Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 5/2018

17.01.2018 | 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

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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
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
verfasst von
Mathieu Nessim Toledano
P. Desbordes
A. Banjar
I. Gardin
P. Vera
P. Ruminy
F. Jardin
H. Tilly
S. Becker
Publikationsdatum
17.01.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2018
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3907-x

Weitere Artikel der Ausgabe 5/2018

European Journal of Nuclear Medicine and Molecular Imaging 5/2018 Zur Ausgabe