Early Stage Diffuse Large B Cell Lymphoma in the Era of PET and Rituximab: Benefits from Radiotherapy in all NCCN International Prognostic Index Risk Groups

Abstract

The use of radiotherapy (RT) remains controversial in the treatment of early stage diffuse large B-cell lymphoma (DLBCL) in the era of rituximab and PETCT, and it is unclear which subgroups of patients may benefit from RT. We sought to retrospectively review modern early stage I-II DLBCL patients treated with rituximab and staged by PETCT to better define which patients benefit from consolidative RT. An IRB approved retrospective review was performed of patients treated at our institution with early stage I-II DLBCL from 1998 to 2017 coinciding with our utilization of R-CHOP and PETCT. Inclusion criteria included AJCC 7th edition stage I-II DLBCL, treatment between the years of 1998-2017, chemotherapy as first line management, and age> = 18 years. Patients were excluded if they had prior RT or were diagnosed with multiple malignancies. Relevant clinical information including age, sex, ECOG performance status (PF), LDH values, tumor location (bulky, bony involvement, and extranodal), tumor size, and B symptoms was used to calculate NCCN IPI scores. Kaplan Meier survival analysis and Cox proportional hazards model were utilized for evaluation of prognostic factors of overall survival (OS). Between 1998 and 2017, 1040 adult patients were treated with lymphoma at our institution, with 144 patients with early stage DLBCL meeting inclusion criteria. Of these, 96 received chemotherapy alone while 48 received chemotherapy followed by RT. No prognostic factors examined were significantly correlated with receipt of RT. On univariate analysis, age(p<0.001), LDH (p = 0.005), ECOG PS (p<0.001), extranodal disease (p = 0.004), and NCCN IPI (p<0.001) were significantly correlated with OS. There was no correlation with either bony involvement (p = 0.67) or bulky disease (p = 0.58). Ten-year OS was 70.3% vs. 56.8% (p = 0.075) in favor of RT. When stratified by NCCN IPI risk group, RT trended towards benefit in all subgroups: 10-year OS for Low 100% vs. 80.1% (p = 0.14), Low-Int 73.6% vs. 62.0% (p = 0.095), and High-Int 35% vs. 16.5% (p = 0.096), with too few high-risk patients to analyze. Higher 10-year OS was noted among extranodal patients receiving RT 62.4% vs. 44.9% (p = 0.069) with no significant difference at 5-years following RT for patients with either bulky (79.1% vs. 54.8% (p = 0.37)) or bony (80% vs. 66.7% (p = 0.66)) involvement, respectively. On multivariate analysis, NCCN IPI (HR 2.56 (1.93-3.39), p<0.001) and RT (HR 0.44 (0.25-0.74), p = 0.002) were both significantly correlated with OS. The current analysis supports the use of consolidative RT in early stage DLBCL given an OS benefit noted on MVA that was maintained when controlling for NCCN IPI scores. There was no significant difference seen in bulky disease or bony involvement. Further prospective randomized data is needed to confirm these findings.