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The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma

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Abstract

The choice of a rituximab-based regimen and the prognostic significance of interim 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in primary mediastinal large B cell lymphoma (PMBCL) are debatable. We evaluated the clinical features and outcomes of 95 consecutive patients with PMBCL who were treated between 1985 and 2009. Forty-three patients received rituximab-based chemotherapy, R-VACOP-B (N = 30) or R-CHOP21 (N = 13), whereas 52 patients were treated with VACOP-B (N = 47) or CHOP21 (N = 5). Radiotherapy was not given. Patients who received rituximab had a 5-year progression-free survival (PFS) of 79 % and overall survival (OS) of 97 % compared with 58 % (p = 0.06) and 88 % (p = 0.2), respectively, without rituximab. Five-year PFS in patients treated with R-VACOP-B, R-CHOP21, VACOP-B, and CHOP21 were 83, 69, 62, and 20 %, respectively (p = 0.039). However, direct comparison showed that the difference between PFS rates in patients receiving R-VACOP-B compared to R-CHOP21 was not statistically significant (p = 0.3). None of the standard clinical risk factors predicted for PFS and OS in patients receiving rituximab (R)-chemotherapy. Mid-interim FDG-PET/CT scans were performed in 30/43 patients who received R-chemotherapy. The negative predictive values of mid-PET activity were high (100 % for R-VACOP-B and 86 % for R-CHOP21) while the positive predictive values (PPV) were relatively low (30 and 75 %, respectively). Despite the low PPV, the 5-year PFS for mid-PET-negative patients (N = 16) was significantly higher (94 %) than that for mid-PET-positive (N = 14) patients (57 %, p = 0.015). This retrospective analysis demonstrates that the superiority of VACOP-B over CHOP21 for treatment of PMBCL disappeared once rituximab was added. The potential benefit of using interim PET activity as a guide for continuing therapy in patients with PMBCL remains unclear due to the relatively low PPV.

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References

  1. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (2011) The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 117(19):5019–5032. doi:10.1182/blood-2011-01-293050

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Swerdlow SHCE, Harris NL et al (2008) Classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon

    Google Scholar 

  3. Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD, Chan WC, Zhao T, Haioun C, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Campo E, Montserrat E, Lopez-Guillermo A, Ott G, Muller-Hermelink HK, Connors JM, Braziel R, Grogan TM, Fisher RI, Miller TP, LeBlanc M, Chiorazzi M, Zhao H, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Staudt LM (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 198(6):851–862. doi:10.1084/jem.20031074

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Savage KJ, Monti S, Kutok JL, Cattoretti G, Neuberg D, De Leval L, Kurtin P, Dal Cin P, Ladd C, Feuerhake F, Aguiar RC, Li S, Salles G, Berger F, Jing W, Pinkus GS, Habermann T, Dalla-Favera R, Harris NL, Aster JC, Golub TR, Shipp MA (2003) The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 102(12):3871–3879. doi:10.1182/blood-2003-06-1841

    Article  CAS  PubMed  Google Scholar 

  5. Savage KJ, Al-Rajhi N, Voss N, Paltiel C, Klasa R, Gascoyne RD, Connors JM (2006) Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 17(1):123–130. doi:10.1093/annonc/mdj030

    Article  CAS  PubMed  Google Scholar 

  6. Todeschini G, Secchi S, Morra E, Vitolo U, Orlandi E, Pasini F, Gallo E, Ambrosetti A, Tecchio C, Tarella C, Gabbas A, Gallamini A, Gargantini L, Pizzuti M, Fioritoni G, Gottin L, Rossi G, Lazzarino M, Menestrina F, Paulli M, Palestro M, Cabras MG, Di Vito F, Pizzolo G (2004) Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer 90(2):372–376. doi:10.1038/sj.bjc.6601460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Zinzani PL, Martelli M, Bertini M, Gianni AM, Devizzi L, Federico M, Pangalis G, Michels J, Zucca E, Cantonetti M, Cortelazzo S, Wotherspoon A, Ferreri AJ, Zaja F, Lauria F, De Renzo A, Liberati MA, Falini B, Balzarotti M, Calderoni A, Zaccaria A, Gentilini P, Fattori PP, Pavone E, Angelopoulou MK, Alinari L, Brugiatelli M, Di Renzo N, Bonifazi F, Pileri SA, Cavalli F (2002) Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica 87(12):1258–1264

