Key Dates

Related Announcements

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

Issued by

National Institute of Dental and Craniofacial Research (NIDCR)

National Cancer Institute (NCI)

Purpose

Purpose

Diagnosing and treating lesions of the oral cavity and oropharynx are challenging due to reliance on subjective analyses of clinical features and histopathological diagnostic criteria. High resolution and quantitative tools are needed to enhance the precision of diagnostic approaches for oral pathologies to guide options for treatment. This Notice of Special Interest (NOSI) is to encourage research projects that develop, adapt, optimize, and validate imaging-based applications and data analysis tools to enhance oral disease detection, diagnosis, and treatment. The long-term goal is to facilitate translation of research findings into clinical practice, paving the way for personalized health care through objective measures that promote accurate and timely diagnosis, targeted therapies, and improved patient survival and quality of life.

Background

Pathological lesions in the oral cavity and oropharynx are highly diverse. They include frictional and ulcerative lesions, bacterial and fungal infections, complications of local and systemic conditions, and malignancies. In current clinical practice, differential diagnosis is based on oral examination that includes visual inspection and palpation; however, subtle lesions can pass undetected. Although some innocuous lesions may be readily diagnosed based on their clinical presentation alone, others are not as easily differentiated. It is difficult to distinguish among benign, premalignant, and malignant lesions because many mucosal conditions have a similar appearance. For example, oral cancer may present initially as a small white or red lesion, but diagnosis is often delayed until the lesion becomes unresolved. As a result, oral cancer has one of the lowest five-year survival rates (50% or less) among the major cancer types. Furthermore, dysplasia or micro-invasive carcinoma can be difficult to detect because they can be present in clinically normal-appearing mucosa.

Successful therapeutic management of oral mucosal lesions depends on a definitive, accurate, and timely diagnosis. Despite general accessibility of the mouth during physical examination, oral lesions are often not diagnosed until late stages of disease. Histological analysis of biopsy samples is the gold standard technique for diagnosis of lesions that cannot be differentiated based on clinical appearance alone. The standard approach relies on gross microscopic assessment of atypia that may not always reflect the underlying pathology or disease condition. Histopathological analyses are often complicated by low specificity and sensitivity, in addition to high intra- and inter- observer variability due to reliance on subjective and non-quantitative measures. Results may be further complicated by the quality of the biospecimens and inconsistency in sample preparation. The use of highly subjective measures to diagnose oral lesions can be dangerous because serious conditions, such as oral manifestations and complications of uncontrolled systemic diseases and cancers, may be overlooked. The lack of effective diagnostic and quantitative methods that can replace or complement conventional histopathology has clearly limited the ability of clinicians to consistently and accurately categorize oral pathologies. As a result, treating pathological conditions of the oral cavity is often challenging. New and improved methods are required to detect and analyze early mucosal changes to optimize treatment planning and reduce morbidity and mortality.

Research Objectives

The specific scope of this NOSI is to address challenges of detection, diagnosis and treatment of lesions in the oral cavity and oropharynx. The National Institute of Dental and Craniofacial Research (NIDCR) recognizes the unmet need for more sensitive and quantitative tools for management of oral diseases. A few simple techniques for detecting precancerous and early malignant lesions have been developed over the years to supplement oral examination. However, the utility of these methods is still limited due to their low specificity (e.g., fluorescence, toluidine stain) and high false-negative rate (e.g., brush biopsy for cytology). Considerable progress has been made in precision imaging technologies and methods for the acquisition of anatomical, functional, and molecular imaging data. Improvements in tools for data analyses, display methods, and reporting structures would enable quantification of physiological structures and biological functions for monitoring dynamic biological processes at the cellular and subcellular scales. This NOSI will support research that applies these technological advances to improve diagnosis of oral diseases and lead to more precise, personalized treatment.

This NOSI invites applications that propose to adapt, optimize, and validate existing imaging systems or develop new image-based methodologies and analytic tools capable of improving early detection, diagnosis, and targeted treatment of oral diseases and conditions. Studies may include single or multi-modality in vivo imaging and spectroscopy systems, image-guided intervention and drug delivery systems, image analysis, and molecular imaging probe design and development. This NOSI will support preclinical studies, and studies that use clinical samples or perform secondary analysis of imaging and metadata from existing clinical trials as needed to validate the imaging tools and methods under investigation.

