Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL

• Published in: Oncotarget Vol. 5; no. 12; pp. 4050 - 4059
• Main Authors: Herrmann, Ken, Buck, Andreas K, Schuster, Tibor, Abbrederis, Kathrin, Blümel, Christina, Santi, Ivan, Rudelius, Martina, Wester, Hans-Jürgen, Peschel, Christian, Schwaiger, Markus, Dechow, Tobias, Keller, Ulrich
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 30.06.2014
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Research Paper; Cyclophosphamide - therapeutic use; Disease-Free Survival; Doxorubicin - therapeutic use; Female; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Middle Aged; Positron-Emission Tomography - methods; Prednisone - therapeutic use; Prognosis; Vincristine - therapeutic use
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.1990

Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.