BACKGROUND: Less than half of all patients with aggressive non-Hodgkin's lymphoma (NHL) are cured with standard chemotherapy. Therefore, it is important to distinguish between responders to standard treatment and non-responders who may benefit from an early change to a more effective therapy. This study was intended to assess the value of a midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) scan to predict clinical outcome in patients with aggressive NHL. PATIENTS AND METHODS: Seventy newly diagnosed patients with aggressive NHL, who were treated with doxorubicin-containing chemotherapy, underwent a [(18)F]FDG-PET scan at midtreatment. Presence or absence of abnormal [(18)F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Multivariate analysis was performed to evaluate the effect of the International Prognostic Index (IPI) and early [(18)F]FDG-PET findings on PFS and OS. RESULTS: At midtreatment, 33 patients showed persistent abnormal [(18)F]FDG uptake and none of these patients achieved a durable complete remission (CR), whereas 37 patients showed a negative scan; 31/37 remained in CR, with a median follow-up of 1107 days. Only 6/37 patients either achieved a partial response or relapsed. Comparison between groups indicated a statistically significant association between [(18)F]FDG-PET findings and PFS (P <1 x 10(-5)) and OS (P <1 x 10(-5)). In multivariate analysis, [(18)F]FDG-PET at midtreatment was a stronger prognostic factor for PFS (P <1 x 10(-7)) and OS (P <9 x 10(-6)) than the IPI (P <0.11 and P <0.03, respectively). CONCLUSIONS: Early restaging [(18)F]FDG-PET may be used to tailor induction chemotherapy in patients with aggressive NHL.