    CAS  PubMed  Google Scholar 

  8. Hamlin PA, Portlock CS, Straus DJ, Noy A, Singer A, Horwitz SM, Oconnor OA, Yahalom J, Zelenetz AD, Moskowitz CH (2005) Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999. Br J Haematol 130(5):691–699

    Article  PubMed  Google Scholar 

  9. Ahn HK, Kim SJ, Yun J, Yi JH, Kim JH, Won YW, Kim K, Ko YH, Kim WS (2010) Improved treatment outcome of primary mediastinal large B-cell lymphoma after introduction of rituximab in Korean patients. Int J Hematol 91(3):456–463. doi:10.1007/s12185-010-0536-6

    Article  CAS  PubMed  Google Scholar 

  10. Zinzani PL, Stefoni V, Finolezzi E, Brusamolino E, Cabras MG, Chiappella A, Salvi F, Rossi A, Broccoli A, Martelli M (2009) Rituximab combined with MACOP-B or VACOP-B and radiation therapy in primary mediastinal large B-cell lymphoma: a retrospective study. Clin Lymphoma Myeloma 9(5):381–385. doi:10.3816/CLM.2009.n.074

    Article  CAS  PubMed  Google Scholar 

  11. Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD (2011) Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol 22(3):664–670. doi:10.1093/annonc/mdq418

    Article  CAS  PubMed  Google Scholar 

  12. Hutchings M (2012) How does PET/CT help in selecting therapy for patients with Hodgkin lymphoma? Hematology Am Soc Hematol Educ Program 2012:322–327. doi:10.1182/asheducation-2012.1.322

    PubMed  Google Scholar 

  13. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244–1253

    CAS  PubMed  Google Scholar 

  14. 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 (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. doi:10.1200/JCO.2006.09.2403

    Article  PubMed  Google Scholar 

  15. 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 (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 25(5):571–578. doi:10.1200/JCO.2006.08.2305

    Article  PubMed  Google Scholar 

  16. Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M (2004) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104(3):634–641. doi:10.1182/blood-2003-06-2095

    Article  CAS  PubMed  Google Scholar 

  17. Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H (2011) Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 378(9806):1858–1867. doi:10.1016/S0140-6736(11)61040-4

    Article  CAS  PubMed  Google Scholar 

  18. Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH (2013) Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 368(15):1408–1416. doi:10.1056/NEJMoa1214561

    Article  CAS  PubMed  Google Scholar 

  19. Moskowitz CH, Schoder 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 (2010) Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-cell lymphoma. J Clin Oncol 28(11):1896–1903. doi:10.1200/JCO.2009.26.5942

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Johnson PW, Davies AJ (2008) Primary mediastinal B-cell lymphoma. Hematology Am Soc Hematol Educ Program:349–358. doi:10.1182/asheducation-2008.1.349

  21. Savage KJ, Yenson PR, Shenkier T, Klasa R, Villa D, Goktepe O, Steidl C, Slack GW, Gascoyne RD, Connors JM, Sehn LH (2012) The outcome of primary mediastinal large B-cell lymphoma (PMBCL) in the R-CHOP treatment era. ASH Ann Meeting Abstracts 120(21):303

    Google Scholar 

  22. Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, Lopez-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski (2011) N 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 12(11):1013–1022. doi:10.1016/S1470-2045(11)70235-2

