Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL): A Multicenter, Randomized Phase III Trial

被引：169

作者：

Duehrsen, Ulrich ^{[1
]}

Mueller, Stefan ^{[1
]}

Hertenstein, Bernd ^{[3
]}

Thomssen, Henrike ^{[3
]}

Kotzerke, Joerg ^{[5
]}

Mesters, Rolf ^{[7
]}

Berdel, Wolfgang E. ^{[7
]}

Franzius, Christiane ^{[4
]}

Kroschinsky, Frank ^{[5
]}

Weckesser, Matthias ^{[7
]}

Kofahl-Krause, Dorothea ^{[8
]}

Bengel, Frank M. ^{[8
]}

Duerig, Jan ^{[1
]}

Matschke, Johannes ^{[1
]}

Schmitz, Christine ^{[1
]}

Poeppel, Thorsten ^{[1
]}

Ose, Claudia ^{[2
]}

Brinkmann, Marcus ^{[2
]}

La Rosee, Paul ^{[9
]}

Freesmeyer, Martin ^{[9
]}

Hertel, Andreas ^{[10
]}

Hoeffkes, Heinz-Gert ^{[10
]}

Behringer, Dirk ^{[11
]}

Prange-Krex, Gabriele ^{[6
]}

Wilop, Stefan ^{[12
]}

Krohn, Thomas ^{[12
]}

Holzinger, Jens ^{[13
]}

Griesshammer, Martin ^{[13
]}

Giagounidis, Aristoteles ^{[14
]}

Raghavachar, Aruna ^{[15
]}

Maschmeyer, Georg ^{[16
]}

Brink, Ingo ^{[16
]}

Bernhard, Helga ^{[17
]}

Haberkorn, Uwe ^{[18
]}

Gaska, Tobias ^{[19
]}

Kurch, Lars ^{[20
]}

van Assema, Danielle M. E. ^{[23
]}

Klapper, Wolfram ^{[21
]}

Hoelzer, Dieter ^{[22
]}

Geworski, Lilli ^{[8
]}

Joeckel, Karl-Heinz ^{[2
]}

Scherag, Andre ^{[2
,9
]}

Bockisch, Andreas ^{[1
]}

Rekowski, Jan ^{[2
]}

Huettmann, Andreas ^{[1
]}

机构：

[1] Univ Klinikum Essen, Essen, Germany

[2] Univ Duisburg Essen, Essen, Germany

[3] Klinikum Bremen Mitte, Bremen, Germany

[4] Zentrum Moderne Diagnost, Bremen, Germany

[5] Univ Klinikum Carl Gustav, Dresden, Germany

[6] Onkol Gemeinschaftspraxis, Dresden, Germany

[7] Univ Klinikum Munster, Munster, Germany

[8] Hannover Med Sch, Hannover, Germany

[9] Univ Klinikum Jena, Jena, Germany

[10] Klinikum Fulda, Fulda, Germany

[11] Augusta Kranken Anstalt, Bochum, Germany

[12] Univ Klinikum Aachen, Aachen, Germany

[13] Johannes Wesling Klinikum, Minden, Germany

[14] Helios St Johannes Klin, Duisburg, Germany

[15] Helios Univ Klinikum, Wuppertal, Germany

[16] Klinikum Ernst von Bergmann, Potsdam, Germany

[17] Klinikum Darmstadt, Darmstadt, Germany

[18] Univ Klinikum Heidelberg, Heidelberg, Germany

[19] Bruderkrankenhaus St Josef, Paderborn, Germany

[20] Univ Klinikum Leipzig, Leipzig, Germany

[21] Univ Klinikum Schleswig Holstein, Kiel, Germany

[22] Onkologikum, Frankfurt, Germany

[23] Vrije Univ Med Ctr, Amsterdam, Netherlands

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2018年 / 36卷 / 20期

关键词：

B-CELL LYMPHOMA; FDG-PET; PROGNOSTIC VALUE; ELDERLY-PATIENTS; RITUXIMAB; CHEMOTHERAPY; TRANSPLANTATION; INTENSIFICATION; CYCLES; CHOP;

D O I：

10.1200/JCO.2017.76.8093

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Interim positron emission tomography (PET) using the tracer, [F-18]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the DSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

引用

页码：2024 / +

页数：14

共 37 条

[1]

[Anonymous], COMM TERM CRIT ADV E

[2] Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group [J].

