Initial results of a phase II trial of 18 F-DOPA PET-guided re-irradiation for recurrent high-grade glioma.

Purpose: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine ( ¹⁸ F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether ¹⁸ F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS).
Methods: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus ¹⁸ F-DOPA PET defined tumor.
Results: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing ¹⁸ F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed.
Conclusion: ¹⁸ F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)