Low-Risk Meningioma Study Adds Clarity to Irradiation Role

Leland Rogers, MD

Patients with low-risk meningioma had a 3-year progression-free survival (PFS) that modestly exceeded expectations after gross total resection followed by observation, results of a cooperative group trial showed.

Overall, the 60 patients with had an estimated 3-year PFS of 91.4%, which included some patients subsequently found to have subtotal resection. The patients had an estimated 3-year WHO grade 1 disease overall survival of 98.6%.

In contrast, patients with subtotal resection by central review had an estimated 3-year PFS of 83.1%, which proved inferior to the outcome in a group of patient who had grade 2 meningioma treated with surgery and radiation therapy, Leland Rogers, MD, reported at the American Society for Radiation Oncology (ASTRO) Annual Meeting in Boston, Massachusetts.

“Low-risk patients treated with surgery alone exceeded historical-control PFS expectations at 3 years,” said Rogers, a professor of Radiation Oncology at Virginia Commonwealth University. “Results support surgery followed by observation for patients with newly diagnosed WHO grade 1 meningioma following gross total resection. The results raise questions about management of patients following subtotal resection, a subcohort that may benefit from early radiation therapy. Further follow-up and analyses are required before robust recommendations can be made.”

The findings came from RTOG (now NRG)-0539, a trial designed to determine whether newly diagnosed WHO grade 1 meningioma could be managed by observation following successful gross total resection. As originally conceived, the trial had 3 risk strata: low risk (WHO grade 1), intermediate risk (recurrent grade 1 after gross total or subtotal resection or newly diagnosed WHO grade 2, treated by gross total resection), and high risk (any WHO grade 3 treated by gross total or subtotal resection, recurrent grade 2, and new grade 2 treated by subtotal resection).

Patients in the intermediate-risk strata received 3D conformal radiation therapy or intensity-modulated radiation therapy (IMRT) at a total dose of 54 Gy in 30 fractions. Patients with high-risk disease received IMRT at a total dose of 60 Gy in 30 fractions.

Enrollment for all 3 risk groups has closed. Rogers’ report focused on the patients with low-risk meningioma.

By local assessment, 55 of 60 patients in the low-risk group attained gross total resection, and the remaining 5 patients had subtotal resection. Central review of 49 patients showed that 34 of 44 cases initially judged to have gross total resection actually met criteria for total resection. Additionally, central review found that 1 of 5 patients initially thought to have subtotal resection did not meet the surgical criteria.

Assessment of PFS for all 60 patients in the low-risk group showed that the 3-year PFS compared favorably with the 3-year PFS of 90% derived from historical controls. The estimated 5-year PFS dipped to 89.4%.

Assessment of PFS according to central review of the completeness of surgery showed that patients who had gross total resection had an estimated PFS of 94.3% at both 3 and 5 years. In contrast, patients who had subtotal resection by central review had a 3-year PFS of 83.1%, declining to 72.7% at 5 years.

Patients with low-risk disease that was totally resected had a 79% reduction in the hazard for progression or death at 3 years compared with patients who had subtotally resected low-risk disease. The difference fell just short of statistical significance (P= 0.06).

Illustrating the potential impact of radiation therapy after subtotal resection, Rogers compared PFS for intermediate-risk patients and the low-risk patients with subtotal resection. The intermediate-risk group—which had surgery and radiation therapy—had an estimated PFS of 91.8% at 3 years and 84.5% at 5 years. The difference translated into a hazard ratio of 0.48 versus patients with subtotally resected low-risk disease followed by observation, but did not achieve statistical significance (P= 0.28).

The use of radiation therapy for intermediate-risk disease added minimal toxicity. A single grade 3 infection, which was possibly treatment-related, occurred in the low-risk group versus 2 such infections in the intermediate-risk group, comprising 52 patients.

Reference:

Rogers L, Zhang P, Vogelbaum A, et al. Low-risk meningioma: initial outcomes from NRG Oncology/RTOG-0539. Presented at: 2016 ASTRO Annual Meeting; Boston, Massachusetts, September 25-28, 2016.