Distinguishing Progression from Pseudoprogression in Glioblastoma Using<sup>18</sup>F-Fluciclovine PET
Ali Nabavizadeh, Stephen Bagley, Robert K. Doot, Jeffrey B. Ware, Anthony J. Young, Satyam Ghodasara, Chao Zhao, Hannah Anderson, Erin K. Schubert, Erica L. Carpenter, Jacob E. Till, Fraser Henderson, Austin R. Pantel, H. Isaac Chen, John Y. K. Lee, Nduka Amankulor, Donald M. O’Rourke, Arati Desai, MacLean P. Nasrallah, Steven Brem
Abstract
Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18 Ffluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18 F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18 Ffluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP ($50% viable tumor), mixed TP (,50% and .10% viable tumor), or pseudoprogression (#10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40-to 50-min SUV max (6.64 1 1.88 vs. 4.11 6 1.52, P 5 0.009) than patients with pseudoprogression. A 40-to 50-min SUV max cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40to 50-min SUV max cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18 F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18 F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18 F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.