177Lu-PSMA Therapy in Recurrent High-Grade Glioma
Anna Maria Karlberg, Benedikte Emilie Vindstad, Erik Magnus Berntsen, Håkon Johansen, Silje Kjærnes Øen, Hanne Tøndel, Ole Solheim, Liv Cathrine Heggebø, Jorunn Brekke, Trond Aagedal, Live Eikenes, Tora S. SolheimPurpose:
Patients with recurrent high-grade glioma have poor prognosis and limited treatment options. This pilot study evaluated the feasibility and potential clinical benefit of 177 Lu-PSMA therapy in this patient population.
Patients and Methods:
Eligible patients were selected for treatment based on positive 68 Ga-PSMA-PET findings. 177 Lu-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 177 Lu-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). 68 Ga-PSMA-PET before treatment demonstrated tumor uptake in 9 patients (median SUV max : 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:
177 Lu-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.