The Theoretical Role for Radiotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Secondary Analysis of a Prospective Randomized Controlled Trial.

PURPOSE/OBJECTIVE(S): The role of radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) is unclear. In patients treated with upfront chemotherapy for DLBCL, indications for RT are often considered to be bulky (7.5 cm +) or extranodal disease. This is thought to improve outcomes through improvement in local control. Many trials call into question the actual benefit of RT. Alliance/CALGB 50303 was a randomized phase III trial comparing two chemotherapy regimens for the treatment for DLBCL in which no patients were to receive RT. Our objective was to assess the theoretical impact of RT by assessing outcomes of trial patients.

MATERIALS/METHODS: This secondary analysis was performed using PET/CT images and data from the NCTN/NCORP Data Archive of the National Cancer Institute. Data were originally collected on the Alliance/CALGB 50303 (NCT00118209) clinical trial. Of the 524 registered patients, data and images for 155 patients were available. Two investigators measured the largest sites of nodal involvement on PET/CT and the average was calculated-the largest was used to determine bulky disease. Bulk was defined as nodal disease with maximum diameter greater than or equal to the threshold. Thresholds (in cm) examined included: 5, 6, 7, 7.5, 8, 9, and 10. PFS was estimated for patients with versus without bulky disease and compared using the log-rank test.

RESULTS: Of the 155 evaluable pre-treatment PET/CT image sets, 135 patients had measurable nodal disease. Fifteen patients who did not complete treatment per protocol and four patients with mediastinal B-cell lymphoma were excluded. Of the 116 analyzed patients, 45% had stage IV disease, 88% had an ECOG performance status of 0-1, and one had double-hit lymphoma. IPI was 0-2 in 62% and 3-5 in 38%. Chemotherapy was R-CHOP in 61 and DA-R-EPOCH in 55. Best response was CR in 84 patients (73%), PR in 30 (26%) and SD in 1 (1%). The median follow-up was 5 years and 32 PFS events were observed. Bulky disease was associated with elevated LDH at diagnosis (using 7.5 cm threshold: LDH elevated in 72% with bulky disease v. 40% with non-bulky, p< 0.01) and more frequent use of pegfilgrastim (51% v. 31%, respectively, p = 0.04). Overall, the 5-year PFS rate was 72.3% (95% CI 64.1-81.4). Using a 7.5 cm threshold, 5-year PFS was 62.7% in patients with bulk versus 79.3% in those without (p = 0.14). There were no significant PFS differences (p>0.05) observed at any threshold. The 5-year OS was 86.4% (95% CI 80.2-93.1); no differences in OS by bulk using any threshold were observed.

CONCLUSION: In this secondary analysis of a phase III randomized trial of chemotherapy alone for DLBCL, initial bulk was not shown to be significantly associated with outcomes. Prospective data comparing consolidative RT versus no RT are necessary to determine optimal treatment paradigms.