Norton, UK Partner on Clinical Trial for First-Ever Treatment of Radiation Necrosis

LEXINGTON, Ky. (Jan. 23, 2017) – Radiation therapy saves countless lives, but in rare cases, it can cause a debilitating, long-term complication when used on the brain. Around three to five percent of patients who receive radiation for brain tumors, or arteriovenous malformations (AVM), develop radiation necrosis, where the brain tissue around the targeted lesion becomes injured and dies.
The condition can be disabling, causing severe headaches, nausea and vomiting, cognitive problems and neural dysfunction. A variety of medications have been used to manage symptoms such as steroids and an “off label” combination of vitamin E and pentoxifylline but currently there is no approved cure.
A joint clinical trial at Norton Brownsboro Hospital in Louisville and the University of Kentucky could change that. The trial, led by Dr. Shervin Dashti and Dr. Tom Yao, both from the Norton Neuroscience Institute, and Dr. Justin Fraser at UK is the first in the world to intra-arterially deliver a single, small dose of bevacizumab, a cancer drug known by the name of Avastin, directly to the area of the brain affected by radiation necrosis. Moments before this, the blood-brain barrier is temporarily disrupted so that the drug can reach the lesion. This targeted method allows a much larger amount of the drug to directly reach the affected brain than would otherwise be possible using traditional intravenous delivery, thus amplifying its effect and reducing serious side-effects. Five patients will be enrolled at Norton and five at UK.
While the trial protocol constitutes a novel treatment approach as whole, each component is well-established. The drug, Avastin, has been approved for various cancers since 2004, and in 2011 a randomized, double-blind clinical trial with a small number of participants demonstrated its effectiveness for treating radiation necrosis when delivered by IV. Intra-arterial administration of drugs to the brain is also an established methodology, with thousands of patients having received such delivery of chemotherapy drugs for brain cancers. However, intra-arterial administration of Avastin for radiation necrosis has not been previously undertaken.
Dashti, who serves as co-director of the cerebrovascular and endovascular neurosurgery program at Norton Healthcare, has witnessed the effects of radiation necrosis on patients who have already experienced the trauma of brain cancer or AVM. In addition to the symptoms caused by the condition itself, patients also suffer from side effects of the high doses of steroids used to manage it — insomnia, mood changes, sometimes extreme weight gain.
“There was nothing that worked for treating it and people were being devastated,” he said. “What we’re doing is something completely different and I think it has a chance to really change the way we treat this. Its’ a rare complication, but really devastating when it happens, and this could possibly change the standard of care.”
More than three years ago, Dashti developed the investigational new treatment when two young patients were in desperate need. Aged only 12 and 13, both young girls had developed radiation necrosis after treatment for AVM and were experiencing severe side effects from the steroids. They each had disabling headaches, gained 50 to 60 pounds, missed significant amounts of school or withdrew entirely, and suffered emotionally. One patient experienced focal seizures affecting her arm and leg; the other patient had to be hospitalized for fluid overload.
With no other standard treatment options available, Dashti and Yao presented to the first patient and her family the idea of delivering a single, low dose of Avastin directly to the brain via intra-arterial catheter inserted through the groin. They agreed to try, and within 12 hours of the procedure, the patient’s headaches were completely gone. Brain scans over several months showed continuous and stable improvement, her arm and leg had strengthened to the point that she could walk without help and she was able to return to school. 
Jade Cain, now 16, was the second patient that Dashti and Yao treated with this new approach. She was 11 when the AVM was diagnosed and 13 when she met Dashti. According to her mother, Desiree Fischer, by that time 75 percent of her brain was swollen and she was so depressed that she didn’t want to leave the house.
“We’d been doing three or four months of really strong steroids and she ended up on all other kinds of other medications too because she developed thrush. So that’s what led us to this procedure. She spent a week in the children’s hospital because she was in fluid overload. She couldn’t do any more steroids because that was going to kill her.”
