ASCO 2011: New Developments in Imaging and ASCO Sessions on Imaging Clinical Trials

David Mankoff, MD, PhD

ONCOLOGY talks with Dr. David Mankoff, professor of radiology, medicine, and bioengineering in the department of radiology at the University of Washington in Seattle. Dr. Mankoff will be one of the co-chairs at the upcoming ASCO session on molecular imaging in cancer clinical trials, and he gives us a preview of what some of the highlights of the session are likely to be, as well as some insights into his own work.

-Interviewed by Rachel Warren

ONCOLOGY: While your work is not directly in this area, can we get your opinion on the topic of breast cancer screening as a whole-we know that the recommendation is that people who are 40 to 49 no longer need annual screening, yet a newer study has said that annual screening finds breast cancers earlier and can result in more effective treatment.

MANKOFF: I would first like to make the caveat that I’m not a breast imager and my research isn’t really centered around screening. That said, this is a very confusing and controversial area. The recommendation reviewed studies and some epidemiologic data that were available and came to a different conclusion than had prior recommendations, and I think in general this is an area where there is a fair number of reasonable arguments on both sides. This has become a very individualized decision point for women and their physicians. One of the things that will help is more data, and another is having a better idea of factors that lead to a patient’s risk, because those patients who are at a higher risk for developing early breast cancer are the ones who will benefit from better screening. As a matter of fact there are already recommendations in place for women who have enhanced genetic risk to get screening, with MRI in addition to mammography. Ultimately I think that as we learn more about risk factors and how these techniques perform, we’ll be able to make a better recommendation.

ONCOLOGY: What are the areas of breast imaging and screening in which there are the most exciting new developments?

MANKOFF: I want to start by separating screening and breast imaging, because I think we’re traditionally used to thinking of breast imaging as something we do for cancer detection and then cancer diagnosis. These are areas in which I think there’s been a fair amount of progress in the past few years, in better understanding of how mammography works and some of the newer, digital mammography techniques, the advent of some advanced techniques such as tomosynthesis and the development of other modalities, especially breast MRI and more recently some of the nuclear modalities. I think there have been some very good prospective clinical trials that demonstrate the value of mammography and of breast MRI in high-risk patients and some interesting early data in breast cancer diagnosis with some of the radionuclear breast imaging techniques, but these are at a fairly early stage of clinical trials, and I think as the data emerge it will become a little bit clearer how to use those.

One of the other areas that I think is relatively early in development and not in the clinic yet, is the idea of using more molecularly based techniques to not only detect and diagnose breast cancer, but to help characterize it and to help direct appropriate treatments, based upon everything from how aggressive we think the cancer is likely to be, to how it’s biologically composed. Those techniques are just in the early stages of development but I think-especially since this is the area I work in-some of the most exciting developments coming down the pike.

ONCOLOGY: You’re touching on the specific work you’ve done, say, in the area of endocrine therapy for breast cancer, and the paper on glycolysis you published late last year in the Journal of Nuclear Medicine?[1]

MANKOFF: Yes, as one example of this. I think that through a variety of techniques, including things like PET and some of the advanced MRI techniques and some techniques that are coming down the pike in optical imaging and molecularly targeted ultrasound imaging, there will be a whole host of things that will not only be able to detect breast cancer but to characterize it, and characterizing it I think will be very helpful in developing approaches that are individualized and molecularly targeted. So we’re at an early stage in that development, but it’s a very exciting stage.

ONCOLOGY: Can you tell us the basic concept behind the glycolysis paper?

MANKOFF: We’ve studied a couple of areas-mostly in later-stage breast cancer-and what we’re finding is that, scanning people with fluorodeoxyglucose PET, or FDG-PET, we’ve identified patterns of glucose consumption that we think are predictive of response. And this suggests a couple of things-one is that serial measure of glucose metabolism with FDG-PET can give a very early readout on the success of a variety of treatments including both chemotherapy and endocrine therapy, and that it may actually be true that the pattern of glycolysis can provide some prediction for how aggressive and resistant a tumor is likely to be. We’ve been using PET scanning in breast cancer for some time now as a staging tool and also as a way to follow response to therapy for more advanced disease, but I think that some of these latest findings suggest that we may also be able to use this as a way to understand how tumors work, why some are resistant, and perhaps be able to use this as a very early predictive tool for response to treatment.

ONCOLOGY: Are there others working on targeted breast cancer approaches like this?

MANKOFF: Yes, there are a number of groups working on various aspects of this. For example there are groups at Washington University in St. Louis; in Edmonton, Canada at the BC Cancer Agency; and at Memorial Sloan-Kettering that are also working on these estrogen imaging studies. We hope to be able to put those groups together and develop a multi-center trial to test the approach. We’re using a labeled estrogen-labeled for PET imaging, to be able to look at estrogen receptors in breast cancer, and use that as an in vivo, non-invasive way to predict response to endocrine therapies. I think this is a very exciting development that’s mostly been applied to later-stage breast cancer, but may be helpful across the spectrum in those patients that are candidates for endocrine therapy.

ONCOLOGY: Finally, are there any talks at ASCO that you think will be particularly exciting or informative for your work?

MANKOFF: Yes, there are a number of groups that are beginning to talk about the testing of new imaging techniques in clinical trials. I think the practicing oncologist is very used to using clinical trials as the basis for determining therapy. We in imaging are just beginning to get used to using clinical trials as the basis for choosing appropriate imaging techniques. And we’re now seeing some of these advances in imaging techniques coming into play through a variety of organizations the American College of Radiology Imaging Network, ACRIN. There’s also a great deal of cooperation between societies, for example between ASCO and the Society for Nuclear Medicine, and there will be a session on Friday June 3rd that I’ll also be participating in that discusses how imaging clinical trials and cancer therapy clinical trials can work together, as well as some of the exciting work that’s going on in that area. I would point people in the direction of imaging clinical trial studies, papers, and sessions, in addition to in addition to what you’re used to seeing for therapy clinical trials.

ONCOLOGY: I did notice that on your website you mention translational and clinical trials specifically for imaging, and it was the first time I’d seen that.

MANKOFF: Yes. Actually in the “Trials in Progress Session” at ASCO, two of the ACRIN ongoing trials are being presented. One is the trial of fluorothiamidine-PET, or FLT-PET, to measure early response of breast cancer in the neo-adjuvant setting that is well underway. A second, very exciting, first of its kind trial, of optical imaging in locally advacened breast cancer as a way to measure response. That was an outgrowth of a consortium that was funded by the NCI to develop technology to enable that, and there is a group of centers that have built and tested that technology and are opening up a clinical trial under the auspices of ACRIN, so we’re very excited to see these new techniques-both new probes and new imaging techniques move into the field. I’d encourage folks to go and have a look at the new session entitled, I believe “Protocols in Progress.”

ONCOLOGY: Thank you for your time.

References

1. Linden HM, Mankoff DA. Breast cancer and hormonal stimulation: is glycolysis the first sign of response? J Nucl Med. 2010 Nov;51(11):1663-1664. PMID: 20956476