Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2018

01-05-2018 | Original Article

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

Authors: Mathieu Nessim Toledano, P. Desbordes, A. Banjar, I. Gardin, P. Vera, P. Ruminy, F. Jardin, H. Tilly, S. Becker

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2018

Login to get access

Abstract

Purpose

This study evaluated the predictive significance of total metabolic tumour volume (TMTV) measured on baseline FDG PET/CT and its value in addition to gene expression profiling using a new method of gene analysis (rapid reverse transcriptase multiplex ligation-dependent probe amplification assay, RT-MLPA) in patients with diffuse large B-cell lymphoma treated with R-CHOP or R-CHOP-like chemotherapies.

Methods

The analysis included 114 patients. TMTV was measured using a 41% SUVmax threshold and tumours were classified into GCB or ABC subtypes according to the RT-MLPA assay.

Results

The median follow-up was 40 months. the 5-year progression-free survival (PFS) was 54% and the 5-year overall survival (OS) was 62%. The optimal TMTV cut-off value was 261 cm3. In 59 patients with a high TMTV the 5-year PFS and OS were 37% and 39%, respectively, in comparison with 72% and 83%, respectively, in 55 patients with a low TMTV (p = 0.0002 for PFS, p < 0.0001 for OS). ABC status was significantly associated with a worse prognosis. TMTV combined with molecular data identified three groups with very different outcomes: (1) patients with a low TMTV whatever their phenotype (n = 55), (2) patients with a high TMTV and GCB phenotype (n = 33), and (3) patients with a high TMTV and ABC phenotype (n = 26). In the three groups, 5-year PFS rates were 72%, 51% and 17% (p < 0.0001), and 5-year OS rates were 83%, 55% and 17% (p < 0.0001), respectively. In multivariate analysis, TMTV, ABC/GCB phenotype and International Prognostic Index were independent predictive factors for both PFS and OS (p < 0.05 for both).

Conclusions

This integrated risk model could lead to more accurate selection of patients that would allow better individualization of therapy.
Appendix
Available only for authorised users
Literature
1.
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
2.
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
3.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.CrossRefPubMed
4.
Tilly H, Gomes da Silva M, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v116–25.CrossRefPubMed
5.
Meignan M, Itti E, Gallamini A, Younes A. FDG PET/CT imaging as a biomarker in lymphoma. Eur J Nucl Med Mol Imaging. 2015;42:623–33.CrossRefPubMed
6.
7.
Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller 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
8.
Sasanelli M, Meignan M, Haioun C, Berriolo-Riedinger A, Casasnovas RO, 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
9.
Song MK, Chung JS, Shin HJ, Lee SM, Lee SE, Lee HS, 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
10.
Kim J, Hong J, Kim SG, Hwang KH, Kim M, Ahn HK, et al. Prognostic value of metabolic tumor volume estimated by 18F-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
11.
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
12.
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(2):99–105.PubMed
13.
Ceriani L, Martelli M, Zinzani PL, Ferreri AJ, Botto B, Stelitano C, et al. Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma. Blood. 2015;126:950–6.CrossRefPubMed
14.
Kanoun S, Rossi C, Berriolo-Riedinger A, Dygai-Cochet I, Cochet A, Humbert O, et al. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:1735–43.CrossRefPubMed
15.
Cottereau AS, Becker S, Broussais F, Casasnovas O, Kanoun S, Roques M, et al. Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL). Ann Oncol. 2016;27(4):719–24.CrossRefPubMed
16.
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.CrossRefPubMed
17.
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937–47.CrossRefPubMed
18.
Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359:2313–23.CrossRefPubMed
19.
Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2003;100:9991–6.CrossRefPubMedPubMedCentral
20.
Sandoval-Sus JD, Chavez J, Dalia S. A new therapeutic era in GCB and ABC diffuse large B-cell lymphoma molecular subtypes: a cell of origin-driven review. Curr Cancer Drug Targets. 2016;16(4):305–22.CrossRefPubMed
21.
Bohers E, Mareschal S, Bouzelfen A, Marchand V, Ruminy P, Maingonnat C, et al. Targetable activating mutations are very frequent in GCB and ABC diffuse large B-cell lymphoma. Genes Chromosomes Cancer. 2014;53(2):144–53.CrossRefPubMed
22.
Lanic H, Mareschal S, Mechken F, Picquenot JM, Cornic M, Maingonnat C, et al. Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma. Leuk Lymphoma. 2012;53:34–42.CrossRefPubMed
23.
Cottereau AS, 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;22(15):3801–9.CrossRefPubMed
24.
Eldering E, Spek CA, Aberson HL, Grummels A, Derks IA, de Vos AF, et al. Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Nucleic Acids Res. 2003;31(23):e153.CrossRefPubMedPubMedCentral
25.
Mareschal S, Ruminy P, Bagacean C, Marchand V, Cornic M, Jais JP, et al. Accurate classification of germinal center B-cell-like/activated B-cell-like diffuse large B-cell lymphoma using a simple and rapid reverse transcriptase-multiplex ligation-dependent probe amplification assay. J Mol Diagn. 2015;17(3):273–83CrossRef
26.
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
27.
Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour PET imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.CrossRefPubMed
28.
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
29.
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(5):e0124165.CrossRefPubMedPubMedCentral
30.
Rimsza LM, Leblanc ML, Unger JM, Miller TP, Grogan TM, Persky DO, et al. Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2008;112:3425–33.CrossRefPubMedPubMedCentral
31.
Gu K, Weisenburger DD, Fu K, Chan WC, Greiner TC, Aoun P, et al. Cell of origin fails to predict survival in patients with diffuse large B-cell lymphoma treated with autologous hematopoietic stem cell transplantation. Hematol Oncol. 2012;30:143–9.CrossRefPubMed
32.
Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol. 2011;29:4079–87.CrossRefPubMed
33.
Gutiérrez-García G, Cardesa-Salzmann T, Climent F, González-Barca E, Mercadal S, Mate JL, et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011;117(18):4836–43.CrossRefPubMed
34.
Read JA, Koff JL, Nastoupil LJ, Williams JN, Cohen JB, Flowers CR. Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms. Clin Lymphoma Myeloma Leuk. 2014;14:460–467.e2.CrossRefPubMedPubMedCentral
35.
Rayman N, Lam KH, van der Holt B, Koss C, Veldhuizen D, Budel LM, et al. Prognostic relevance of immunohistochemical subclassification of diffuse large B-cell lymphoma in two prospective phase III clinical trials. Clin Lymphoma Myeloma Leuk. 2011;11(1):23–32.CrossRefPubMed
Metadata
Title
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
Authors
Mathieu Nessim Toledano
P. Desbordes
A. Banjar
I. Gardin
P. Vera
P. Ruminy
F. Jardin
H. Tilly
S. Becker
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3907-x

Other articles of this Issue 5/2018

European Journal of Nuclear Medicine and Molecular Imaging 5/2018 Go to the issue

Original Article

Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and paraganglioma in the pediatric population

Original Article

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer

Letter to the Editor

Interim FDG PET/CT in primary mediastinal diffuse large B-cell lymphoma: really almost useless procedure?

Original Article

The diagnostic value of 18F–FDG-PET/CT and MRI in suspected vertebral osteomyelitis – a prospective study

Original Article

Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy

Review Article

Targeting PSMA by radioligands in non-prostate disease—current status and future perspectives