Consolidation Radiotherapy Improved Survival In Limited Stage Diffuse Large B-Cell Lymphoma (Dlbcl): A Nationwide Multi-Institutional Registry Of 816 Cases In Thailand

Introduction additional benefit of consolidation radiotherapy (RT) following chemotherapy in limited stage DLBCL remains controversial. Previous 5 randomized trials, 4 trials before rituximab era (SWOG 8736, ECOG 1484, GELA 93-1 and 93-4 studies) and 1 trial with R-CHOP combination (Lysa/Goelams 02-03), could not demonstrate a remarkable benefit of RT. purpose of this study is to explore the benefit of combined modality treatment including the combination of RT and rituximab (R)-based chemotherapy in limited stage DLBCL.Methods From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were a total of 2,399 patients with DLBCL. We included patients with limited stage DLBCL receiving CHOP/CHOP-liked chemotherapy +/- R and +/- RT. baseline patient characteristics and clinical outcomes were analyzed according to treatment modalities.Results A total of 816 patients with a median age of 56 years (range, 15-91) were included in the study. Male:female was 1:1.1. Majority of patients had primary extranodal diseases (58%), stage II (68%), good performance status (89%), normal LDH (55%) and no B-symptoms (59%). IPI scores were 0 (30.6%), 1(45%), 2 (20%) and 3 (3.9%), respectively. modalities of treatment were CHOP alone (48.5%), R-CHOP (26.5%), CHOP+RT (17.9%) and R-CHOP+RT (7.1%). Patients in R-CHOP group were older than in other groups ( P =0.001) (Table 1).There was a higher proportion of patients in stage II disease in R-CHOP (74.1%) and R-CHOP+RT (74.1%) groups than in CHOP (66.9%) and CHOP+RT (57.5%) groups ( P =0.007), whereas the patients were relatively equally distributed between the IPI scores. Complete response (CR) rate was higher in R-CHOP+RT group (82.8%) than in R-CHOP (75%), CHOP+RT (70%) and CHOP groups (58%) ( P u003c0.001). CR was independently associated with consolidation RT (OR 0.65, 95%CI: 0.45-0.97), rituximab-based therapy (OR 0.66; 95%CI: 0.55-0.79) and IPI score (OR 1.90; 95%CI: 1.41-2.57). With a median follow up of 52 months, 4-year progression free survival (PFS) were 76.4%, 69.4%, 61.4% and 49.9% in R-CHOP+RT, R-CHOP, CHOP+RT and CHOP alone, respectively, ( P u003c0.001) (Figure. 1). corresponding figures of 4-year OS for each group were 78.6%, 76.3%, 64.3% and 59.6%, respectively ( P u003c0.001) (Figure. 2). Multivariate analysis showed that factors associated with survivals were consolidation RT (HR for PFS 0.63, 95%CI: 0.48-0.82; HR for OS 0.70, 95%CI: 0.53-0.94), rituximab-based therapy (HR for PFS 0.72, 95%CI: 0.64-0.83; HR for OS 0.69, 95%CI: 0.60-0.81) and IPI scores (HR for PFS 1.87, 95%CI: 1.54-2.26; HR for OS 1.96, 95%CI: 1.60-2.41)ConclusionIn limited stage DLBCL, consolidation RT plus R-CHOP yielded a superior outcome compared to R-CHOP, CHOP + RT and CHOP alone. Thus, RT continues to have an important role and should not be omitted in management of limited stage DLBCL in rituximab era.| Clinical characteristics | CHOP alone (n= 396) | CHOP + RT (n = 146) | R-CHOP alone (n = 216) | R-CHOP + RT (n = 58) | p-value || --------------------------------------------------------------------------------------------------- | ----------------------------------------------- | ---------------------------------------------- | ------------------------------------------------ | --------------------------------------------- | ------- || Male | 211 (53%) | 75(51.4%) | 125 (57.9%) | 24 (41.4%) | 0.14 || Median age (years) | 56 (15-90) | 52 (15-86) | 60 (17-91) | 55 (15-81) | 0.001 || Age ≥ 60 | 155 (39.1%) | 51 (34.9%) | 109 (50.5%) | 20 (34.5%) | 0.008 || Primary extranodal disease | 226 (57.1% | 79 (54.1%) | 136 (63.0% | 34 (58.6%) | 0.35 || Stage Stage I Stage II | 131 (33.1%) 269 (66.9%) | 62 (42.5%) 84 (57.5%) | 56 (25.9%) 160 (74.1) | 15 (25.9%) 43 (74.1%) | 0.007 || B-symptom | 116 (32.6%) | 47 (36.2%) | 58 (31.4%) | 13 (28.9%) | 0.76 || HIV seropositivity | 15 (4.6%) | 9 (7.0%) | - | - | 0.004 || High serum LDH | 173 (43.7%) | 74 (50.7%) | 95 (44.0%) | 26 (44.8%) | 0.51 || ECOG ≥ 2 | 31 (7.8%) | 22 (15.1%) | 25 (11.6%) | 7 (12.1%) | 0.08 || IPI Low (IPI =0-1) Low-intermediate (IPI =2) High-intermediate (IPI = 3) | 312 (78.8%) 75 (18.9%) 9 (2.3%) | 107(73.3%) 32 (29.1%) 7 (4.8%) | 157 (72.7%) 48 (22.2%) 11 (5.1%) | 46 (79.3%) 9 (15.5%) 3 (5.2%) | 0.35 || Response Overall response Complete response | 258 (65.2%) 230 (58.1%) | 116(79.4%) 103(70.5%) | 179 (82.9%) 162 (75%) | 51 (88%) 48 (82.8%) | u003c.0001 |Table 1. Comparison of characteristics of patients according to treatment modalities![Figure 1.][1] Figure 1. The Kaplan-Meier plots of PFS according to treatment groups![Figure 2.][1] Figure 2. The Kaplan-Meier plots of OS according to treatment groupsDisclosures Khuhapinant: Roche: Honoraria. [1]: pending:yes