177Lu-PSMA Therapy in Recurrent High-Grade Glioma

PURPOSE: Patients with recurrent high-grade glioma have poor prognosis and limited treatment options. This pilot study evaluated the feasibility and potential clinical benefit of 177Lu-PSMA therapy in this patient population. PATIENTS AND METHODS: Eligible patients were selected for treatment based on positive 68Ga-PSMA-PET findings. 177Lu-PSMA (7.4 GBq/200 mCi) was administered at 6-8-week intervals and continued as long as well-tolerated. The safety, tolerability, and efficacy of 177Lu-PSMA were assessed in each treatment cycle using PET/MRI, SPECT/CT, blood tests, neurological tests, and patient-reported outcome measures. RESULTS: Ten patients were enrolled (WHO grade 4 glioblastoma, n=6; WHO grade 4 astrocytoma, n=1; WHO grade 3 astrocytoma, n=3). 68Ga-PSMA-PET before treatment demonstrated tumor uptake in 9 patients (median SUVmax: 6.4, IQR: 4.2-9.0). Six patients received treatment (20 cycles total; range: 1-7 per patient). Median absorbed dose per cycle was 0.9 Gy (IQR: 0.8-1.1) for tumors, 2.6 Gy (IQR: 1.9-3.2) for kidneys, and 1.7 Gy (IQR: 1.5-2.2) for parotid glands. No CTCAE grade 3-4 toxicities occurred. The most common patient-reported symptoms were fatigue, transient xerostomia, and nausea. Median survival from treatment initiation was 187 days (range: 87-756) and the median progression-free survival was 45 days (range: 41-335). MRI (RANO 2.0) demonstrated stable disease in half of the patients during all or part of the treatment course. CONCLUSIONS: 177Lu-PSMA therapy was feasible and well-tolerated. Radiologic stabilization was observed in a subset of patients, but strategies to increase tumor dose delivery may be needed to improve efficacy.