NeuroVoices: Matthew Shepard, MD, on Use of GammaTile in Neurosurgery, Removal of Tumors

Matthew Shepard, MD

There are several different types of brain tumors, ranging from very small to large in size and encompassing various parts of the brain and body. Benign brain tumors tend to be slow-growing brain tumors while malignant brain tumors tend to be fast-growing. General signs and symptoms caused by brain tumors may include: headache, nausea or vomiting, eye problems, losing feeling or movement in an arm or a leg, speech issues, memory problems, seizures, and personality or behavior changes, among others.

There are several different common benign and malignant central nervous system (CNS) tumors, including gliomas, which support the function of neurons, and germ cell tumors, which form in the center of the brain and can spread elsewhere in the brain and spinal cord. Spinal cord tumors, another type of CNS-related tumor, can cause motor problems and a loss of muscle control, as well as other symptoms such as issues with bowel or bladder control or sexual dysfunction. A radiation therapy, GammaTile, is revolutionizing the postoperative management of these tumors, by delaying treatment site recurrence and improving overall survival.

GammaTile is a small bioresorbable collagen tile placed at the tumor site by a neurosurgeon immediately following tumor removal. The FDA-cleared therapy is designed to provide radiation where needed, while protecting healthy tissue and minimizing radiation side effects, including hair loss. As part of a new iteration of NeuroVoices, Matthew Shepard, MD, a neurosurgeon at Allegheny Health Network (AHN), sat down to discuss the capabilities of GammaTile, and how its incorporated into clinical care. He provided perspective on the mechanistic advantages of this approach, how it could potentially be used outside its indication, and the unanswered questions clinicians may encounter.

NeurologyLive^®: When you're seeing a patient within the first 90 days after tumor removal, what are the key factors you're monitoring?

Matthew Shepard, MD: When patients undergo gamma tile treatment, they've usually endured significant challenges prior to that. Many have already undergone intense chemotherapy, potentially multiple surgeries in the same area we're not currently operating on. Often, these patients have also received conventional radiation therapy like gamma knife or other external beam radiation methods. As a result, they can be quite frail. During the initial post-operative phase, we're actively evaluating them for new neurological deficits, seizures, hydrocephalus, cerebrospinal fluid leaks, wound healing complications, and this continues over the weeks and months following surgery. The first 24 to 48 hours after surgery are generally the highest risk period for serious complications. However, even beyond that timeframe, such as up to three months after surgery, patients who've undergone multiple surgeries, radiation doses, and chemotherapy sessions, are at high risk for issues like wound non-healing or wound breakdown. Unfortunately, the literature indicates infection rates after gamma tile implantation and wound dehiscence rates are around 3 to 5%, which is not unusually high considering the high-risk nature of these patients. So, it seems that adding gamma tile and brachytherapy doesn't significantly increase these risks according to current literature.

Mechanistically, how does this approach contribute to enhancing neurological function and overall well-being?

Certainly. The advantage of gamma tile lies in its targeted impact. When we remove a brain tumor, achieving complete negative tissue margins isn't always possible due to the limitations of brain surgery. There's often at least some residual microscopic disease. This is where chemotherapy and radiation come in. Unlike conventional radiation methods, like Gamma Knife, which penetrate deeper into normal brain tissue, gamma tile's radiation seeds only penetrate a few millimeters. This targets high-risk areas with remaining disease while minimizing radiation exposure to healthy brain tissue. Some evidence in the literature suggests this might reduce long-term complications compared to conventional treatments, particularly radiation necrosis.

Though FDA-cleared for malignant and recurrent brain tumors, what broader implications might this technology have?

Currently, the primary focus is on brain tumor patients. However, the question arises whether we can integrate this technology earlier in treatment courses and if it's comparable to or better than other conventional adjuvant treatments. This applies not only to metastatic and primary brain tumors like glioblastomas, but also to non-malignant brain tumors such as atypical or anaplastic meningiomas. While these tumors don't spread as rapidly as primary brain tumors, they do have a higher recurrence rate. Could gamma tile be used during their initial surgical resection? For example, the standard procedure for removing a brain metastasis involves surgery and adjuvant stereotactic radiosurgery like gamma knife. But if patients can't return for various reasons, they miss out on adjuvant treatment. If we implanted gamma tile seeds during surgery, it would ensure all patients receive adjuvant radiation. Additionally, ongoing clinical trials are exploring whether adjuvant radiation with gamma tile versus standard radiation can improve local control, progression-free survival, and potentially overall survival for both metastatic and primary brain tumor patients.

How have we expanded our understanding of gamma tile, and what areas still require further exploration?

That's a great question. Currently, we possess a substantial amount of valuable retrospective data from the gamma tile approach. Moreover, there are even some non-randomized prospective studies dedicated to examining gamma tile's impact. However, our next step is to broaden our research to encompass prospective trials, which is already underway in certain centers. This avenue of research will ultimately help us determine whether this technology is truly leading to positive advancements.

In the realm of treating diseases like glioblastoma, our current protocols have remained relatively unchanged for several decades. Could gamma tile be the catalyst for incremental progress? It's important to recognize that brain cancer won't be conquered by a single surgery or technology. Instead, it will be the culmination of many incremental advancements over time. Therefore, collaboration is crucial. Neurosurgeons, neuro-oncologists, and radiation oncologists all need to work in synergy to harness these technological breakthroughs. Our aim is to leverage these advancements to decipher whether they indeed lead to positive outcomes for patients. I'm optimistic that they will, but this requires diligent data collection, meticulous study designs, and thorough execution.

Transcript edited for clarity by artificial intelligence.