NIH/NCI – Approaches to Identify and Care for Individuals with Inherited Cancer Syndromes (U01 Clinical Trial Required)

August 13, 2018 by School of Medicine Webmaster

This Funding Opportunity Announcement (FOA) is associated with the Beau Biden Cancer MoonshotSM Initiative that is intended to accelerate cancer research. The purpose of this FOA is to increase case ascertainment and appropriate follow-up care, optimizing the delivery of evidence-based healthcare for individuals at high risk of cancer due to an inherited genetic susceptibility. Specifically, this FOA targets the following area designated as a scientific priority by the Blue Ribbon Panel (BRP) Recommendation G:

“To realize the potential of cancer prevention and early detection in our nation, NCI should sponsor an initiative to improve the current state of early detection, genetic testing, genetic counseling, and knowledge landscape of the mechanisms and biomarkers associated with cancer development. This initiative should include demonstration projects that will show how cancer screening programs can simultaneously save lives, improve quality of life, and reduce healthcare costs.”

This Funding Opportunity Announcement (FOA) invites multiple Program Director/Principal Investigator (multi-PD/PI) U01 application for projects aimed at identifying best practices to improve case ascertainment and follow-up care of hereditary cancers, with the goal of improving prevention and detection.

Beau Biden Cancer Moonshot Initiative

NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot’s ambitious goal of making a decade’s worth of progress in cancer prevention, diagnosis, and treatment in just 5 years, now called the Beau Biden Cancer MoonshotSM Initiative.  The BRP was charged with assessing the state of the science in specific areas and identifying major research opportunities that could uniquely benefit from the support of the Cancer Moonshot and could lead to significant advances in our understanding of cancer and in how to intervene in its initiation and progression. The recommendations focused on areas in which a coordinated effort could profoundly accelerate the pace of progress in the fight against cancer and were not intended to replace existing cancer programs, initiatives, and policies already underway. The BRP final report was approved by the National Cancer Advisory Board and included a recommendation for Cancer Prevention and Early Detection in Individuals at High Risk for Cancer. The 21st Century Cures Act was signed into law in December 2016 dedicating new funds to support efforts associated with the Beau Biden Cancer MoonshotSM Initiative, including support for this FOA.


It is estimated that up to 10% of all cancers may be associated with an inherited genetic mutation that contributed to the risk of developing cancer. Clinical genetic testing for selected inherited cancer syndromes has been available since the 1990s. Since then, research and technological advances have identified multiple genes associated with numerous hereditary cancer syndromes. Clinical testing has evolved from a focus on one gene or a limited set of genes to panel tests that cover a wide variety of genes that have reported associations with one or more cancer types. During this time period, insurance coverage for genetic counseling and testing has increased and, for the most part, is based on family history criteria in addition to personal history of cancer. Despite the availability of genetic testing, a substantial number of those at risk are not identified and thus may not benefit from available prevention and early-detection approaches.

The benefits of genetic counseling and testing are that risks of cancer are clarified and appropriate preventive follow-up care is provided to high risk individuals. In addition, for those diagnosed with cancer, the results may have implications for treatment as well as prevention of other cancer risks. These benefits accrue to both the individual and the individual’s family. While optimum approaches based on personal and family history will increase ascertainment, these are selective screening approaches that will identify many, but not all, who carry a mutation. Small family size or incomplete or unknown family history reduces the ability to identify affected families. Tumor-based tests, in addition to identifying cases after the cancer has occurred, are not 100% sensitive and may not be done on all cancer cases. Development of innovative approaches to identify individuals at risk, expansion of family-based testing utilization and optimization of follow-up healthcare management are critical elements for improving health outcomes of individuals with an inherited susceptibility to cancer.

Approaches for case ascertainment and appropriate follow-up healthcare of families and affected individuals should have a broad focus on multiple hereditary cancer syndromes. Genes are associated with multiple cancer types, and a cancer type may be associated with multiple genes. For example, hereditary breast-ovarian cancer syndrome associated with BRCA1 and BRCA2 genetic alterations is associated with an increased risk of developing breast and ovarian cancers as well as aggressive prostate, pancreatic, and other cancers. Lynch syndrome is associated with an increased risk of colon, endometrial, ovarian, urologic, and other rare cancers. Thus, in practice, multiple syndromes and multiple genes are considered when pursuing testing. Despite the advances in the types and availability of genetic testing, opportunities to counsel and test individuals at high risk of cancer mutations are often missed, especially among low-socioeconomic, minority groups and other underserved populations.

