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November 11, 2010

Research Notes

IMRT research presented

Research by investigators at the University of Pittsburgh Cancer Institute (UPCI) on the use of intensity-modulated radiotherapy (IMRT) in treating patients with anal carcinoma was presented recently at the American Society for Radiation Oncology annual meeting. IMRT is a radiation therapy technique that delivers precise radiation to tumors while sparing the surrounding normal tissue.

Among the results reported were:

PET/CT IMRT cuts toxicity

A study led by UPMC Cancer Centers radiation oncology resident Regiane de Andrade and overseen by Dwight E. Heron, vice chair of the Department of Radiation Oncology in the School of Medicine, found that PET/CT-based IMRT may control and treat cancers of the anus effectively when combined with chemotherapy.

The research revealed that patients with anal carcinoma who had diagnostic PET/CT imaging as part of their radiation treatment planning had excellent response rates to treatment and experienced fewer overall toxicities.

While chemoradiation has become the standard of care for treating patients with anal carcinoma, typically resulting in good disease control and the ability to avoid a colostomy, treatment-related toxicities can be significant and cause patients to delay or even cease treatment. “While treatment options for patients with anal cancers have come a long way, they can still be physically debilitating,” said de Andrade. “With IMRT we can decrease toxicities and improve patients’ compliance with treatment.”

The study reviewed the experiences of 31 patients treated for cancers of the anus at UPMC Cancer Centers between March 2003 and March 2009. All patients underwent PET/CT imaging before treatment to better assess the extent of their disease and to identify accurately the tumors to be targeted. All patients received chemotherapy concurrent with radiation and all completed the planned treatment with few toxic side effects and excellent control of the disease.

The combination of PET/CT and IMRT allows for more accurate tumor localization for radiation delivery while reducing toxicity to the rest of the body, said de Andrade.

Proper rad dosage cuts toxicity

Patients with anal carcinoma who are undergoing IMRT and concurrent chemotherapy experience fewer side effects associated with gastrointestinal toxicity when safe radiation dosage is well established, UPCI researchers found.

The identification of optimal IMRT dosimetric parameters can help guide radiation oncologists across the country and internationally in treating patients with anal cancer who must receive concurrent IMRT and chemotherapy.

S. Gillianne DeFoe, chief resident of radiation oncology at UPMC Cancer Centers, who was overseen by Sushil Beriwal, a School of Medicine faculty member in radiation oncology and director of the Department of Radiation Oncology at Magee-Womens Hospital, reviewed the treatment of 58 patients with anal cancer who were treated with chemotherapy concurrently with IMRT at UPMC Cancer Centers between March 2003 and March 2009.

When patients experience gastrointestinal toxicity, they often need several breaks during their radiation treatment. The breaks allow patients to recover from the toxicities of treatment but negatively affect clinical outcomes.

Clinical factors such as a patient’s age and stage of disease could not determine whether a patient would experience gastrointestinal toxicity from this combination of treatments, but researchers found that by exceeding the small bowel dose beyond the threshold volume, the rate of gastrointestinal toxicity quadrupled.

DeFoe said, “IMRT is one of the most advanced treatment options we can offer patients, but in order for this technique to be effectively utilized, we need to set guidelines for its use. By reviewing the cases of patients who came through UPMC Cancer Centers in the last six years, we determined that if we can limit the dose of small bowel radiation to a certain volume, we can further reduce the toxicity of treatment.”

NSAIDs’ anti-cancer power studied

Non-steroidal anti-inflammatory drugs (NSAIDs) prevent colon cancer by triggering diseased stem cells to self-destruct, according to researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine. Their findings, reported in the Proceedings of the National Academy of Sciences, could lead to new strategies to protect people at high risk for the disease.

Doctors have long known that NSAIDs, such as aspirin, can lower the risk of colon cancer, but it’s not been clear how they do it, said senior investigator Lin Zhang, a faculty member in the School of Medicine’s Department of Pharmacology and Chemical Biology and UPCI.

