Although R-CHOP chemotherapy followed by involved field radiotherapy is often used to treat patients with Stage III/IV diffuse large B-cell lymphoma, there is limited evidence to support this approach. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the Held 2014,r Phan 2010r and Lowry et al 2011 papers.r
Held et alr conducted a trial to investigate the benefit of adding radiotherapy for elderly patients with bulky or extra lymphatic disease. 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 to worse outcomes in OS were seen at three years in RICOVER-noRTh (63% vs 78%).
Phan et alr compared consolidative IFRT (30-39.6Gy) with R-CHOP chemotherapy only in 469 patients with DLBCL (190 stage I-II, 279 stage III-IV). 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 etr randomised 460 patients with aggressive NHL (predominantly DLBCL) to receive either 40-45Gy in 20-23 fractions or 30Gy in 15 fractions. 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, PFS or OS. There was a trend towards less toxicity in lower dose arm however only the difference in reported erythema was significant.
In the MINT Trial,r Rituximab decreased, but did not eliminate the adverse prognostic affect of MTD in young patients with good-prognosis DLBCL. The study provides indirect support for the use of consolidative radiotherapy for the bulky sites and provided the basis for the UNFOLDER trial which formally evaluates the impact of consolidative radiotherapy bulky sites.
||Number of patients
||Phan et al, 2010r
||469 (142 - RT/327 - No RT)
||5yr: 89% vs 66% (p=0.008)
||Stage III and IV patients
|Progression Free Survival
||5yr: 76% vs 55% (p=0.003)
|Rate of within-radiation field progression
||Lowry et al. 2011r
||No significant difference
95%CI = 0.68-1.4, (p=0.89)
|Median 5.6 yr follow-up
Figure 1. Freedom from local progression, progression-free survival and overall survival results demonstrate no significant difference in outcomes between high and low dose arms.
© Lowry et al, 2011.r
Figure 2. (A) Overall and (B) progression-free survival of patients achieving complete remission after treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, with and without radiotherapy (RT).
© Phan 2010r