Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

Chemotherapy followed by consolidation radiation therapy (RT) is a recognized treatment
paradigm for DLBCL. This was initially established based on the results of 2 randomized
trials conducted in the 1980s-1990s. In these studies patients were treated with 30Gy after
chemotherapy (ECOG study) or 40-55Gy (SWOG study). A British National Lymphoma Investigation
study showed no difference in freedom from local progression, progression-free survival or
overall survival in between patients receiving 30Gy and 40-45Gy. Additionally systemic
therapy for DLBCL has significantly improved since these initial studies, with the addition
of rituximab to standard chemotherapy.

In a phase II study at Duke University patients with DLBCL NOS or primary mediastinal B-cell
lymphoma were treated to 19.5-20Gy after achieving complete response to 4-6 cycles of
chemotherapy containing rituximab. With a median follow-up of 43 months, there was only 1
local recurrence. The 5-year local control rate was 98%. Progression-free and overall
survival at 5 years was 81% and 88%. Therefore, there is emerging evidence of long term
favorable outcomes in localized DLBCL, while decreasing the risk of late effects by reducing
the dose and volume of RT.

All participants will receive 20Gy instead of 30-36Gy after completion of at least 3 cycles
of rituximab with combination chemotherapy. Participants must have a negative post
chemotherapy PET-CT to participate in this study.

Inclusion Criteria:

- Histological documentation of stage I-IV diffuse large B-cell lymphoma, not otherwise
specified (DLBCL NOS) and all entities within this category as defined in the WHO
classification. Double hit, triple hit, double expressor and triple expressor
phenotypes are eligible.

- Completion of at least 3 cycles of rituximab-containing, anthracycline-based
combination chemotherapy

- Negative post-chemotherapy PET-CT scan

- Absolute neutrophil count greater than 1000 and platelet count greater than 40,000

- Negative pregnancy test in women of child-bearing potential

- Signed study specific informed consent

Exclusion Criteria:

- Primary central nervous system lymphoma, primary cutaneous DLBCL, leg type.
T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large
B-cell lymphoma, or other distinct non-Hodgkin lymphomas arising from large B-cells
included in the WHO classification

- Any absolute contraindications to irradiation