Research Forefronts

Q&A with David A. Fishman, M.D.
Professor of Obstetrics and Gynecology

Ovarian cancer is the most lethal gynecological cancer because it is undetected until it reaches an advanced stage, when treatments are not especially effective. If the cancer is found early and surgically removed before it grows outside the ovaries, 90 percent of those afflicted are still alive five years later. But only 19 percent of cases are found that early. The American Cancer Society estimates that this year there will be some 22, 430 new cases of ovarian cancer in the United States and that about 15,280 women will die of the disease.

Dr. Fishman is director of the National Cancer Institute’s National Ovarian Cancer Early Detection Program, and he is leading an NCI-supported clinical trial using a new ultrasound technology in combination with a contrast agent that may help detect ovarian cancer at an early stage. The trial is taking place at NYU Cancer Institute and Vanderbilt University. Women who wish to learn more about the trial should call the National Ovarian Cancer Early Detection Program at NYU Cancer Institute, 212-731-5345.

Q: Why is it so difficult to detect ovarian cancer early?

A: The ovaries are relatively small organs, about 2 by 4 centimeters (about 1 by 1.6 inches) inside the pelvis. Surrounded by 23 feet of small bowel and nine feet of colon, the ovaries may be very difficult to feel on physical examination. Ovarian masses can easily be missed by simple palpation. And the imaging technologies we have for the breast—mammography, ultrasound, digital mammography, MRI—have not proven effective for detecting early stage ovarian cancer, which is incredible considering the explosive growth of these technologies over the last 20 years. Presently there is no blood test that can accurately detect early-stage ovarian cancer.

Q: Why would a contrast agent be helpful?

A:  The ovaries can be seen by using CT and PET scans, ultrasound, and MRI. But by the time we see a mass, it's almost always advanced-stage ovarian cancer. So we asked whether we could take advantage of our understanding of the biology of cancer to devise a way to detect early-stage cancer. In order for a cancer to grow, it has to create its own unique blood supply with vessels that plug into the normal tissue's blood vessels. This process of acquiring its own blood supply is called tumor angiogenesis.

Q: How does the contrast agent plug into that unique blood supply?

A: We wondered whether we could visualize these early vascular changes before a mass is actually seen on the ovary, because the blood vessels are there long before a mass is seen. An ovary could look normal at this stage, but it could be full of cancer.  So if we have the right technology, these early vascular changes should be detectable. 

Q: What did you find?

A: In cardiology, contrast agents have been used for decades for cardiac angiography (a medical imaging technique used to visualize the heart’s blood vessels).  Some of the newer agents are about the size of a red blood cell, so they're about five to seven microns in diameter. These contrast agents should be able to delineate vessels that range from one to 10 microns in diameter, which is what we need to see.

Q: Do the agents stick to the blood vessels?

A: They go through them. Think of a flashlight illuminating a hole in the darkness. What ultrasound can do is visualize these individual contrast agents as they percolate through blood vessels that are so small no imaging technology can see them.

Q: Aren’t there tiny blood vessels near the ovaries, which are surrounded by other internal organs?

A: Absolutely. Every organ has blood vessels that are small. But we're using ultrasound and we're giving the patient the contrast agent intravenously.  We are watching the ovary the whole time and observing the inflow of the contrast agent, which looks like white dots. Those dots are delineating the micro-vessels that otherwise could not be seen. What we have found is that it is possible to quantify differences in inflow and outflow that can discriminate between early-stage cancer and normal. Typically, the contrast agent starts filling the ovary within 30 seconds after injection, and we watch the ovary for three minutes. Within that time the ovary is lit up like a Christmas tree. At the end of three minutes it's washed out, there's no more contrast, and it's not lit anymore.

Q: If there is a mass, is the outflow faster or slower?

A: It's much slower because the contrast agent is cleared much more slowly from cancer due to the abnormal blood vessels.

Q: Is the contrast agent called Definity being tested only at NYU?

A: I'm the principal investigator and Dr. Arthur Fleischer coordinates our collaborators at Vanderbilt University. So at present there are only two sites in the United States participating in the clinical study. Women who are going to have their ovaries removed for whatever reason are eligible to participate.

Q: Are you excited by the findings so far?

A: Yes, but this is research, it's not yet proven. Our numbers are small, but so far we have not missed one cancer. In fact we've detected several cancers that couldn’t be found with conventional ultrasound. And we have found three early-stage cancers: one on the ovary, two in the fallopian tube. Although our results are extremely promising, we need to evaluate more women to achieve clinical validation before this technology can be used for patient care.