The mysteries of mantle cell lymphoma–do PET scans provide a clue?

Sunken shipwrecks give up their secrets more easily than the disease recognised as mantle cell lymphoma (MCL). Not until the 1990s was MCL universally recognised as a distinct pathologic entity, and to this day it is grouped variably with low-grade or aggressive lymphomas by different authors [1]. No consensus exists on optimal management of MCL and published guidelines are generally painted with a broad brush [2]. Positron emission tomography has emerged as a powerful tool in the management patients with diffuse large B-cell lymphoma and Hodgkin lymphoma, providing excellent prognostic information at the conclusion of planned therapy and now showing promise as an aid to guide decisions early in therapy [3]. What better circumstances than a frustrating disease such as MCL to utilise a powerful prognostic tool such as [F]fluoro-2deoxy-D-glucose Positron Emission Tomography (FDG-PET). In this issue, Brepoels and colleagues describe their observations regarding the utility of a remarkable 239 FDG-PET scans in 37 MCL patients at University Hospital Gasthuisberg in Belgium [4]. The authors found that baseline FDG-PET studies demonstrated increased staging sensitivity when compared with Computed Tomography (CT) scans – although skeletal uptake on FDG-PET was woefully insensitive for marrow involvement, and higher SUV values correlated with blastoid histology generally recognised as a marker of aggressive biology. Post-therapy FDG-PET results, however, were no more predictive of 2 year progression-free survival than CT scans and when the two modalities were combined in accordance with consensus response criteria, there was no difference in 2 year progression-free survival between complete and partial responders. This finding is disappointing to clinicians hoping to identify who is at greatest risk for a poor outcome and thus candidates for aggressive consolidative strategies. Similarly there was no difference in outcome between the partial and complete responders when assessed early in the course of therapy. Although this largely negative study is valuable as the largest published collection of data on the value of FDG-PET, all definitive conclusions are tempered by the reality that this is an unplanned retrospective analysis of studies done in an uncontrolled fashion by several clinicians over time, risking substantial clinical bias on when the studies were performed and on whom. Despite that, we are fortunate that the patients were apparently managed in a somewhat consistent fashion with anthracycline-containing induction chemotherapy regimens. Furthermore, the study is strengthened by the experience of the nuclear medicine physicians in critical analysis of FDG-PET results. The failure of this analysis to establish any clear clinical scenario in which FDG-PET was helpful in MCL is best understood after reviewing the strength of FDG-PET in diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). FDGPET as an adjunct to CT substantially increases the predictive accuracy of relapse risk after curative intent therapy and is now incorporated into most practice and clinical research guidelines in assessing efficacy in the primary treatment for HL and DLBCL [5]. Accordingly, although post-remission adjuvant management with agents such as interferon or rituximab have not been found useful for an unselected DLBCL population, post-therapy FDGPET is now utilised to identify patients at highest risk