“Our study shows NSAIDs target stem cells that have accumulated mutations that could lead to cancer development and initiate a biochemical pathway that makes those cells undergo programmed cell death, a process called apoptosis,” Zhang said.

The researchers studied mice that have a genetic defect similar to one that is present in patients with familial adenomatous polyposis, a condition that accounts for about 1 percent of all cases of colorectal cancer and typically is present in non-hereditary colon cancer as well.

Mice that ate the NSAID sulindac in their feed within a week had markedly elevated rates of apoptosis in their intestinal polyps, and specifically in stem cells that had accumulated some dangerous precancerous changes causing abnormal cell signaling, the researchers found.

If the mice also lacked a gene called SMAC, which makes a protein that is released during apoptosis, sulindac was less effective at killing the diseased stem cells. “That leads us to think that SMAC is an important regulator of this process,” Zhang said.

He and his team then took a closer look at polyps removed from patients and found higher levels of apoptosis in cells with stem cell features among those who were taking NSAIDs. The findings indicate that apoptosis measures could be a useful way of assessing the effectiveness of cancer-prevention drugs and could lead to the development of new agents to further sensitize abnormal stem cells to NSAIDs.

Co-authors of the paper included Jian Yu, Wei Qiu, Xinwei Wang and Brian Leibowitz of pathology, Robert E. Schoen of medicine and Zhang lab staff member Hongtao Liu, all from UPCI; and researchers from the Hubrecht Institute for Developmental Biology and Stem Cell Research, the Ontario Cancer Institute and the Hiroshima University Graduate School of Public Health.

The research was funded by grants from the National Institutes of Health, the American Cancer Society and the Flight Attendant Medical Research Institute.

DOE funds research on efficient buildings

The Swanson School of Engineering and Center for Energy will join a team of researchers who are developing technologies to make buildings more energy efficient.

The project, funded up to $122 million by the Department of Energy over the next five years, is led by Penn State, which will establish an Energy Innovation Hub at the Philadelphia Navy Yard clean energy campus, and will bring together leading researchers from academia, two U.S. national laboratories and the private sector in an effort to develop energy-efficient building designs.

The Pitt team, which will account for at least $2 million of the research, will be led by mechanical engineering and materials science faculty member Laura Schaefer, deputy director of the Mascaro Center for Sustainable Innovation and associate director of the Center for Energy.

Buildings account for nearly 40 percent of U.S. energy consumption and carbon emissions. Developing systems to improve building efficiency will reduce energy use, cut pollution and create jobs in the building efficiency industry.

Schaefer said the Pitt team will aim to improve technologies that take into account all aspects of a building.

“We are interested in a comprehensive approach that keeps in mind the systems that operate within a building, the way a workplace is subdivided and constructed, the building envelope — such as the outer walls, roof, windows — and how all of these components interact with each other to maintain the same quality of work life or productivity in that building while using less energy for the same or better conditions.”

The technologies the Pitt team will research include walls that can turn their insulation on or off, using natural wind currents over “sails” to produce a building’s electricity, dynamic controls that turn a building into a thinking organism and rerouting steam that is a byproduct of a building’s heating system for other purposes, such as heating water.

Other members of the Pitt team include William Clark, Daniel Cole, Mark Kimber, Jeffrey Vipperman and Lisa Weiland of the Department of Mechanical Engineering and Materials Science, and Amy Landis and Melissa Bilec of the Department of Civil and Environmental Engineering.

REES receives U.S. Russia grant

The Center for Russian and East European Studies recently was awarded a grant through the U.S. Russia Foundation’s “Entrepreneurship, Economic Development and Rule of Law” program for a partnership project with the International Market Institute (IMI) in Samara, Russia.

The grant will support two seminars to be held in Samara and in Pittsburgh in 2010-11, both involving Pitt and IMI faculty members and local government officials from the Samara region. The government officials will receive practical training on increasing the effectiveness of local governments in supporting regional economic development, including two weeks of intensive training in Pittsburgh to be organized by the Graduate School of Public and International Affairs.

