Bridging Surgical Treatment and Chemoradiation for Glioblastoma Patients
A new technology that delivers postsurgical radiation may bridge the gap between surgical treatment and chemoradiation for patients with glioblastomas.
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- On October 11, 2022, GT Medical announced the first participant enrolled in the GammaTile Enhanced Stupp ALTernative (GESTALT) trial. While this trial is still in its infancy, if the results are favorable, it may influence protocols for treating glioblastomas (GBMs) and bridge the gap between surgery and chemoradiation.
PharmaNewsIntelligence interviewed Clark Chen, MD, the Lyle French Chair and Head of the Department of Neurosurgery, University of Minnesota Medical School, to discuss the technology and the procedure in detail.
According to the National Brain Tumor Society (NBTS), each year, approximately 13,000 people in the United States are diagnosed with glioblastoma. Chen stated that “glioblastoma is the most aggressive form of brain cancer and the most common form of brain cancer.”
Current Treatment for Glioblastomas
Chen explained the current treatment protocols for glioblastomas and the drawbacks of this treatment method.
Protocols
“Right now, providers must do surgery to remove as much tumor as possible. That surgery involves removing a piece of the skull to get into the brain. And clinicians wait four to six weeks after the surgery before we treat them with chemotherapy and radiation therapy,” he noted.
The waiting period is a significant point of interest for many patients and providers. Chen shared that during wound healing, after the surgery, providers do not want chemotherapy and radiation to disrupt the healing process. “If the wound breaks down, clinicians must then treat the infection, which will further delay therapy,” he justified.
Concerns with the Current Protocol
Despite worries about wound healing, waiting four to six weeks before beginning chemotherapy and radiation is less than ideal. Chen posed multiple questions, including what happens to the microscopic tumors providers cannot remove during the surgery.
“The brain is eloquent. Surgeons remove the area where it's predominantly tumor, but there will be areas where there are tentacles of microscopic tumors that go through the brain that we don't see at the time of surgery. We don't remove those areas because they're predominantly normal, just with some amount of tumor in there,” he argued.
The main concern is that during the four-to-six-week waiting period these microscopic tumors that were not removed continue to grow.
“There's been a number of studies that show that these microscopic tumors grow during that period. And it's estimated that somewhere between 20% and 90% of tumors will grow during this time. The median is about 50%. Clinicians could say very reasonably, based on many studies, at least 50% of the tumor will grow right next to where you finish the surgery,” revealed Chen.
He continued, “a meta-analysis of all these studies shows that if there is tumor growth during this period, patients are 1.8 times — almost two-fold — more likely to die from the disease because the tumor's growing while the provider is waiting..”
The NBTS states that 10,000 people in the US will die yearly from glioblastoma. With the understanding that this is a rather deadly disease, providers are constantly looking for ways to reduce the mortality risk.
GESTALT Trial
The current phase I clinical trial hopes to address the concerns associated with the waiting period between surgery and chemotherapy or radiation. In this clinical trial, GammaTiles are put into the patient’s brain following tumor extraction to minimize or reduce growth before chemotherapy.
GammaTiles
Chen revealed that the GammaTile comprises radioactive seeds embedded in collagen, which dissolves over time, eliminating the need for surgical removal.
“The surgeon removes the tumor and applies radiation therapy through these radioactive seeds around the surgical area. While waiting those four to six weeks, providers are treating these microscopic tumors that can grow and cause problems,” he added.
PharmaNewsIntelligence asked Chen to elaborate on the design of the tiles developed by GT Medical: “The idea was straightforward but brilliant. During surgery, surgeons insert collagen sponges to achieve hemostasis and stop the bleeding.”
The company then thought, why not embed radiotherapy since collagen sponges are already inserted?
“The beauty of embedding the seeds in collagen is that the collagen takes about three months to dissolve. For the duration of the time when the radioactive seeds are active, the confirmation of the cavities is held intact. They're not collapsing, causing radiation seeds to get closer to one another, causing radiation damage,” he commented.
“The company took a surgical practice that's routinely done and said, ‘Why can't we add therapy to what is already put into patients' brains?’ In doing so, they also prevent one of the major complications of putting seeds into the brain; the collapse of the resection cavity causing the seeds to get closer together was a big deal. It could cause great damage in the area where there's a collapse.”
A Feasibility Study
Chen emphasizes that this study does not compare this treatment to others. “The GESTALT study is not meant to demonstrate survival differences. The GESTALT study is for the researchers to demonstrate the safety of this approach,” he stressed.
In this study, the GammaTiles are inserted, as previously mentioned, and then, patients undergo chemotherapy when the radiation dies down.
“Doctors are adding more radiation to the area. So, the study is designed to determine whether this approach is safe and the patient can tolerate this new treatment,” noted Chen.
He explained that, while the current release stated that the first patient had been dosed, they aim to recruit approximately 60 participants to better understand this approach's feasibility.
Patient Recruitment
Beyond explaining the basic tenants of the study, Chen shared some additional details on patient recruitment with PharmaNewsIntelligence.
“The study focuses on a type of glioblastoma that does not have an isocitrate dehydrogenase mutation. These are certain mutations that give patients a different prognosis. So, the other clinicians and I are only picking out the isocitrate dehydrogenase (IDH) wild-type tumors,” he revealed.
Additionally, the recommending surgeon should feel that a growth total resection — meaning that all of the visible parts of the tumor can be resected — is possible.
“Clinicians can put these tiles in because the radiation range is very short. It extends maybe eight millimeters out. The range of the tile’s radiation is small, so it doesn't radiate and get to the wound to prevent it from healing,” explained Chen. However, because the range is so small, if too much of the tumor is left behind, the tiles will not reach it, defeating the overall purpose of this treatment.
Participants in the study must meet additional criteria, including the following:
- being 18 or older
- having a tumor in the cerebrum and not in the cerebellum
- able to undergo subsequent chemoradiation
- able to take care of themselves
- have one single solitary tumor
Looking Ahead
While this study is still in its very early stages, Chen discussed future directions and implications with PharmaNewsIntelligence.
Randomized Clinical Trials
If this approach shows promise, researchers will need to conduct a randomized study comparing the old way of doing things to this new way. And if that study shows a difference, the old way will die away,” he asserted. “Why would providers ever let tumors grow uncontrollably if they could treat them immediately? This study lays the foundation for a future study to compare the old way of waiting four to six weeks before treatment versus the immediate treatment with GammaTiles.”
A randomized clinical trial would measure the overall survival rate of the GammaTile protocol and compare it to the current protocol.
Implications
If this trial's and subsequent trials' results are favorable, this technology could be the standard of care for patients with glioblastoma. Down the line, studies may even consider determining whether this technology can minimize the length or dosage of postsurgical chemoradiation.
Editor's Note: This article has been edited to reflect that a meta-analysis has already been done and to clarify some quotes.
