Clinical Characteristics and Outcomes of Limited-Stage Primary Extranodal Versus Nodal Diffuse Large B-Cell Lymphoma (DLBCL) in Thailand: A Nationwide Multi-Institutional Registry of 920 Cases in Thailand

Introduction

The difference in origin between nodal and extranodal DLBCL may contribute to the distinct clinical outcomes and prognoses. Previous studies including patients with both limited and advanced diseases showed various clinical results. The purpose is to study the clinical characteristics, and outcomes of patients with limited stage DLBCL according to the primary site of lymphoma.

Methods

From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were 920 patients with limited stage DLBCL, excluding those with primary central nervous system lymphoma. The baseline patient characteristics and clinical outcomes were analyzed according to the primary site of diseases.

Results

Majority of patients had extranodal diseases (n= 535, 58.2%) while the other 385 cases (41.8%) had nodal DLBCL. The five most common primary sites of extranodal disease were Waldeyer ring (12.2%), stomach (7.3%), intestine (6.8%), sinonasal cavity (6.7%) and breast (2.8%) (Figure 1). Baseline characteristics, treatment and responses were well balanced between the two groups except for a slightly higher proportion of stage I disease in extranodal DLBCL (36.8% vs 28.8%, P=0.01) (Table 1). Two-third of patients received CHOP chemotherapy while the others were treated with R-CHOP. Radiotherapy (RT) was delivered to one-fifth of the patients in each group. Overall response rates were comparable between patients with nodal and extranodal diseases (68.6% vs 66.7%). With a median follow up of 52 months, there were no significant differences of progression free (PFS) (57.6 vs. 60.8%, P=0.46) and overall survival (OS) (63.1% vs. 65.6%, P=0.20) between patients with extranodal and nodal diseases. Among patients with extranodal manifestations, those with primary lymphoma at pancreas & gall bladder, pleura & lung, adrenal gland & kidney and intestine had the worst 4-year OS (33.3%, 39.3%, 53.3%, and 53.7%, respectively) (Figure 2). RT improved PFS (71.7% vs. 54.5%, P=0.03) and OS (74.7% vs. 62.9%, P=0.02) only in primary nodal DLBCL. The two prognostic factors for survivals were being treated with R-CHOP (HR for PFS 0.84, 95%CI: 0.74-0.96; HR for OS 0.70, 95%CI: 0.55-0.91) and the IPI scores (HR for PFS 1.49, 95%CI: 1.24-1.80; HR for OS 1.86, 95%CI: 1.37-2.51).

Conclusion

Among limited stage DLBCL in Thailand, primary extranodal disease was more common than the nodal manifestations. Primary sites of origins did not affect baseline characteristics as well as the outcomes. Patients with unusual site lymphomas, however, had an inferior survivals warranted a further investigational therapy.

 

Clinical characteristics	Nodal DLBCL (n = 385)	Extranodal DLBCL (n = 535)	p-value
Male	205 (53.2%)	294 (55%)	0.60
Median age (years)	54.9	56.2	0.23
Stage   Stage I   Stage II	111 (28.8%) 274 (71.2%)	197 (36.8%) 338 (63.2%)	0.01
HIV seropositivity	11 (3.4%)	19 (4.3%)	0.53
Age ≥ 60	164 (42.6%)	230 (43%)	0.90
High serum LDH	183 (47.5%)	230 (43%)	0.17
ECOG ≥ 2	46 (11.9%)	60 (11.2%)	0.73
IPI   Low (IPI = 0-1)   Low-intermediate (IPI =2)   High-intermediate (IPI = 3)	285 (74.0%) 81 (21.0%) 19 (4.9%)	406 (75.9%) 108 (20.2%) 21 (3.9%)	0.82
Chemotherapy regimens   R-CHOP   CHOP	98 (29.0%) 227 (67.2%)	160 (33.7%) 286 (60.2%)	0.25
Radiotherapy	94 (24.9%)	120 (22.8%)	0.46
Response   Overall response   Complete response	261 (68.6%) 227 (59.7%)	352 (66.7%) 322 (61%)	0.24

Table 1. The clinical characteristics of limited stage DLBCL according to disease of origin

*IPI: International prognostic index

Figure 1. Sites of origin among limited stage DLBCL

Figure 2. Overall survival of patients with limited stage DLBCL according to primary sites of lymphoma