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despina kontos study

PHILADELPHIA — Diverse diseases like breast cancer can present challenges for clinicians, specifically on a cellular level. While one patient’s tumor may differ from another’s, the cells within the tumor of a single patient can also vary greatly. This can be problematic, considering that an examination of a tumor usually relies on a biopsy, which only captures a small sample of the cells.

According to a new study from researchers at Penn Medicine, Magnetic Resonance Imaging (MRI) and an emerging field of medicine called radiomics — which uses algorithms to extract a large amount of features from medical images — could help to characterize the heterogeneity of cancer cells within a tumor and allow for a better understanding of the causes and progression of a person’s individual disease. The findings were published in Clinical Cancer Research.

“If we’re only taking out a little piece of a tissue from one part of a tumor, that does not give the full picture of a person’s disease and of his or her response to specific therapies,” said principal investigator Despina Kontos, PhD, an associate professor of Radiology in the Perelman School of Medicine at the University of Pennsylvania. “We know that in a lot of instances, patients are over-treated, getting therapy that may not be beneficial. Or, conversely, patients who need more aggressive therapy may not end up receiving it. The method we currently have for choosing the appropriate treatment for patients with breast cancer is not perfect, so the more steps we can take toward more personalized treatment approaches, the better.”

Kontos and her colleagues wanted to determine whether they could use imaging and radiomics for more personalized tumor characterization. Using MRI, the researchers extracted 60 radiomic features, or biomarkers, from 95 women with primary invasive breast cancer. After following up with the patients 10 years later, the group found that a scan that showed high tumor heterogeneity at the time of diagnosis — meaning a high diversity of cells — could successfully predict a cancer recurrence.

“Our study shows that imaging has the potential to capture the whole tumor’s behavior without doing a procedure that is invasive or limited by sampling error,” said the study’s lead author Rhea Chitalia, a PhD candidate in the School of Engineering and Applied Science at the University of Pennsylvania. “Women who had more heterogeneous tumors tended to have a greater risk of tumor recurrence.”

The researchers retrospectively analyzed patient scans from a 2002-2006 clinical trial conducted at Penn Medicine. For each woman, the group generated a “signal enhancement ratio” (SER) map and from it, extracted various imaging features in order to understand the relationship between those features and conventional biomarkers (such as gene mutations or hormone receptor status) and patient outcomes.

They found that their algorithm was able to successfully predict recurrence-free survival after 10 years. To validate their findings, the group compared their results to an independent sample of 163 patients with breast cancer from the publicly available Cancer Imaging Archive.

While imaging may not completely replace the need for tumor biopsies, radiologic methods could augment what is currently the “gold standard” of care, Kontos said, by giving a more detailed profile of a patient’s disease and guiding personalized treatment. Next steps for the research team will include expanding the analysis to a larger patient cohort and also further exploring which specific markers are more predictive of particular outcomes.

“We’ve just touched the tip of the iceberg,” Kontos said. “Our results and the validation study give us confidence that there are many opportunities for these markers to be used in a prognostic and potentially a predictive setting.”

This study was supported by the National Cancer Institute at the National Institutes of Health. Additional Penn authors include Jennifer Rowland, Elizabeth S. McDonald, Lauren Pantalone, Eric A. Cohen, Aimilia Gastounioti, Michael Feldman, Mitchell D. Schnall, and Emily F. Conant.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $425 million awarded in the 2018 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Home Care and Hospice Services, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 40,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2018, Penn Medicine provided more than $525 million to benefit our community.

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