NEIM-05 PURSUE: RESULTS FROM A PROSPECTIVE, PHASE 2B TRIAL TO DEFINE IMAGE INTERPRETATION CRITERIA FOR(18)F-FLUCICLOVINE-PET FOR DETECTION OF RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY

BACKGROUND: After radiation therapy (RT) for brain metastases (BM), differentiating radiation necrosis from tumor recurrence remains challenging. PURSUE (NCT04410367) evaluated various measures of lesion (18)F-fluciclovine uptake to establish image interpretation criteria (IIC) for (18)F-fluciclovine-PET to accurately diagnose recurrent BM. METHODS: Patients with solid tumor BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent (18)F-fluciclovine-PET (185 MBq) <42 days post-MRI and 1-21 days pre-craniotomy. Lesion (18)F-fluciclovine uptake was qualitatively rated as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland) by three independent blinded readers. The primary endpoint was diagnostic performance of different uptake thresholds on qualitative reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]) and dynamic measures. IIC were determined by committee and subsequently used to assess the diagnostic performance of (18)F-fluciclovine. RESULTS: All 23 reference lesions from 23 enrolled patients underwent histopathological analysis; 10 (43%) were pathologically-confirmed BM recurrence. The highest performing qualitative measure was ‘marked’, rendering 92-100% sensitivity and 40-80% specificity across readers. SUV(max) was a reader-independent, high-performing quantitative metric (AUC 0.87, SUV(max) threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, IIC was established as: “Lesions with (18)F-fluciclovine uptake of SUV(max) equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely.” Application of the IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% PPV, and 83-85% NPV across the readers. CONCLUSIONS: PURSUE is the first prospective, multicenter trial to establish IIC for (18)F-fluciclovine-PET for suspected recurrent BM after RT, verified by histopathology. Finalized IIC demonstrated excellent diagnostic performance for (18)F-fluciclovine and will help evaluate (18)F-fluciclovine-PET in future studies.