Barrington, Sally F. ;

Mikhaeel, N. George ;

Kostakoglu, Lale ;

Meignan, Michel ;

Hutchings, Martin ;

Mueeller, Stefan P. ;

Schwartz, Lawrence H. ;

Zucca, Emanuele ;

Fisher, Richard I. ;

Trotman, Judith ;

Hoekstra, Otto S. ;

Hicks, Rodney J. ;

O'Doherty, Michael J. ;

Hustinx, Roland ;

Biggi, Alberto ;

Cheson, Bruce D. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3048-+

[3]

Brusamolino E, 2006, HAEMATOLOGICA, V91, P496

[4] SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma [J].

Casasnovas, Rene -Olivier ;

Meignan, Michel ;

Berriolo-Riedinger, Alina ;

Bardet, Stephane ;

Julian, Anne ;

Thieblemont, Catherine ;

Vera, Pierre ;

Bologna, Serge ;

Briere, Josette ;

Jais, Jean-Philippe ;

Haioun, Corinne ;

Coiffier, Bertrand ;

Morschhauser, Franck .

BLOOD, 2011, 118 (01) :37-43

[5] Revised response criteria for malignant lymphoma [J].

Cheson, Bruce D. ;

Pfistner, Beate ;

Juweid, Malik E. ;

Gascoyne, Randy D. ;

Specht, Lena ;

Horning, Sandra J. ;

Coiffier, Bertrand ;

Fisher, Richard I. ;

Hagenbeek, Anton ;

Zucca, Emanuele ;

Rosen, Steven T. ;

Stroobants, Sigrid ;

Lister, T. Andrew ;

Hoppe, Richard T. ;

Dreyling, Martin ;

Tobinai, Kensei ;

Vose, Julie M. ;

Connors, Joseph M. ;

Federico, Massimo ;

Diehl, Volker .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586

[6] Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles [J].

Cunningham, David ;

Hawkes, Eliza A. ;

Jack, Andrew ;

Qian, Wendi ;

Smith, Paul ;

Mouncey, Paul ;

Pocock, Christopher ;

Ardeshna, Kirit M. ;

Radford, John A. ;

McMillan, Andrew ;

Davies, John ;

Turner, Deborah ;

Kruger, Anton ;

Johnson, Peter ;

Gambell, Joanna ;

Linch, David .

LANCET, 2013, 381 (9880) :1817-1826

[7] Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry [J].

Ellin, Fredrik ;

Landstrom, Jenny ;

Jerkeman, Mats ;

Relander, Thomas .

BLOOD, 2014, 124 (10) :1570-1577

[8] COMPARISON OF A STANDARD REGIMEN (CHOP) WITH 3 INTENSIVE CHEMOTHERAPY REGIMENS FOR ADVANCED NON-HODGKINS-LYMPHOMA [J].

FISHER, RI ;

GAYNOR, ER ;

DAHLBERG, S ;

OKEN, MM ;

GROGAN, TM ;

MIZE, EM ;

GLICK, JH ;

COLTMAN, CA ;

MILLER, TP .

NEW ENGLAND JOURNAL OF MEDICINE, 1993, 328 (14) :1002-1006

[9]

Geworski L, 2002, J NUCL MED, V43, P635

[10] Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era [J].

Gisselbrecht, Christian ;

Glass, Bertram ;

Mounier, Nicolas ;

Gill, Devinder Singh ;

Linch, David C. ;

Trneny, Marek ;

Bosly, Andre ;

Ketterer, Nicolas ;

Shpilberg, Ofer ;

Hagberg, Hans ;

Ma, David ;

Briere, Josette ;

Moskowitz, Craig H. ;

Schmitz, Norbert .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (27) :4184-4190

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