Pre-treatment total metabolic tumour volumes in lymphoma: Does quantity matter?

Positron emission tomography/computed tomography (PET/CT) is used for the staging of lymphomas. Clinical information, such as Ann Arbor stage and number of involved sites, is derived from baseline staging and correlates with tumour volume. With modern imaging software, exact measures of total metabolic tumour volumes (tMTV) can be determined, in a semi- or fully-automated manner. Several technical factors, such as tumour segmentation and PET/CT technology influence tMTV and there is no consensus on a standardized uptake value (SUV) thresholding method, or how to include the volumes in the bone marrow and spleen. In diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, and Hodgkin lymphoma, tMTV has been shown to predict progression-free survival and/or overall survival, after adjustments for clinical risk scores. However, most studies have used receiver operating curves to determine the optimal cut-off for tMTV and many studies did not include a training-validation approach, which led to the risk of overestimation of the independent prognostic value of tMTV. The identified cut-off values are heterogeneous, even when the same SUV thresholding method is used. Future studies should focus on testing tMTV in homogeneously-treated cohorts and seek to validate identified cut-off values externally so that a prognostic value can be documented, over and above currently used clinical surrogates for tumour volume.