Potential impact of [18F]-FACBC PET in radiotherapy target definition of glioma

Abstract Purpose The aim of the study was to compare [18F]-FACBC positron emission tomography (PET)-based radiotherapy (RT) volumes to magnetic resonance (MR)-based volumes and investigate the potential impact of including [18F]-FACBC PET in RT treatment planning for gliomas. Methods MR- and PET-defined gross tumor volumes (GTVs) were independently contoured on pre-operative [18F]-FACBC PET/MR images in 24 patients with primary or recurrent low- or high-grade glioma. MR GTVs were defined from regions of contrast-enhancement on T1-weighted (ce-T1) sequences. For non-enhancing tumors or non-enhancing tumor components, regions of FLAIR hyperintensity were also included. PET-based GTVs were delineated using a tumor-to-background ratio (TBR) threshold of 2. GTVs were expanded by an isotropic margin to form clinical target volumes (CTVs). Volumetric analysis was performed using size comparisons, Dice coefficients (DC), overlap coefficients (OC) and Hausdorff distances (HD). Results PET GTVs were overall significantly smaller than MR GTVs, with median values of 14.8 ccm (6.5–26.7 ccm) and 28.5 ccm (17.2–62.7 ccm), respectively (p = 0.011). No significant volume difference was found between PET and MR volumes when MR volumes were based on ce-T1 only, but PET-based GTVs and CTVs were significantly smaller than MR-based GTVs and CTVs when the latter included FLAIR hyperintensity (p < 0.01). Similarity metrics showed a high degree of concordance between PET and MR volumes in cases where MR volumes were based on ce-T1 only, particularly for CTVs (DC: 0.88 (0.82–0.94), OC: 0.98 (0.96–0.99), HD: 0.86 cm (0.7–1.4 cm)). In comparison, for cases including FLAIR hyperintensity, MR CTVs had a high overlap with PET CTVs (OC: 0.99 (0.96–0.99)), but otherwise significantly lower degree of concordance (DC: 0.66 (0.46–0.81), p < 0.01, HD: 2.65 cm (2.22–3.85 cm), p < 0.001). Conclusion [18F]-FACBC PET underestimates tumor extension compared to FLAIR in contrast negative tumors and tumors containing non-enhancing components, indicating reduced sensitivity to low-grade tumor tissue and microscopic tumor infiltration. Inclusion of [18F]-FACBC PET as supplement to MR in RT planning for glioma could however help identify regions of highly malignant tumor, to facilitate target volume reduction and dose escalation strategies.