Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients.

ABSTRACT

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18F-FLT PET as a prognostic marker for NENs in comparison with 18F-FDG PET and Ki-67 index. METHODS: One hundred patients were PET-scanned with both 18F-FLT and 18F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18F-FLT uptake was also investigated. RESULTS: Thirty-seven percent of patients had a positive 18F-FLT PET scan, and 49% had 18F-FDG PET-positive foci. Patients with a high 18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18F-FLT uptake. No correlation was found between Ki-67 index and 18F-FLT uptake. In a multivariate analysis 18F-FLT, 18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18F-FDG and Ki-67 remained significant. CONCLUSION: 18F-FLT PET has prognostic value in NEN patients but when 18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas 18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18F-FLT in addition to 18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18F-FLT PET in NENs remains to be established.