Positron Emission Tomography Guided Therapy of Aggressive Non-Hodgkin's Lymphomas (PETAL trial): Correlation between Clinical Variables and PET Parameters.

Positron emission tomography (PET) performed after a few cycles of chemotherapy (interim-PET) in aggressive lymphomas correlates with long-term outcome: While the majority of patients with a negative interim-PET scan enjoy long-lasting remissions, patients with persistent pathological glucose uptake almost invariably relapse. The multicenter PETAL trial was initiated in Germany in 2008 to resolve the question whether a change in treatment protocol may improve the outcome of patients with a positive interim-PET scan (ClinicalTrials.gov Identifier: NCT00554164).

The PETAL trial is open for patients with newly diagnosed aggressive B cell or T cell non-Hodgkin's lymphomas between 18 and 80 years of age with a performance status of 0 to 3 according to the Eastern Cooperative Oncology Group scale and a positive PET scan before starting any lymphoma-directed therapy. Interim-PET is done after 2 cycles of the CHOP protocol (cyclophosphamide, doxorubicine, vincristine, prednisone; plus rituximab (R) in CD20-positive lymphomas) administered at a 14-day interval. Precautions were taken to minimize the risk of false-positive interim-PET results. First, the interval between the second (R-)CHOP cycle and the interim-PET scan is three weeks. Second, hematopoietic growth factors accelerating blood cell recovery are not allowed after the second cycle of chemotherapy. Third, quantitative standard uptake value (SUV)-based assessment rather than exclusive visual interpretation is used for interim-PET evaluation as described by Lin et al (J Nucl Med 48: 1626, 2007).

So far, a total of 266 patients have been recruited into the trial. A negative pre-treatment scan was observed in 18 patients, the majority of whom had complete lymphoma resection. 196 patients have reached interim-PET scanning, 168 with diffuse large B cell lymphoma (86%), 11 with grade 3a/b follicular lymphoma (6%), and 17 with peripheral T cell lymphoma (8%). Median SUVmax at staging did not differ across these three lymphoma subgroups. However, the SUVmax reduction at interim-PET was significantly lower in T-cell lymphomas as compared to B-cell lymphomas. Six patients (3%) with a low SUV at staging (<10) were rated as non-responders by quantitative, but as responders by visual assessment. Maximum SUV at staging and SUV reduction after two cycles of (R-)CHOP were independent of the International Prognostic Index (IPI). In contrast to lymphoma patients with baseline SUV values below 30, patients with higher SUV values almost invariably met the predefined criteria for therapy response (p = 0,033, Fisher's exact test). With a median follow up of less than six months, lymphoma relapses across all IPI risk groups have occurred more frequently in patients with a positive interim-PET scan than in patients with a negative scan. Neither absolute baseline SUVmax levels nor magnitude of SUVmax reduction at interim-PET were predictive of relapse.

A combined strategy of SUV-based quantitative and visual qualitative interim-PET assessment is feasible in a multicenter randomized trial designed to guide treatment in lymphoma patients. In this largest series of interim-PET scanning in aggressive lymphoma reported so far, interim-PET response and the IPI risk score proved to be independent. With an as yet short follow-up period relapses were unevenly distributed between PET responders and non-responders. The PETAL trial will help define criteria for interim-PET scanning and response prediction. Recruitment into the trial continues.

Hüttmann:Roche: Research Funding; Amgen: Research Funding. Duehrsen:Amgen: Research Funding; Roche: Research Funding.