• Imaging Plays Critical Role in Precision Medicine Explosion

    Precision medicine is being demonstrated in countless radiology and imaging departments across the country. By Mike Bassett

    April 1, 2016

    Although U.S. President Barack Obama first introduced a Precision Medicine Initiative in 2015, radiologists and other physicians have been working for quite some time to individualize each patient’s healthcare based on his or her unique characteristics.

    “We have been involved in this initiative on some level for quite a while,” said Mitchell Schnall, M.D., Ph.D., chairman of the Department of Radiology at the University of Pennsylvania (Penn).“But over the last couple of decades, there has been an explosion in our ability to gather information and define an individual and that person’s disease in a much more granular way, and with much more extensive information than before.”

    This has led to what Dr. Schnall calls the “aggressive promotion”of the idea that patients and their diseases can not only be characterized by traditional methods, but by using more advanced information tools as well.

    “As a result, some people loosely think of or define precision based on molecularly driven medicine,” he said. “I personally think—and we at Penn have tried to take a broader view—that precision medicine involves using any of the advanced diagnostic information that is available to help individualize care.” And imaging plays a critical role in that process, Dr. Schnall said.

    Precision Medicine Could Improve COPD Treatment

    This emphasis on individualized care or precision medicine is being demonstrated in countless ways in radiology and medical imaging departments across the country.

    In an RSNA 2015 session, Ella Kazerooni, M.D., professor of cardiothoracic radiology at the University of Michigan (UM), Ann Arbor, discussed how some of the concepts of precision medicine can be applied in her area of thoracic radiology—specifically constructive obstructive pulmonary disease (COPD).

    When she was a medical student, Dr. Kazerooni said COPD was classified as a basic condition. “There was emphysema, there was asthma and there was chronic bronchitis, and that’s all we knew about COPD,” Dr. Kazerooni said. “And we treated patients based on how they fit into these platforms.”

    COPD is a very common disease that affects over 24 million Americans, according to the COPD Foundation. “That means there are tens of millions of data points around us, sitting in medical records and in our image repositories,” Dr. Kazerooni said.

    She and her colleagues at UM have developed a software tool for chest CT scans that allows physicians to better distinguish early-stage small airway disease (or pre-emphysema) from the more severe damage caused by emphysema.

    Ideally, this will allow physicians to tailor patient-specific treatments. For example, this approach could help physicians more precisely identify patients with a severe disease who should be transplant candidates, or those with a less severe disease who are potentially treatable.

    Progesterone Receptors as Cancer Biomarkers

    At the University of Wisconsin (UW), Madison, Amy Fowler,M.D., Ph.D., assistant professor in the breast imaging section in the Department of Radiology, is investigating molecular imaging biomarkers to assess early therapeutic response for breast cancer.

    As Dr. Fowler points out, the majority of breast cancers express estrogen and progesterone receptors—important biomarkers used to determine prognosis and predict the benefits that come from endocrine hormone therapies for cancer patients.

    But up to half of patients may not respond to endocrine therapy even though they have estrogen-positive breast cancer. The challenge is to determine more precisely whether a patient’s breast tumor is endocrine-sensitive so physicians can apply the correct therapy to an individual patient as quickly as possible.

    “Some of the imaging work we first tested using mouse models of breast cancer during my training at Washington University in St. Louis, which we are now developing for patients here at the University of Wisconsin, is looking at ‘downstream’ targets Professional receptors,” Dr. Fowler said.

    The idea is that changes in progesterone receptors as seen on imaging can serve as an early-response biomarker to endocrine therapy.

    “When estrogen is activating a tumor, it results in proliferation,but it also turns on the gene for progesterone receptor,”she explained. “We can look to see how functional an estrogen pathway is in a tumor by looking downstream at the progesterone receptor to see whether we can better predict response to therapy.”

    In a study published in the December 2014 issue of Clinical Cancer Research, Dr. Fowler and colleagues determined that PET imaging of estrogen receptor-positive breast tumors with the radio pharmaceutical [18F]FFNP (to measure progesterone receptor[PgR] levels) before endocrine therapy and shortly after treatment was an effective approach to predict treatment response.

    “In fact, using the [18F]FFNP tracer was an effective way to see in real time whether the endocrine agent we were using was functional,”Dr. Fowler said. “We could see changes as early as three days before we could see any size change in the tumor."

    The ability to determine early which endocrine agents aren't working could be critical considering the list of agents is fairly long, said Dr. Fowler, who received a 2014-2015 Philips Health care/RSNA Research Seed Grant to research the impact of endocrine-resistant estrogen receptor-alpha variants on [18F]Fluoroestradiol(FES) imaging of breast cancer.

    “There are no good algorithms—particularly in a metastatic setting—for knowing which agent you should start with and which agent you should switch to if the first doesn’t work," Dr. Fowler said. “So this may be one approach to learn quickly if another is not working,”she added. “Or to explore more sophisticated tools—such as tumor genomics—to examine whether there is some mutation we don’t expect and don’t test for clinically that is causing resistances to the endocrine therapy.”

    A Personalized Approach to Cancer Screening

    At Penn, researchers are working to advance the concept of precision medicine as it pertains to cancer screening.

    Dr. Schnall serves as a primary investigator for the Penn Center for Personalized Cancer Screening, which is pursuing three separate projects: the evaluation of the comparative effectiveness of new imaging technologies such as to mosynthesis andabbreviated MRI; the assessment of a new tool called the Breast Complexity Index to predict individual screening outcomes; and the development of an online decision aid to help women—together with providers—make informed decisions about when to undergo mammo graphic screening.

    Cancer screening traditionally follows a “one size fits all” approach, but a more personalized approach should be possible considering the amount of information physicians have about their patients, Dr. Schnall said.

    “Before patients even come in for a mammogram, we know a lot about these women,” he said. “And if we have a single mammogram,we know a lot about the phenotype of their breasts. So if we know the risks a woman has of developing cancer, of having false positives, or false negatives due to breast density, we can potentially present them with likely outcomes given various sorts of screening."

    More patients will be utilizing decision aids which may potentially lead to better shared decision making regarding screening.“Decision aids will be geared toward patients and primary care doctors,” Dr. Schnall said. “They will help a woman understand where she fits in regarding likely screening outcomes, and help her make a decision about what screening is right for her.”






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