18F-FDG PET/CT for early response assessment in diffuse large B-cell lymphoma: poor predictive value of international harmonization project interpretation.

UNLABELLED PET using (18)F-FDG has prognostic value when performed at the completion of initial chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). (18)F-FDG PET may also be predictive of outcome when performed during the treatment course of DLBCL, but robust prospective studies and standardization of (18)F-FDG PET interpretation in this setting are lacking. METHODS In this prospective study, patients with advanced-stage DLBCL were treated with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and (18)F-FDG PET/CT was performed after cycle 2 or 3 and at the end of therapy. The (18)F-FDG PET/CT scans were interpreted according to the International Harmonization Project for Response Criteria in Lymphoma, and the maximum standardized uptake value (SUV) of the most (18)F-FDG-avid lesions was recorded. RESULTS Fifty patients were enrolled, and all underwent interim (18)F-FDG PET/CT. At a median follow-up of 33.9 mo, the positive predictive value (PPV) of interim (18)F-FDG PET/CT for relapse or progression was 42%, and the negative predictive value (NPV) was 77%. Interim (18)F-FDG PET/CT was significantly associated with event-free survival (P = 0.017) and with progression-free survival (P = 0.04) but not with overall survival (P = 0.08). End-of-therapy (18)F-FDG PET/CT had high PPV and NPV (71% and 80%, respectively) and was significantly associated with event-free survival, progression-free survival, and overall survival (P < 0.001). SUV measurements did not discriminate patients who relapsed or progressed from those who remained in remission. CONCLUSION When performed after 2 cycles of immunochemotherapy and interpreted according to International Harmonization Project criteria, early response assessment with PET/CT has a high NPV but low PPV in patients with advanced-stage DLBCL. Prospective trials are required to validate different criteria for the interpretation of interim (18)F-FDG PET/CT and establish the role of interim (18)F-FDG PET/CT in the management of patients with DLBCL.