Tile-Based Radiation Tops Standard for Resected Brain Metastases

CHICAGO — Radioactive tiles implanted immediately after the surgical resection of a newly diagnosed brain metastasis improved local control over standard stereotactic radiotherapy (SRT) given weeks later, findings of a phase III trial showed.

Median time to recurrence at the surgical bed was not reached with the Cesium-131 tiles (GammaTile), as compared with 17.4 months with SRT (HR 0.06, 95% CI 0.01-0.46, P=0.007). At 1 year, the cumulative incidence of recurrence at the cavity site was 1.3% and 15.4%, respectively, reported Jeffrey Weinberg, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Tile-based radiation also improved surgical bed recurrence-free survival (RFS) and was associated with improved overall survival versus SRT:

• Surgical bed RFS: median not reached vs 10.9 months (HR 0.48, 95% CI 0.30-0.76, P=0.0021)
• Overall survival: median 42.5 vs 17.6 months (HR 0.59, 95% CI 0.37-0.96, P=0.032)

“The cancer was less likely to grow back in the treated area, patients were less likely to have negative imaging changes on their follow-up MRI scans, and patients have a lower risk of death,” Weinberg said during a press conference at the American Society of Clinical Oncology (ASCO) annual meeting. “And this increased efficacy did not come with increased side effects.”

Approximately 10% to 30% of cancer patients develop brain metastases, with surgery indicated for large or symptomatic tumors. Patients undergoing resection typically receive SRT to the walls of the cavity 2 to 4 weeks later.

If SRT is not given within 4 weeks, the risk of local recurrence increases from 2.3% to close to 50%, said Weinberg, but there can be significant logistical challenges.

“Some patients never return to receive their SRT, and frequently systemic therapy is held as we wait the completion of the postoperative radiation,” he said.

The tile-based approach — where the edges of the tumor cavity are essentially wallpapered with the radioactive 2 × 2 cm tiles — has an advantage in that treatment compliance following surgery is ensured, said Weinberg, and it also may hold biological advantages over SRT. “We believe that it may work better for larger cavities and can deliver a higher dose rate to the cavity surface.”

ASCO-designated expert David Schiff, MD, of the University of Virginia School of Medicine in Charlottesville, said the exciting results “may represent a new standard of care,” but also sounded notes of caution about the lack of patient details in the presentation and post-randomization exclusions, which can favor investigational therapies.

“The final issue that I’m struggling with is the overall survival results,” he said. “These overall survival results aren’t easily explained, and that potentially suggests some imbalance in patient characteristics between the two groups.”

Estimates of survival at 2 years were 61.7% in the tile-based radiation arm and 35.7% in the SRT arm, though Weinberg cautioned that the trial was not sufficiently powered for this analysis.

Prior trials supporting cavity radiosurgery have shown no survival benefit, said Schiff, and he added that survival in the overwhelming majority of patients with brain metastases is driven by systemic control of the cancer rather than central nervous system disease.

Study Details

ROADS (Radiation One and Done Study) was a phase III trial that from 2021 to 2025 enrolled 230 patients with a new brain lesion (2-7 cm) requiring surgical resection at 32 U.S. centers. In the investigational arm, tiles were placed at the time of the surgery while SRT was scheduled for 2 to 4 weeks after surgery.

Some patients did not have surgery or were not eligible for other reasons, resulting in a modified intent-to-treat population of 204 participants. Participants in both arms received maximum safe resection of their metastatic tumor and SRT for non-index lesions. The median number of lesions in each arm was 1.8.

Mapping and selecting the number of tiles was done preoperatively, with dose planning performed postoperatively, said Weinberg. The tiles emit about 100-120 Gy at the surface, with lower levels beyond that. About 90% of the dose is emitted by about 5 weeks.

He told MedPage Today that 150 U.S. centers are involved in placing tiles and credentialed to do so.

The study’s co-primary endpoints were surgical bed recurrence and surgical bed RFS. Secondary endpoints included survival, safety, and other outcomes.

In total, 18 participants in the SRT arm never received it. Delays in postoperative SRT included prolonged recovery, insurance issues, weather events, rehospitalizations, and a patient’s or investigator’s decision.

This highlights an unseen advantage with the tiles — patients get the treatment, said Weinberg. “That benefit is both a logistical one and seems to be a biological one — being able to target the walls of the resection cavity right as they’re rolling out of the operating room,” he said.

No significant differences were observed in the frequency of leptomeningeal disease or radiation necrosis and in neurocognitive functioning or quality-of-life measures.

An analysis of time to either surgical bed recurrence or radiation necrosis, performed due to the fact that radiographic findings can be misinterpreted, also favored the tile-based radiation arm, said Weinberg.

Serious adverse event (AE) rates were similar between groups. Grade ≥3 AEs occurred in 18% of the tile-based radiotherapy arm and 19% of the SRT arm. Radiation necrosis occurred in 7.8% and 6.9%, respectively.