Early Trial Shows Injectable Agent Illuminates Cancer During Surgery

Contact: Samiha Khanna
Phone: 919-419-5069
Email: samiha.khanna@duke.edu

Early Trial Shows Injectable Agent Illuminates Cancer During Surgery 

DURHAM, N.C. — Doctors at the Duke University School of Medicine have tested a new injectable agent that causes cancer cells in a tumor to fluoresce, potentially increasing a surgeon’s ability to locate and remove all of a cancerous tumor on the first attempt. The imaging technology was developed through collaboration with scientists at Duke, the Massachusetts Institute of Technology (MIT) and Lumicell Inc.

A vial of LUM015. (Melodi Javid Whitley/ Duke Medicine)

According to findings published January 6 in Science Translational Medicine, a trial at Duke University Medical Center in 15 patients undergoing surgery for soft-tissue sarcoma or breast cancer found that the injectable agent, a blue liquid called LUM015 (loom – fifteen), identified cancerous tissue in human patients without adverse effects.

Cancer surgeons currently rely on cross-sectional imaging such as MRIs and CT scans to guide them as they remove a tumor and its surrounding tissue. But in many cases some cancerous tissue around the tumor is undetected and remains in the patient, sometimes requiring a second surgery and radiation therapy.

“At the time of surgery, a pathologist can examine the tissue for cancer cells at the edge of the tumor using a microscope, but because of the size of cancer it’s impossible to review the entire surface during surgery,” said senior author David Kirsch, M.D., Ph.D., a professor of radiation oncology and pharmacology and cancer biology at Duke University School of Medicine. “The goal is to give surgeons a practical and quick technology that allows them to scan the tumor bed during surgery to look for any residual fluorescence.”

Researchers around the globe are pursuing techniques to help surgeons better visualize cancer, some using a similar mechanism as LUM015, which is activated by enzymes. But the Duke trial described in the journal is the first protease-activated imaging agent for cancer that has been tested for safety in humans, Kirsch said.

LUM015 was developed by Lumicell, a company started by researchers at MIT and involving Kirsch. In companion experiments in mice described in the journal, LUM015 accumulated in tumors where it creates fluorescence in tumor tissue that is on average five times brighter than regular muscle. The resulting signals aren’t visible to the naked eye and must be detected by a handheld imaging device with a sensitive camera, which Lumicell is also developing, Kirsch said.

In the operating room after a tumor is removed, surgeons would place the handheld imaging device on the cut surface. The device would alert them to areas with fluorescent cancer cells.

Going into surgery, the goal is always to remove 100 percent of the tumor, plus a margin of normal tissue around the edges, explained senior author Brian Brigman, M.D., Ph.D., chief of orthopedic oncology at Duke. Pathologists then analyze the margins over several days and determine whether they are clear.

“This pathologic technique to determine whether tumor remains in the patient is the best system we have currently, and has been in use for decades, but it’s not as accurate as we would like,” said Brigman, who is also the director of the sarcoma program at the Duke Cancer Institute. “If this technology is successful in subsequent trials, it would significantly change our treatment of sarcoma. If we can increase the cases where 100 percent of the tumor is removed, we could prevent subsequent operations and potentially cancer recurrence. Knowing where there is residual disease can also guide radiation therapy, or even reduce how much radiation a patient will receive.”

Researchers at Massachusetts General Hospital are currently evaluating the safety and efficacy of LUM015 and the Lumicell imaging device in a prospective study of 50 women with breast cancer. Afterward, Kirsch said, multiple institutions would likely evaluate whether the technology can decrease the number of patients needing subsequent operations following initial breast cancer removal.

In addition to Kirsch and Brigman, study authors include Melodi Javid Whitley, Diana M. Cardona, Alexander L. Lazarides, Ivan Spasojevic, Jorge M. Ferrer, Joan Cahill, Chang-Lung Lee, Matija Snuderl, Dan G. Blazer III, E. Shelley Hwang, Rachel A. Greenup, Paul J. Mosca, Jeffrey K. Mito, Kyle C. Cuneo, Nicole A. Larrier, Erin K. O’Reilly, Richard F. Riedel, William C. Eward, Assistant Professor in Orthopaedic Surgery, David B. Strasfeld, Dai Fukumura, Rakesh K. Jain, W. David Lee, Linda G. Griffith and Moungi G. Bawendi.

Duke author Kirsch and MIT authors Griffith, Bawendi, Ferrer and W. David Lee hold interest in or are involved with Lumicell Inc., a company commercializing LUM015 and the imaging system. Duke and MIT hold a patent on the imaging device technology. More detailed conflict-of-interest information is included in the manuscript published by Science Translational Medicine.

The study was funded in part by an American Society of Clinical Oncology Advanced Clinical Research Award to Kirsch, the National Institutes of Health (NIH) (T32GM007171), a National Cancer Institute Small Business Innovation Research award to Lumicell Inc. (1U43CA165024), the NIH National Center for Advancing Translational Science (UL1TR001117), and Duke Comprehensive Cancer Center Support (5P30-CA-014236-38). Lumicell Inc. provided the imaging agents.

