Sites of extranodal involvement are prognostic in patients with diffuse large B‐cell lymphoma in the rituximab era: An analysis of the Surveillance, Epidemiology and End Results database

Abstract

Approximately a third of the patients with diffuse large B-cell lymphoma present with extranodal involvement. Our study aims to identify primary extranodal sites of disease associated with prognosis in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. A secondary objective is to describe epidemiological and clinical characteristics of patients with extranodal DLBCL. We included adult patients from the Surveillance, Epidemiology and End Results (SEER) database (2004)(2005)(2006)(2007)(2008)(2009) in whom DLBCL was the first malignancy diagnosed. Extranodal primary sites were divided into 12 groups according to the topography code reported by SEER. Multivariate overall survival (OS) analyses were performed using Cox proportional-hazard regression models adjusted for age, sex, race, and stage. From a total of 25,992 adult DLBCL patients included in our analysis, 32% presented with extranodal primary sites. Gastrointestinal tract (34%), head/neck (H&N; 14%), and skin/soft tissue (11%) were the most common. In comparison with nodal DLBCL, patients with extranodal involvement were older (with exception of skeletal sites) and presented with earlier stages. In the multivariate analysis, sites associated with worse OS rates were gastrointestinal (Hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.15-1.33; P <0.001), pulmonary (HR 1.59, 95% CI 1.38-1.83; P <0.001), and liver/pancreas (HR 1.58, 95% CI 1.35-1.85; P <0.001), whereas H&N was associated with better survival (HR 0.79, 95% CI 0.70-0.89; P <0.001). In this population-based study, primary extranodal sites of involvement are associated with distinct outcomes in patients with DLBCL. Gastrointestinal, pulmonary, and liver/pancreas sites had a significant worse outcome than nodal sites.

Validation of clinical prognostic indices for diffuse large B-cell lymphoma in the National Cancer Data Base

“…This new clinically useful index has been validated in a separate British Columbia Cancer Agency population-based database as part of the original study, showing higher CPE than the IPI (77 vs. 74 %), and confirmed its superiority in other subsequent DLBCL series (for example, CPE was 75 vs. 70 % in the study by Mian et al [21][22][23][24]). Specific anatomical sites of lymphoma origin also have a prognostic value and may derive heterogeneous benefits from immunochemotherapy [10,16]. In all iterations of the IPI, age [60 years was the strongest predictor of survival [3,6].…”

“…For example, in 2005 the death rate was 432 (per 100,000 person-years) for Americans aged 45-54 years and 2,137 for those aged 65-74 years [25]. The crude dichotomization of age at 60 years is a significant culprit of the IPI, particularly considering the median age at DLBCL diagnosis in the USA, which is 66 years [16]. Our analysis shows a nonlinear, exponential relationship between age and relative hazard of death in DLBCL.…”

“…High-risk extranodal primary sites (central nervous system, lung, liver, pancreas, gastrointestinal tract, and bone marrow) were further distinguished based on prior epidemiologic studies [8,16]. Because a nonlinear relationship between age and OS was evident, we transformed age using a fractional polynomial-a method that avoids model misspecification and information loss occurring when a continuous variable is coarsely categorized [17].…”

Gender Aspects in Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue: Does Sex Matter?

“…By contrast, follicular lymphoma and marginal zone lymphoma rated nearly identical (1.0-1.2) in both sexes. In addition, association of gender with distinct clinical features has been analyzed in various smaller analyses [6], revealing that extranodal involvement of the breast, thyroid and respiratory system is more likely in female patients with DLBCL [6,7]. …”

A rare case of the upper extremity diffuse large B-cell lymphoma mimicking soft tissue sarcoma in an elderly patient

“…Most of the times, disease primarily occurs in the lymph nodes, but extranodal involvement is not uncommon. About 30% of DLBCL cases present with disease outside the lymph nodes, which may incur different clinicopathologic features and prognosis for these patients (1)(2)(3). Cases involving soft tissues often mimic other entities like sarcoma.…”