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A radiation therapy implant demonstrated significantly improved surgical bed control and longer overall survival compared to standard stereotactic radiotherapy (SRT) after resection of large brain metastases, according to a phase 3 trial.

At 1 year, recurrence at the surgical bed was 1.3% in patients treated with GammaTile (GT Medical Technologies) — an FDA-cleared bioabsorbable collagen tile embedded with cesium-131 radiation seeds — compared with 15.4% in patients who received multiple sessions of SRT. Two-year overall survival was also nearly double in the GammaTile group: 61.7% vs 35.7%. 

This study “showed the cancer was less likely to grow back in the treated area” with the GammaTile, said lead investigator Jeffrey Weinberg, MD, a neurosurgeon at MD Anderson Cancer Center in Houston, who presented the findings at the American Society of Clinical Oncology annual meeting. Additionally, “the increased efficacy did not come with increased side effects.”

Up to 30% of patients with cancer develop brain metastases. While SRT after surgery significantly reduces the risk for recurrence compared to surgery alone, some patients never receive it and others may experience delays in treatment, which could increase recurrence risk, Weinberg explained. Insurance issues, surgical complications, even the weather can get in the way, he added. 

In the current trial, Weinberg and colleagues evaluated whether implanting the GammaTile during surgery could help sidestep these logistical issues and improve local tumor control in patients with large brain metastases.

Overall, patients with new large brain metastases (2-7 cm in diameter) were randomized to GammaTile or SRT. The modified intention-to-treat population included 103 patients in the GammaTile group and 101 patients in the SRT group. 

Patients in both groups had a mean of 1.8 metastases. Most patients in the SRT arm were scheduled for 3-5 sessions starting 2-4 weeks after surgery. Metastases other than the index lesion were treated with SRT in the GammaTile arm.

Treatment with GammaTile significantly prolonged the time to surgical bed recurrence. The median time to surgical bed recurrence was not reached in the GammaTile group and was 17.4 months with SRT. The cumulative incidence of surgical bed recurrence at 1 year was also significantly lower in the GammaTile group: 1.3% vs 15.4% with SRT.

Additionally, median overall survival was longer in the GammaTile group — 42.5 months vs 17.6 months with SRT — as was surgical bed recurrence-free survival (not reached vs 10.9 months). 

There was no significant difference between the groups in quality of life, neurocognition, leptomeningeal disease incidence, or adverse events, including radiation necrosis. 

Study discussant David Schiff, MD, a neuro-oncologist at the University of Virginia in Charlottesville, said, “If this proof of concept holds, GammaTiles would largely supplant cavity radiosurgery for this indication, particularly for larger metastases where standard radiosurgery may struggle” because of safety issues. 

Schiff, however, raised several caveats.

Among the 101 patients randomly assigned to SRT, 18 never received it and were not included in the outcomes analysis, potentially favoring the GammaTile arm.

However, Schiff noted, “You could argue that makes it more of a real-world comparison where some patients never make it to a postoperative radiosurgery.” 

Schiff also found the overall survival benefit “surprising” because “overall survival in patients with brain metastases is driven by systemic control of disease, not CNS death.” 

Previous trials comparing SRT with observation for brain metastases have shown no overall survival difference, “so these results aren’t easily explained, and potentially suggest some imbalance in patient characteristics between the two groups,” he said.

Weinberg acknowledged the concern and noted that the trial wasn’t powered to detect an overall survival difference between the two groups. If the survival benefit is real, Weinberg said it could be because radiation was delivered immediately at surgery, potentially avoiding delays or missed postoperative treatment.

The work was funded by GT Medical Technologies. Weinberg is an advisor and disclosed honoraria and travel expense from the company. Schiff is an advisor for Curis, Exelixis, and Orbus. 

M. Alexander Otto is a physician assistant and award-wining journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net