Advertisement

Medical Oncology

, 34:29 | Cite as

Analysis of prognostic value of complete response by PET–CT and further stratification by clinical and biological markers in DLBCL patients

  • Yusuke KanemasaEmail author
  • Tatsu Shimoyama
  • Yuki Sasaki
  • Miho Tamura
  • Takeshi Sawada
  • Yasushi Omuro
  • Tsunekazu Hishima
  • Yoshiharu Maeda
Original Paper

Abstract

Positron emission tomography–computed tomography (PET–CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET–CT. We validated the prognostic value of CR by PET–CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN–IPI) and cell of origin (COO) to patients with CR by PET–CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET–CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET–CT and 71 patients by CT only. Patients with CR by PET–CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN–IPI had a dismal outcome despite achieving CR by PET–CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET–CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET–CT was a better predictor of survival outcomes than CR by CT only. The NCCN–IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET–CT.

Keywords

Diffuse large B cell lymphoma Positron emission tomography Computed tomography NCCN–IPI Cell of origin 

Notes

Acknowledgements

We would like to thank all the patients who took part in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

References

  1. 1.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: France IARC Press; 2008. p. 233–7.Google Scholar
  2. 2.
    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(4):235–42. doi: 10.1056/NEJMoa011795.CrossRefPubMedGoogle Scholar
  3. 3.
    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(19):3121–7. doi: 10.1200/jco.2005.05.1003.CrossRefPubMedGoogle Scholar
  4. 4.
    Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105–16. doi: 10.1016/s1470-2045(08)70002-0.CrossRefPubMedGoogle Scholar
  5. 5.
    Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12(11):1013–22. doi: 10.1016/s1470-2045(11)70235-2.CrossRefPubMedGoogle Scholar
  6. 6.
    Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Program. 2011;2011:498–505. doi: 10.1182/asheducation-2011.1.498.Google Scholar
  7. 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(27):3048–58. doi: 10.1200/jco.2013.53.5229.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68. doi: 10.1200/jco.2013.54.8800.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Adams HJ, Nievelstein RA, Kwee TC. Prognostic value of complete remission status at end-of-treatment FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: systematic review and meta-analysis. Br J Haematol. 2015;170(2):185–91. doi: 10.1111/bjh.13420.CrossRefPubMedGoogle Scholar
  10. 10.
    A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329(14):987–94. Doi: 10.1056/nejm199309303291402.
  11. 11.
    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(6):837–42. doi: 10.1182/blood-2013-09-524108.CrossRefPubMedGoogle Scholar
  12. 12.
    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(22):2313–23. doi: 10.1056/NEJMoa0802885.CrossRefPubMedGoogle Scholar
  13. 13.
    Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82. doi: 10.1182/blood-2003-05-1545.CrossRefPubMedGoogle Scholar
  14. 14.
    Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17(4):1244.PubMedGoogle Scholar
  15. 15.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8. doi: 10.1038/bmt.2012.244.CrossRefPubMedGoogle Scholar
  16. 16.
    Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin’s disease and non-Hodgkin’s lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood. 1999;94(2):429–33.PubMedGoogle Scholar
  17. 17.
    Avril N, Rose CA, Schelling M, Dose J, Kuhn W, Bense S, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol. 2000;18(20):3495–502.PubMedGoogle Scholar
  18. 18.
    Tyler DS, Onaitis M, Kherani A, Hata A, Nicholson E, Keogan M, et al. Positron emission tomography scanning in malignant melanoma. Cancer. 2000;89(5):1019–25.CrossRefPubMedGoogle Scholar
  19. 19.
    Micallef IN, Maurer MJ, Wiseman GA, Nikcevich DA, Kurtin PJ, Cannon MW, et al. Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood. 2011;118(15):4053–61. doi: 10.1182/blood-2011-02-336990.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pregno P, Chiappella A, Bello M, Botto B, Ferrero S, Franceschetti S, et al. 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. doi: 10.1182/blood-2011-06-359943.CrossRefPubMedGoogle Scholar
