R01CA249016

Radiomics and Pathomics to Predict Upstaging of DCIS - Abstract

Ductal carcinomas in situ (DCIS) of the breast are a heterogeneous group of neoplastic lesions that are usually detected by screening mammography. The workup generally includes a percutaneous (core) biopsy (BX) for histologic confirmation, followed by multiparametric MRI (MPMRI), breast-conserving excision, and adjuvant radiation. Approximately 20-25% of patients with core BX-confirmed DCIS are upstaged to invasive carcinoma upon pathology of resected tissue. Foreknowledge of this would dictate a more aggressive surgical intervention, including sentinel node biopsy for axillary staging. Furthermore, another 20-25% of patients are judged to have low-risk disease, and current thought is that such women may have better outcomes in an active surveillance setting, and this is being tested in clinical trials.

The ultimate goal and the overall impact of this project is to use machine learning to identify biochemical (SA1) or imaging (SA2) biomarkers, as well as their combination (SA3), to discriminate indolent from aggressive DCIS, as determined by upstaging upon excisional biopsy. The major hypothesis to be tested in this work is that hypoxia and expression of hypoxia-related proteins (HRPs) can discriminate aggressive from more indolent DCIS, and that this can be used for decision support. Expression of HRPs is optimally characterized by immunohistochemistry (IHC), and we have deployed methods for multiplexed IHC, as well as methods for advanced analytics using machine learning (Pathomics). We have also shown that hypoxic habitats within breast cancers can be identified from MPMRI using machine learning (Radiomics). We thus propose to use Pathomics of core biopsies and Radiomics of MPMRI to determine the presence and extent of hypoxic habitats in DCIS prior to surgery to predict subsequent upstaging after surgical resection.

This work will be performed in Aim 1 for Pathomics and Aim 2 for Radiomics, and Aim 3 will develop combined radio-pathomics predictors. Each aim will contain:

(A) Retrospective arms for training, tuning, and testing; and
(B) Prospective internal and external cohorts for rigorous validation.

For the retrospective studies, we have identified 604 cases wherein women with DCIS obtained core BX, MPMRI, and surgery with pathology at Moffitt in the last 10 years. Internal prospective studies will accrue approximately 6 women/month who have consented to the Total Cancer Care® protocol and who have their complete workup at Moffitt. External validation cohorts will be accrued at UCSF and at Advent Health.

At the end of this work, we will have developed a risk model for DCIS that can be deployed prior to surgery to guide decisions along the spectrum from active surveillance at one end to more extensive surgical intervention at the other. This is expected to lay a foundation for subsequent interventional trials. Additionally, the inclusion of hypoxia as a central hypothesis has high potential to illuminate components of the natural history of this disease.

H. Lee Moffitt Cancer Center And Research Institute Hospital

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Tampa, Florida 336129497 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 382% from $699,147 to $3,369,053.