Scientific Studies

The BLOODPAC Consortium has conceptualized and initiated two liquid biopsy clinical studies for cross-platform validation, multi-modal high-content, and longitudinal monitoring. Complete datasets from both studies will be submitted to the BLOODPAC Data Commons and analyzed. The studies have successfully incorporated the frameworks established by the BLOODPAC Consortium around pre-analytical minimum technical data elements and patient context data elements.

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“BLOODPAC demonstrates the value of establishing open lines of collaboration among multiple stakeholders. This type of broad engagement allows for a better understanding of clinical, scientific and regulatory questions related to liquid biopsy that will ultimately drive the field forward and better serve the needs of patients”

— Julia Beaver, Director, Division of Oncology 1, FDA

Development of a Blood Profiling Atlas to Understand Spatiotemporal Evolution of Breast Cancer in Patients (BloodPAC-007)

  • Supported by the Breast Cancer Research Foundation: BCRF-16-189

    BloodPAC-007 is a BCRF-funded study with an active protocol collecting and analyzing longitudinal blood specimens from metastatic breast cancer patients for a multi-platform, multi-analyte blood profiling analysis with the potential to accelerate the development of safe and effective blood diagnostic technologies for patient benefit. This study is motivated by the need for more precise clinical diagnosis of metastatic breast cancers at the molecular level. It is aimed at collecting data along the spatio-temporal evolution of the disease and the patient care continuum, from initial metastatic diagnosis through progression to metastasis, response to therapy and monitoring of minimal residual disease.

    This study will aggregate, make freely available, and harmonize for further analysis, raw datasets from circulating tumor cells (CTC), cell-free DNA (cfDNA), and extracellular RNA (exRNA) assays as well as relevant clinical data (e.g. clinical diagnosis, treatment history and outcomes), and sample preparation and handling protocols. The goal is to develop an open, well-curated public database hosted at the BLOODPAC Data Commons that can be a source of valid scientific evidence. The de-identified patient data will include data items to conform to the BLOODPAC Consortium recommendations for the required and recommended minimum technical data requirements for patient results and clinical data.

    BLOODPAC-007 is led by Walter Reed National Military Medical Center (WRNMMC) Murtha Cancer Center (MCC) (Col. Craig D. Shriver, MD FACS) and University of Southern California (USC) (Dr. Peter Kuhn, PhD), a BLOODPAC member, in collaboration with other BLOODPAC members: Novartis Pharmaceuticals, Foundation Medicine, Thermo Fisher and University of Michigan.

    Study takeaways: The study demonstrated high concordance between three cfDNA targeted sequencing platforms, particularly for detecting clinically actionable PIK3CA and ESR1 variants. It also highlighted that combining cfDNA and CTC analyses can enhance the tumor-derived information obtained from a blood sample. Furthermore, the study established a collaborative, multicenter framework and generated real-world data, now available in the BLOODPAC Data Commons, serving as a valuable reference for future study designs aimed at identifying comprehensive liquid biopsy biomarkers.

Pre-analytic Variables in the Liquid Biopsy for Prostate Cancer: Specimen Acquisition and Patient Context Factors that Impact Results (BloodPAC-0042)

  • BLOODPAC-0042 is a PCF-funded study with an active protocol collecting and analyzing blood specimens from metastatic prostate cancer patients to asses the impact of differences in specimen acquisition and patient context factors that occur in a routine clinical practice setting on circulating tumor cell (CTC) and cell-free DNA (cfDNA) assay results. The protocol focuses on on pre-analytic variables that affect assay results independent of the conduct of the assay itself. It is essential to understand the variance introduced by each factor in order to effectively use these tests as prediction and treatment monitoring biomarkers.

    BLOODPAC-0042 aims to develop standards for the validation and regulatory approval of blood-based biomarkers (liquid biopsy) and contribute the pre-analytic patient context variable data generated by the study to the BLOODPAC Data Commons to make it available to the research community. Five cohorts will be analyzed to determine the reproducibility of CTC enumeration and cfDNA quantitation results in response to pre-analytic specimen acquisition variables (variability of results within a two week period, 24-hour period and tube draw order) and patient context factors (fasting status and anti-emetic intervention) and develop SOPs that allow for consistency of the assay results for the following tests:

    a) CTC enumeration using the FDA-cleared CellSearch® assay for the context of use as a response indicator biomarker that strongly associates with survival.

    b) CTC enumeration and tumor profiling using the Epic Sciences platform for the context of use as a response indicator biomarker that accurately reflects the effect of a treatment, as well as a predictive treatment selection biomarker to guide the choice between a taxane or AR-directed therapy in the second line.

    c) cfDNA results obtained from the MSK Center for Molecular Oncology assay and Thermo Fisher Oncomine™ Pan-Cancer Cell-Free Assay for the context of use as a response indicator and/or predictive biomarker.

    BLOODPAC-0042 is led by Drs. Howard Scher, Daniel Danila, and Lakshmi Ramanathan at Memorial Sloan Kettering Cancer Center (MSKCC), a BLOODPAC member, in collaboration with other BLOODPAC members: Epic Sciences and Thermo Fisher and external collaborator: Menarini Silicon Biosystems.

    Study takeaways: The preliminary MSK-ACCESS data from BPAC-0042 explores pre-analytic variables in liquid biopsy for prostate cancer, focusing on specimen acquisition and patient context factors that impact results. While mutation detection showed high concordance in short interval test-retest samples, discordance observed near the assay's limit of detection may hold clinical relevance. Additionally, the study found that acquiring tissue through biopsy has a substantial effect on the concentration of tumor-derived DNA present in circulation.

JUST FREAKING DO IT! (JFDI) Program

  • The JUST FREAKING DO IT! program is a community effort that aims to increase quality and consistency of ctDNA analysis through inter-laboratory testing of well-recognized analytical tools and reference materials. JFDI proficiency testing will include measurements of repeatability, reproducibility, sensitivity, specificity, assay conversion rate, accuracy and precision, as well as other metrics fundamental to ctDNA analysis. 

    Over the past seven years, the JFDI effort has evolved from testing one type of contrived material donated by Thermo Fisher Scientific (JFDI Phase 1) to thoroughly evaluating four different types of control materials that are commercially available broadly across the liquid biopsy research community (JFDI Phase 2).

    As a following step, the JFDI Phase III is attempting to expand the established testing paradigm to incorporate recommendations from the generic protocols for analytical performance and compare the findings of the contrived material testing to relevant clinical samples harboring similar mutations to those tested with contrived samples.