Purpose: 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. Patients and 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%. Conclusion: 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.

We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline ¹⁸F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Methods: From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and ¹⁸F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmax_patient), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan–Meier survival analyses were performed. Results: With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmax_patient were 375 cm³ and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmax_patient were adverse factors for PFS (P = 0.027 and P = 0.0003, respectively) and for OS (P = 0.0007 and P = 0.0095, respectively). In multivariate analysis, only Dmax_patient was significantly associated with PFS (P = 0.0014) whereas both factors remained significant for OS (P = 0.037 and P = 0.0029, respectively). Combining MTV (>384 cm³) and Dmax_patient (>58 cm) yielded 3 risk groups for PFS (P = 0.0003) and OS (P = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, n = 18), low with no adverse factor (94% and 97%, n = 36), and an intermediate category with 1 adverse factor (73% and 88%, n = 41). Conclusion: Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.

We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin9s lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after two cycles of doxorubicine, bleomycin, vinblastine, dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. IPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale. The prognostic value of TMTV was evaluated and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p147cm³) group (n=46) vs. 92% and 98% in the low TMTV group (≤147cm³). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared to the current staging systems proposed by EORTC/GELA, GHSG, or NCCN groups. TMTV and iPET2 were independently prognostic and combined identified four risk groups: low (TMTV≤147+DS1-3; 5y-PFS 95%), low-intermediate (TMTV>147+DS1-3; 5y-PFS 81.6%), high-intermediate (TMTV≤147+DS4-5; 5y-PFS 50%) and high (TMTV>147+DS4-5; 5y-PFS 25%). TMTV improves baseline risk stratification of early stage HL patients compared to current staging systems and the predictive value of early PET response as well. Key points Baseline metabolic tumor volume is a strong prognostic factor in early stage HL. Baseline metabolic tumor volume impacts the early response to treatment and combined with early PET improves risk stratification.

Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment 18F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL). Experimental Design: For 81 newly diagnosed patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen, TMTV was computed using the 41% SUVmax thresholding method. According to the gene expression profile, determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology, a subset of 57 patients was classified in germinal center B (GCB) or activated B-cell (ABC) subtypes and MYC or BCL2 overexpressed. Results: Median follow-up was 64 months. Five-year progression-free survival (PFS) and overall survival (OS) were 60% and 63% in the whole population. Median pretherapy TMTV was 320 cm3 (25th–75th percentiles 106–668 cm3). With a 300 cm3 cutoff, patients with high TMTV (n = 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P = 0.0023, P = 0.0047). ABC status, MYC, or BCL2 overexpression and both overexpression (“dual expressor,” DE) were significantly associated with a worse PFS and OS. TMTV combined with molecular data allowed a significant better risk substratification of ABC/GCB patients, on PFS and OS. High TMTV individualized in molecular-low-risk patients a group with a poor outcome (MYC, PFS=51%, OS=55% BCL2, PFS=49%, OS=49% or DE PFS=50%, OS=50%) and a group with a good outcome (MYC, PFS=93%, OS=93% BCL2, PFS=86%, OS=86%, or DE PFS=81%, OS=81%). Conclusions: The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy. Clin Cancer Res; 22(15); 3801–9. ©2016 AACR.

Background Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and identification of prognostic factors at diagnosis is needed. Patients and methods The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline 18-Fluorodeoxyglucose positron-emission tomography/computed tomography was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% SUVmax threshold method and an optimal cut-off point for binary outcomes was determined and compared to others prognostic factors. Results With a median follow-up of 23 months, 2-year progression free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230cm³, n=53), vs. 71% for those with a low TMTV0, (p230cm³ and PIT>1, n=33,) from those with good prognosis (TMTV0≤230cm³ and PIT≤1, n=40 ) : 19% vs. 73% 2-year PFS (p<0.0001) and 43% vs. 81% 2-year OS respectively (p=0.0002). Thirty one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68 % 2-year OS. Conclusion TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.