Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

Meignan, Michel; Sasanelli, Myriam; Casasnovas, Olivier; Luminari, Stefano; Fioroni, Federica; Coriani, Chiara; Masset, H.; Itti, Emmanuel; Gobbi, Paolo G.; Merli, Francesco; Versari, Annibale

doi:10.1007/s00259-014-2705-y

Cited by 157 publications

(146 citation statements)

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“…We used a 41% SUV max threshold as recommended by European guidelines (25), and already tested in Hodgkin lymphoma, DLBCL (23). In the current study, a tumor volume greater than 300 cm 3 was associated with a dismal outcome.…”

Section: Discussionmentioning

confidence: 98%

“…Several parameters were measured: (i) TMTV was obtained by summing the metabolic volumes of all nodal and extranodal lesions. This method used the 41% SUV max threshold method, as recommended by European Association of Nuclear Medicine (EANM), and because of its high interobserver reproducibility already described in lymphoma (23). A volume of interest was set around each lesion (node or organ involvement) as described previously (10,13,23).…”

Section: Pet/ct Parametersmentioning

confidence: 99%

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Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma

Cottereau

Lanic

Mareschal

et al. 2016

Clinical Cancer Research

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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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Section: Discussionmentioning

confidence: 98%

Section: Pet/ct Parametersmentioning

confidence: 99%

Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma

Cottereau

Lanic

Mareschal

et al. 2016

Clinical Cancer Research

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156

133

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“…As expected TMTV >225 cm 3 was related to advanced disease with more frequent Ann Arbor stage IV. The methodology used in this paper for TMTV computation is highly reproducible (interobserver κ=0.9) and relies on EANM guidelines in using a fixed SUVmax threshold of 41 % for each individual tumour volume measurement [11,12]. The volume computed corresponds to the part of the tumour with the highest SUV.…”

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confidence: 99%

“…The volume computed corresponds to the part of the tumour with the highest SUV. Consequently it gives an index of TMTV linked to the portion of the tumour with maximal metabolic activity that in HL most probably reflects the accessory cells [11]. By contrast, in the few previously published studies analysing the impact of TMTV on outcome in HL the nonmetabolic part of the tumours was included in the delineation of the mean tumour volume.…”

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confidence: 99%

Baseline metabolic tumour volume in Hodgkin lymphoma: the prognostic value of accessory cells

Meignan

2014

Eur J Nucl Med Mol Imaging

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At the present time Hodgkin lymphoma (HL) can be cured in more than 80 % of all patients [1]. Over 90 % of patients with early-stage HL are cured with contemporary combinedmodality therapy, but there are still 25 -30 % of patients with advanced-stage disease who are not cured with the ABVD regimen alone [1,2]. The International Prognostic Score (IPS) fails to recognize these patients with a high risk of treatment failure since the range of outcomes it delineates has narrowed with treatment improvement [1]. Although clinical prognostic scores continue to be routinely used, the need to identify patients with poorer risk has focused research on the tumoral microenvironment to find valuable prognostic information. Indeed, the tumour tissue in HL is composed of a few scattered neoplastic cells called Hodgkin and ReedSternberg (HRS) cells, which account for less than 1 % of all the cells found in biopsy specimens, that are surrounded by an overwhelming population of nonneoplastic mononuclear bystander cells. These cells (CCR4-expressing cell subsets, including eosinophils, histiocytes, macrophages, plasma cells, and Th2 and Treg lymphocytes) are recruited by chemokines produced by the HRS cells and induce the expression of antiapoptotic proteins in HRS cells and their immortalization via a paracrine loop [3,4]. There is an intimate relationship between the HRS cells and reactive cells of the microenvironment that enables the tumour to thrive and evade immune surveillance. Some recent studies have suggested a prognostic role for the nonneoplastic surrounding cells.In classic HL (CHL) tumour-associated macrophages (TAMs) have been shown to be associated with inferior outcomes [5]. Steidl et al. showed that a macrophage gene expression signature is associated with primary treatment failure in CHL and subsequently showed, using an independent validation cohort, that an increase in CD68-positive macrophages in the microenvironment is associated with inferior outcomes [5]. In the E2496 Intergroup trial, a multicentre phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in 287 patients with locally extensive and advanced stage CHL, increased CD68 or CD163 expression was significantly associated with inferior 5-year failure-free survival (FFS; 64 % vs. 78 % and 63 % vs. 82 %) and 5-year overall survival (OS; 81 % vs. 94 % and 81 % vs. 96 %). Multivariate analysis with clinical and biological factors linked to FFS (lymphocyte count, stage 4 disease) and OS (age ≥45 years) showed that increased CD68 or CD163 expression are significant independent predictors of inferior FFS and OS [6]. However, prognostic indices using these results in routine have not yet been built.HL is a lymphoma showing FDG avidity with 100 % of patients positive at baseline, and FDG PET is currently the most accurate staging modality [7]. It has been shown that different mechanisms of glucose uptake, e.g. via GLUT1 in HRS cells and via GLUT3 in the microenvironment, contribute to PET positivity of the tumour [8]. In a recent study...

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“…They demonstrated that a fixed 41% SUVmax threshold is appropriate to define TMTV with excellent inter-observer reproducibility. 60 In three studies investigating MTV in a total of over 400 patients with DLBCL, it was found that a high MTV was associated with worse OS and PFS [61][62][63] and that MTV was an independent prognostic factor of PFS and OS by multivariate analysis. 61,62 TLG failed to predict PFS and was less predictive of OS than TMTV in 114 patients with DLBCL.…”

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confidence: 99%

The Role of Functional Imaging in Lymphoma: Current Controversies and Future Directions

2014

Lymphoma and Chronic Lymphocytic Leukemias

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Fluorodeoxyglucose positron emission tomography (FDG-PET)/computerized tomography (CT) has revolutionized the management of several lymphoma subtypes, yet controversy remains regarding its cost-effectiveness and the appropriate interpretation of equivocal or false-positive PET scans. In this review, we examine the current evidence base informing the management of these controversial aspects of PET, and look ahead to the emerging uses of PET imaging and the application of novel tracers and quantification tools.

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Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

Abstract: Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

Cited by 157 publications

References 28 publications

Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma

Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma

Baseline metabolic tumour volume in Hodgkin lymphoma: the prognostic value of accessory cells

The Role of Functional Imaging in Lymphoma: Current Controversies and Future Directions

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