For This Doctor, It Really Is Brain Surgery
Growing up in Africa, the young Arnold Etame had no idea he would one day be a neurosurgeon. In fact, it wasn’t until he was exposed to medicinal chemistry following his undergraduate education at the State University of New York at New Paltz that he developed an interest in general medicine at all.
Later, when he arrived at the University of Iowa as a medical student, he was introduced to neurosurgery.
“My first mentors as a medical student at Iowa were neurosurgeon scientists who studied malignant brain tumors such as glioblastoma,” Etame said. “As I spent more time with mentors and learned more about the challenges of treating glioblastoma, I became very inspired and committed myself towards the journey of researching and developing therapies for glioblastoma through clinical trials. This journey took me to the University of Michigan for neurosurgery residency and subsequently to the renowned Labatt Brain Tumour Research Centre at the University of Toronto.”
That career trajectory also sparked Etame’s interest in becoming a neurosurgical oncologist at an academic comprehensive cancer center. He said he wanted a position where he could treat brain tumors, but he wanted to study them, as well, to improve patient experiences and outcomes. At the time, most glioblastoma patients survived less than two years following even the most aggressive treatment of surgery, radiation and chemotherapy.
“I knew we needed to come up with a better approach to treatment malignant brain cancers,” Etame said. “Yet we couldn’t because there was a knowledge gap in our understanding the biology of these tumors. We needed to understand the key biological factors that render these tumors resistant to chemotherapy and radiation therapy to develop effective therapies for these cancers.”
That knowledge gap has decreased, Etame said, but there is still much work to do in this field.
Awake Craniotomies
When he arrived at Moffitt Cancer Center in 2012, he had his lab and he forged ahead. At the time the Department of Neuro-Oncology was much smaller, but that didn’t stop his work as both a researcher and a surgeon.
“I perform craniotomies for resection of these aggressive brain cancers,” Etame said. “A craniotomy is the preferred first option for malignant brain tumors because if you remove as much of the tumor as possible, the outcomes will be better.”
Etame performs awake craniotomies, where the patient is conscious and under sedation yet still able to communicate. This allows the patient to be tested as the tumor is removed. It also allows the surgeon to correlate brain anatomy to function.
Mostly, this technique is used when tumors are close to areas of language and movement and is an option for patients who cannot tolerate general anesthesia.
“Because the brain has no sensation when you remove tissue, patients do not really have any perception of pain,” Etame said. “Patients can be very comfortable during this operation, but they do get a little bit of anesthesia.”
Most patients who undergo this procedure return home within a day or two, he said.
“When you operate on a brain tumor, you’re not actually on the tumor,” Etame said. “You’re working on the brain and it’s important to know what critical structures are around the tumor since this is a key determinant of excellent surgical outcomes.”
Using tractography, which essentially makes maps of the key white matter fibers for brain function, can help surgeons like Etame navigate the brain. Tractography tells surgeons where fibers associated with the tumor are located and when combined with a functional MRI can provide insight on function and structure.
Etame has developed a robust awake brain surgery program at Moffitt, which is just part of the neuro-oncology and neurosurgery program at the cancer center.
Neurosurgery falls under a large umbrella, Etame said, and the path forward varies on a patient’s individual diagnosis and needs.
Quieting Glioblastoma Stem Cells
Today, statistics are improving for brain cancer patients, even if it’s slightly. Strategies used at Moffitt through clinical trials and maximum-safe resection of tumors have helped patients survive longer than three or four years after treatment. Through his research and a new clinical trial, Etame hopes to continue improving on those numbers.
“A common scenario is that following the removal of a tumor and treatment with chemoradiation, the MRI looks good for a long time with no sign of cancer,” Etame said. “But then over time, you start to see disease in areas of the brain that previously appeared normal.”
That’s because in cancers like glioblastoma, tumor stem cells have already spread throughout the brain. At the time of removal of the main tumor, the stem cells are in an inactive state and do not appear as a tumor. However, at some point these “quiet” stem cells become reactivated and grow into very aggressive cancers that are highly resistant. This is the key challenge in glioblastoma treatment.
“My research is based on understanding what genetic changes are associated with the reactivation of those stem cells and how we can target them,” he said. “If we can keep those stem cells ‘quiet’ for a longer duration, we can prolong survival. So how do we delay that reactivation?”
Etame suspects that by identifying a pathway that is important in the reactivation process, a specific drug can be used to target that pathway and hinder its ability to reengage. He has been awarded three fundings by the National Institutes of Health on his innovative thinking on developing glioblastoma therapies.
The hypothesis is if a drug can make it into the tumor tissue and prevent reactivation of cancer stem cells or even kill cancer stem cells, that could prolong patient survival, along with chemotherapy and radiation. While Etame has been involved in plenty of clinical trials before, this is his first as the investigator who came up with the concept.
“It’s a long road when you start at the lab level and then bring something to the patients, so it’s exciting,” Etame said. “We have a drug that we can test its ability to get into the brain and prevent aggressive reactivation of glioblastoma stem cells.”
It’s a career trajectory that brings him back to why he got interested in neuro oncology in the first place.
