Management of Meningiomas and the Role of Cooperative Group Trials

Dr. Leland Rogers, a professor of radiation oncology at Virginia Commonwealth University, visited Barrow to discuss the management of meningiomas and how cooperative group trials may help answer questions such as whether or not radiation therapy should be used after surgery for these tumors. (Watch the presentation here.)

Meningiomas originate in the protective layers of tissue between the skull and the brain, which are known as the meninges.

According to the Central Brain Tumor Registry of the United States, meningiomas are the most commonly reported of all tumors that occur inside the skull, representing 36.1 percent of all intracranial tumors.

“When we’re treating meningiomas, we’re trying to focus on a moving target,” Rogers said. “I don’t mean that the meningioma is moving – I mean the grade. What grade of tumor are you dealing with? Do you need to be more aggressive about it?”

According to 2005 data from the Central Brain Tumor Registry, 90 percent of meningiomas are benign (WHO Grade I), 5 percent are atypical (Grade II), and 3 to 5 percent are malignant (Grade III).

Rogers said that for the 2005 report, most tumors were graded according to 1993 World Health Organization criteria. WHO established new criteria for grading meningiomas in 2000 and again in 2007.

Rogers noted a 2012 study from Trondheim University Hospital in Norway that looked at a group of patients whose tumors were graded before 2000 and then regraded them. According to pre-2000 criteria, 17.9 percent of the meningiomas in this group were Grade II. That number increased to 25.5 percent using 2000 criteria and 30.1 percent using 2007 criteria.

Rogers said the increase from 2000 to 2007 can be attributed to the brain invasion requirement that was added. As of 2007, an otherwise Grade I tumor must be considered Grade II if there is any brain invasion.

“These evolving criteria haven’t just been completed to make our lives more difficult,” he said. “They’ve actually resulted in better outcomes for patients and better understanding of what’s going on.”

Surgical resection is the gold standard treatment for meningiomas, but Rogers said the hot clinical question is what to do after a Grade II meningioma has been surgically removed. More specifically, should radiation therapy be used?

“I think the argument should revolve around the apparent fact that recurrence of a WHO Grade II meningioma is bad,” he said. “These patients do poorly.”

Rogers said Grade II meningiomas have a seven- to eight-fold increased risk of recurrence and a two- to three-fold increased risk of death at five years after surgery.

Rogers discussed two similar phase II trials that have recently closed. The EORTC 22042-26042 trial involved giving high-dose radiotherapy to people who had a Grade II meningioma that was completely removed and an even higher dose to those who had residual tumor after surgery.

Rogers has submitted for publication the initial results of the NRG Oncology/RTOG-0539 trial, which involved observing low-risk meningiomas and using radiotherapy to treat intermediate- and high-risk meningiomas. This trial used a lower dose of radiation than the EORTC trial.

The initial results of the RTOG trial focused on the intermediate risk group, which consisted of people who had a recurrent Grade I meningioma or a new Grade II meningioma that had been surgically removed.

“We thought that they were going to have similar outcomes, and this study kind of confirms that,” Rogers said. “A recurrent, lower-grade meningioma kind of acts like the next grade.”

The progression-free survival three years after registration was at 96 percent and the local tumor recurrence rate was at 2 percent. This trial did not involve neurocognitive or quality-of-life testing, which Rogers said will be incorporated in NRG Oncology’s phase III study.

Rogers is working on the proposal for the phase III study, which will include people with newly diagnosed Grade II meningiomas that have been surgically removed. The participants will be randomly selected for observation or radiation therapy. This study will use a higher dose of radiation than the RTOG study.

A similar study, the ROAM/EORTC-1308 trial, recently opened in England. This study is also randomizing patients between observation and radiation therapy following surgery for a Grade II meningioma. Rogers said the NRG Oncology study will do more thorough quality-of-life testing than the ROAM trial.

“I think if we show that you can give radiation after gross total resection and the local recurrence risks are lower, that’s going to be insufficient in some surgeons’ minds,” Rogers said. “We’re going to have to show that quality of life is not harmed by having radiation.”

NRG Oncology is awaiting funding for another study, which will involve the use of checkpoint inhibitors along with radiosurgery for all or part of the tumor, depending on previous treatments and dose constraints. The study will include patients with a recurrent Grade II or Grade III meningioma, or a Grade I meningioma that has recurred more than one time after prior surgery and radiation therapy.

“Large cooperative group and randomized trials will help us get to the bottom of complex and contentious issues for our patients with meningioma,” Rogers said.

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