remains the leading cause of cancer mortality for both men and women in the
United States, killing more patients than the next five most common cancers
combined. These sobering statistics are compounded by the inescapable fact that
there have been only the most modest of improvements in five year survival
rates. The Lung PRG report noted that progress will continue to be limited in
the future by the absence of a well-defined mechanism and infrastructure to
enroll patients in trials and systematically collect and archive tissue.
Progress has also been limited in applying new therapeutic approaches for
patients with stage I and II lung cancer, in verifying the clinical utility of
molecular predictors of prognosis or response to treatment, and in being able
to rapidly and efficiently perform phase I and II studies of new targeted
therapies with defined biologic endpoints. It is thus clear that we must take
drastic and bold actions if we are to positively impact these statistics.
Accordingly, the 2015 Vision of the I2 Lung Cancer Team is to
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Significantly and measurably reduce the morbidity and mortality attributable to
lung cancer by 2015.
In order to accomplish this Vision, the integrated plan targets 3 critical
strategies:
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Reducing the risk for lung cancer by achieving more effective tobacco control
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Improving the likelihood of cure by accomplishing earlier detection and
treatment of early lung cancer and pre-cancer
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Introduction of novel targeted therapies through tight coupling with ongoing or
planned biology initiatives.
In order to implement these critical strategies, we are also proposing that
lung cancer be a major focus of activity for:
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Genomic and proteomic research
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In vivo imaging
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Biospecimen acquisition and analysis
Our implementation plan has been crafted as a comprehensive approach that does
not duplicate existing or planned initiatives. Rather, we will build upon those
initiatives with a lung-specific focus, and for those initiatives without such
a focus, we request redirection of efforts to include a lung cancer focus. We
are not suggesting that all existing activities related to lung cancer
pre-clinical and clinical research be included in the scope of the I2 Lung
Team. Instead, we strongly suggest that the Team focus on high opportunity and
potentially high return strategies. We believe that the efforts of the Team
should not be diverted by the incorporation of incremental strategies but
should instead focus on transformational strategies.
Finally, we recognize the unique opportunity for the Lung Cancer Integration
and Implementation Team to develop strategic alliances with the two parallel
Integration and Implementation teams focused, respectively, on Imaging and
Bioinformatics.
There is no single operational focus within NCI dedicated for lung cancer
initiatives in prevention, diagnosis and therapy. We therefore propose to
establish a "Virtual Distributed Corporate" model (I2 Lung Cancer) to manage
the business plan. In order to operationalize this business model, we also
propose to create the position of Program Director for I2 Lung Cancer, a
nationally recognized lung cancer clinical or basic researcher, with extensive
administrative experience. Alternatively a small tightly integrated team,
appointed by the NCI Director, could be constituted to serve in this capacity.
The activities necessary to accomplish the proposed outcome(s) will be
implemented and accomplished through NCI Divisions, Programs, and Branches
chosen as "best of breed" with proven and documented areas of expertise, and
accomplished using a variety of funding mechanisms.
We also propose the immediate creation of a Lung Cancer Scientific Advisory
Committee (LCSAC) to serve as an advisory body to provide scientifically
grounded advice to the NCI Director (through the Program Director of I2 Lung
Cancer) on the status of cross-cutting lung cancer research activities across
research entities. The goal is to adopt a comprehensive approach to the lung
cancer problem by evaluating the success of existing efforts in lung cancer
biology, screening, prevention and therapy; and to catalog and review novel
concepts and data regarding new agents, diagnostics, and emerging technologies
emanating from the Lung SPOREs (Specialized Programs of Research Excellence),
NCI program project (P01) applications and other research initiatives. This
committee would also identify critical questions and unmet needs across the
spectrum of lung cancer research.
The LCSAC will be led by the Program Director of the I2 Lung Cancer. The
committee would include a broad and appropriate representation of about 12 to
15 intramural and extramural scientists representing the various NCI Divisions,
research entities (SPOREs, cancer centers, cooperative groups, community
oncologists, regulatory agencies, industry, and patient advocacy groups) and
disciplines (clinicians, biologists, epidemiologists, behavioral scientists
imagers, tobacco addiction and tobacco control, experts in
pharmacokinetics/pharmacogenomics and specialists in molecular diagnostics).
The committee will be appointed by the Director of the NCI, and will meet in
person at least twice a year initially and by monthly teleconferencing.
In order to achieve synergy with the Clinical Trials Working Group (CTWG)
recommendations, we propose to create a Lung Cancer Scientific Steering
Subcommittee constituted as a subcommittee of the proposed LCSAC to provide
advice to the NCI Director on the conduct, oversight, and implementation of
lung cancer clinical trials across the Institute, to involve the broad oncology
community, facilitate open communication and increase the involvement of
patients and community oncologists in clinical trials.
We also recommend an augmentation of the current Cancer Intervention and
Surveillance Modeling Network (CISNET) to derive applicable metrics by which
the I2 Lung Team will measure its impact on both patient and societal levels.
