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PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study

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Abstract

Purpose

We aimed to compare the standardized central review of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42–51, 2011; Trotman et al., J Clin Oncol 29:3194–3200, 2011) to scan review at local centres.

Methods

PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579–586, 2007; Juweid et al., J Clin Oncol 25:571–578, 2007; Shankar et al., J Nucl Med 47:1059–1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257–1260, 2009; Meignan et al., Leuk Lymphoma 51:2171–2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824–1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes.

Results

Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUVmax) of 11.7 (range 4.6–35.6). There was no significant association between baseline SUVmax and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p = 0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8–4.6] or 5PS with a cut-off ≥3 (p = 0.12; HR 2.0; 95 % CI 0.8–4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0 % (95 % CI 3.7–55.8 %) versus 61.4 % (95 % CI 45.4–74.1 %) in PET-negative patients (p = 0.01; HR 3.1; 95 % CI 1.2–7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75 %. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1 % (95 % CI 10.2–55.0 %) vs 64.6 % (95 % CI 47.0–77.6 %) for PET-negative patients (p = 0.002; HR 3.3; 95 % CI 1.5–7.4), with a PPV of 66.7 %.

Conclusion

We confirm that FDG PET/CT status when applying the 5PS with a cut-off ≥4 is strongly predictive of outcome after first-line immunochemotherapy for FL. Further efforts to refine the criteria for assessing minimal residual FDG uptake in FL should provide a reproducible platform for response assessment in future prospective studies of a PET-adapted approach.

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References

  1. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011;377:42–51. doi:10.1016/S0140-6736(10)62175-7.

    Article  CAS  PubMed  Google Scholar 

  2. Trotman J, Fournier M, Lamy T, Seymour JF, Sonet A, Janikova A, et al. Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. J Clin Oncol 2011;29:3194–200. doi:10.1200/JCO.2011.35.0736.

    Article  PubMed  Google Scholar 

  3. 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. doi:10.1200/JCO.2006.09.2403.

    Article  PubMed  Google Scholar 

  4. Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. 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;25:571–8. doi:10.1200/JCO.2006.08.2305.

    Article  PubMed  Google Scholar 

  5. Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp J, Lammertsma AA, et al. Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 2006;47:1059–66.

    CAS  PubMed  Google Scholar 

  6. Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma 2009;50:1257–60. doi:10.1080/10428190903040048.

    Article  PubMed  Google Scholar 

  7. Meignan M, Gallamini A, Haioun C, Polliack A. Report on the Second International Workshop on interim positron emission tomography in lymphoma held in Menton, France, 8–9 April 2010. Leuk Lymphoma 2010;51:2171–80. doi:10.3109/10428194.2010.529208.

    Article  PubMed  Google Scholar 

  8. Barrington SF, Qian W, Somer EJ, Franceschetto A, Bagni B, Brun E, et al. 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;37:1824–33. doi:10.1007/s00259-010-1490-5.

    Article  PubMed  Google Scholar 

  9. Buske C, Hoster E, Dreyling M, Hasford J, Unterhalt M, Hiddemann W. The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood 2006;108:1504–8.

    Article  CAS  PubMed  Google Scholar 

  10. Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol 2009;27:4555–62.

    Article  PubMed  Google Scholar 

  11. Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, et al. Follicular lymphoma international prognostic index. Blood 2004;104:1258–65.

    Article  PubMed  Google Scholar 

  12. Bachy E, Brice P, Delarue R, Brousse N, Haioun C, Le Gouill S, et al. Long-term follow-up of patients with newly diagnosed follicular lymphoma in the prerituximab era: effect of response quality on survival–a study from the groupe d’etude des lymphomes de l’adulte. J Clin Oncol 2010;28:822–9.

    Article  PubMed  Google Scholar 

  13. Buckstein R, Pennell N, Berinstein NL. What is remission in follicular lymphoma and what is its relevance? Best Pract Res Clin Haematol 2005;18:27–56.

    Article  PubMed  Google Scholar 

  14. Bishu S, Quigley JM, Bishu SR, Olsasky SM, Stem RA, Shostrom VK, et al. Predictive value and diagnostic accuracy of F-18-fluoro-deoxy-glucose positron emission tomography treated grade 1 and 2 follicular lymphoma. Leuk Lymphoma 2007;48:1548–55.

