The key evidence for the use of this protocol comes from the ECOG 1484,r SWOG 0014r and GELArr trials.
Most of the studies investigating the role of consolidative radiotherapy were performed in comparison to CHOP-based chemotherapy, and predate the use of rituximab. The evidence for the role of radiotherapy was equivocal with one study demonstrating an improvement in local control and progression free survivalr for combined modality treatment (3 x R-CHOP followed by 30-40Gy involved field radiotherapy) when compared to chemotherapy alone.
A recent retrospective matched-pair analysis study from the MD Anderson Cancer Center provides new data regarding the efficacy of RT following R-CHOP for stage I and II patients with DLBCL. It showed significant improvement in OS and PFS in patients receiving consolidation RT after R-CHOP. The 5-year OS and PFS with consolidative RT were 92% and 82% respectively, while without RT, the OS and PFS were 73% and 68%. In this study, none of the patients experienced treatment failure in the RT field.r
In contrast, the GELA studies in elderly patients are frequently quoted as a reason not to give IFRT as it did not affect event-free survival.rr However, relapses occurred in irradiated sites alone at rates of 23% and 21% (LNH 93-1 and 93-4, respectively). The IFRT inferior results compared with other studies raise the question of QA, delays and actual administration of the RT affecting the results.
More intensive chemotherapy with ACVBP also appeared to be superior to 3xCHOP with involved field radiotherapy. However, this was at the cost of significantly higher rates of toxicity with only 80% of patients in the chemotherapy group completing all treatment, as compared to 98% of the combined modality group.r
Other studies looked at efficacy and dose:
The SWOG 0014rphase II study delivering R-CHOP plus involved-field radiotherapy, demonstrated a 2 year PFS of 93% and OS of 96%. In a UK RCT comparing 30Gy in 15 fractions with 40-45Gy in 20-23 fractions, there was no significant difference in the rate of within-radiation field progression for aggressive lymphoma overall (˜80% DLBCL) (HR =0.98, 95% CI=0.68-1.4, p=0.89), with a trend towards lower toxicity in the low dose arm. Hence R-CHOP followed by 30Gy in 15 fractions has become an accepted standard regimen for aggressive NHL.r
Held et al. reported an analysis of two prospectively treated cohorts from the RICOVER-60 trial which provided strong support for adding RT (36Gy) to sites of bulky disease (>/=7.5cm) for elderly patients (61-80 years old) with aggressive B-cell lymphoma. These patients had received from 6-8 cycles of CHOP-14 with or without rituximab, using 2x2 factorial design, with R-CHOP-14 x 6 proving to be the superior arm. However, the authors acknowledge that a prospective study is needed to ascertain whether all subjects would benefit from RT for bulky disease or whether it could be omitted in cases of PET negativity after immunochemotherapy.r
Figure 1. (A) Progression-free and (B) overall survival of 60 eligible patients enrolled in a Southwest Oncology Group (SWOG) trial of three cycles of R-CHOP followed by 30-40 involved-field radiation therapy.
© 2008 American Society of Clinical Oncologyr