Role of Modern Imaging with FDG-PET/CT in Aggressive Lymphoma

  • Judith TrotmanEmail author
  • Michel Meignan
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


Use of imaging for staging and response assessment of aggressive lymphomas has appropriately moved from anatomic imaging with CT scanning alone to capturing both anatomic and metabolic information with combined PET-CT. The poorer prognosis of patients who fail to obtain a complete metabolic response after rituximab-chemotherapy has driven interim PET-CT assessment applying the 5-point scale or measuring changes in the standardised uptake value (ΔSUV). However with variations in chemotherapy regimen, timing and methodology across studies, the positive predictive value of interim PET remains too low to recommend its uniform application in routine clinical practice.

More recently, PET studies across a range of lymphomas including DLBCL and peripheral T-cell lymphoma suggest that calculation of the baseline total metabolic tumour volume (TMTV) may more accurately quantify tumour burden for determining prognosis. With standardisation of PET acquisition and the use of more sophisticated software, total metabolic tumour volume (TMTV) calculations are becoming feasible. TMTV has the potential to provide the single most efficient and relevant means of informing clinicians and patients of their disease burden. Given the poorer prognosis of patients with higher TMTV, this has potential to be integrated with end-of-induction PET and the molecular profile of lymphoma to better identify patients for whom a standard approach will provide a high probability of cure and those for whom more aggressive approaches could be applied. Translating the knowledge acquired from sophisticated technology into a simple reproducible message to convey prognosis and tailor therapy for patients across an increasingly complex spectrum of aggressive lymphomas is the current challenge for the PET physician and haematologist research collaborations.


Total metabolic tumour volume Interim PET End-of-induction PET 


  1. 1.
    Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. Scholar
  2. 2.
    Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, Wiseman GA, Kostakoglu L, Scheidhauer K, Buck A, Naumann R, Spaepen K, Hicks RJ, Weber WA, Reske SN, Schwaiger M, Schwartz LH, Zijlstra JM, Siegel BA, Cheson BD. Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging Subcommittee of International Harmonization Project in lymphoma. J Clin Oncol. 2007;25(5):571–8. Scholar
  3. 3.
    El-Galaly TC, Villa D, Alzahrani M, Hansen JW, Sehn LH, Wilson D, de Nully Brown P, Loft A, Iyer V, Johnsen HE. Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: a Danish–Canadian study of 443 patients with diffuse-large B-cell lymphoma. Am J Hematol. 2015;90(11):1041–6.CrossRefGoogle Scholar
  4. 4.
    Khan AB, Barrington SF, Mikhaeel NG, Hunt AA, Cameron L, Morris T, Carr R. PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood. 2013;122(1):61–7.CrossRefGoogle Scholar
  5. 5.
    Raanani P, Shasha Y, Perry C, Metser U, Naparstek E, Apter S, Nagler A, Polliack A, Ben-Bassat I, Even-Sapir E. Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in the PET/CT era? Ann Oncol. 2006;17(1):117–22. Scholar
  6. 6.
    Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Müeller SP, Schwartz LH, Zucca E, Fisher RI, Trotman J. 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(27):3048–58.CrossRefGoogle Scholar
  7. 7.
    Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–67.CrossRefGoogle Scholar
  8. 8.
    Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on interim-PET-scan in lymphoma. Leuk Lymphoma. 2009;50(8):1257–60. Scholar
  9. 9.
    Barrington SF, O’Doherty MJ. Limitations of PET for imaging lymphoma. Eur J Nucl Med Mol Imaging. 2003;30:S117–27.
  10. 10.
    Cook GJ, Wegner EA, Fogelman I. Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging. Semin Nucl Med. 2004;34(2):122–33.CrossRefGoogle Scholar
  11. 11.
    Barrington SF, Mikhaeel NG. When should FDG-PET be used in the modern management of lymphoma? Br J Haematol. 2013;164(3):315–28.CrossRefGoogle Scholar
  12. 12.
    Berthet L, Cochet A, Kanoun S, Berriolo-Riedinger A, Humbert O, Toubeau M, Dygai-Cochet I, Legouge C, Casasnovas O, Brunotte F. In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy. J Nucl Med. 2013;54(8):1244–50.CrossRefGoogle Scholar
  13. 13.
