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June 9, 2016

Research Notes

Changing advanced breast cancer care standard

Surgery to remove the primary tumor in women diagnosed with stage IV breast cancer, followed by the standard combination of therapies, adds months to patients’ lives when compared with standard therapy alone, a clinical trial led by a University of Pittsburgh Cancer Institute (UPCI) faculty member revealed.

The results of the phase III randomized, controlled trial were presented at the American Society of Clinical Oncology (ASCO) annual meeting. The study was selected for the society’s “Best of ASCO,” an effort to condense the research “most relevant and significant to oncology” into a two-day program to increase global access to cutting-edge science.

Principal investigator Atilla Soran, surgery faculty member in the School of Medicine and breast surgical oncologist with UPMC CancerCenter, began the trial in 2007, ultimately recruiting a total of 274 women newly diagnosed with stage IV breast cancer from 25 institutions. Half the women received standard therapy, which avoids surgery and consists of a combination of chemotherapy, hormonal therapy and targeted therapy, while the other half first had surgery to remove their primary breast tumor, followed by the standard therapy.

At about 40 months after diagnosis, the women who received the surgery plus standard therapy lived an average of nine months longer than those who received standard therapy alone. Nearly 42 percent of the women who received surgery lived to five years after diagnosis, compared with fewer than 25 percent of the women who did not receive surgery.

The trial also showed that surgery in younger women with less aggressive cancers resulted in longer average survival than in women with more aggressive cancers that had spread to the liver or lungs.

“Our thinking is similar to how you might approach a battle against two enemies,” said Soran. “First you quickly dispatch one army — the primary tumor — leaving you to concentrate all your efforts on battling the second army — any remaining cancer.”

The research was funded primarily by the Turkish Federation of Societies for Breast Diseases. The study received scientific advisement from UPMC and assistance with statistical analysis from epidemiologists at the Graduate School of Public Health.

3-D bioprinted
model may reduce cancer treatment

UPCI researchers and Carnegie Mellon University (CMU) materials and biomedical engineers will address the overdiagnosis and overtreatment of a noninvasive precancerous breast tumor by creating the first 3-D bioprinted breast ductal structure to identify markers for low-risk premalignant disease.

Improvements in mammography screening have resulted in earlier detection of invasive breast cancer, and this is also associated with an increase in the detection of noninvasive breast cancer, such as ductal carcinoma in situ (DCIS), the earliest form of breast cancer where the disease has not spread out of the milk duct. Over 60,000 women are diagnosed with DCIS each year, and the majority of noninvasive lesions will not progress to invasive diseases if left untreated. However, the majority of these women undergo unnecessary surgeries, treatments and therapy.

Said Adrian Lee, faculty member in the School of Medicine’s pharmacology and chemical biology department: “More research is required to identify the minority of DCIS lesions that will progress to invasive disease and thus require treatment. Our hope is that our research will reveal novel biomarkers that will be useful for predicting which DCIS are likely to progress. We can then offer personalized therapy to those who require intervention, while reducing the overtreatment of DCIS in those who don’t. This could have a major impact upon thousands of women each year.”

After printing a breast ductal system in the laboratory, the researchers then will grow DCIS cells in the printed duct. By printing a replica of a mouse ductal system, experts will be able to create a unique model to study why some DCIS progress to invasion while others remain indolent. Genes involved in progression may serve as biomarkers indicating the need to treat DCIS.

The scientists were awarded nearly $800,000 from the Office of the Assistant Secretary of Defense for Health Affairs.

Arrhythmia’s
negative impact after lung transplant

Cardiac arrhythmia is a common complication following lung transplantation, and one that has a significant negative impact on long-term patient survival, concludes the largest study of its kind to date. The results, published online in the Journal of Thoracic and Cardiovascular Surgery, provide critical information that it is hoped will lead to better care of transplant recipients.

Arrhythmia, a rapid and irregular heartbeat, can lead to chest pain, stroke and heart failure. In addition, the blood-thinning drugs often used to treat atrial fibrillation, the most common type of arrhythmia, carry risks of heavy bleeding.

Said lead researcher Jonathan D’Cunha, faculty member in the School of Medicine’s Department of Cardiothoracic Surgery and chief of lung transplantation for UPMC: “Arrhythmias present a lot of challenges for both physicians and patients. After noticing this complication in many of our lung transplant recipients, we decided to investigate how often and when it was happening, as well as any risk factors. Now that we have a better understanding of these events, we can develop a standardized treatment plan and better educate patients in advance.”