“It was really hard to deal with all of that, and obviously wasn’t very pleasant,” Cain said. “I missed a lot of my childhood during that time.”
The treatment that Dashti pioneered worked as well for Cain as for the first patient. Her headaches immediately resolved, she was weaned off of steroids within four weeks, and soon returned to school. An MRI ten months later revealed that cerebral edema had completely resolved.
“The response was the most amazing complete response after one treatment, and the imaging response was unbelievable. It’s a very visual thing —before the treatment, it looked like someone put a bomb in there. But it was like a miraculous recovery for both of them,” Dashti said.
The radical success with these two young patients motivated Dashti to start a clinical trial for the treatment. He and Yao asked Fraser, director of cerebrovascular surgery and surgical director of the comprehensive stroke center at UK, to partner with them. Fraser describes their joint effort as a “natural collaboration” after years of working alongside each other in local and professional activities.
“We’re in this position of facing an uncommon complication of a treatment that is becoming more commonly used, and we don’t have a great way to fix it,” Fraser said. “What’s special about our procedure is that patients getting the drug once, very directly to the brain, as opposed to a complete course of the drug that can cause serious systemic side effects. We’re developing an option to get the drug where it needs to go, locally, safely, and we only have to give it once.”
The trial is supported by both institutions and has received expert project management support from the UK Center for Clinical and Translational Science.
“When you read in the news that a clinical trial has been done on x, y, or z, they trot out guys like me — the principal investigators. But what’s behind the curtain of any clinical trial is an army of people who are ensuring that we follow the protocol and that we’re safeguarding patients. You’re asking a lot of a person when you sit them down and say, ‘Hey you’ve got this problem, and I think I have a treatment that might work for you but we haven’t totally proven it yet. Would you like to participate in the study?’ It’s a very vulnerable position for a patient,” Fraser said. “The onus really is on us as physicians, scientists, and research staff to recognize that and take every available measures to ensure that we are consenting people with appropriate informed consent, recording every single issue, and that we give patients opportunities to withdraw from the study if they want to.”
Dashti and Yao’s second patient, Cain, had a final angiogram of her brain in March 2016. It showed that everything was clear. And, because she had to be partially awake during part of the procedure, she was able to see the dye dispersing through her brain.
“It was really cool. It would light up like fireworks where the dye was going through the vessels,” she said.
Cain, Fischer, and their family have shown their gratitude for the care and treatment received from both Norton Neuroscience Institute and Norton Children’s Hospital by raising more than $20,000 for the Children’s Hospital Foundation. Their fundraising efforts have included a variety of yearly arts-based programs — such as a raffle for a painting, and performances by “The Dancing Divas”, a non-profit organization that empowers women to achieve personal growth, strength, and health through dance. At the decision of Cain and Fischer, these funds are directed specifically to support research on radiation necrosis.
“From the steroid use, my child who weighed 105 pounds went up to 160 pounds in one month. Had this treatment already been approved, we could have omitted all that. She battled to get the weight off, and to overcome poor body self-image,” Fischer said. “I wish it had been approved way before. And I hate that my child is the one who had to go through it, but I tell her, ‘You have no idea what you’ve done — you’ve paved the way so other people hopefully won’t have go through what you went through.”
If you are interested in learning about participating in this study, please contact Elodie Elayi at elodie.elayi@uky.edu or visit review the study information at ClinicalTrials.gov.  
For general information about participating in research, including a list of studies at UK and access to national studies, visit www.ukclinicalresearch.com.
MEDIA CONTACT: Mallory Powell, mallory.powell@uky.edu; Lynne Choate, Lynne.Choate@nortonhealthcare.org.

