Progression-Free Survival in Patients with WHO-2 Meningioma Undergoing Active Surveillance Based on DOTATATE PET Evidence of Gross Total Resection: Prospective Observational Study

Abstract

MRI is the standard of care for meningioma radiotherapy planning, but lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. NRG-BN003 (NCT03180268) randomizes patients with WHO-2 meningiomas and MRI-determined gross total resection (GTR) to observation or 60 Gy IMRT to the resection bed. More sensitive and specific imaging biomarkers than MRI may improve clinical outcomes in meningioma by limiting unnecessary irradiation of normal tissues and improving radiotherapy targeting. [68Ga]-DOTATATE, a PET radiotracer targeting somatostatin receptor 2 (SSTR2) is a highly sensitive and specific meningioma biomarker. Our dedicated DOTATATE brain PET/MRI and PET/CT protocol allows meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective IRB-approved observational trial (NCT04081701) has imaged >100 patients with meningioma. In the sub-analysis presented here, we prospectively evaluated PFS in patients with WHO-2 tumors and postoperative GTR as determined by [68Ga]-DOTATATE brain PET/MRI or PET/CT who were managed solely with active surveillance. We hypothesized that the PFS of patients with GTR by PET managed with active surveillance would be higher than reported PFS data for patients with MRI-determined GTR, using NRG-BN003's observation arm (randomized trial comparing observation to fractionated RT) as a reference standard. From the cohort of >100 patients with SSTR2-positive brain neoplasms enrolled between 9/2019 and 10/2022 and imaged according to our previously published protocol, a sub-cohort of patients were selected with WHO-2 meningioma, postoperative findings of GTR, and postoperative active surveillance with periodic MRI every 3-6 months. Kaplan-Meier survival analysis was performed. A total of 12 patients met inclusion criteria. Mean patient age was 64 years and 5 (42%) were female. Mean follow up period was 23.4 months (range: 7-38). 83% (10/12) patients underwent postoperative PET/MRI and 17% (2/12) underwent PET/CT. 2 patients (17%) progressed, at 22 and 34 months, respectively; the remainder remain progression-free. Both patients who had progression were successfully salvaged with focal fractionated radiosurgery. Kaplan-Meier analysis demonstrated PFS at almost 3 years to be 75%, which is substantially higher than the reported 3-year PFS of 60% in the literature. Overall survival was 100%. [68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas, thereby improving clinical outcomes. In this cohort of patients with completely resected WHO-2 meningiomas (as assessed by postoperative gadolinium-enhanced MRI and DOTATATE PET) who are conservatively managed, recurrences have been rare and amenable to radiosurgical salvage.