    Article  CAS  PubMed  Google Scholar 

  15. Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, et al. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res 2008;14:7088–94.

    Article  CAS  PubMed  Google Scholar 

  16. Janikova A, Bolcak K, Pavlik T, Mayer J, Kral Z. Value of [18F]fluorodeoxyglucose positron emission tomography in the management of follicular lymphoma: the end of a dilemma? Clin Lymphoma Myeloma 2008;8:287–93.

    Article  PubMed  Google Scholar 

  17. Le Dortz L, De Guibert S, Bayat S, Devillers A, Houot R, Rolland Y, et al. Diagnostic and prognostic impact of 18F-FDG PET/CT in follicular lymphoma. Eur J Nucl Med Mol Imaging 2010;37:2307–14.

    Article  PubMed  Google Scholar 

  18. Lopci E, Santi I, Derenzini E, Fonti C, Savelli G, Bertagna F, et al. FDG-PET in the assessment of patients with follicular lymphoma treated by ibritumomab tiuxetan Y 90: multicentric study. Ann Oncol 2010;21:1877–83.

    Article  CAS  PubMed  Google Scholar 

  19. Zinzani PL, Musuraca G, Alinari L, Fanti S, Tani M, Stefoni V, et al. Predictive role of positron emission tomography in the outcome of patients with follicular lymphoma. Clin Lymphoma Myeloma 2007;7:291–5.

    Article  PubMed  Google Scholar 

  20. Dupuis J, Berriolo-Riedinger A, Julian A, Brice P, Tychyj-Pinel C, Tilly H, et al. Impact of [(18)F]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;30:4317–22. doi:10.1200/JCO.2012.43.0934.

    Article  CAS  PubMed  Google Scholar 

  21. Itti E, Juweid ME, Haioun C, Yeddes I, Hamza-Maaloul F, El Bez I, et al. Improvement of early 18F-FDG PET interpretation in diffuse large B-cell lymphoma: importance of the reference background. J Nucl Med 2010;51:1857–62. doi:10.2967/jnumed.110.080556.

    Article  PubMed  Google Scholar 

  22. Meignan M, Gallamini A, Itti E, Barrington S, Haioun C, Polliack A. Report on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26–27 September 2011 and Menton 2011 consensus. Leuk Lymphoma 2012;53:1876–81. doi:10.3109/10428194.2012.677535.

    Article  PubMed  Google Scholar 

  23. Gao X, Xue Z, Xing J, Lee DY, Gottschalk SM, Heslop HE, et al. Computer-assisted quantitative evaluation of therapeutic responses for lymphoma using serial PET/CT imaging. Acad Radiol 2010;17:479–88. doi:10.1016/j.acra.2009.10.026.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Wöhrer S, Jaeger U, Kletter K, Becherer A, Hauswirth A, Turetschek K, et al. 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading. Ann Oncol 2006;17:780–4.

    Article  PubMed  Google Scholar 

  25. Blum RH, Seymour JF, Wirth A, MacManus M, Hicks RJ. Frequent impact of [18F]fluorodeoxyglucose positron emission tomography on the staging and management of patients with indolent non-Hodgkin’s lymphoma. Clin Lymphoma 2003;4:43–9.

    Article  PubMed  Google Scholar 

  26. Elstrom R, Guan L, Baker G, Nakhoda K, Vergilio JA, Zhuang H, et al. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 2003;101:3875–6.

    Article  CAS  PubMed  Google Scholar 

  27. Jerusalem G, Beguin Y, Najjar F, Hustinx R, Fassotte MF, Rigo P, et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin’s lymphoma (NHL). Ann Oncol 2001;12:825–30.

    Article  CAS  PubMed  Google Scholar 

  28. Karam M, Novak L, Cyriac J, Ali A, Nazeer T, Nugent F. Role of fluorine-18 fluoro-deoxyglucose positron emission tomography scan in the evaluation and follow-up of patients with low-grade lymphomas. Cancer 2006;107:175–83.

    Article  PubMed  Google Scholar 

  29. Najjar F, Hustinx R, Jerusalem G, Fillet G, Rigo P. Positron emission tomography (PET) for staging low-grade non-Hodgkin’s lymphomas (NHL). Cancer Biother Radiopharm 2001;16:297–304.

