Preoperative Embolization Linked to Relapse-Free Survival in Meningioma

HOUSTON — Preoperative embolization of meningioma was associated with improved relapse-free survival (RFS) in a retrospective propensity-matched review.

Surgery without embolization was associated with a median RFS of 8.6 years versus not reached in the embolization group, although the difference did not achieve statistical significance by log rank analysis. In a Cox regression model, preoperative embolization was associated with a significant, 49% lower likelihood of relapse or death. Embolization was not linked to lower likelihood of gross total resection (GTR), and those with subtotal resection after embolization had better RFS.

In a subgroup of patients with tissue available for RNA sequencing, preoperative embolization was associated with changes in gene expression consistent with a hypoxic effect on tumor cells, as Alexander F. Haddad, MD, of the University of California San Francisco (UCSF), reported at the Society for NeuroOncology meeting.

Despite inherent limitations from the retrospective analysis design, the results showed that “preoperative embolization increases time to recurrence in patients with subtotal resection and induces transcriptomic changes indicative of hypoxia in meningiomas,” said Haddad.

“This is just the start of what we’re going to look at,” he added. “We want to consider tumor volumes and percentage of the tumor embolized and then think about spatially specific sampling and sequencing and looking at differences between embolized versus non-embolized regions of the tumor.”

Because of their location and blood supply, meningiomas are well suited for embolization and probably account for 80-90% of preoperative embolizations in brain cancer, said senior investigator Manish Aghi, MD, PhD, also of UCSF.

Use of embolization has evolved through clinical experience, as no formal guidelines exist. The retrospective analysis could help inform future use.

“The study demonstrates at a biologic level that this procedure, which we’ve been using for 20 or 30 years, is doing exactly what we intended, which is reassuring,” said Aghi. “It’s cutting off the blood supply to the tumors and causing hypoxic cell death. I would hope that this provides validation to the community that this is absolutely a great procedure.”

“I suspect [embolization] is underused, but I think we’re making great strides,” he added. “I think that not every hospital has integrated access to embolization for tumors. So they may have endovascular doing vascular pathologies like aneurysms, but they may not have folks available to help with tumor cases the way that an academic medical center might. In healthcare in general, where there is a procedure to be done, gaps get filled, and there is nothing about this [procedure] that couldn’t be done at any community hospital.”

A limited medical literature exists to provide information about outcomes with preoperative embolization for meningiomas, Haddad noted in his introduction to the study. Even fewer studies have examined how embolization affects tumors at a molecular level.

To add to the paucity of existing data, investigators at UCSF reviewed records for patients who had surgery for WHO grade 2 meningiomas from 1997 to 2021. They identified 357 procedures, 36% of which included preoperative embolization. The primary objectives were to determine how preoperative embolization affected oncologic outcomes and how embolization affects meningioma tumor cells at a molecular level.

Haddad and colleagues performed univariate and multivariate analyses, as well as a propensity-matched analysis. The analyses showed that embolized tumors tended to be larger and that subsequent surgery less frequently resulted in GTR. However, with propensity matching that included tumor size, rates of GTR were similar.

“That suggests that it’s really the tumor size that is driving reduced gross total resection in embolized tumors,” said Haddad.

In the multivariate analysis, preoperative embolization had a significant association with improved RFS (HR 0.51, 95% CI 0.29-0.91, P=0.021). Other independent predictors were lack of brain invasion (HR 0.43, 95% CI 0.23-0.82, P=0.010) and subtotal resection (HR 2.09, 95% CI 1.15-3.76, P=0.016).

An analysis of RFS by surgical outcome (GTR versus subtotal) suggested that embolization did not significantly affect RFS in patients with GTR. However, among patients with subtotal resection, median RFS was more than doubled with preoperative embolization (16.2 vs 5.9 years, P=0.045). Multivariable analysis showed that preoperative embolization reduced the RFS hazard by 68% in patients with subtotal resection (P=0.005).

The molecular analysis included 200 patients. An initial analysis showed that embolized tumors had preoperative upregulation of several genes, notably DLL4 and APO-D, both of which are associated with hypoxia. A subsequent gene-ontology enrichment analysis showed that multiple hypoxia-associated genes were upregulated following embolization.