Although R-CHOP chemotherapy followed by involved field radiotherapy (RT) is often used to treat patients with stage III/IV diffuse large B-cell lymphoma, there is limited evidence to support this approach. The reference committee supported publication of the protocol on the basis of the information summarised below. The reference committee was most strongly influenced by the Held et al. 2014, Phan et al. 2010 and Lowry et al 2011 papers.rrr
Held et al. 2014 conducted a trial to investigate the benefit of adding radiotherapy for elderly patients with bulky or extra lymphatic disease.r They compared patients receiving the best arm of the RICOVER-60 trial (6xR-CHOP-14+2R plus IFRT: 36Gy to sites of initial bulky disease) with patients receiving the same immunochemotherapy without RT (RICOVER noRTh). The intention to treat analysis on patients with bulky disease showed fewer relapses in the group receiving RT. Trends towards worse outcomes in overall survival (OS) were seen at three years in RICOVER-noRTh (63% vs 78%).
Phan et al. 2010 in a retrospective study compared consolidative IFRT (30-39.6Gy) with R-CHOP chemotherapy only in 469 patients with DLBCL (190 stage I-II, 279 stage III-IV).r The study demonstrated that consolidation RT significantly improved OS and PFS after R-CHOP chemotherapy. In the patients with stage III-IV disease 5yr OS was 89% for RT and 66% without. PFS was 76% with RT vs 55% with R-CHOP only.
Lowry et al. 2011 randomised 460 patients with aggressive NHL (predominantly DLBCL) to receive either 40-45Gy in 20-23 fractions or 30Gy in 15 fractions.r Overall response rate (ORR) was 91% in both arms of the trial, there was also no significant difference detected in the rate of within radiation-field progression, progression free survival (PFS) or OS. There was a trend towards less toxicity in lower dose arm however only the difference in reported erythema was significant.
The MINT Trial showed rituximab decreased, but did not eliminate, the adverse prognostic effect of maximum tumour diameter (MTD) in young patients with good-prognosis DLBCL.r The study provides indirect support for the use of consolidative radiotherapy for the bulky sites.
The UNFOLDER trial randomised patients to R-CHOP-21 versus R-CHOP-14, as well as a randomisation to bulky and extralympahtic disease irradiation or observation alone.r Although as yet unpublished, in a planned interim analysis, there were significant differences favouring the addition of RT and all subsequent patients received consolidative RT. These results are currently only in abstract form.
A non-randomised comparison of the OPTIMAL>60 trial in bulky disease patients which omitted radiotherapy (39.6 Gy) if PET negative post R-CHOP to the RICOVER-60 was non inferior (2 year PFS 79% vs 75%; 2 year OS 89% vs 78%).r These results are also currently only in abstract form.
Figure 1. (A) OS and (B) PFS of patients achieving complete remission after treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, with and without RT.
© Clin Oncol 2010r