title: Baseline Metabolic Tumor Volume Predicts Outcome in High-Tumor-Burden Follicular Lymphoma: A Pooled Analysis of Three Multicenter Studies.
abstract: OBJECTIVE
  Identifying patients at high risk of progression and early death among those with high-tumor-burden follicular lymphoma (FL) is unsatisfactory with current prognostic models. This study aimed to determine the prognostic impact of the total metabolic tumor volume (TMTV) measured at baseline with [18F]fluorodeoxyglucose/positron emission tomography-computed tomography ([18F]FDG/PET-CT) scans and its added value to these models.
  
  
  METHODS
  A pooled analysis was performed by using patient data and centrally reviewed baseline PET-CT scans for 185 patients with FL who were receiving immunochemotherapy within three prospective trials. TMTV was computed by using the 41% maximum standardized uptake value thresholding method, and the optimal cutoff for survival prediction was determined.
  
  
  RESULTS
  Median age was 55 years, 92% of patients had stage III to IV disease, 37% had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5, and 31% had a FLIPI2 score of 3 to 5. With a median follow-up of 64 months, overall 5-year progression-free survival (PFS) was 55% and overall survival (OS) was 92%. Median TMTV was 297 cm3(quartile 1 through quartile 3, 135 to 567 cm3). The optimal cutoff identified was 510 cm3, with a markedly inferior survival in the 29% of patients with TMTV > 510 cm3. Five-year PFS was 33% versus 65% (hazard ratio [HR], 2.90; P < .001), and 5-year OS was 85% versus 95% (HR, 3.45; P = .010). On multivariable analysis, TMTV (HR, 2.3; P = .002) and FLIPI2 score (HR, 2.2; P = .002) were independent predictors of PFS. In combination, they identify three risk groups: high TMTV and intermediate-to-high FLIPI2 score with 5-year PFS of 20% (HR, 5.0; P < .001), high TMTV or intermediate-to-high FLIPI2 score with 5-year PFS of 46% (HR, 2.1; P = .007), and low TMTV and low FLIP2 with 5-year PFS of 69%.
  
  
  CONCLUSIONS
  Baseline TMTV is a strong independent predictor of outcome in FL. In combination with FLIPI2 score, it identifies patients at high risk of early progression. It warrants further validation as a biomarker for development of first-line PET-adapted approaches in FL.
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Michel
authors.initials: M
authors.lastname: Meignan
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Anne Ségolène
authors.initials: AS
authors.lastname: Cottereau
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Annibale
authors.initials: A
authors.lastname: Versari
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Loïc
authors.initials: L
authors.lastname: Chartier
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Sami
authors.initials: S
authors.lastname: Boussetta
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Grassi
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: René-Olivier
authors.initials: RO
authors.lastname: Casasnovas
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Tarantino
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Julien
authors.initials: J
authors.lastname: Dubreuil
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.affiliation: Michel Meignan, Anne Ségolène Cottereau, Jehan Dupuis, and Corinne Haioun, Université Paris-Est Créteil, Créteil; Loïc Chartier, Sami Boussetta, and Julien Dubreuil, Centre Hospitalier Lyon Sud; Gilles Salles, Université Claude Bernard Lyon 1, Pierre Bénite; René-Olivier Casasnovas, Centre Hospitalier Universitaire-Dijon, Dijon; Hervé Tilly, Université de Rouen, Rouen, France; Annibale Versari and Ilaria Grassi, Santa Maria Nuova Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico; Stefano Luminari, Arcispedale S. Maria Nuova IRCCS, University of Modena and Reggio Emilia, Reggio Emilia; Vittoria Tarantino and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; and Judith Trotman, University of Sydney, Concord, New South Wales, Australia.
authors.forename: Judith
authors.initials: J
authors.lastname: Trotman