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European Journal of Nuclear Medicine and Molecular Imaging

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01-09-2018 | Original Article

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma

Authors: Pierre Decazes, Stéphanie Becker, Mathieu Nessim Toledano, Pierre Vera, Paul Desbordes, Fabrice Jardin, Hervé Tilly, Isabelle Gardin

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2018

Abstract

Introduction

Our aim was to study the prognostic value of two new ¹⁸F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor–host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation.

Methods

We retrospectively included 215 patients with DLBCL. Patients underwent initial ¹⁸F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman’s rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis.

Results

TVSR was poorly correlated with TMTV (ρ = 0.5) and TTS (ρ = 0.26), while TTS was highly correlated with TMTV (ρ = 0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm³ for TMTV and 6.0 cm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters.

Conclusions

TVSR measured on the initial ¹⁸F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.

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Tilly H, Gomes da Silva M, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v116–25.CrossRefPubMed

Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116:2040–5.CrossRefPubMedPubMedCentral

Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121–7.CrossRefPubMed

Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378:1858–67.CrossRefPubMed

International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987–94.CrossRef

Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced international prognostic index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123:837–42.CrossRefPubMedPubMedCentral

Meignan M, Sasanelli M, Casasnovas RO, Luminari S, Fioroni F, Coriani C, et al. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients. Eur J Nucl Med Mol Imaging. 2014;41:1113–22.CrossRefPubMed

Barrington SF, Kluge R. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas. Eur J Nucl Med Mol Imaging. 2017;44:97–110.CrossRefPubMedPubMedCentral

Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Müeller SP, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the international conference on malignant lymphomas imaging working group. J Clin Oncol. 2014;32:3048–58.CrossRefPubMedPubMedCentral

10.

Sasanelli M, Meignan M, Haioun C, Berriolo-Riedinger A, Casasnovas R-O, Biggi A, et al. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:2017–22.CrossRefPubMed

11.

Song M-K, Chung J-S, Shin H-J, Lee S-M, Lee S-E, Lee H-S, et al. Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement. Ann Hematol. 2012;91:697–703.CrossRefPubMed

12.

Kim J, Hong J, Kim SG, Hwang KH, Kim M, Ahn HK, et al. Prognostic value of metabolic tumor volume estimated by (18) F-FDG positron emission tomography/computed tomography in patients with diffuse large B-cell lymphoma of stage II or III disease. Nucl Med Mol Imaging. 2014;48:187–95.CrossRefPubMedPubMedCentral

13.

Xie M, Wu K, Liu Y, Jiang Q, Xie Y. Predictive value of F-18 FDG PET/CT quantization parameters in diffuse large B cell lymphoma: a meta-analysis with 702 participants. Med Oncol. 2015;32:446.CrossRefPubMed

14.

Xie M, Zhai W, Cheng S, Zhang H, Xie Y, He W. Predictive value of F-18 FDG PET/CT quantization parameters for progression-free survival in patients with diffuse large B-cell lymphoma. Hematology. 2016;21:99–105.PubMed

15.

Cottereau A-S, Lanic H, Mareschal S, Meignan M, Vera P, Tilly H, et al. Molecular profile and FDG-PET/CT total metabolic tumor volume improve risk classification at diagnosis for patients with Diffuse Large B Cell Lymphoma. Clin Cancer Res. 2016; clincanres.2825.2015.

16.

Rachinel N, Salles G. The host-tumor interface in B-cell non-Hodgkin lymphoma: a new world to investigate. Curr Hematol Malig Rep. 2009;4:196–201.CrossRefPubMed

17.

Lorensen WE, Cline HE. Marching Cubes: A High Resolution 3D Surface Construction Algorithm. Proceedings of the 14th Annual Conference on Computer Graphics and Interactive Techniques [Internet]. New York, NY, USA: ACM; 1987. p. 163–169.

18.

Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, et al. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003;102:4284–9.CrossRefPubMed

19.

Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.CrossRefPubMed

20.

Rao L, Wang X, Zong Z, Chen Z, Shi X, Yi C, et al. PET-CT for Evaluation of Spleen and Liver 18F-FDG Diffuse Uptake Without Lymph Node Enlargement in Lymphoma. Medicine (Baltimore). 2016;95.

21.

Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.CrossRefPubMed

22.

Team RDC. R: a language and environment for statistical computing [internet]. R Foundation for Statistical Computing: Vienna; 2008. Available from: http://www.R-project.org

23.

Chalkidou A, O’Doherty MJ, Marsden PK. False discovery rates in PET and CT studies with texture features: a systematic review. PLoS One. 2015;10:e0124165.CrossRefPubMedPubMedCentral

24.

Toledano MN, Desbordes P, Banjar A, Gardin I, Vera P, Ruminy P, et al. Combination of baseline FDG PET/CT total metabolic tumour volume and gene expression profile have a robust predictive value in patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2018;

25.

Ilyas H, Mikhaeel NG, Dunn JT, Rahman F, Møller H, Smith D, et al. Defining the optimal method for measuring baseline metabolic tumour volume in diffuse large B cell lymphoma. Eur J Nucl Med Mol Imaging. 2018.

26.

Ben Bouallègue F, Tabaa YA, Kafrouni M, Cartron G, Vauchot F, Mariano-Goulart D. Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas. Med Phys. 2017;44:4608–19.CrossRefPubMed

27.

Bukovsky A, Caudle MR, Wimalasena J, Keenan JA, Elder RF. The role of the host-tumor interface and cell hybridization in invasive cancer. Med Hypotheses. 2001;57:729–35.CrossRefPubMed

28.

Yu Y, Decazes P, Gardin I, Vera P, Ruan S. 3D Lymphoma Segmentation in PET/CT Images Based on Fully Connected CRFs. Molecular Imaging, Reconstruction and Analysis of Moving Body Organs, and Stroke Imaging and Treatment. Springer, Cham; 2017.

29.

Grossiord É, Talbot H, Passat N, Meignan M, Najman L. Automated 3D lymphoma lesion segmentation from PET/CT characteristics. 2017 I.E. 14th International Symposium on Biomedical Imaging (ISBI 2017). 2017. p. 174–8.

30.

Cottereau AS, Versari A, Luminari S, Dupuis J, Chartier L, Casasnovas R-O, et al. Prognostic model for high tumor burden follicular lymphoma integrating baseline and end induction PET: a LYSA/FIL study. Blood. 2018.

Title: Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma
Authors: Pierre Decazes
Stéphanie Becker
Mathieu Nessim Toledano
Pierre Vera
Paul Desbordes
Fabrice Jardin
Hervé Tilly
Isabelle Gardin
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-018-4041-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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