    Article  CAS  PubMed  Google Scholar 

  30. Tsukamoto N, Kojima M, Hasegawa M, Oriuchi N, Matsushima T, Yokohama A, et al. The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer 2007;110:652–9.

    Article  PubMed  Google Scholar 

  31. Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I, et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med 2010;51:25–30.

    Article  PubMed  Google Scholar 

  32. Wirth A, Foo M, Seymour JF, Macmanus MP, Hicks RJ. Impact of [18F] fluorodeoxyglucose positron emission tomography on staging and management of early-stage follicular non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 2008;71:213–9.

    Article  PubMed  Google Scholar 

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Acknowledgments

The PRIMA study was organized by the Groupe d’Etude des Lymphomes de l’Adulte (GELA, now LYSA, Pierre-Bénite, France) with the financial support of Roche Pharma. We thank the GELA-RC team and in particular D. Germain, Project Manager, and the local data management teams within GELA, the Australia Leukaemia Lymphoma Group and the Czech Lymphoma Group. We also acknowledge the following haematologists and PET physicians who submitted the PET scans for central review:

France T. Lamy, E. Garin, H. Tilly, P. Véra, D. Decaudin, V. Edeline, J. Gabarre, A. Hallaj, B. Salles, J.L. Pelletier, P. Colombat, J.L. Beaulieu, C. Sebban, S. Cimarreli, M. Janvier, J.L. Alberini, O. Casanovas, A. Barriolo-Riedinger, J.-L. Harrousseau, O. Couturier, F. Kraeber-Bodere, C. Ferme, D. Lumbroso, D. Guyotat, A.M. Dubois, F. Bauduer, C. Galy-Lacour, D. Bordessoule, J. Monteil, O. Fitoussi, S. Cosculuella-Jarrige, J.-M. Karsenti, L. Tessonier, E. Jourdan, P. Soubeyran, F. Bonichon, A.L. Cazeau; Australia J. Trotman, M. Fulham, J. Estell, P. Marlton, M. Hertzberg, S. Gruenewald, I. Lewis, C. Tiley; Belgium A. Bosly, T. Vander Borght, E. Van Den Neste, M. Lonneux, A. Van Hoof, L. De Ceunicik; Czech Republic A. Oborilova, M. Trneny, H. Siffnerova, J. Prausova, O. Belohlavek, K. Bolcak; Israel O. Shpilberg; Netherlands T. Hageenbeek.

Authorship contributions

The data design, collation and analysis were performed principally by C. Tychyj-Pinel, F. Ricard, M. Fournier, M. Fulham, G. Salles and J. Trotman. Data interpretation, manuscript writing, critique and final approval were performed by all authors.

Conflicts of interest

None.

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Authors and Affiliations

  1. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service de Médecine Nucléaire, Pierre-Bénite, France

    Christelle Tychyj-Pinel & Fabien Ricard

  2. Faculté de Médecine, UCB Lyon 1, Université de Lyon, Lyon, France

    Fabien Ricard & Gilles Salles

  3. Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Sydney, Australia

    Michael Fulham

  4. Sydney Medical School, University of Sydney, Sydney, Australia

    Michael Fulham & Judith Trotman

  5. The Lymphoma Academic Research Organisation (LYSARC), Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    Marion Fournier

  6. Médicine Nucléaire, CHU Henri Mondor, Créteil, France

    Michel Meignan

  7. Service d’Hématologie, CHU, Rennes, France

    Thierry Lamy

  8. Service de Médecine Nucléaire, Centre Henri Becquerel, Rouen, France

    Pierre Vera

  9. QuantIF (Litis EA4108), Rouen University, Rouen, France

    Pierre Vera

  10. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’Hématologie, Pierre-Bénite, France

    Gilles Salles

  11. Department of Haematology, Concord Hospital, Hospital Rd, Concord, NSW, 2139, Australia

    Judith Trotman

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  1. Christelle Tychyj-Pinel
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Correspondence to Judith Trotman.

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Tychyj-Pinel, C., Ricard, F., Fulham, M. et al. PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study. Eur J Nucl Med Mol Imaging 41, 408–415 (2014). https://doi.org/10.1007/s00259-013-2441-8

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  • DOI: https://doi.org/10.1007/s00259-013-2441-8

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