18F-FDG PET/CT for Early Response Assessment in Diffuse Large B-Cell Lymphoma: Poor Predictive Value of International Harmonization Project Interpretation

PET using F-18-FDG has prognostic value when performed at the completion of initial chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). F-18-FDG PET may also be predictive of outcome when performed during the treatment course of DLBCL, but robust prospective studies and standardization of F-18-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 F-18-FDG PET/CT was performed after cycle 2 or 3 and at the end of therapy. The F-18-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 F-18-FDG-avid lesions was recorded. Results: Fifty patients were enrolled, and all underwent interim F-18-FDG PET/CT. At a median follow-up of 33.9 mo, the positive predictive value (PPV) of interim F-18-FDG PET/CT for relapse or progression was 42%, and the negative predictive value (NPV) was 77%. Interim F-18-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 F-18-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 F-18-FDG PET/CT and establish the role of interim F-18-FDG PET/CT in the management of patients with DLBCL.