A phase III randomized controlled trial of radiation dose optimization in non-Hodgkin lymphoma-diffuse large B-cell lymphoma (DOBL study): Study protocol and design

BackgroundRadiation therapy for diffuse large B-cell lymphoma (DLBCL) has shown improvement in progression free survival. There is uncertainty about the optimal radiation dose, with heterogeneous doses being used, ranging from 30 to 55 Gy. This trial tests the efficacy of using reduced radiation dose in DLBCL without compromising on long-term outcomes. AimsThe primary aim is to assess the noninferiority, as assessed by 2-year event free survival (EFS), of a dose de-escalated dose (36 Gy) for DLBCL as compared with a standard dose (45 Gy). MethodsThe Dose Optimization in B cell Lymphomas (DOBL) study is a randomized phase-III noninferiority trial in a uniform cohort of DLBCL patients receiving immunochemotherapy (R-CHOP). Patients with stages I to IV of DLBCL eligible for radiotherapy (RT) after completion of at least four cycles of R-CHOP will be included in the study. Patients will be randomized to standard RT dose of 45 Gy in 25 fractions or reduced dose of 36 Gy in 20 fractions using involved site radiotherapy (ISRT) technique. It is a noninferiority design using a 7% noninferiority margin with a hazard ratio of 1.3, alpha of 0.05, and beta of 0.80. A total of 760 patients will be accrued. Two-year EFS is the primary outcome measure that will be studied. The experimental arm will be stopped and switched over to control arm if on interim analysis, 25% events occur in the experimental arm. DiscussionThe study is designed to test the noninferiority of radiation dose de-escalation in a uniform cohort of patients diagnosed with DLBCL and treated with R-CHOP regimen in the post-positron emission tomography (PET) era. The trial is rigorously designed and is straightforward to implement. It is statistically powered to answer if reducing the radiation doses does not compromise the clinical outcome in the given patient cohort. This trial will effectively set the standards in radiotherapy doses for DLBCL in the contemporary era.