Researchers examined the medical records of 652 UPMC patients who underwent a single or double lung transplant.

They found that about 30 percent developed arrhythmia, most often during the first week following surgery. Risk factors for a postoperative arrhythmia included being older and having had a previous heart surgery.

Researchers also found that transplant recipients who developed an arrhythmia were 1.6 times more likely to die within five years than those who didn’t, a finding D’Cunha attributed more to the potential complications of treating arrhythmia than the abnormal heartbeats themselves.

“Our study suggests that we may need to treat patients with blood thinners only for a short amount of time — until they are out of the window of highest risk — which will hopefully improve long-term outcomes,” D’Cunha said.

In addition, because arrhythmia after lung transplant can be an anxiety-provoking experience for patients, the findings will allow surgeons to better prepare patients and families for what to expect.

“Most importantly, based on the results of this study, we can now predict, with a reasonable degree of certainty, when arrhythmia will happen,” D’Cunha said. “This allows us to begin to standardize our treatment approach and improve patient care in the postoperative setting.”

Other Pitt members of the research team included Alex D’Angelo, Ernest Chan, J.W. Awori Hayanga, David Odell, Joseph Pilewski, Maria Crespo, Matthew Morrell, Norihisa Shigemura, James Luketich, Christian Bermudez and Andrew Althouse.

Crystal transistor may lower energy consumption of
electronics

Two Swanson School of Engineering researchers received a $496,272 grant from the National Science Foundation to study two-dimensional semiconductors with the goal of demonstrating a switch that requires less power than conventional silicon-based transistors.

Said principal investigator Susan Fullerton, chemical and petroleum engineering faculty member: “As electronic devices continue to become more integrated into our daily lives, more energy is required to power these devices. On a large scale, decreasing the power requirements of electronics would impact global energy consumption.”

Eric Beckman, the George M. Bevier Professor of Chemical and Petroleum Engineering, will join Fullerton as co-principal investigator of the study, “A New Approach to Explore the Semiconductor-to-Metal Phase Transition in Two-Dimensional (2-D) Crystals Using Ionomers.”

The individual layers of 2-D crystals can be isolated to make electronic devices that are a single atom or molecule thick. Semiconductor researchers have been studying these materials extensively for the past decade as a potential low-voltage replacement for traditional complementary metal-oxide-semiconductor (CMOS) electronics.

The key is triggering the material to switch very abruptly from a state in which the flow of charge is restricted (insulator) to a state in which charge can flow easily (conductor) and to do this at low voltage.

Fullerton and Beckman will use a type of polymer electrolyte called an ionomer to induce this abrupt switching in the 2-D crystal with an applied field. Theoretical predictions indicate that the material can switch states from an insulator to a conductor when a sufficient amount of strain is applied, and Fullerton and Beckman will deliver that strain at low voltage by custom-synthesized ionomers.

PCPs should screen for skin cancer

Skin cancer screenings by primary care physicians (PCPs) during routine office visits improve the detection of potentially deadly melanomas and find them earlier, according to School of Medicine researchers.

Lead author was Laura Ferris, faculty member in the Department of Dermatology and member of the melanoma program, University of Pittsburgh Cancer Institute.

Rates of melanoma, the most dangerous form of skin cancer, are increasing, and skin cancer screenings are one of the most important steps for early detection and treatment, said Ferris. Typically, patients receive skin checks by setting up an appointment with a dermatologist.

PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.

On average, the melanomas detected in the group who received a screening at a primary care visit were nearly twice as thin as those detected in the group that was not screened by a PCP. Thinner melanomas have a better prognosis than thicker ones that are more advanced.

In addition, only 5 percent of people in the screening group had especially worrisome melanomas that were thicker than 1 millimeter — which are more likely to metastasize and require a biopsy of a nearby lymph node — while 20 percent of the unscreened group did.

“The PCP screenings prevented a lot of people from needing more aggressive therapy,” Ferris said.

Another important finding was that nearly half of the screened patients were men, who are more likely to get and die from melanoma than women but have been underrepresented in other skin cancer screenings.

Funding was provided by a National Cancer Institute specialized program of research excellence grant in skin cancer.

Additional Pitt researchers included Melissa Saul, Francis Solano, Erica Neuren, Jian-Min Yuan and John Kirkwood. Colleagues from Brown and Harvard also contributed.

—Compiled by Marty Levine

 

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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