Imaging Follicular Lymphoma Using Positron Emission Tomography With [<sup>18</sup>F]Fluorodeoxyglucose: To What Purpose?
Authors: Sally F. Barrington, N. George Mikhaeel
Journal: Journal of Clinical Oncology (2012)

Positron emission tomography (PET) with [F]fluorodeoxyglucose (FDG) is not as well established for use in follicular lymphoma (FL) as it is for Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). The likely reason is that the clinical benefit of functional imaging is less well defined in FL, which is often an incurable, remitting, and relapsing condition for which treatment is aimed at disease control and prolonging survival. FL is almost always FDG avid. In one study, FDG uptake was seen in all but seven of 140 patients (5%), and disease was limited to the bone marrow or the skin. PET could therefore be a useful tool to stage FL. This might be particularly important in the distinction between early-stage localized disease, which is potentially curable with involved-field radiotherapy (IFRT), and advanced disease, which is incurable and treated with chemotherapy. Several retrospective studies have indicated that PET detects more lesions than computed tomography (CT), with a potential to alter management through upstaging or changing the size of the radiotherapy field. Management changes were indicated because of additional disease findings on PET in 18% to 29% of patients with FL; this increased to 45% to 50% when only patients with limited-stage disease as determined by CT were considered. This suggests that there might be a rationale for using PET for imaging of patients with limited-stage disease to avoid futile IFRT. The outcome of IFRT for localized FL staged by PET has not yet been reported; therefore, it is not known whether the improved staging accuracy will result in improved outcome. Indolent lymphomas tend to have lower uptake than aggressive lymphomas. One study showed that using receiver operating characteristic analysis, an optimal threshold for the standardized uptake value (SUV) of 10 allowed aggressive lymphomas to be distinguished from indolent lymphomas in 69 patients who underwent biopsy with sensitivity and specificity of 71% and 81%, respectively. Higher uptake has also been observed in patients with indolent lymphomas who undergo transformation. Thus, there may be a rationale for using PET to identify the most appropriate site for biopsy in patients with FL at diagnosis and with suspected transformation. More recently, interest has turned to the role of PET in response assessment after chemotherapy and radioimmunotherapy. Reports suggested that patients with PET-positive scans had worse outcomes than patients with PET-negative scans in untreated and relapsed/refractory disease. These studies, however, involved heterogeneous groups with respect to stage, treatment, and the timing of PET scans. Last year, Journal of Clinical Oncology published a study that reported the results of postinduction PET-CT scans in 122 patients with FL who were enrolled onto the Primary Rituximab and Maintenance (PRIMA) trial. Patients were treated with rituximab plus six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus eight cycles of cyclophosphamide, vincristine, and prednisone (R-CVP) and randomly assigned to observation or 2 years of maintenance rituximab. Patients with PET-positive scans after induction had significantly worse outcomes than patients with PET-negative scans. Progression-free survival (PFS) rates were 32.9% and 70.7% (P .001), and overall survival (OS) rates were 78.5% and 96.5% (P .0011) for patients with PET-positive and PET-negative scans, respectively, with a median follow-up of 42 months. There was a significant difference in PFS for patients according to PET status in the observation but not in the maintenance arm, probably because of better outcomes and inadequate patient numbers in the maintenance arm. PET-based response assessment was more predictive than conventional response assessment using international working criteria (IWC). In the multivariate Cox analyses, both PET-based and IWCbased responses were significant, but the IWC was only significant for progressive disease or stable disease (7% of patients) versus the remainder of the study patients. Within the IWC-defined responders (93%), PET was positive in 38% of patients with partial response and 18% of patients with complete response or complete response unconfirmed. The study was limited by its retrospective nature and the PET methodology. The PET-CT result was the interpretation by the local investigator of an imaging report that did not make reference to standardized criteria for PET reporting, which had not been developed at that time. Reports were given by more than 40 physicians, and acquisition parameters for PET were not specified. Despite these drawbacks, the study presented the first evidence that PET-CT might be a useful therapeutic end point in FL and identified a cohort of patients with less favorable outcome treated in a clinical trial. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 35 DECEMBER 1