Read the full article in Science Translational Medicine here, and more about the study at:

January 6
New technology makes tumors glow, aids in surgery, New York Daily News   (Kirsch et al)

Department of Orthopaedic Surgery Welcomes Janet Prvu Bettger, ScD, FAHA

Janet Pvru Bettger, ScD, FAHAJanet Prvu Bettger, ScD, FAHA has joined Duke Orthopaedics as an Associate Professor in the orthopaedic surgery department, and the inaugural director of our health policy and implementation research program, the only program of its kind in an orthopaedic department.

Dr. Bettger’s research is dedicated to improving health care quality and care coordination for older adults with chronic conditions and those at risk for functional decline. She is the principal investigator on a national Patient-Centered Outcomes Research Institute (PCORI) grant to study the comparative effectiveness of rehabilitation and a PI on two NIH funded studies to examine outcomes after inpatient rehabilitation. Related to these large database studies is the implementation research she leads on transitional care and interdisciplinary interventions to prevent adverse events. Dr. Bettger is leading a multi-site, transitional care health care quality collaborative in Ohio funded by the Centers of Disease Control and Prevention and the State of Ohio, and is a co-investigator on the RECOVER Trial in China, a randomized controlled trial of early supported discharge and transitional care in rural China.

Janet grew up in Canada and finished her kinesiology degree at Western University before moving to the U.S. to study models of integrated care to reduce post-acute disability. After living in the Midwest and in Seattle, she drove back across the country where on her fifth day in Boston she met her husband Mark, a Rhode Island native and recent Berklee College of Music grad.

They married and lived in Boston while Janet worked in state government and completed her doctorate at Boston University. They moved to Philadelphia and got their dog Cooper (now 9), had their son Alex (now 8), Janet completed postdoctoral fellowships at the University of Pennsylvania, and Mark completed his MBA. February 2010 brought 75 inches of snow to Philadelphia and the Bettger’s were happy to be recruited to Duke that spring. The year of 2016 brings some exciting changes for the Bettgers as Mark transitions from DOCR to General Internal Medicine as their new department administrator and Janet transitions from the Duke School of Nursing to join the Department of Orthopaedic Surgery’s faculty. They are looking forward to the adventures ahead!

Department of Orthopaedic Surgery Welcomes Timothy Sell, PhD, PT

Timothy Sell, PhD, PT

Timothy Sell, PhD, PT has joined Duke Orthopaedics as an Associate Professor and the director of the K-lab. He has over 100 publications, and this last year held close to one million dollars in external funding for his research work.

Tim was born in Las Vegas, NV, and went to high school in Cincinnati, OH. He received a Bachelor of Science in Physical Therapy, a Master of Science in Human Movement Science (Biomechanics Focus) from the University of North Carolina at Chapel Hill, and completed his PhD in Rehabilitation Science from the University of Pittsburgh.

During his research career, Tim has focused on the role of functional joint stability in the prevention of musculoskeletal injuries; in recovery following injury; and in re-establishing neuromuscular control following surgery.  He has conducted research in many different populations from youth athletes to masters athletes; recreational active individuals to professional athletes; and in military servicemen and women.

Tim is married to Cindy Sell, who is a Registered Nurse and an operating room manager.  She is also currently in graduate school (University of Pittsburgh) completing her Master of Science in Nursing Administration.  Cindy is from Reidsville, NC, and both Tim and Cindy call NC home.  They’ve missed the mountains and ocean during their fourteen years in Pittsburgh and are looking forward to taking their three Golden Retrievers hiking in the mountains and swimming in the ocean.

Department of Orthopaedic Surgery Welcomes Marcus Roll, PT, DPT

Dr. Clewley's Family HikingThe Department of Orthopaedic Surgery would like to welcome Marcus Roll, PT, DPT as a Doctor of Physical Therapy Division Faculty Development Resident. Marcus is returning to Duke after graduating from Duke’s DPT program in 2011, and practicing clinically at both the Rancho Los Amigos National Rehabilitation Center in Los Angeles County, CA on the Adult Brain Injury Service, and most recently, on the Neurology and Neurosurgery services at the University of North Carolina Hospital. His clinical interests include gait analysis and neurologic rehabilitation.

Marcus grew up on a farm in Illinois and received his undergraduate degree at the University of Illinois at Urbana Champaign. Marcus lives in Durham with his wife, Erin Bristow, an RN at Duke Regional’s Emergency Department, their two year old daughter, Emilia, and, soon, their second daughter, who will arrive in later January 2016. Their family enjoys hiking, cooking, and weekly trips to the Durham Farmer’s Market.

Department of Orthopaedic Surgery Welcomes Derek Clewley, PT, DPT

Derek Clewley Family Picture

The Department of Orthopaedic Surgery would like to welcome Derek Clewley, PT, DPT as a faculty member within the Doctor of Physical Therapy division.  Derek grew up in Montana and lived in Atlanta for the past 10 years.  He completed graduate school training at the University of Montana, followed by a fellowship in manual therapy, and is a PhD candidate at Rocky Mountain University of Health Professions in Utah.  Derek’s research interests include manual physical therapy and chronic pain management.   He has significant experience in program development and management including prior role as residency and fellowship director at BenchMark Rehab Partners.  His wife, a chemical engineer, along with their two children Gavin (5 years) and Amelia (3 years) have enjoyed the transition to North Carolina.  Outside of work, he enjoys training for half and full marathons, being outside, and attempting to burn off excess energy with his children.