R01CA256969

Optimizing Pancreatic Cancer Management with Next Generation Imaging and Liquid Biopsy - Project Summary:

Pancreatic ductal adenocarcinoma (PDA) will become the 2nd leading cause of cancer deaths in the United States by 2030. Most patients with PDA present with nonresectable/metastatic disease, and systemic chemotherapy is the anchoring treatment in these patients. Surgery is an option in the minority of patients (~30%) who present with localized disease, though most develop early recurrence after a highly morbid surgery due to occult metastases.

Therefore, neoadjuvant therapy (NAT) is an emerging standard approach, but is only beneficial if the selected systemic therapy is effective. Indeed, for all patients with PDA, metastatic or otherwise, the duration of effective systemic therapy is the most important factor in their survival.

There is a critical unmet need for accurate and timely assessment of treatment response in order to:

1) Get patients on effective systemic therapy as soon as possible and keep them on it as long as possible,
2) Expeditiously discontinue toxic, costly and ineffective therapies, and
3) Facilitate evidence-based personalized clinical decisions regarding curative-intent surgery.

Current management of PDA relies principally on computed tomography (CT) and tumor markers (CA19-9). However, these tools are not sensitive enough and are too slow for adjudicating benefit in patients with rapidly lethal metastatic disease, and for identifying suitable candidates most likely to benefit from surgery after NAT.

We now have cutting-edge tools for more precise quantification of disease burden at the molecular and metabolic levels. We have previously shown that mutant KRAS circulating tumor (CT)DNA can be detected with high sensitivity in PDA, tends to drop rapidly with effective therapy, and may be a more dynamic predictor of therapy response than CA19-9. We have also shown that metabolic imaging with hybrid integrated 18-fluoro-deoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) improves the detection of subtle metastases that are occult on CT, early response assessment in patients with nonresectable/metastatic PDA, and prediction of pathological response to NAT in patients who undergo resection.

Building on these promising results, we hypothesize that the appropriate combination of KRAS CT DNA and PET/MRI biomarkers will enable timely assessment of the clinical utility of therapy in PDA patients.

In Aim 1, we will define thresholds for early chemotherapy switch in unresectable/metastatic PDA using dynamic and quantitative changes in KRAS CT DNA and FDG PET/MRI biomarkers for use in future prospective trials.

In Aim 2, we will construct, test and validate a model of surgical benefit or futility for patients with potentially resectable PDA using dynamic KRAS CT DNA and FDG PET/MRI response data.

Our overarching goal is to integrate reliable biomarkers that can accurately guide therapy and enable precision medicine to improve outcomes of patients with this deadly disease.

Fred Hutchinson Cancer Center

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]

Seattle, Washington 981094433 United States

Single Zip Code

Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (R01 Clinical Trial Optional) (PAR-19-363)

Amendment Since initial award the End Date has been extended from 03/31/26 to 03/31/27 and the total obligations have increased 391% from $624,558 to $3,065,786.