title: Prognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies.
abstract: BACKGROUND
  The value of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET) imaging in response assessment after first-line rituximab chemotherapy for follicular lymphoma has been documented. We analysed the application of the five-point Deauville scale (5PS; used to score FDG uptake on PET images) in a large cohort derived from three studies, to assess the correlation between post-induction PET status and survival in patients with follicular lymphoma.
  
  
  METHODS
  In this pooled analysis, we used data from three multicentre prospective studies of first-line rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma (the PRIMA study, the PET-Folliculaire study, and the Fondazione Italiana Linfomi FOLL05 study). Patients included in this analysis received at least six cycles of rituximab and chemotherapy before response assessment with conventional contrast-enhanced CT and PET low-dose CT (PET). We included only patients who had a PET scan within 3 months of the last dose of induction rituximab. Patient data, including conventional CT-based response assessment, were recorded for all patients undergoing PET review. Scans undergoing central PET review were scored independently by three reviewers according to the 5PS. The primary endpoints were progression-free survival and overall survival according to the 5PS score of post-induction PET scan (ie, positive [≥4 points] or negative [<4 points]), analysed in the central review population.
  
  
  RESULTS
  Between Dec 24, 2004, and Sept 22, 2010, 439 of the patients enrolled in the three studies underwent local PET assessment, 246 of whom had centrally reviewed post-induction scans. 41 (17%) of 246 patients had a positive post-induction PET scan according to a cutoff of 4 or higher on the 5PS, with substantial reporter concordance. With a median follow-up of 54·8 months (IQR 39·7-68·5; range 7·7-90·1), the hazard ratio (HR) for progression-free survival for patients with a positive PET scan versus those with a negative PET scan was 3·9 (95% CI 2·5-5·9; p<0·0001), and for overall survival was 6·7 (2·4-18·5; p=0·0002). For patients with a positive PET scan, 23·2% (95% CI 11·1-37·9) of patients were progression free at 4 years compared with 63·4% (55·9-70·0) of those who had a negative PET scan (p<0·0001); 4-year overall survival was 87·2% (95% CI 71·9-94·5) versus 97·1% (93·2-98·8), respectively (p<0·0001). Conventional CT-based response (ie, complete response or unconfirmed complete response vs partial response) was weakly predictive of progression-free survival (HR 1·7 [95% CI 1·1-2·5]; p=0·017).
  
  
  CONCLUSIONS
  PET-CT rather than contrast-enhanced CT scanning should be considered as a new standard for response assessment of follicular lymphoma in clinical practice, and could help guide response-adapted therapy.
  
  
  BACKGROUND
  Groupe d'Etude des Lymphomes de l'Adulte (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health.
authors.affiliation: Haematology Department, Concord Hospital, University of Sydney, Sydney, NSW, Australia. Electronic address: judith.trotman@sswahs.nsw.gov.au.
authors.forename: Judith
authors.initials: J
authors.lastname: Trotman
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.affiliation: Department of Biostatistics, The Lymphoma Academic Research Organisation (LYSARC), Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Boussetta
authors.affiliation: Nuclear Medicine Department, Santa Maria Nuova Hospital, IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Annibale
authors.initials: A
authors.lastname: Versari
authors.affiliation: Unité Hémopathies Lymphoïdes, Hopital Henri Mondor, Creteil, France.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Service de Médecine Nucléaire, Centre Hospitalier Alpes Léman, Contamine sur Arve, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Tychyj
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.affiliation: Service de Médecine Nucléaire, Centre Georges Francois Leclerc, Dijon, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Berriolo-Riedinger
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Franceschetto
authors.affiliation: Service de Médecine Nucléaire, Hôpital Perpan, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Julian
authors.affiliation: Service de Médecine Nucléaire, Hospices Civils de Lyon, Université Lyon 1, Pierre-Bénite, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Ricard
authors.affiliation: Nuclear Medicine Department, San Gerardo Hospital, University of Milano Bicocca, Monza, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Guerra
authors.affiliation: Unité Hémopathies Lymphoïdes, Hôpital Henri Mondor and Université Paris Est Créteil, Créteil, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.affiliation: Department of Medicine, University Hospital and School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Irene
authors.initials: I
authors.lastname: Biasoli
authors.affiliation: Département d'Hématologie, UMR918, Centre Henri Becquerel, Université de Rouen, Rouen, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.affiliation: Service d'Hématologie, Hospices Civils de Lyon, Université Lyon 1, Pierre-Bénite, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Service de Médecine Nucléaire, Hôpital Henri Mondor and Université Paris Est Créteil, Créteil, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Meignan