At the conclusion of the project, Pitt and IMI faculty expect to develop a handbook on best practices for dissemination to local governments throughout Russia.

Drug spending examined

Medicare patients in regions that spend the most on prescription medications are not necessarily getting better quality care, according to a new study of spending practices from the Graduate School of Public Health (GSPH) in conjunction with researchers from Harvard.

The findings, published in the Nov. 3 Online First issue of the New England Journal of Medicine, reveal great variation across the country in both drug spending and the rate of inappropriate prescriptions for the elderly.

Lead investigator Yuting Zhang, a faculty member in health economics, said that even after demographic characteristics such as age, sex, individual health status and insurance coverage are taken into account, it is clear that Medicare drug spending varies broadly among hospital-referral regions (HRRs).

“Higher spending can be justified if it’s for drugs that are necessary and appropriate and improve patients’ health,” she said. “But if certain drugs are being incorrectly prescribed to seniors, then that can lead to complications and expensive interventions, such as hospitalization. As we try to reform health care to get costs under control, we need a better understanding of how spending differs regionally to make a positive impact.”

Zhang and her colleagues assessed two measures of prescription quality from the Healthcare Effectiveness Data and Information Set. One measure indicates whether a Medicare beneficiary receives at least one high-risk drug, such as some antihistamines and muscle relaxants, which should be avoided in the elderly. The other assesses whether Medicare beneficiaries who have dementia, chronic kidney failure or a history of pelvic or hip fractures are given prescriptions in the outpatient setting for drugs that should not be given to patients with those conditions.

Using pharmacy event and medical claims data as well as zip code information for more than 500,000 Medicare beneficiaries, the researchers determined that there was broad variation across regions in the quality of prescribing after adjustment for demographic variables and level of health risk.

For example, at the top of the scale, 44 percent of elderly beneficiaries in Alexandria, La., used high-risk drugs while only 11 percent in the Bronx, N.Y., did.

Regions where beneficiaries were more likely to be given prescriptions for high-risk or potentially harmful drugs did not necessarily spend more on drugs overall than regions where beneficiaries were less likely to use high-risk or harmful drugs.

In addition, the researchers found that regions where non-drug medical spending was higher also were the places where there was a greater likelihood of high-risk or harmful drugs being prescribed for Medicare beneficiaries.

“That contradicts the idea that high spending leads to better prescription practices,” Zhang noted.

Rad-chemo combo may treat head, neck cancers

Stereotactic body radiotherapy (SBRT), a radiation therapy procedure that precisely delivers a large dose of radiation to tumors, may effectively control and treat head and neck cancers when combined with the chemotherapy cetuximab, according to researchers from the University of Pittsburgh Cancer Institute (UPCI).

The results of the research were presented recently at the American Society for Radiation Oncology annual meeting.

The study, led by otolaryngology faculty member Dwight E. Heron, vice chair of the Department of Radiation Oncology in the School of Medicine, enrolled 24 patients with recurrent head and neck cancers who had undergone radiation therapy treatment previously.

For this study, Heron and his team combined cetuximab, which has been shown to enhance the effect of radiation therapy in patients with newly diagnosed head and neck cancers, and SBRT. By combining the two, treatment time was reduced from six weeks to one week while improving the side effects of re-treatment.

Patients received cetuximab a week before and during the two-week course of SBRT. The study showed that the regimen is a safe treatment option and may improve overall patient survival rates.

According to Heron, the study is important because surgical treatments for many patients with recurrent, locally advanced head and neck cancers often are limited, while other treatments either fail to control the disease progression or are too toxic.

“While therapies for head and neck cancers have improved over the years, too many patients suffer relapses,” said Heron. “When surgery and certain combinations of chemotherapy and radiation therapy are deemed either high risk or too toxic as treatment options, very specialized radiation therapy strategies are frequently considered. Unfortunately, conventional radiation therapy, including intensity-modulated radiation therapy, often has debilitating side effects for this subset of patients, and we are often faced with the challenge of how to treat their cancers aggressively while limiting the risk of side effects.”


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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