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Purpose  To determine whether interim 3′-deoxy-3′-[ 18 F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim  18 F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH).    Methods  Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18–24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS.    Results  iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1–3) in 53 (58%) and positive (DS = 4–5) in 39 (42%) patients. Of the 67 iFLT-PET/CT-negative patients, 7 (10.4%) progressed at a median of 14.1 months whereas 14/25 (56.0%) iFLT-PET/CT-positive patients progressed at a median of 7.8 months ( P  < .0001). Of the 53 Deauville-negative patients, 9 (17.0%) progressed at a median of 14.1 months whereas 12/39 (30.8%) Deauville-positive patients progressed at a median of 5.6 months ( P  = .11). In multivariate analysis, including iFLT-PET/CT, PERCIST, interim TLG, and interim SUV max , only iFLT-PET/CT was an independent predictor for 3- and 5-year PFS ( P  < .0001 and  P  = .001, respectively).    Conclusions  In patients with DLBCL given R-CHOP/R-EPOCH, iFLT-PET/CT is a superior independent predictor of outcome compared with iFDG-PET/CT.    Supplementary Information  The online version contains supplementary material available at 10.1007/s00259-021-05353-9.

european journal of nuclear medicine and molecular imaging

18F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study