Power From a Partnership

LEXINGTON, Ky. (Jan. 23, 2017) — At first blush, most would not think that the Weisenberger Mill and the University of Kentucky have much in common.
Perhaps, that is what makes this unique partnership so, well, powerful.
These two Kentucky icons have been serving the people of the Commonwealth since 1865 but it was a recent collaboration that has brought these two institutions even closer together.
Weisenberger Mill is a small, family-owned business in Midway, Kentucky. Located on the South Elkhorn Creek, Weisenberger Mill manufacturers flour and cornmeal to create a suite of about 60 different products. Six generations of Weisenbergers have operated the mill at its current location.
The reason August Weisenberger, a German immigrant, chose that location to start his milling operation was because of the Elkhorn. The creek has powered the mill’s twin turbine since the 1800s.
In the 1980s, Weisenberger Mill hired David Brown Kinloch, president of Shaker Landing Hydro Associates, to work on the turbines. It was Kinloch’s first hydroelectric installation in Kentucky, and his experience working with the Weisenbergers left a favorable impression.
Hydro technology continued to evolve over the years, and when Kinloch had a vision for a next-generation of power generation, he immediately thought of his first install.
Wind turbines use variable speed generators to maximize efficiency. Though the technology works remarkably well for wind energy, no one has adapted variable speed generation at a hydroelectric plant.
That was until Kinloch, Weisenberger Mill and the UK Center for Applied Energy Research (CAER) decided to partner on this pioneering initiative.
“We received a U.S. Department of Energy (DOE) grant to install a variable speed generator at Weisenbeger Mill,” Kinloch said. “This is a technology that was developed by the wind industry and most wind turbines use this same technology. But it’s never been tried by the hydro industry, and DOE was very interested in us trying it here, on a small demonstration scale.”
CAER assisted in writing the DOE grant for the project and CAER’s Jim Neathery analyzed data on the project to verify if the new generator was beneficial.
Kinloch noted that he hoped that the new generator would increase efficiency by 10 to 15 percent. Suffice to say, he and Neathery were blown away by the results.
“The experiment actually worked much better than we were expecting,” Kinloch said. “We were expecting to get 10 to 15 percent more power out of this new generation, and we’re actually getting 96 percent more power out of it.
“One of the reasons that we found out was that the old generator was operating at the wrong speed. It was running too fast. By slowing the generator down, we’re able to get the turbine into a much more optimal efficiency range. And by doing that we’re able to get the power output up significantly. Close to doubling the power output.”
The results have been so positive, Kinloch said that his company is in the process of installing the new technology on four new larger hydroelectric plants they are building at existing dams on the Kentucky River.
He said the project would not have been possible without the assistance from CAER.
“The Department of Energy didn’t have any question about what the results were because we had UK CAER crunching the numbers,” Kinloch said. “Their trustworthiness is iron clad, and that credibility is what the Center for Applied Energy Research really gave this project.”

UK's Gatton College Launches Professional Finance Master's Degree

LEXINGTON, Ky. (Jan. 23, 2017) — If you have a passion for the business world, in particular a desire to work in the finance industry, yet wonder how you can obtain and develop the skills needed for such a career, the University of Kentucky’s Gatton College of Business and Economics has some very good news for you.
The Gatton College is launching a new professional Master of Science in Finance (MSF) degree, and is accepting applications for the program, which will welcome its first class in fall 2017. On Thursday, Jan. 26, from 5:30-7 p.m. in the Gatton College’s Woodward Hall (550 S. Limestone), the college will host an Open House featuring its One Year MBA program; students will also be able to get more information and speak with faculty about the new MSF program.
“The MSF degree program broadens students’ career opportunities in the finance and banking industries by providing rigorous and focused training in finance, and sharpening their skills for the fast-changing and competitive world of modern finance,” said Mark Liu, associate professor of finance in the Gatton College, who will direct and teach in the MSF program. “Job candidates with MSF degrees are highly desired in finance-specialized industries, particularly investment banking and asset management companies, and are sought after by corporate treasury departments. The job opportunities in these industries are substantial, intellectually stimulating and high-paying.”
Beginning each fall, the MSF program consists of a 10-month, 30-credit-hour, 10-course curriculum. The MSF program is not just for finance or business majors; there are no specific course prerequisites other than college-level math and introductory statistics. Work experience is not required for admission. All applicants are automatically considered for merit-based scholarships.
All MSF classes will be offered in the brand new state-of-the-art Seale Finance Learning Center in the new Gatton College building, which opened in October 2016. MSF students will also gain firsthand asset portfolio management experience by participating in Gatton’s $5 million student-managed investment fund.
“This unique program is the only MSF program in the Commonwealth, and serves an important regional and national need for educating skilled and qualified financial management professionals,” said Gatton College Dean David W. Blackwell. “This program leverages Gatton’s nationally recognized strength in finance to train students for these critical careers.”
Gatton’s Department of Finance and Quantitative Analysis has been part of the international CFA (Chartered Financial Analyst) Institute’s University Recognition Program since 2012, which recognizes its success in preparing students to earn the CFA credential, and the MSF program will prepare students who wish to sit for the CFA exams. MSF students will also be able to take advantage of comprehensive, business and finance focused career development services through Gatton’s Graham Office of Career Management.
The MSF degree is one of three professional master’s programs in the Gatton College, which prepare students for specific professional positions. It joins the college’s MBA programs for students interested in advancing their careers across disciplines, and the master’s degree in accounting which prepares students to pass the CPA examination.
For more information about the MSF degree, visit the Gatton College website at http://gatton.uky.edu/programs/masters/master-science-finance.