  21. 21.
    Adams HJ, Kwee TC, Fijnheer R, Dubois SV, Nievelstein RA, de Klerk JM. Bone marrow 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B-cell lymphoma. Am J Hematol. 2014;89(7):726–31. doi: 10.1002/ajh.23730.CrossRefPubMedGoogle Scholar
  22. 22.
    Adams HJ, Kwee TC, Fijnheer R, Dubois SV, Nievelstein RA, de Klerk JM. Direct comparison of visual and quantitative bone marrow FDG-PET/CT findings with bone marrow biopsy results in diffuse large B-cell lymphoma: does bone marrow FDG-PET/CT live up to its promise? Acta Radiol (Stockholm, Sweden: 1987). 2015;56(10):1230–5. doi: 10.1177/0284185114554824.Google Scholar
  23. 23.
    Hong J, Lee Y, Park Y, Kim SG, Hwang KH, Park SH, et al. Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma. Ann Hematol. 2012;91(5):687–95. doi: 10.1007/s00277-011-1353-6.CrossRefPubMedGoogle Scholar
  24. 24.
    Dorth JA, Prosnitz LR, Broadwater G, Diehl LF, Beaven AW, Coleman RE, et al. Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging. Int J Radiat Oncol Biol Phys. 2012;84(3):762–7. doi: 10.1016/j.ijrobp.2011.12.067.CrossRefPubMedGoogle Scholar
  25. 25.
    Marcheselli L, Marcheselli R, Bari A, Liardo EV, Morabito F, Baldini L, et al. Radiation therapy improves treatment outcome in patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2011;52(10):1867–72. doi: 10.3109/10428194.2011.585526.CrossRefPubMedGoogle Scholar
  26. 26.
    Phan J, Mazloom A, Medeiros LJ, Zreik TG, Wogan C, Shihadeh F, et al. Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol. 2010;28(27):4170–6. doi: 10.1200/jco.2009.27.3441.CrossRefPubMedGoogle Scholar
  27. 27.
    Shi Z, Das S, Okwan-Duodu D, Esiashvili N, Flowers C, Chen Z, et al. Patterns of failure in advanced stage diffuse large B-cell lymphoma patients after complete response to R-CHOP immunochemotherapy and the emerging role of consolidative radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86(3):569–77. doi: 10.1016/j.ijrobp.2013.02.007.CrossRefPubMedGoogle Scholar
  28. 28.
    Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, et al. 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. doi: 10.1182/blood-2006-08-038257.CrossRefPubMedGoogle Scholar
  29. 29.
    Bishton MJ, Hughes S, Richardson F, James E, Bessell E, Sovani V, et al. Delineating outcomes of patients with diffuse large b cell lymphoma using the national comprehensive cancer network-international prognostic index and positron emission tomography-defined remission status; a population-based analysis. Br J Haematol. 2016;172(2):246–54. doi: 10.1111/bjh.13831.CrossRefPubMedGoogle Scholar
  30. 30.
    Adams HJ, de Klerk JM, Fijnheer R, Heggelman BG, Dubois SV, Nievelstein RA, et al. Residual anatomical disease in diffuse large B-cell lymphoma patients with FDG-PET-based complete response After first-line R-CHOP therapy: does it have any prognostic value? J Comput Assist Tomogr. 2015;39(5):810–5. doi: 10.1097/rct.0000000000000270.CrossRefPubMedGoogle Scholar
  31. 31.
    de Jong D, Rosenwald A, Chhanabhai M, Gaulard P, Klapper W, Lee A, et al. Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications—a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol. 2007;25(7):805–12. doi: 10.1200/jco.2006.09.4490.CrossRefPubMedGoogle Scholar
  32. 32.
    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. Clinical Lymphoma, Myeloma & Leukemia. 2014;14(6):460–7. doi: 10.1016/j.clml.2014.05.002.CrossRefGoogle Scholar
  33. 33.
    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(5):579–86. doi: 10.1200/jco.2006.09.2403.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yusuke Kanemasa
    • 1
    Email author
  • Tatsu Shimoyama
    • 1
  • Yuki Sasaki
    • 2
  • Miho Tamura
    • 1
  • Takeshi Sawada
    • 1
  • Yasushi Omuro
    • 1
  • Tsunekazu Hishima
    • 3
  • Yoshiharu Maeda
    • 1
  1. 1.Department of Medical OncologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  2. 2.Department of Clinical Research SupportTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  3. 3.Department of PathologyTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan

Personalised recommendations