Canary Ovarian Program infographic
Check out our infographic to view Canary’s progress in the field of ovarian cancer early detection.
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Check out our infographic to view Canary’s progress in the field of ovarian cancer early detection.
The goal of the ovarian research program is to develop a strategy to accurately identify ovarian cancers that would otherwise be lethal at a stage when they are readily curable.
If ovarian cancer is caught early, the five-year survival rate for ovarian cancer patients is greater than 90 percent, yet less than 25 percent are found this early.
The Canary ovarian cancer team was formed in 2005 in response to the need for tools to detect lethal types of ovarian cancer at an early stage, with the highest curability. Since that time, the team has completed collaborative projects in biomarker discovery, validation, molecular imaging, and screening modeling, and the group has moved blood and imaging tests into clinical trials. The team has also served as a model for collaborative teamwork in the field of early detection.
There is a need for new imaging technologies that not only reliably visualize ovarian cancer with enhanced sensitivity and specificity but also differentiate between benign and malignant disease.
Ultrasound is a widely available imaging technology that lacks ionizing radiation, is relatively cost-effective, and allows a dynamic evaluation of the region of interest in real time. In current clinical practice, screening for ovarian cancer may include transvaginal ultrasound imaging of ovaries, combined with a blood test for the biomarker CA-125. However, these screening methods produce many false-positive results and unnecessary surgeries.
The ovarian cancer team will test a new technique, photoacoustic imaging (PAI), for its ability to meet these needs in ovarian cancer screening.
Another molecular imaging modality that holds promise for imaging ovarian cancer is enhanced ultrasound using targeted microbubble technology. Recent FDA approval for using targeted microbubbles in humans has opened the door to advance this study. Studies using targeted microbubbles in prostate cancer patients are underway at Stanford, with plans to expand to studies in additional cancer types, including ovarian cancer.
We are adapting traditional ultrasound imaging with an emerging non-ionizing photoacoustic imaging (PAI) technique that essentially lets us “hear” light.
PAI strategies allow deeper tissue penetration than optics alone while preserving the spatial and temporal resolution advantages of ultrasound.
Therefore, tissues within a human body can be more clearly visualized at a depth that is clinically relevant. Because hemoglobin is one of the primary molecules present naturally that produce a photoacoustic signal, PAI is especially suitable for detecting blood vessels associated with tumors, as well as monitoring changes in blood vessel growth that can accompany tumor formation and growth.
At Stanford, we have engineered a new PAI device that is being tested for visualization of prostate cancer. We are adapting this device for use in ovarian cancer imaging.
After development and pre-clinical testing of the device, we will move into the clinical setting to test in patients. Our goal is to reliably visualize cancer even from several centimeters deep inside ovarian tissue. We propose the following specific aims:
1. Refine and validate a combined transvaginal ultrasound and photoacoustic-imaging device by imaging models of ovarian tissue and surgically removed human ovaries. In this aim, we will adapt the current transrectal ultrasound and PAI system shown in figure 1, to develop the probe for transvaginal imaging of ovaries.
2. Conduct a pilot test of the combined transvaginal ultrasound and PAI instrument in patients undergoing ovarian cancer excision surgery. Fully optimized dual-modality transvaginal ultrasound and PAI with well-defined image metrics have the potential to further enhance the sensitivity and specificity of standard transvaginal ultrasound imaging of ovaries prior to surgery. In this study, we will test the efficacy of the combined device for clinical ovarian imaging. We anticipate that the combined procedure should not be more uncomfortable than a traditional transvaginal ultrasound procedure, since both are done with a hand-held transvaginal device of similar dimensions. The combined transvaginal ultrasound-PAI can be done at the time of traditional ultrasound, and in preclinical studies adds less than five to 10 minutes to each procedure.
The primary objective of this specific aim is to assess the combined instrument performance in a clinical setting, to understand the limitations of this instrumentation, to help improve the next-generation instrument design, and to understand how to integrate the combined transvaginal ultrasound and photoacoustic imaging into the standard clinical ultrasound workflow.
One of the challenging aspects of building a test for early detection of ovarian cancer is understanding the earliest stages of ovarian cancer growth.
Two key characteristics of ovarian cancer growth influence the development of an early detection test: the size at which a tumor progresses from early stage, treatable disease to incurable disease, and the amount of time the tumor spends as early stage, treatable disease, i.e. the window of opportunity for early detection. Canary research supported two modeling efforts to help address these critical pieces of knowledge.
The first comprised an analysis of tumors found in fallopian tubes and ovaries removed from healthy women at high risk for ovarian cancer. By comparing the size and stage of these previously undetected tumors with tumors from women diagnosed with ovarian cancer, the researchers were able to model both the size of early stage tumors and the length of time tumors spend in early stage before progressing.
The second effort modeled the mortality reduction and cost-effectiveness achievable by currently available screening tests using data on the natural history of ovarian cancer, survival after ovarian cancer diagnosis, and blood biomarker levels from clinical trials.
The Canary Ovarian Cancer team includes physicians who focus on gynecologic diseases and ovarian cancer, molecular imaging experts, and those who focus on biomarker evaluation and molecular diagnostics.
Past and present members include:
- Patrick Brown, M.D., Ph.D., Stanford University
- Charles Drescher, M.D., University of Washington and Fred Hutchinson Cancer Research Center
- Sanjiv Sam Gambhir, M.D., Ph.D., Stanford University
- Peter Laird, Ph.D., Van Andel Research Institute
- Martin McIntosh, Ph.D., Fred Hutchinson Cancer Research Center
- Brad Nelson, Ph.D., British Columbia Cancer Agency
- Muneesh Tewari, M.D., Ph.D., University of Michigan
- Nicole Urban, Sc.D., Fred Hutchinson Cancer Research Center
Novel Markers Trial (NMT)
The Novel Markers Trial (NMT) was launched in 2009 by the Pacific Ovarian Cancer Research Consortium (POCRC), a collaborative team of scientists led by Canary team member Dr. Nicole Urban who was awarded a five-year SPORE grant by the National Cancer Institute.
Previous clinical trials of ovarian cancer screening programs mostly involved a single biomarker (CA-125) as a blood test. The NMT incorporates a second blood-based biomarker (HE4) into the screening protocols for clinical decision-making. Furthermore, the trial uses a new computational algorithm to determine whether the biomarker signals the presence of cancer. The study is determining the predictive value for malignant ovarian cancer of a screening program that includes the two blood biomarkers, the new algorithm to decipher a cancer signature from blood biomarkers, and ultrasound as an imaging modality.
The five-year study has enrolled its goal of 1,200 women, divided into three risk groups depending on the mutation status of certain cancer risk genes, family history of ovarian cancer, and other factors that may influence a woman’s risk of ovarian cancer. The study has determined that HE4 is useful as a confirmatory screen when rising CA-125 is used alone as a primary screen. The screening protocol was found to be feasible and acceptable to women and physicians and did not result in excessive imaging, surgical consults or surgeries. Thousands of well-characterized samples, including blood and tissue specimens, are now stored in a central repository for use in future studies. The NMT is under consideration to be made available nationally through an NCI-funded cancer research cooperative group.
For more detailed information about this screening trial, please visit the POCRC website.
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