Prospective Study of 3'-Deoxy-3'-18F-Fluorothymidine PET for Early Interim Response Assessment in Advanced-Stage B-Cell Lymphoma

Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. PET with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced-stage B-cell lymphoma, we investigated the prognostic and predictive value of (18)F-FLT PET in comparison to standard imaging with (18)F-FDG PET and clinical outcome. Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) followed by 3 cycles of ICE (ifosfamide, carboplatin, etoposide). (18)F-FLT PET was performed at baseline and at interim (iPET) after 1-2 cycles of therapy. (18)F-FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progression-free survival (PFS) and overall survival (OS) was investigated. With a median follow-up of 51 mo, PFS and OS were 71% and 86%, respectively. (18)F-FLT iPET, analyzed visually (using a 5-point score) or semiquantitatively (using SUV and ΔSUV) predicted both PFS and OS (P < 0.01 for all parameters). Residual (18)F-FLT SUVmax on iPET was associated with an inferior PFS (hazard ratio, 1.26, P = 0.001) and OS (hazard ratio, 1.27, P = 0.002). When (18)F-FDG PET was used, findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan. Baseline PET imaging parameters, including SUV, proliferative volume, or metabolic tumor volume, did not correlate with outcome. (18)F-FLT PET after 1-2 cycles of chemotherapy predicts PFS and OS, and a negative (18)F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of (18)F-FLT iPET remains too low to justify changes in patient management.