Dataset Information

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.

ABSTRACT:

Background

Radiation 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.

Aims

The 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).

Methods

The 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, α of 0.05, and β 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.

Discussion

The 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.

SUBMITTER: Goda JS

PROVIDER: S-EPMC7941552 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown.In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites.DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m(2)), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for <18.5 vs 18.5 to 22.4 kg/m(2)), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for >400 kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs; inflammatory bowel disease was associated with gastrointestinal DLBCL; and farming and hair dye use were associated with mediastinal DLBCL.Our results support a complex and multifactorial etiology for DLBCL with some variation in risk observed by sex and anatomical site.