    Mittal BR, Manohar K, Malhotra P, Das R, Kashyap R, Bhattacharya A, Varma N, Varma S. Can fluorodeoxyglucose positron emission tomography/computed tomography avoid negative iliac crest biopsies in evaluation of marrow involvement by lymphoma at time of initial staging? Leuk Lymphoma. 2011;52(11):2111–6. Scholar
  14. 14.
    Ngeow JY, Quek RH, Ng DC, Hee SW, Tao M, Lim LC, Tan YH, Lim ST. High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma. Ann Oncol. 2009;20(9):1543–7. Scholar
  15. 15.
    Pelosi E, Penna D, Douroukas A, Bello M, Amati A, Arena V, Passera R, Bisi G. Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study. Q J Nucl Med Mol Imaging. 2011;55(4):469–75.PubMedGoogle Scholar
  16. 16.
    Cheson BD. Hodgkin lymphoma: protecting the victims of our success. J Clin Oncol. 2012;30(36):4456–7.CrossRefGoogle Scholar
  17. 17.
    El-Galaly TC, d’Amore F, Mylam KJ, de Nully Brown P, Bogsted M, Bukh A, Specht L, Loft A, Iyer V, Hjorthaug K, Nielsen AL, Christiansen I, Madsen C, Johnsen HE, Hutchings M. Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol. 2012;30(36):4508–14.Google Scholar
  18. 18.
    O’Doherty MJ, Barrington SF, Campbell M, Lowe J, Bradbeer CS. PET scanning and the human immunodeficiency virus-positive patient. J Nucl Med. 1997;38(10):1575–83.Google Scholar
  19. 19.
    Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D. Follicular lymphoma international prognostic index. Blood. 2004;104:1258.CrossRefGoogle Scholar
  20. 20.
    Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61.CrossRefGoogle Scholar
  21. 21.
    Zhou Z, Sehn LH, Rademaker AW, Gordon LI, LaCasce AS, Crosby-Thompson A, Vanderplas A, Zelenetz AD, Abel GA, Rodriguez MA. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRefGoogle Scholar
  22. 22.
    Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U, Morabito F, Martelli M, Brusamolino E, Iannitto E. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood. 2004;103(7):2474–9.CrossRefGoogle Scholar
  23. 23.
    Meignan M, Sasanelli M, Casasnovas RO, Luminari S, Fioroni F, Coriani C, Masset H, Itti E, Gobbi PG, Merli F, Versari A. Eur J Nucl Med Mol Imaging. 2014;41(6):1113–22. Epub 2014 Feb 26.CrossRefPubMedGoogle Scholar
  24. 24.
    Cottereau A-S, Lanic H, Mareschal S, Meignan M, Vera P, Tilly H, Jardin F, Becker S. 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. 2016a;22(15):3801–9.CrossRefGoogle Scholar
  25. 25.
    Sasanelli M, Meignan M, Haioun C, Berriolo-Riedinger A, Casasnovas R-O, Biggi A, Gallamini A, Siegel BA, Cashen AF, Véra P. 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(11):2017–22.CrossRefGoogle Scholar
  26. 26.
    Casasnovas O, Cottereau ASKS, Oberic L, Thieblemont C, Haioun C, et al. Baseline total metabolic volume (TMTV0) predicts the outcome of patients with diffuse large B cell lymphoma (DLBCL) enrolled in the LNH07-3B LYSA trial. Hematol Oncol. 2015;33:100–80.Google Scholar
  27. 27.
    Ceriani L, Martelli M, Zinzani PL, Ferreri AJM, Botto B, Stelitano C, Gotti M, Cabras MG, Rigacci L, Gargantini L, Merli F, Pinotti G, Mannina D, Luminari S, Stathis A, Russo E, Cavalli F, Giovanella L, Johnson PWM, Zucca E. Blood. 2015.
  28. 28.
    Tout M, Casasnovas O, Meignan M, Lamy T, Morschhauser F, Salles G, Gyan E, Haioun C, Mercier M, Feugier P, Boussetta S, Paintaud G, Ternant D, Cartron G. Blood. 2017.
  29. 29.
    Moskowitz CH, Schöder H, Teruya-Feldstein J, Sima C, Iasonos A, Portlock CS, Straus D, Noy A, Palomba ML, O’Connor OA, Horwitz S, Weaver SA, Meikle JL, Filippa DA, Caravelli JF, Hamlin PA, Zelenetz AD. Risk-adapted dose-dense Immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-cell lymphoma. J Clin Oncol. 2010;28(11):1896–903.
