Meignan Michel, Cottereau Anne Ségolène, Versari Annibale, Chartier Loïc, Dupuis Jehan, Boussetta Sami, Grassi Ilaria, Casasnovas René-Olivier, Haioun Corinne, Tilly Hervé, Tarantino Vittoria, Dubreuil Julien, Federico Massimo, Salles Gilles, Luminari Stefano, Trotman Judith
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.
J Clin Oncol. 2016 Oct 20;34(30):3618-3626. doi: 10.1200/JCO.2016.66.9440. Epub 2016 Sep 30.
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 [F]fluorodeoxyglucose/positron emission tomography-computed tomography ([F]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 cm (quartile 1 through quartile 3, 135 to 567 cm). The optimal cutoff identified was 510 cm, with a markedly inferior survival in the 29% of patients with TMTV > 510 cm. 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.
在高肿瘤负荷滤泡性淋巴瘤（FL）患者中，利用当前的预后模型来识别具有疾病进展和早期死亡高风险的患者并不理想。本研究旨在确定通过[F]氟脱氧葡萄糖/正电子发射断层扫描-计算机断层扫描（[F]FDG/PET-CT）扫描在基线时测量的总代谢肿瘤体积（TMTV）的预后影响及其对这些模型的附加值。
通过使用患者数据并对185例接受免疫化疗的FL患者的基线PET-CT扫描进行集中审查，进行了一项汇总分析，这些患者来自三项前瞻性试验。使用41%最大标准化摄取值阈值法计算TMTV，并确定生存预测的最佳临界值。
中位年龄为55岁，92%的患者患有III至IV期疾病，37%的患者滤泡性淋巴瘤国际预后指数（FLIPI）评分为3至5，31%的患者FLIPI2评分为3至5。中位随访64个月，5年无进展生存率（PFS）总体为55%，总生存率（OS）为92%。中位TMTV为297 cm（四分位数1至四分位数3，135至567 cm）。确定的最佳临界值为510 cm，TMTV>510 cm的29%患者的生存率明显较差。5年PFS为33%对65%（风险比[HR]，2.90；P<.001），5年OS为85%对95%（HR，3.45；P = .010）。多变量分析显示，TMTV（HR，2.3；P = .002）和FLIPI2评分（HR，2.2；P = .002）是PFS的独立预测因素。综合来看，它们可识别出三个风险组：高TMTV和中高FLIPI2评分组，5年PFS为20%（HR，5.0；P<.001）；高TMTV或中高FLIPI2评分组，5年PFS为46%（HR，2.1；P = .007）；低TMTV和低FLIP2组，5年PFS为69%。
基线TMTV是FL预后的有力独立预测因素。与FLIPI2评分相结合，它可识别出早期进展高风险的患者。作为FL一线PET适应性治疗方法开发的生物标志物，它值得进一步验证。
