UNFOLDER TRIAL TRIAL
UNFOLDER TRIAL PLUS

RT to bulky disease was applied as involved-field RT. A central RT reference panel developed an individual RT plan for each patient. Start of RT was planned to be 3 to 6 weeks after the last chemotherapy cycle. Patients with initial bulky disease (defined as lymphoma masses or conglomerates with diameter ≥ 7.5 cm) or extralymphatic involvement were to receive RT to these areas if complete remission (CR), unconfirmed CR (CRu), or partial remission (PR) was achieved after chemotherapy except when these lymphoma manifestations were completely removed by surgery.

UNFOLDER TRIAL PLUS

3 Rituximab (375 mg/m 2) was administered every 2 weeks together with CHOP-14 plus two additional administrations at 2 and 4 weeks, respectively, after the last chemotherapy cycle. 3 CHOP-14 with granulocyte colony-stimulating factor support was repeated every 2 weeks.

UNFOLDER TRIAL TRIAL

These patients were compared with the patients treated in the randomization phase of the RICOVER-60 trial receiving identical immunochemotherapy but with additional RT (36 Gy) to bulky disease and sites of extralymphatic involvement.Ī prephase treatment (vincristine 1 mg on day −7 and prednisone or prednisolone 100 mg orally from day −7 to −1 before first R-CHOP) was mandatory.

In this amendment, designated as the RICOVER-noRTh study, patients received 6×R-CHOP–14+2R, but without RT. The randomization phase of the RICOVER-60 trial was stopped after a planned interim analysis revealed that the predefined stopping rules were fulfilled, and an amendment was implemented. The trial was planned in a two × two factorial design. Patients were randomly assigned to six or eight cycles of CHOP-14 with or without eight applications of rituximab. 3 Briefly, patients with any disease stage or International Prognostic Index (IPI) risk group were eligible if they had previously untreated aggressive B-cell non-Hodgkin lymphoma and were age 61 to 80 years. The characteristics of patients in the RICOVER-60 trial have been described in detail. All patients provided written informed consent. The protocol was approved by the ethics review committee of each participating center. The RICOVER-60 trial was performed in accordance with the Helsinki Declaration. 3 To address the role of RT within this concept, an additional cohort of patients, designated as RICOVER-noRTh, was treated with this arm, but without RT, in an amendment to the RICOVER-60 trial, and this cohort was compared with patients who had received the same immunochemotherapy plus RT to bulky disease and extralymphatic involvements in the randomization phase of the same trial. Six cycles of R-CHOP–14+2R (R-CHOP–14 plus two additional applications of rituximab) was the best of the four treatment arms and significantly improved event-free survival (EFS), PFS, and OS over six cycles of CHOP-14. Additive RT was administered to sites of initial bulky disease (≥ 7.5 cm) and extralymphatic involvement. In the RICOVER-60 (Six Versus Eight Cycles of Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive CD20+ B-Cell Lymphomas) trial, elderly patients were randomly assigned to six or eight cycles of CHOP-14 (CHOP administered once every 2 weeks) with or without eight administrations of rituximab.

5 Regarding stage III to IV disease, two trials suggested that the addition of RT to bulky disease (> 10 cm) improved both PFS and OS in patients in CR after CHOP-like chemotherapy. 4 In contrast, the GELA (Groupe d'Etudes des Lymphomes de l'Adulte) 93-4 trial failed to demonstrate a benefit of involved-field RT (40 Gy) after four cycles of CHOP in patients age > 60 years with localized stage I or II disease. In the prerituximab era, patients with localized stage I or II disease treated in the ECOG (Eastern Cooperative Oncology Group) 1484 trial experienced improved progression-free (PFS) but not overall survival (OS) with involved-field RT (30 Gy) after achieving complete remission (CR) with CHOP. Pepakura alternative.The addition of rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy (R-CHOP) has improved the outcome of patients with aggressive B-cell lymphoma, 1– 3 and with more effective systemic immunochemotherapy, the question of additive radiotherapy (RT) is of renewed interest.

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