  30. 30.
    Itti E, Lin C, Dupuis J, Paone G, Capacchione D, Rahmouni A, Haioun C, Meignan M. Prognostic value of interim 18F-FDG PET in patients with diffuse large B-cell lymphoma: SUV-based assessment at 4 cycles of chemotherapy. J Nucl Med. 2009;50(4):527–33. Scholar
  31. 31.
    Lin C, Itti E, Haioun C, Petegnief Y, Luciani A, Dupuis J, Paone G, Talbot JN, Rahmouni A, Meignan M. Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis. J Nucl Med. 2007;48(10):1626–32. Scholar
  32. 32.
    Barnes JA, LaCasce AS, Zukotynski K, Israel D, Feng Y, Neuberg D, Toomey CE, Hochberg EP, Canellos GP, Abramson JS. End-of-treatment but not interim PET scan predicts outcome in nonbulky limited-stage Hodgkin’s lymphoma. Ann Oncol. 2011;22(4):910–5.
  33. 33.
    Gallamini A, Rigacci L, Merli F, Nassi L, Bosi A, Capodanno I, Luminari S, Vitolo U, Sancetta R, Iannitto E, Trentin L, Stelitano C, Tavera S, Biggi A, Castagnoli A, Versari A, Gregianin M, Pelosi E, Torchio P, Levis A. The predictive value of positron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin’s disease. Haematologica. 2006;91(4):475–81.PubMedGoogle Scholar
  34. 34.
    Pregno P, Chiappella A, Bello M, Botto B, Ferrero S, Franceschetti S, Giunta F, Ladetto M, Limerutti G, Menga M, Nicolosi M, Priolo G, Puccini B, Rigacci L, Salvi F, Vaggelli L, Passera R, Bisi G, Vitolo U. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood. 2012;119(9):2066–73.CrossRefGoogle Scholar
  35. 35.
    Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, Patti C, Loft A, Di Raimondo F, D’Amore F, Biggi A, Vitolo U, Stelitano C, Sancetta R, Trentin L, Luminari S, Iannitto E, Viviani S, Pierri I, Levis A. Early interim 2- F-18 Fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25(24):3746–52.
  36. 36.
    Markova J, Kobe C, Skopalova M, Klaskova K, Dedeckova K, Plutschow A, Eich HT, Dietlein M, Engert A, Kozak T. FDG-PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin’s lymphoma has a high negative predictive value. Ann Oncol. 2009;20(7):1270–4. Scholar
  37. 37.
    Barrington SF, Qian W, Somer EJ, Franceschetto A, Bagni B, Brun E, Almquist H, Loft A, Hojgaard L, Federico M, Gallamini A, Smith P, Johnson P, Radford J, O’Doherty MJ. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2010;37(10):1824–33.
  38. 38.
    Itti E, Meignan M, Berriolo-Riedinger A, Biggi A, Cashen AF, Vera P, Tilly H, Siegel BA, Gallamini A, Casasnovas RO, Haioun C. An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and DeltaSUVmax. Eur J Nucl Med Mol Imaging. 2013;40(9):1312–20.CrossRefGoogle Scholar
  39. 39.
    Strobel K, Schaefer NG, Renner C, Veit-Haibach P, Husarik D, Koma AY, Hany TF. Cost-effective therapy remission assessment in lymphoma patients using 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography: is an end of treatment exam necessary in all patients? Ann Oncol. 2007;18(4):658–64.CrossRefGoogle Scholar
  40. 40.
    Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, Meignan M, Malkowski B, Hofman MS, Barrington SF. International validation study for interim PET in ABVD-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90.CrossRefGoogle Scholar
  41. 41.
    Mamot C, Klingbiel D, Renner C, Pabst T, Hitz F, Mey U, Pless M, Bargetzi M, Krasniqi F, Gigli F, Hany T, Samarin A, Rusterholz C, Biaggi C, Zucca E, Martinelli G. (Suppl 1; abst 15) final results of a prospective evaluation of the predictive value of interim PET in patients with DLBCL under R-CHOP-14 (SAKK 38/07). Hematol Oncol. 2013;31:100–1.Google Scholar
  42. 42.
    Dupuis J, Berriolo-Riedinger A, Julian A, Brice P, Tychyj-Pinel C, Tilly H, Mounier N, Gallamini A, Feugier P, Soubeyran P, Colombat P, Laurent G, Berenger N, Casasnovas RO, Vera P, Paone G, Xerri L, Salles G, Haioun C, Meignan M, Ghesquieres H, Cartron G, Seymour JF, Delfau-Larue MH, Offner F, Soubeyran P, Perrot A, Brice P, Bouabdallah R, Sonet A, Dupuis J, Catalano JV, Delmer A, Jardin F, Verney A, Dartigues P, Salles G, Le Gouill S, De Guibert S, Planche L, Brice P, Dupuis J, Cartron G, Van Hoof A, Gyan E, Tilly H, Fruchart C, Deconinck E, Fitoussi O, Gastaud L, Delwail V, Gabarre J, Gressin R, Blanc M, Foussard C, Salles G. Impact of [18F]Fluorodeoxyglucose positron emission tomography response evaluation in patients with high-tumor burden follicular lymphoma treated with Immunochemotherapy: a prospective study from the Groupe d’Etudes des Lymphomes de l’Adulte and GOELAMS. J Clin Oncol. 2012;30(35):4317–22.CrossRefGoogle Scholar
  43. 43.
    Fan Y, Zhang Y, Yang Z, Ying Z, Zhou N, Liu C, Song Y, Zhu J, Wang X. Evaluating early interim fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography with the SUVmax-liver-based interpretation for predicting the outcome in diffuse large B-cell lymphoma. Leuk Lymphoma. 2017;58:1–9.CrossRefGoogle Scholar
  44. 44.
    Casasnovas RO, Ysebaert L, Thieblemont C, Bachy E, Feugier P, Delmer A, Tricot S, Gabarre J, Andre M, Fruchart C, Mounier N, Delarue R, Meignan M, Berriolo-Riedinger A, Bardet S, Emile JF, Jais JP, Haioun C, Tilly H, Morschhauser F. Blood. 2017;130(11):1315–26. Epub 2017 Jul 12.CrossRefPubMedGoogle Scholar
  45. 45.
    Cottereau A, Becker S, Broussais F, Casasnovas O, Kanoun S, Roques M, Charrier N, Bertrand S, Delarue R, Bonnet C. Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL). Ann Oncol. 2016b;27(4):719–24.CrossRefGoogle Scholar
  46. 46.
    Martelli M, Ceriani L, Zucca E, Zinzani PL, Ferreri AJ, Vitolo U, Stelitano C, Brusamolino E, Cabras MG, Rigacci L. [18F] fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol. 2014;32(17):1769–75.CrossRefGoogle Scholar
  47. 47.
    Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, Seymour J, Kelly K, Gribben J, Pfreunschuh M. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 2017;28(7):1436–47.CrossRefGoogle Scholar
  48. 48.
    Horwitz S, Coiffier B, Foss F, Prince H, Sokol L, Greenwood M, Caballero D, Morschhauser F, Pinter-Brown L, Iyer SP. Utility of 18fluoro-deoxyglucose positron emission tomography for prognosis and response assessments in a phase 2 study of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015;26(4):774–9.CrossRefGoogle Scholar
  49. 49.
    Kim SJ, Choi JY, Hyun SH, Ki C-S, Oh D, Ahn YC, Ko YH, Choi S, Jung S-H, Khong P-L. Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma, nasal type: a multicentre, retrospective analysis. Lancet Haematol. 2015;2(2):e66–74.CrossRefGoogle Scholar
  50. 50.
    El-Galaly TC, Mylam KJ, Bøgsted M, Brown P, Rossing M, Gang AO, Haglund A, Arboe B, Clausen MR, Jensen P, Pedersen M, Bukh A, Jensen BA, Poulsen CB, d’Amore F, Hutchings M. Role of routine imaging in detecting recurrent lymphoma: a review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma. Am J Hematol. 2014;89(6):575–80.
  51. 51.
    Truong Q, Shah N, Knestrick M, Curley B, Hu Y, Craig M, Hamadani M. Limited utility of surveillance imaging for detecting disease relapse in patients with non-Hodgkin lymphoma in first complete remission. Clin Lymphoma Myeloma Leuk. 2014;14(1):50–5.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Haematology, Concord Repatriation General HospitalUniversity of SydneyConcordAustralia
  2. 2.LYSA Imaging, Hôpitaux Universitaires Henri MondorCréteilFrance

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