With the widespread availability of multi-gene panel tests, research should address the best methods to identify, counsel and manage individuals for a broad array of cancer family syndromes. Knowledge gaps exist in how to best deliver counseling, testing and follow-up care across diverse populations, for example, those with low income and the uninsured, and across multiple healthcare settings such as rural areas, private or solo practices, community hospitals, and larger healthcare systems. A variety of effective screening modalities tailored to specific populations and healthcare settings are required to maximize case ascertainment, prevent cancer, and improve cancer outcomes among those at high risk of cancer, while minimizing harms. These approaches should be tested to determine best practices tailored to the appropriate population and healthcare setting. Widespread population-based implementation of genetic testing must also address psychological, biobehavioral and ethical questions and concerns such as adequacy of informed consent to address both benefits and harms, communication of risks, outreach to relatives, adequate follow-up care, and potential harms such as discrimination in workplace and life insurance.

To address these challenges and optimize identification and care for individuals with inherited cancer syndromes, innovative approaches are needed across a variety of clinical care settings with outreach to racially/ethnically, socioeconomically, and geographically diverse populations. Although genetic testing for inherited cancer syndromes has been available in the clinical setting for over 20 years, there remain many gaps in our knowledge and the process of care delivery that demand devoting our energies and creativity to benefit the families at risk. This Funding Opportunity Announcement (FOA) aims to identify best practices to improve case ascertainment of hereditary cancers, with the goal of improving prevention and detection by inviting U01 applications for projects focused on problems such as those described below.

Specific Areas of Research Interest

Applications submitted to this FOA should focus on methods to increase case ascertainment and appropriate follow-up care to optimize the delivery of evidence-based healthcare for individuals at high risk of cancer due to an inherited genetic susceptibility.

Specifically, the FOA aims to foster and advance scientific efforts focused on:

  1. developing and testing strategies to increase case ascertainment and follow-up care of hereditary cancers through different approaches;
  2. developing, testing, and adopting evidence-based healthcare delivery models for hereditary cancer prevention and detection;
  3. testing sustainable implementation strategies across at least two healthcare settings (e.g. community, academic, specialty practice, primary care, underserved urban, rural areas) representing diverse populations (e.g. race and ethnicity, socioeconomic status);
  4. studying the behavioral and psychosocial outcomes of counseling and testing on at-risk individuals and the impact on their follow-up care; and
  5. identifying sustainable healthcare delivery approaches.

To accomplish the overall goals, the FOA supports studies that develop and test care delivery models to:

  1. identify those at risk for hereditary cancer syndromes and provide appropriate genetic counseling, testing and evidence-based medical follow-up care and management across the healthcare continuum;
  2. focus on a variety of populations and healthcare settings; and
  3. provide counseling, test interpretation of results and guideline concordant follow-up care for high risk individuals and families.

To meet the research goals of this program, the U01 research applications will be expected to:

  • develop, test and adopt strategies to increase case ascertainment and follow-up care and improve evidence-based healthcare delivery for individuals with an inherited susceptibility to cancer across the continuum of healthcare from identification through follow-up;
  • focus on multiple hereditary cancer syndromes;
  • include at least two different healthcare settings (e.g., community setting such as Federally Qualified Health Centers and underserved areas such as urban and rural) representing underserved and diverse populations (e.g., race and ethnicity and socioeconomic status);
  • compare more than one strategy which may include usual care; and
  • focus on interventions that can be implemented and sustained.

Studies developing new genetic testing panels or risk models/decision tools or identifying new markers of risk are not included in this FOA.

Research questions of interest may include, but are not limited to, the following:

  • What strategies (e.g., targeting one or more of patient, family, provider and healthcare setting) and complementary approaches (e.g., tumor-based testing and family history-based ascertainment) will improve case ascertainment and follow-up care for individuals with an inherited susceptibility to cancer in a variety of healthcare settings (e.g., solo, small group or large group practices) across diverse populations (e.g., race and ethnicity and socioeconomic status)?
  • What are the best strategies for identification, counseling, testing, and clinical management of at-risk relatives in a variety of healthcare settings? How can these be widely adopted and sustained?
  • What are the best practices for provision and coordination of follow-up care for the proband and at-risk relatives, including care transitions (e.g., pediatric to adult), with the greatest impact on adherence?
  • How can technology be utilized to improve case ascertainment, counseling, testing, follow-up adherence, and registry development?
  • What are the optimum strategies to reach and provide follow-up care for diverse communities such as rural, racial/ethnic minorities and underserved/low-socioeconomic groups?
  • How can the behavioral and psychosocial impact of genetic testing and follow-up care on the individual and/or family be assessed and addressed effectively to optimize clinical decision making?
  • What strategies are needed to train and support a workforce capable of improving case ascertainment, cascade screening, and follow-up care in healthcare systems?

This FOA solicits multi-PD/PI U01 applications, with academic expertise to interpret and validate the success of the ascertainment and follow-up strategies. This approach will provide complementary multidisciplinary expertise to cover the multifaceted challenges of care coordination in this patient population. Although each U01 will be an independent entity, funded investigators will meet annually to share knowledge and data to inform care delivery to high-risk populations.

Deadline:  December 9, 2018 (letters of intent); January 9, 2019 (full proposals)


Filed Under: Funding Opportunities