Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment 18 F-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% SUV max 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 cm 3 (25th-75th percentiles 106-668 cm 3 ). With a 300 cm 3 cutoff, patients with high TMTV (n ¼ 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P ¼ 0.0023, P ¼ 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, PFS¼51%, OS¼55% BCL2, PFS¼49%, OS¼49% or DE PFS¼50%, OS¼50%) and a group with a good outcome (MYC, PFS¼93%, OS¼93% BCL2, PFS¼86%, OS¼86%, or DE PFS¼81%, OS¼81%). Conclusions:The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy.

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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.

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.

This integrated risk model could lead to more accurate selection of patients that would allow better individualization of therapy.

Background Hand surgeons treat trapeziometacarpal arthrosis as if everyone with the disease presents for treatment despite evidence that suggests that trapeziometacarpal arthrosis is a normal part of human aging for which-it seems safe to assume-most people never seek medical attention. Questions/purposes The aims of our study were (1) to confirm the prevalence of radiographic trapeziometacarpal arthrosis in a very large sample and to determine if age and sex are associated with (2) any radiographic evidence of trapeziometacarpal arthrosis; and (3) radiographic evidence of severe trapeziometacarpal arthrosis.Methods A total of 2321 patients 31 years or older with radiographs obtained during treatment of a distal radius fracture at a tertiary care medical center emergency department between 2002 and 2012 were analyzed. Trapeziometacarpal arthrosis was graded using the 3-point scale of Sodha et al. (none, definite, destroyed trapeziometacarpal joint); we used regression analyses to determine the association of age (in 10-year age groups) and sex with the presence of trapeziometacarpal arthrosis. Results The prevalence of trapeziometacarpal arthrosis steadily increased to 85% between the ages of 71 and 80 years and reached 100% in women (with 50% of them being classified as severe) aged 91 years or older and 93% in men of 81 years or older. Severe arthrosis was more prevalent at earlier ages among women and reached 35% in women and 34% in men who were 81 years or older. Logistic regression identified higher age as the strongest factor associated with trapeziometacarpal arthrosis, but sex was also a factor.

The purpose of this study was to compare in a large series of peripheral T cell lymphoma, as a model of diffuse disease, the prognostic value of baseline total metabolic tumor volume (TMTV) measured on 18 F-FDG PET/CT with adaptive thresholding methods with TMTV measured with a fixed 41% SUV max threshold method. Methods: One hundred six patients with peripheral T cell lymphoma, staged with PET/CT, were enrolled from 5 Lymphoma Study Association centers. In this series, TMTV computed with the 41% SUV max threshold is a strong predictor of outcome. On a dedicated workstation, we measured the TMTV with 4 adaptive thresholding methods based on characteristic image parameters: Daisne (Da) modified, based on signal-to-background ratio; Nestle (Ns), based on tumor and background intensities; Fit, including a 3-dimensional geometric model based on spatial resolution (Fit); and Black (Bl), based on mean SUV max . The TMTV values obtained with each adaptive method were compared with those obtained with the 41% SUV max method. Their respective prognostic impacts on outcome prediction were compared using receiver-operatingcharacteristic (ROC) curve analysis and Kaplan-Meier survival curves. Results: The median value of TMTV 41% , TMTV Da , TMTV Ns , TMTV Fit , and TMTV Bl were, respectively, 231 cm 3 (range, 5-3,824), 175 cm 3 (range, 8-3,510), 198 cm 3 (range, 3-3,934), 175 cm 3 (range, 8-3,512), and 333 cm 3 (range, 3-5,113). The intraclass correlation coefficients were excellent, from 0.972 to 0.988, for TMTV Da , TMTV Fit , and TMTV Ns , and less good for TMTV Bl (0.856). The mean differences obtained from the Bland-Altman plots were 48.5, 47.2, 19.5, and 2253.3 cm 3 , respectively. Except for Black, there was no significant difference within the methods between the ROC curves (P . 0.4) for progression-free survival and overall survival. Survival curves with the ROC optimal cutoff for each method separated the same groups of low-risk (volume # cutoff) from high-risk patients (volume . cutoff), with similar 2-y progression-free survival (range, 66%-72% vs. 26%-29%; hazard ratio, 3.7-4.1) and 2-y overall survival (79%-83% vs. 50%-53%; hazard ratio, 3.0-3.5). Conclusion: The prognostic value of TMTV remained quite similar whatever the methods, adaptive or 41% SUV max , supporting its use as a strong prognosticator in lymphoma. However, for implementation of TMTV in clinical trials 1 single method easily applicable in a multicentric PET review must be selected and kept all along the trial. PET/ CT with 18 F-FDG has been recognized as the best imaging tool for staging and response assessment in FDG-avid lymphoma. The last International Conference on Malignant Lymphoma recommendations (1) encourage investigating the quantitative analysis of 18 F-FDG PET/CT at staging. In this regard, the measurement of the total metabolic tumor volume (TMTV), which gives an estimation of the total tumor burden, has gained special interest. Indeed, several series have shown that TMTV was predictive of outcome in different lymphoma subtypes: d...

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes on current therapy. We investigated whether response assessed with PET/CT combined with baseline total metabolic tumor volume (TMTV) could detect early relapse or refractory disease. From 7 European centers, 140 patients with nodal PTCL who underwent baseline PET/CT were selected. Forty-three had interim PET (iPET) performed after 2 cycles (iPET2), 95 had iPET performed after 3 or 4 cycles (iPET3/4), and 96 had end-of-treatment PET (eotPET). Baseline TMTV was computed with a 41% SUV threshold, and PET response was reported using the Deauville 5-point scale. With a median of 43 mo of follow-up, the 2-y progression-free survival (PFS) and overall survival (OS) were 51% and 67%, respectively. iPET2-positive patients (Deauville score ≥ 4) had a significantly worse outcome than iPET2-negative patients ( < 0.0001, hazard ratio of 6.8 for PFS; < 0.0001, hazard ratio of 6.6 for OS). The value of iPET3/4 was also confirmed for PFS ( < 0.0001) and OS ( < 0.0001). The 2-y PFS and OS for iPET3/4-positive ( = 28) and iPET3/4-negative ( = 67) patients were 16% and 32% versus 75% and 85%, respectively. The eotPET results also reflected patient outcome. A model combining TMTV and iPET3/4 stratified the population into distinct risk groups (TMTV ≤ 230 cm and iPET3/4-negative [2-y PFS/OS, 79%/85%]; TMTV > 230 cm and iPET3/4-negative [59%/84%]; TMTV ≤ 230 cm and iPET3/4-positive [42%/50%]; TMTV > 230 cm and iPET3/4-positive [0%/18%]). iPET response is predictive of outcome and allows early detection of high-risk PTCL patients. Combining iPET with TMTV improves risk stratification in individual patients.