Proposed Initiatives
Fewer than 40% of providers currently recommend specific treatment for tobacco
use. Furthermore, even with combined behavioral and pharmacologic
interventions, quit rates are no more than 15-25%. Therefore, the NCI
integrated plan proposes a multi-pronged transdisciplinary approach to improve
the success rates of smoking cessation and prevention in order to have a
significant impact on the 2015 lung cancer goals. Specifically, initiatives
that address both the etiology and treatment of tobacco use are proposed:
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Genetics of Nicotine Dependency: Advance the discovery of how tobacco
dependency occurs and the linkages between biology and behavior by exploring
the role of gene variants in the nicotine dependent phenotype. The goal is to
more effectively prevent tobacco use and increase the chances of successful
cessation through identification of drug targets.
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Targeted Pharmacotherapy: Fund research on the development of molecularly
targeted therapies to improve the success rate of the treatment of tobacco use
and dependence.
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Imaging research: Support functional neuro-imaging studies to characterize the
neural substrates of addiction.
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Promote testing of nicotine vaccines that have a potential role in treatment of
addiction and also may provide a future opportunity to prevent addiction.
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Liaison with Nanotechnology Initiative for targeted delivery of novel
nanoparticle-based therapies.
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Dissemination/Implementation of Effective Cessation Interventions: Support
efforts to optimize the delivery of effective treatments to clinical and
community environments - along with feedback mechanisms so that the delivery
process serves as an additional component of discovery.
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Policy: Support analyses on the role of policy change (e.g. clean indoor air
laws, coverage of medications by health plans, tobacco tax increases) on
tobacco use uptake, dependence and cessation for more strategic decisions on
what interventions can have the greatest impact.
Nearly 60% of patients diagnosed with lung cancer die within one year of their
diagnosis and nearly 75% die within two years. Therefore this plan highlights
the need for effective and validated early detection techniques, and builds
upon the lung specific projects of I2 Imaging recommendations to leverage
several of its lung cancer-specific objectives at substantial cost savings.
Proposed Initiatives
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Allocate resources for the maintenance and oversight of the American College of
Radiology Imaging Network (ACRIN)/National Lung Screening Trial (NLST) Specimen
Biorepository both during and after the period of the trial to oversee the
quality and integrity of samples, development of seamless integration of
biospecimens with all associated metadata, and ensure the optimal uses of these
depletable archives for the most promising molecular research. Also, fund
advertising of the repository to the scientific community.
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Fund collection of remnant tissue specimens from participants with proven lung
cancers diagnosed within the ACRIN-NLST initiative, and incorporate biospecimen
and imaging data within the Image Archive being established.
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Fund collection of pathology tissue from lung cancer cases diagnosed in the
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) Trial.
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Promote standardized procedures and employ technologies that have demonstrated
utility and feasibility through peer-reviewed publications. Such an initiative
could potentially be part of the proposed NCI-wide Molecular Biomarkers
Initiative, once approved.
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Bootstrap on existing initiatives that promote the development and validation
of in vivo imaging in early lung cancer detection.
Targeted drug development is impeded because only a fraction of the molecular
targets involved in lung tumorigenesis has been identified in small numbers of
subjects. With large-scale sequencing now a viable tool for discovery, a unique
opportunity exists to create a well-defined strategy to systematically identify
all the genomic and epigenomic lesions associated with lung cancer. These
genetic insights and advances in biology will drive new drug development and
help in monitoring of therapy response. Success requires coordinated efforts to
improve target identification, and the development of functional imaging
agents, and novel clinical trial methodologies.
Proposed Initiatives
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Identify all the genomic and epigenomic lesions associated with lung cancer in
coordination with the Human Cancer Genome Project Initiative proposed by Drs.
Eric Lander and Lee Hartwell. Launch parallel lung-specific projects as proof
of principle studies to systematically characterize lung cancer and transform
treatment, by improving selection of therapeutic targets with higher efficacy
and decreased side effects; identification of patients most likely to respond,
rational development of combination therapies; resolution of cancer into
homogeneous groups; improved understanding of the molecular events triggered by
carcinogenic exposures, and refined estimates of susceptibility.
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Define the contribution of inflammation, infection, and injury to lung
carcinogenesis, with the aim of identifying appropriate targets for cancer
treatment and prevention. It is recognized that the microenvironment may also
be an important factor in developing therapeutic approaches.
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Speed the translation of above findings to clinical care and propose an
alternative drug delivery system initiative for lung cancer treatment or
prevention, synergizing with the NCI Nanotechnology initiative. The goal is to
promote delivery of multiple payloads for combination therapy, and use of
reporting systems to target receptors and avoid systemic toxicities,
potentially allowing use of agents at concentrations previously unattainable.
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Advance the science of imaging response assessment with molecular imaging
technologies that directly reflect response to targeted therapies and by
providing uniform, high quality imaging acquisition, quality control, and
analysis and creation of a lung cancer meta-directory within the conduct of
clinical trials.
Proposed Distribution of Lung Cancer Dollars:
Approximately 8 million dollars each year over the next five years plus an additional 40 million dollars for leveraged activities.
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