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8.05.2014

Miller School Researchers Win $3 Million NIH/NCI Grant to Study Prostate Cancer Management

The National Institutes of Health/National Cancer Institute has awarded researchers at the Miller School of Medicine $3 million in funding over five years to explore breakthrough uses of MRI imaging and genetic signatures in managing prostate cancer diagnosis and treatment.

“This is a very important shot in the arm for our imaging group and for collaborations by our investigators in radiation oncology, urology, pathology and radiology,” said Alan Pollack, M.D., Ph.D., professor and Chair of the Department of Radiation Oncology, member of the Sylvester Comprehensive Cancer Center, and the lead investigator. “We currently diagnose a lot of prostate cancers that are caught very early, and we often don’t know who should be treated and who shouldn’t, or when to bring them to treatment.”

The reason, he explains, is that current diagnostic methodologies don’t do a good job of identifying the tumor in some locations in the prostate, and whether it is indolent or an aggressive form of the cancer. Conventional ultrasound imaging only has a 50 percent certainty of identifying abnormalities in the prostate as cancer, and an estimated 30 percent of significant cancers are missed entirely. As a result, when cancer is found, or just suspected, the response is often overdiagnosis and overtreatment — two problems being targeted by NIH/NCI through its research funding.

“We know that approximately two-thirds of men diagnosed with prostate cancer don’t require treatment, yet 90 percent of them will seek out treatment, even though the cancer won’t reduce their quantity or quality of life,” said Sanoj Punnen, M.D., assistant professor of clinical urology and another of the study’s investigators. “Most prostate cancer is so slow-growing that the average man is far more likely to die with it than of it.”

The alternative is “active surveillance,” during which the patient’s cancer is closely monitored but not treated with medications, radiation or surgery. This response, however, also has its downsides.

“About one out of every four patients who are initially selected for active surveillance as a treatment option for prostate cancer will fail due to the fact that current diagnostic schemes underestimate the true grade and extent of cancer. The research from this current funded proposal will help reduce the misclassification rates in these patients and significantly improve outcomes in many of the men who elect active surveillance,” said Dipen Parekh, M.D., professor and Chairman of the Department of Urology, and one of the study’s investigators. “Dr. Pollack and his team should be congratulated for this wonderful accomplishment in what is an incredibly challenging funding environment.”

The foundation for the study is an advanced imaging technology known as multiparametric MRI, or MP-MRI. The Miller School researchers will be exploring the potential of unique MP-MRI analysis software developed by Radka Stoyanova, Ph.D., associate professor and Director of Imaging and Biomarkers Research in the Department of Radiation Oncology, that categorizes prostate tumors into “habitats.” Combined with molecular analyses from MRI-directed prostate biopsies, they expect to do a better job of finding aggressive tumors at the earliest possible stages, and improve the selection of patients for active surveillance versus treatment.

“MP-MRI consists of anatomical and functional imaging sequences, with more than 1,500 images associated with a single exam,” said Stoyanova. “Powerful pattern-recognition techniques then provide optimal extraction of the imaging information.”

Analyzing the image patterns will allow the researchers to segment the cancers into habitats with different radiographic characteristics that will help determine their degree of aggressiveness or indolence. The patterns and habitats can then be superimposed over an ultrasound taken as a biopsy is being performed. Fusing them together provides much more information, and helps better direct the biopsy to areas of higher risk that harbor more aggressive disease.

“MRI allows you to get an image of the whole prostate,” said Punnen. “It also uses multiple parameters to more accurately identify regions of the prostate that are likely to be harboring aggressive tumors. By using this information to guide the location of the biopsy needles, we can do a better job of sampling the tumor that is most likely to be driving the risk of cancer progression.”

The use of MP-MRI will generate large quantities of data, and what the researchers have proposed is considered quite novel.

“The study design includes finer examination of many quantitative imaging features using radiomics, an advanced image analysis process that captures information beyond the localization of the tumor in a high throughput manner,” said Stoyanova. “More specifically, macroscopic image-based features can be related with genomic and proteomic patterns.

“Radiomics data are in a format that is amicable for building descriptive and predictive models relating image features to phenotypes or gene-protein signatures. We will correlate the imaging radiomics features with biopsy results, as well as with gene-expression analysis of the biopsy tissues.”

“This may give us the ability to find an association between molecular characteristics and imaging characteristics,” said Pollack. “The benefit is that we will be much more able to sort out which patients need treatment and which don’t. The data also could be applied to men who are going to undergo treatment, because it might be pertinent to them as well.

“The other thing about the grant is that it brings together urology, radiation oncology, radiology and pathology in what is truly a group effort. This is team science at its best. What we are proposing is very new, and the Miller School is far out ahead of the curve.”

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