Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma.
OBJECTIVE
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease.


METHODS
The best arm of the RICOVER-60 trial (6×R-CHOP-14+2R [R-CHOP administered once every 2 weeks plus two additional applications of rituximab] plus involved-field RT [36 Gy] to sites of initial bulky [≥ 7.5 cm] disease and extralymphatic involvement) was compared with a cohort receiving the same immunochemotherapy but without RT in an amendment to the RICOVER-60 trial (RICOVER-noRTh) in a prospective fashion.


RESULTS
After a median observation time of 39 months, 164 of 166 RICOVER-noRTh patients were evaluable. In a multivariable analysis of the intention-to-treat population adjusting for International Prognostic Index risk factors and age (> 70 years), event-free survival (EFS) of patients with bulky disease was inferior without additive RT (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.5; P = .005), with trends for inferior progression-free (PFS; HR, 1.8; 95% CI, 1.0 to 3.3; P = .058) and overall survival (OS; HR, 1.6; 95% CI, 0.9 to 3.1; P = .127). In a per-protocol analysis with 11 patients in RICOVER-noRTh excluded for receiving unplanned RT, multivariable analysis revealed HRs of 2.7 (95% CI, 1.3 to 5.9; P = .011) for EFS, 4.4 (95% CI, 1.8 to 10.6; P = .001) for PFS, and 4.3 (95% CI, 1.7 to 11.1; P = .002) for OS for patients not receiving RT to bulky disease.


CONCLUSIONS
Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma. Whether RT can be spared in patients with (metabolic) complete remission after immunochemotherapy must be addressed in appropriately designed prospective trials.
Gerhard Held, Niels Murawski, Jochen Fleckenstein, Viola Pöschel, Carsten Zwick, Jörg Bittenbring, Jörg Schubert, Christian Rübe, and Michael Pfreundschuh, Universitätsklinikum des Saarlandes, Homburg; Marita Ziepert and Markus Löffler, Universität Leipzig, Leipzig; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Sibylla Wilhelm, Städtisches Klinikum Karlsruhe, Karlsruhe; and Norbert Schmitz, Asklepios-Klinik St Georg, Hamburg, Germany.
Gerhard
G
Held
Niels
N
Murawski
Marita
M
Ziepert
Jochen
J
Fleckenstein
Viola
V
Pöschel
Carsten
C
Zwick
Jörg
J
Bittenbring
Mathias
M
Hänel
Sibylla
S
Wilhelm
Jörg
J
Schubert
Norbert
N
Schmitz
Markus
M
Löffler
Christian
C
Rübe
Michael
M
Pfreundschuh
D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone