Metabolic heterogeneity on baseline 18FDG-PET/CT scan is a predictor of outcome in primary mediastinal B-cell lymphoma

An important unmet need in the management of primary mediastinal B-cell lymphoma (PMBCL) is to identify the patients for whom first line therapy will fail, in order to intervene before the lymphoma becomes refractory. High heterogeneity of intratumoral 18F-fluorodeoxyglucose (18FDG) uptake distribution on positron emission tomography/computed tomography (PET/CT) scans has been suggested as a possible marker of chemo-resistance in solid tumors. In the present study, we investigated the prognostic value of metabolic heterogeneity (MH) in 103 PMBCL patients prospectively enrolled in the International Extranodal Lymphoma Study Group (IELSG) 26 study, aimed at clarifying the role of PET in this lymphoma subtype. MH was estimated using the area under curve of cumulative SUV-volume histogram (AUC-CSH) method. Progression-free survival (PFS) at 5 years was 94% versus 73% in low and high MH groups, respectively (p=0.0001). In a Cox model of progression-free survival including dichotomized MH, metabolic tumor volume (MTV), total lesion glycolysis (TLG), international prognostic index (IPI) and tumor bulk (mediastinal mass >10 cm), as well as age as a continuous variable, only TLG (p<0.001) and MH (p<0.001) retained statistical significance. Using these two features to construct a simple prognostic model resulted in early and accurate (PPV=89% and NPV≥90%) identification of patients at high risk of progression, at a point that would allow the use of risk-adapted treatments. This may provide an important opportunity for the design of future trials, aimed at helping the minority of patients who harbor chemorefractory PMBCL. The study is registered to www.clinicaltrials.gov as NCT00944567.