GoinGlobal Helps UK Students With Local, International Job, Internship Searches

LEXINGTON, Ky. (Jan. 23, 2017) — University of Kentucky has partnered with GoinGlobal to help job- and internship-seekers find opportunities at home and abroad. The addition of this expert-created career resource strengthens UK’s investment in student career development and its commitment to globalization.
In a period of strong globalization and mobility, an increasing number of UK students want to experience life and work in another country, and are preparing themselves to be globally engaged professionals. Using the complete toolkit of GoinGlobal resources, which provides guides to major cities and countries around the world, UK students, faculty and staff can now access resources that assist them in seeking and finding occupational opportunities and prepare them for valuable cross-cultural experiences.
Sue Roberts, associate provost for internationalization, said she is particularly thrilled with collaboration from key campus stakeholders to fund and set-up GoinGlobal, which will make it available to all students, whatever their major is. Sponsoring offices include the UK International Center, the James W. Stuckert Career Center, the Graham Office of Career Management in the Gatton College of Business and Economics, and Engineering Career Development in the College of Engineering.
“I am so pleased that all UK students will now have access to this valuable resource as they consider their options after graduation,” Roberts said. “Working overseas for a period is an increasingly attractive option, even for those who see themselves based in the U.S. in the long term. Employers value the cross-cultural skills, as well as the specific professional experiences, attained by those who have chosen to work in a different country. At UK we are committed to opening the doors to global opportunities for our students, and GoinGlobal helps us do this.”
The GoinGlobal site, which is translated into more than 50 languages, allows users to create a personal account, set job search criteria, and request notifications about new job listings. Users can also access the employer directory to search for possible future employers, and they can save their favorite companies for future reference.
The GoinGlobal database includes overviews of professional organizations and other personal networking information and opportunities relevant to the user’s interests, skills and career aspirations. In addition, there are useful country profiles that include details on living abroad, such as financial considerations, cultural advice, cost of living, housing, and related information.
Further, the site includes an internship section allowing web users to search by country, native language, keywords and other rubrics, and it includes a nonprofit section which retrieves data from Idealist and Devex job boards, two of the leading job search sites in the nonprofit sector.
In addition, for UK’s international students seeking U.S. employment, the site offers a searchable H1-B database, dating back to 2009. H1-B is a work visa that many students will pursue after completing their practical training period. Those interested will be able to research companies and see how many H1-B petitions each company submitted in the past to the U.S. government.
The site is accessible on the UK International Center’s website at www.uky.edu/international/GoinGlobal.
In addition to the helpful online tutorials that are embedded and easily accessible in GoinGlobal, the International Center, in partnership with the Career Center, will host multiple training sessions throughout the year, where UK students, faculty and staff will be able to see a demo of GoinGlobal’s key features and capabilities.
For questions about GoinGlobal and how to use it, please email ukcareercenter@uky.edu or call the James W. Stuckert Career Center at 859-257-2746.