Collagen ‘Tile’ Delivers Postsurgical Radiation in Glioblastoma
Following tumor removal in patients with recurrent glioblastomaan absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.
The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.
Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, Department of Neurosurgery, University of Minnesota Medical School, Minneapolis.
“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Chen told Medscape Medical News.
If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.
This is the first clinical series describing GT use since its approval by the US Food and Drug Administration (FDA) for recurrent brain cancer.
The findings were presented at the American Association of Neurological Surgeons (AANS) 2022 Annual Meeting, and were published recently in Neuro-Oncology Advances.
GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.
The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.
Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.
The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Chen said.
GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.
It also avoids the up-to-6-weeks patients have to wait post-surgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Chen.
“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.
With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.
The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma.. They were all having surgery for recurrent tumors.
“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Chen said.
Six participants had 06-Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.
The mean follow-up from initial diagnosis was 733 days (2 years).
Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.
Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Chen noted.
He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.
As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, I added.
“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”
One and Done
Among the 22 participants, 18 had neurological symptoms at baseline. There were no new neurologic deficits that developed after GT placement.
In addition, GT therapy improved “local control”—preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.
The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.
Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Chen noted.
“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.
A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Chen said. However, I have added that from his experience of him, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.
“One of the beauties of this therapy is it’s a one-and-done deal,” he said.
Commenting for Medscape Medical NewsWilliam T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of Neurosurgical Oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”
These new data “underscore that GT is safe in patients who have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Curry, who was not involved with the research.
“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.
However, Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.
In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Curry said.
Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.
The study received no outside funding . Chen and Curry have disclosed no relevant financial relationships.
American Association of Neurological Surgeons (AANS) 2022 Annual Meeting: Abstract 452. Presented May 2, 2022.
Neuro-Oncol Adv. Published onlineDecember 27, 2021. full-text
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