R01CA257610

Integrated Radiomic and Liquid Biopsy Monitoring in SWOG S1802: A Phase 3 Therapeutic Trial for Metastatic Prostate Cancer - Abstract

Prostate cancer (PC) afflicts more men in the U.S. than any other malignancy and is the second leading cause of cancer death in this population. Recently, new therapies have improved survival in some men but have offered little benefit to others. Tissue profiling has identified genes and pathways associated with resistance and progression to advanced disease, but little is known about the dynamics of when and how such changes arise during therapy. Such insights can only be gained through minimally invasive monitoring that allows repeated disease profiling over time.

Our multidisciplinary team has developed and tested two such minimally invasive monitoring capabilities: the first is multi-parametric liquid biopsy, which involves streamlined analysis of blood samples that simultaneously measures PC-relevant cellular and molecular features from single circulating tumor cells and matched plasma cell-free nucleic acids. The second is radiomic analysis, which involves high-throughput extraction of quantitative metrics to identify PC-relevant phenomic imaging features. By synergizing the strengths of the two methods, our goal is to test the hypothesis that liquid biopsy and radiomic techniques can be applied jointly to monitor metastatic PC noninvasively over time, culminating in new prognostic and predictive tools to guide therapy.

To maximize the impact of our findings, liquid biopsy profiling and radiomic analysis will be integrated into Southwest Oncology (SWOG) S1802, a phase 3 prospective therapeutic trial for over 1200 men with newly diagnosed metastatic castrate-sensitive prostate cancer (MCSPC) treated with standard systemic therapy alone or in combination with definitive treatment of the primary tumor. Notably, SWOG and the other participating cooperative groups have reviewed and approved this proposal (see letters of support), and the requisite blood samples and CT scans are already being collected as part of the active protocol.

In this unique setting, we will pursue three specific aims. We will:

1. Use multi-parametric liquid biopsies to monitor the evolving cellular and molecular landscape of MCSPC during treatment in S1802.
2. Use radiomic analysis of CT scans to monitor the evolving radiographic landscape of MCSPC during treatment in S1802.
3. Integrate cellular, molecular, and radiomic data to develop composite disease monitoring models predictive of progression-free survival (PFS) and overall survival (OS).

Importantly, liquid biopsies and CT images will be matched within patients and analyzed at key inflection points over the course of the trial: at diagnosis, after initiation of systemic therapy, after definitive therapy, and at disease progression. In this way, the proposed work will illuminate when and how PC-relevant phenotypes arise during therapy, and how they relate to clinical outcomes. In particular, we will better understand which components of the liquid biopsy – circulating cells, plasma, or both – most accurately reflect the tumor's evolving molecular profile, which radiomic metrics most closely correlate with these molecular features and can serve as early cost-effective indicators of emerging resistance, and which composite models combining liquid biopsy and radiomic features best predict PFS and OS and can serve as powerful minimally-invasive tools to monitor and adjust therapy.

University Of Southern California

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]

California United States

State-Wide

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

Amendment Since initial award the total obligations have increased 382% from $706,071 to $3,403,254.