Examples of research projects may include, but are not limited to the following:

• Leverage advances in image capture, processing, contrast, resolution, and molecular identity to help locate lesions that are not detectable by currently used approaches, to enhance early detection of mucosal changes prior to their progression to a clinical lesion state, and to characterize and grade oral lesions and conditions in determining the extent and severity of disease.
• Develop image-derived classifiers or biomarkers capable of reflecting structural and morphological changes within tissues for screening and monitoring oral lesions, and for tracking lesion progression over time, mapping spatial heterogeneity within the lesion, and independent evaluation of different lesions within an individual.
• Combine imaging methods for visualization of oral lesions with molecular biomarkers to improve precision and accuracy of diagnosis and treatment.
• Develop multimodal, multiparameter, and multiplex imaging technologies that will lead to new ways of studying oral biology and diseases.
• Optimize single cell imaging to define cellular/tissue heterogeneity in oral lesions at initial appearance and during disease progression.
• Develop imaging methodologies to assess dynamic or longitudinal evaluation of molecular characteristics and cell populations of oral cancer and its microenvironment.
• Develop intraoperative image-guided biopsy, surgery, and ablative therapies to optimize disease management.
• Develop theranostic imaging agents that target biological pathways and processes to aid in identifying early markers for oral lesions and conditions integrated with drug delivery and other therapeutic interventions as well as monitoring therapeutic responses and complications.

Projects that are not appropriate for this NOSI include:

• Develop reagents (e.g., probes, contrast agents) without using them in an imaging application to address a defined oral pathological problem.
• Focus on hardware development, computer software use or training, data generation, data mining, data storage, or computational modeling and simulation without applying them in an imaging-based application to address a defined oral pathological problem.
• Biomarker discovery.

Scientific interests of partnering NIH Institute, the National Cancer Institute (NCI) are delineated below:

The National Cancer Institute (NCI): NCI is interested in R01 research projects using in vitro and/or in vivo imaging for the study of soft tissue cancerous lesions of the head and neck area (e.g., tumors of the oral cavity, oropharynx, hypopharynx, larynx, trachea, nasal cavity and paranasal sinuses, salivary glands, and mucosal melanoma) in relation to early detection, prediction, diagnosis, prognosis, and image-guided treatment, as well as evaluation of cancer aggressiveness and response to treatment. NCI will support projects where proof-of-principle of the proposed technology or methodology has already been established and supportive preliminary data are available. Research investigation that explores combination of imaging studies with pathologic and multi-omics approaches including molecular biomarkers found in liquid biopsies or machine learning approaches applied directly to an in vitro image based application to address a defined oral pathological problem are highly encouraged.

NCI also encourages applications to develop context- appropriate tools for use in low- and middle-income countries (LMICs), given that oral cancer burden is high in other parts of the world, especially in Asia. Incidence is driven by tobacco smoking and alcohol use, but also smokeless tobacco and betel quid, which are major carcinogenic exposures in LMICs. Populations in LMICs can benefit from new approaches for discriminating pre-cancer and cancer from non-malignancy oral lesions as well as approaches for secondary prevention/treatment of pre-cancer that can be performed by health workers at the point-of-care.

Applicants are strongly encouraged to contact the Scientific/Research contacts listed in Section VII to discuss the relevance of the proposed studies before submitting the application.

Application and Submission Information

This notice applies to due dates on or after October 5, 2021, and subsequent receipt dates through September 10, 2024.

Submit applications for this initiative in response to one of the following funding opportunity announcement (FOA) or the subsequent reissued equivalent through the expiration date of this notice:

• PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the parent funding opportunity announcement must be followed, with the following additions:

• For funding consideration, applicants must include NOT-DE-21-010 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Zhong Chen, MD, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-7083
Email: zhong.chen@nih.gov

Orlando Lopez, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
(301) 402-4243
Email: orlando.lopez@nih.gov

For inquiries related to in vitro imaging, please contact

Miguel Ossandon, M.S. (for In vitro imaging)
National Cancer Institute (NCI)
Telephone: 240-276-5680
Email: ossandom@mail.nih.gov

For inquiries related to in vivo imaging, please contact:

Yisong Wang, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-620-0690
Email: Yisong.wang@nih.gov

For inquiry related to globa health, please contact:

Paul C. Pearlman, Ph.D.
Center for Global Health
National Cancer Institute (NCI)
Telephone: 240-276-5354
Email: paul.pearlman@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov