Norman Lehman, UofL professor of pathology and biochemistry and molecular genetics, led the study of the origins of uncommon brain tumors called astroblastomas that most often affect children and young adults.

“This research gives us a new understanding of how childhood brain tumors with origins in early embryonic development arise,” Lehman said. “It could lead to detection very early in the formation of these types of tumors, new treatments or potentially even strategies to prevent their formation.”

The research, published this week in , revealed two distinct subtypes of these tumors, one that develops in early childhood, the other developing later in life.

The type of astroblastoma that occurs in young children is derived from radial glia that arise very early in the embryonic brain and are biologically related to tumors known as ependymomas. The other type of astroblastoma, typically occurring in young adults, is derived from later neural stem cells called outer radial glia and are biologically related to astrocytomas.

The research also has implications in understanding differences in tumor occurrence based on sex.

“The early-development astroblastoma tumor appears to occur exclusively in females, which may give us a better understanding of why certain types of tumors not involving the reproductive system are found more frequently in males or females,” Lehman said.

Lehman also said the tumors’ mechanisms likely involve alterations in DNA methylation that could possibly be exploited to detect tumor development early on or mitigate their development, but also are associated with other types of neural conditions.

“The altered genes that are associated with the development of these tumors are genes that also are associated with developmental neurocognitive disorders such as autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia,” he said.

Contributors to the work included Brian Williams and Akshitkumar Mistry, both assistant professors in the UofL Department of Neurological Surgery and neurosurgeons with UofL Health, UofL biochemistry and molecular genetics graduate student Müge Sak and former UofL pathology resident Khaled Alkhateeb.

“We have very few treatments for brain tumors,” Mistry said. “If we can get to the bottom of this very rare brain tumor in terms of its biological origins or its biological behavior, then that knowledge could be applied to some of the other aggressive brain cancers. The question is, how does this sort of research apply to other tumors that are not well understood, and can we gain insight into those other tumors to hopefully figure out how they’re behaving?”

Other important contributors included developmental biologist Nathalie Spassky of the Institut de Biologie de l’École Normale Supérieure in Paris and Kenneth Aldape of the National Cancer Institute Center for Cancer Research.��

Neurosurgeons performing the procedure are Joseph S. Neimat, MD, chair of the Department of Neurosurgery, and Brian J. Williams, MD, assistant professor and director of the Brain Tumor Program. Both practice with University of Louisville Physicians.

According to the National Brain Tumor Society, more than 688,000 Americans are living with a brain tumor. In the past, some tumors were considered too difficult to reach. However, the minimally invasive NeuroBlate laser is now allowing neurosurgeons to remove tumors and lesions that would traditionally be considered inoperable.

NeuroBlate laser therapy can be precisely controlled to kill abnormal tissue while doing as little harm as possible to surrounding healthy tissue. It also can be used in patients who have lesions in areas of the brain that are difficult to access by traditional open surgery without harming essential functions like speech, vision and muscle control.

The procedure is performed at Jewish Hospital, a part of KentuckyOne Health. The NeuroBlate��System from Monteris Medical��is a robotic laser technology that uses real-time magnetic resonance imaging (MRI) to precisely guide a laser probe. The laser applies heat to the growth, in controlled amounts, until the diseased tissue is destroyed. It can be used on tumors and lesions in many locations in the brain, near the surface or deep inside.

“The procedure is performed while the patient is in an MRI machine, so physicians can see the lesion and surrounding healthy tissue to apply laser energy where it is needed. The temperature of nearby healthy tissue is monitored to help ensure that it is protected as much as possible,” Neimat said. “We are thrilled to have this technology at our fingertips, to be able to help more people suffering from brain tumors and lesions.”

Rather than making a large opening in the skull, the NeuroBlate laser technology requires just a small hole, about the diameter of a pencil. The procedure is considered minimally-invasive surgery, a type of procedure that generally involves less pain, discomfort and scarring than traditional surgery, and allows patients to go home and resume normal activity sooner.

“Laser interstitial thermal therapy or ‘LITT’ offers patients suffering from difficult-to-access or recurrent brain tumors a minimally invasive option for local treatment of their disease,” Williams said. “Because the recovery is quite a bit quicker than with traditional open surgery, patients are able to expeditiously move on to radiation and chemotherapy.”

The NeuroBlate System was cleared by the FDA in April 2013 and is in use at more than 20 of the nation’s leading health care institutions. It also was licensed by Health Canada in September 2014 as the first and only minimally invasive robotic laser thermal therapy tool available in that country.

Patients seeking appointments with Neimat and Williams should contact UofL Physicians-Neurosurgery at 502-588-6000.

Neuro-oncology experts from across North America provided an��audience the latest developments on the best current practices and future treatment directions for patients with primary gliomas using surgery, radiation and chemotherapy at the second annual James Graham Brown Cancer Center Neuro-oncology Symposium at UofL��earlier this month.

Eric Burton, MD, assistant professor in the UofL Department of Neurology and director of neuro-oncology at the James Graham Brown Cancer Center, organized the symposium, sponsored by UofL Department of Neurology and JGBCC, a part of KentuckyOne Health. Burton talked with Mark Hebert for about brain tumors prior to the event.

Among the speakers was Raymond Sawaya, MD, chair and professor of the Department of Neurosurgery at the University of Texas MD Anderson Cancer Center, who explained that radical surgical procedures to remove as much of a glioblastoma as possible most often results in improved overall survival for the patient. He described how cortical mapping and advanced imaging can allow surgeons to remove more of the tumor while preserving functionality and reducing potential deficits in the patient.

Shiao Woo, MD, chair and professor in the UofL Department of Radiation Oncology, outlined the latest developments in radiation treatment for gliomas, including the use of molecular characteristics in guiding treatment choices.

Michael Prados, MD, the Charles B Wilson Chair in Neurosurgery and professor emeritus at the University of California San Francisco, shared his most recent research to establish protocols for treatment plans using precision medicine.

Kenneth Aldape, MD, senior scientist and director of MacFeeters-Hamilton Brain Tumor Centre at Toronto General Hospital, concluded the program with a discussion of the need to identify tumors as precisely as possible to achieve better outcomes for patients experiencing glioma. Aldape participated in the development of new tumor classifications by the World Health Organization released earlier this year. The classifications allow researchers to identify the tumors by not only histological, but also molecular composition, which will allow researchers to develop more precise therapies for treating specific tumors.

Photos from the symposium are .��