Highlights PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients with biochemically recurrent prostate cancer. The true positive rate for PSMA PET/MRI was significantly greater in patients who were post prostatectomy for primary treatment. 40% of patients with a PSA value less than 0.2 ng/mL had a positive PSMA PET/MRI read compared to 9% on MRI.

BACKGROUND MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. BN003 (NCT03180268) randomizes patients with WHO-2 meningiomas and MRI-determined GTR to observation or 60 Gy IMRT to the resection bed. More sensitive and specific imaging biomarkers may improve clinical outcomes in meningioma by limiting unnecessary radiation of normal tissues and improving radiation targeting. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors and postoperative GTR by [68Ga]-DOTATATE PET/MRI who were managed solely with active surveillance. We hypothesized that the PFS of patients with GTR by PET/MRI managed with active surveillance would be higher than for patients with MRI-determined GTR, using NRG-BN003’s observation arm (randomized trial comparing observation to fractionated radiotherapy) as a reference standard. METHODS 92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 8 patients met inclusion criteria (WHO-2 meningioma & postoperative PET/MR GTR) and were followed with SOC MRI. Kaplan-Meier survival analysis was performed. RESULTS 5/8 subjects (62.5%) were women; the mean age was 67 years. MRI follow-up data were available for a mean of 19.75 months (range: 7-38 months). One subject (12.5%) progressed at 21 months; the remainder remain progression-free. Kaplan-Meier analysis demonstrated 3-year PFS to be 80%, which is substantially higher than the reported 3-year PFS of 69% in the literature. CONCLUSIONS [68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas.

BACKGROUND Current postoperative management recommendations for meningioma lack Level 1 evidence. NRG-0539 (NCT00895622) treated recurrent WHO-1 and newly diagnosed and completely resected (by postoperative MRI) WHO-2 meningiomas with postoperative fractionated radiotherapy to 54 Gy, but 3 year PFS remained below 60%. MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. More sensitive and specific imaging biomarkers are needed to improve RT guidance and thereby clinical outcomes in meningioma. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors who did not achieve GTR by [68Ga]-DOTATATE PET/MRI, managed with PET/MR guided RT, hypothesizing that the PFS of patients with STR by PET/MRI managed with PET/MR guided RT would be higher than for comparable patients enrolled on NRG 0539. METHODS 92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 7 patients met inclusion criteria (WHO-2 meningioma; postoperative PET/MR with residual activity) who underwent PET/MR-guided RT, followed with SOC MRI. Kaplan-Meier survival analysis was performed. RESULTS 5/7 subjects (71%) were women; the mean age was 50.7 years. MRI follow-up data were available for a mean of 18.7 months (range: 16-24 months). All patients remain progression-free at this time; Kaplan-Meier analysis demonstrated 2-year PFS to be 100%, which is substantially higher than reported PFS in this clinical population using standard-of-care MRI-guided RT. CONCLUSIONS [68Ga]-DOTATATE PET/MR-guidance can improve PFS following postoperative RT in subtotally resected WHO-2 meningiomas.

PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of three approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method.METHODSPatients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), based on pathology findings and follow up MRI appearance. Lesions were reclassified using the following methods: absolute SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), and SUVR to the pituitary gland (SUVRpit). Diagnostic performance of the three methods was compared using contingency tables and McNemar’s test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden’s J statistics.RESULTS166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, and SUVRpit of meningioma were significantly higher than those of PTC (P<0.0001). The optimal thresholds for SUV, SUVRsss, and SUVRpit were 4.65, 3.23, and 0.260, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, and SUVRpit revealed AUC of 0.932, 0.910, and 0.915, respectively (P<0.0001).CONCLUSIONWe found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.23. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [68Ga]-DOTATATE PET/MRI in meningioma patients. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701