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J Clin Oncol. 2016 Oct 20;34(30):3618-3626. doi: 10.1200/JCO.2016.66.9440. Epub 2016 Sep 30.

Baseline Metabolic Tumor Volume Predicts Outcome in High-Tumor-Burden Follicular Lymphoma: A Pooled Analysis of Three Multicenter Studies.

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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.



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.


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.


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%.


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.


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