ArticlesPrognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies
Introduction
Follicular lymphoma is a highly prevalent lymphoma with heterogeneous clinical behaviour. Initially sensitive to rituximab chemotherapy, it is characterised by recurrent relapses and risk of histological transformation. Although traditionally thought to be incurable, the longer remissions and extended survival of most patients in the modern therapeutic era challenges this notion, since the median age at diagnosis is 63 years.1, 2 Many patients can now expect to die from other causes while in remission, or with asymptomatic disease. Nonetheless, with substantial variability in the clinical course of follicular lymphoma, patients with a particularly poor outlook are not easily identifiable by either pretreatment prognostic indices (eg, the Follicular Lymphoma International Prognostic Index [FLIPI]3 and FLIPI24), or conventional response assessment with the 1999 International Workshop Criteria (IWC) to standardise response for non-Hodgkin lymphoma.5 Assessment with the IWC involves complex calculations on contrast-enhanced CT of lymph-node dimensions to distinguish complete response, unconfirmed complete response, and partial response from stable or progressive disease, and formal response classification is often not done in routine clinical practice.
PET-CT (PET) with 18F-fluorodeoxyglucose (FDG) after induction therapy is a powerful prognostic imaging method in Hodgkin's and diffuse large B-cell lymphoma. It has been shown to be better than the IWC criteria for the categorisation of response and prognosis and has been recommended since the 2007 International Harmonization Project (IHP) revised criteria for response assessment of these lymphoma types.6, 7 However, the IHP criteria precluded use of PET for response assessment of follicular lymphoma outside the research setting.6, 7
Three prospective cooperative group studies8, 9, 10 of first-line therapy for patients with high-tumour-burden follicular lymphoma showed that FDG uptake is a universal characteristic of follicular lymphoma and therefore emphasised the value of PET in staging and response assessment. In two of these studies,8, 9 a score of 4 points or higher on the recently recommended five-point scale (5PS, also known as the Deauville criteria; panel 1),11 applied during the central review of PET images, was strongly predictive of progression-free survival,9, 12 providing evidence to support the application of the 5PS to response assessment in follicular lymphoma, as now recommended in the 2014 Lugano Classification13 and International Conference on Malignant Lymphoma (ICML) Imaging Working Group consensus guidelines14 for response assessment of FDG-avid lymphomas.
We assessed the independent application of the 5PS to a large cohort derived from these studies8, 9, 10 to provide a more precise correlation between PET status after induction therapy and survival. The objective of this pooled analysis was to confirm the primary role of PET response assessment in follicular lymphoma.
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Study design and participants
In this pooled analysis, we used data from three multicentre prospective studies: the two Lymphoma Study Association (formerly Groupe d'Etudes des Lymphomes de l'Adulte) studies—the PRIMA (Primary Rituximab and Maintenance) study15 of rituximab with cyclophosphamide, vincristine, and prednisolone (R-CVP) or cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and the PET-Folliculaire (PET-FL) study9 of PET assessment during and after rituximab plus CHOP (R-CHOP)—and the
Results
439 patients with post-induction PET scans were enrolled in the three studies between Dec 24, 2004, and Sept 22, 2010: 122 in PRIMA, 112 in the PET-FL, and 205 in the FOLL05 study. Only 85 patients' scans from PRIMA and 121 patients' scans from FOLL05 were submitted for central review, and of those submitted scans several were excluded because PET or CT data were incomplete or not in DICOM format, with scans from 61 (72%) of 85 patients in PRIMA and 79 (65%) of 121 patients in FOLL05 of
Discussion
Increasingly effective therapy for follicular lymphoma now challenges assumptions of the incurable nature of this indolent lymphoma,20 because most patients can now expect extended survival after first-line immunochemotherapy. However, the poor discriminatory capacity of the 1999 IWC contrast-enhanced CT-based response assessment consigns most responding patients (with an unconfirmed complete response or partial response) to an uncertain remission in which only close clinical follow-up
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