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

Cottereau, Anne‐Ségolène; Lanic, Hélène; Mareschal, Sylvain; Meignan, Michel; Véra, Pierre; Tilly, Hervé; Jardin, Fabrice; Becker, Stéphanie

doi:10.1158/1078-0432.ccr-15-2825

Cited by 158 publications

(153 citation statements)

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“…However, standardized phantom experiments confirmed the similarity of image characteristics between centers and patients' data comparison between adaptive techniques, and the 41% threshold was similar within centers. Indeed, TMTVs were all over 5 cm 3 , with a median of 231 cm 3 , an order of magnitude of volume where PET systems have similar detection capability.…”

Section: Discussionmentioning

confidence: 99%

“…A major overestimation was observed with TMTV Bl compared with TMTV 41% . The differences between methods increased for the high-TMTV group, with a proportional error for TMTV values greater than 500 cm 3 . Looking at TMTV under 500 cm 3 , the mean differences between 41% SUV max and adaptive methods were really reduced: 21.8 6 36.3 for TMTV Da (Fig.…”

Section: Tmtv Measurementmentioning

confidence: 96%

“…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: diffuse large B cell lymphoma (2,3), Hodgkin lymphoma (4), peripheral T cell lymphoma (PTCL) (5), and follicular lymphoma (6). In these studies, different methods of TMTV measurement were used; all were based on a fixed thresholding principle to determine the metabolic volume of local tumors.…”

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confidence: 99%

“…It can be relative, using a percentage of the maximum uptake. A threshold of 41% of the SUV max within the lesion, recommended by the European Association of Nuclear Medicine for solid tumors (7), has been used in patients with Hodgkin lymphoma (4), diffuse large B cell lymphoma (3), and PTCL (5), with a good interobserver reproducibility. However, because lymphomas are heterogeneous disease with several tumor sites with a wide range of volumes, SUVs, and tumor background ratios, the adaptive segmentation methods might be of interest for TMTV measurement and could be proposed as an alternative to fixed thresholding methods.…”

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confidence: 99%

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Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

et al. 2016

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Tmtv Measurementmentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

et al. 2016

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“…, Herv e Tilly 3,4 , Fabrice Jardin 3,4 , and St ephanie Becker 1,2 We thank Adams and colleagues for their interest in our research (1) on the prognostic value of baseline total metabolic tumor volume (TMTV) combined with molecular data in patients with diffuse large B-cell lymphoma (DLBCL). They give us the opportunity to discuss TMTV and clinical prognostic indices.…”

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Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL—Response

Lanic

Mareschal

Meignan³

et al. 2016

Clinical Cancer Research

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We thank Adams and colleagues for their interest in our research (1) on the prognostic value of baseline total metabolic tumor volume (TMTV) combined with molecular data in patients with diffuse large B-cell lymphoma (DLBCL). They give us the opportunity to discuss TMTV and clinical prognostic indices.Adams and colleagues underlined the strong role of clinical indices, especially National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), the new one developed for DLBCL since the introduction of rituximab. We agree with the importance of clinical indices, which have been established on large populations, but it does not reduce the potential interest of quantitative PET metrics and gene expression profiling, which are aimed to improve risk stratification for personalized medicine. In our study, we decided to adjust our results for the age-adjusted IPI (aaIPI) instead of NCCN-IPI because the latter was not yet included in the recent European Society of Medical Oncology (ESMO) recommendations. Moreover, we had tested this index in our population. It was predictive of progression-free survival (PFS) and overall survival (OS) even better than reported by Adams and colleagues (2): high NCCN-IPI (>3) was significantly associated with a lower PFS and OS (P ¼ 0.0031 and P ¼ 0.0194). However aaIPI > 1 was a better predictor (P ¼ 0.0041 for PFS and P ¼ 0.0075 for OS). Indeed, it is probably difficult to demonstrate the superiority of this important graded score, NCCN-IPI over aaIPI in small groups of patients.The comments by Adams and colleagues led us to combine NCCN-IPI with TMTV, taking high NCCN-IPI and high TMTV as adverse factors. Interestingly, within patients with high NCCN-IPI, two groups of patients could be identified: a group with high TMTV, which had a very poor outcome (5-year PFS ¼ 35%, 5-year OS ¼ 42%), and a group with low TMTV, which had a much better outcome (5-year PFS ¼ 64%, 5-year OS ¼ 69%, P ¼ 0.001 and P ¼ 0.01, respectively). Patients with low NCCN-IPI had an excellent outcome irrespective of their TMTV (5-year PFS ¼ 80%, 5-year OS ¼ 77%; Fig. 1).Adams and colleagues stated that TMTV was not predictive of PFS and OS in DLBCL. However, using another method of TMTV measurement, Mikhaeel and colleagues (3) have recently shown that TMTV was a strong prognosticator of outcome, confirming the results of our group. Adams and colleagues could not demonstrate the prognostic value of TMTV in their study of 73 retrospectively included DLBCL patients (2). This is probably partly due to the small number of patients included in their series and to the shorter follow-up with fewer events than in our study. Moreover, their study revealed some difficulties to use the 41% SUV max threshold method. Because of the software limitation, they could draw only spherical region of interest (ROI) around the 1 Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France.

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Serum level of soluble interleukin‐2 receptor is positively correlated with metabolic tumor volume on ¹⁸F‐FDG PET/CT in newly diagnosed patients with diffuse large B‐cell lymphoma

Senjo¹,

Kanaya²,

Izumiyama³

et al. 2019

Cancer Medicine

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Diffuse large B‐cell lymphoma (DLBCL) is the most frequent subtype of non‐Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18F‐FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18F‐FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin‐2 receptor (sIL‐2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL‐2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm3 or sIL‐2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm3 and sIL‐2R ≥1300 U/mL was significantly associated with worse 5‐year overall survival and event‐free survival. Importantly, each of sIL‐2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN‐IPI high‐intermediate and high‐risk group. Serum level of sIL‐2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18F‐FDG PET/CT that can predict treatment outcomes of patients with DLBCL.

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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

Cited by 158 publications

References 41 publications

Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL—Response

Serum level of soluble interleukin‐2 receptor is positively correlated with metabolic tumor volume on ¹⁸F‐FDG PET/CT in newly diagnosed patients with diffuse large B‐cell lymphoma

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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

Cited by 158 publications

References 41 publications

Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma

Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL—Response

Serum level of soluble interleukin‐2 receptor is positively correlated with metabolic tumor volume on 18F‐FDG PET/CT in newly diagnosed patients with diffuse large B‐cell lymphoma

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Serum level of soluble interleukin‐2 receptor is positively correlated with metabolic tumor volume on ¹⁸F‐FDG PET/CT in newly diagnosed patients with diffuse large B‐cell lymphoma