    Article  CAS  PubMed  Google Scholar 

  23. Henderson TO, Amsterdam A, Bhatia S, Hudson MM, Meadows AT, Neglia JP, Diller LR, Constine LS, Smith RA, Mahoney MC, Morris EA, Montgomery LL, Landier W, Smith SM, Robison LL, Oeffinger KC (2010) Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152(7):444–455. doi:10.7326/0003-4819-152-7-201004060-00009, W144-454

    Article  PubMed Central  PubMed  Google Scholar 

  24. Nieder C, Schill S, Kneschaurek P, Molls M (2007) Comparison of three different mediastinal radiotherapy techniques in female patients: impact on heart sparing and dose to the breasts. Radiother Oncol 82(3):301–307. doi:10.1016/j.radonc.2006.10.015

    Article  PubMed  Google Scholar 

  25. Yoon M, Ahn SH, Kim J, Shin DH, Park SY, Lee SB, Shin KH, Cho KH (2010) Radiation-induced cancers from modern radiotherapy techniques: intensity-modulated radiotherapy versus proton therapy. Int J Radiat Oncol Biol Phys 77(5):1477–1485. doi:10.1016/j.ijrobp.2009.07.011

    Article  PubMed  Google Scholar 

  26. Juweid ME, Wiseman GA, Vose JM, Ritchie JM, Menda Y, Wooldridge JE, Mottaghy FM, Rohren EM, Blumstein NM, Stolpen A, Link BK, Reske SN, Graham MM, Cheson BD (2005) Response assessment of aggressive non-Hodgkin’s lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol 23(21):4652–4661. doi:10.1200/JCO.2005.01.891

    Article  PubMed  Google Scholar 

  27. Moskowitz CH (2012) Interim PET-CT in the management of diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program 2012:397–401. doi:10.1182/asheducation-2012.1.397

    PubMed  Google Scholar 

  28. Haioun C, Itti E, Rahmouni A, Brice P, Rain JD, Belhadj K, Gaulard P, Garderet L, Lepage E, Reyes F, Meignan M (2005) [18F]Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood 106(4):1376–1381. doi:10.1182/blood-2005-01-0272

    Article  CAS  PubMed  Google Scholar 

  29. Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G (2000) Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin’s lymphoma. Haematologica 85(6):613–618

    CAS  PubMed  Google Scholar 

  30. Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G (2002) Early restaging positron emission tomography with (18) F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin’s lymphoma. Ann Oncol 13(9):1356–1363

    Article  CAS  PubMed  Google Scholar 

  31. Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, Vera P, Bologna S, Briere J, Jais JP, Haioun C, Coiffier B, Morschhauser F SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood 118 (1):37–43. doi:10.1182/blood-2010-12-327767

  32. 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 (2011) 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 119(9):2066–2073. doi:10.1182/blood-2011-06-359943

    Article  Google Scholar 

  33. Moskowitz C, Hamlin PA Jr, Maragulia J, Meikle J, Zelenetz AD (2010) Sequential dose-dense RCHOP followed by ICE consolidation (MSKCC protocol 01-142) without radiotherapy for patients with primary mediastinal large B cell lymphoma. ASH Ann Meeting Abstracts 116(21):420

    Google Scholar 

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Authors and Affiliations

  1. Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 5265601, Israel

    Abraham Avigdor, Meirav Kedmi, Elena Ribakovsy, Miriam Berkowicz, Yaron Davidovitz, Abraham Kneller, Drorit Merkel, Yulia Volchek, Avichai Shimoni, Isaac Ben-Bassat & Arnon Nagler

  2. Department of Nuclear Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 5265601, Israel

    Tima Davidson & Elinor Goshen

  3. Department of Diagnostic Imaging, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 5265601, Israel

    Sara Apter

  4. Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel

    Tsvi Sirotkin

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  1. Abraham Avigdor
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Correspondence to Abraham Avigdor.

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Avigdor, A., Sirotkin, T., Kedmi, M. et al. The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma. Ann Hematol 93, 1297–1304 (2014). https://doi.org/10.1007/s00277-014-2043-y

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