Localized DLBCL of the Tonsil: A U.S. Population-Based Survival Analysis
Authors: Florindez Jorge A , Lossos Izidore S. , Alderuccio Juan Pablo 
Published: November 2021

Abstract
INTRODUCTION: The Waldeyer ring represents a common location of diffuse large B-cell lymphoma (DLBCL) arising in the head and neck. Within the Waldeyer ring, tonsils are the most common site. Chemotherapy with or without consolidation with radiotherapy are the most common approaches. However, the benefit of radiotherapy over chemotherapy as a single approach in patients with localized DLBCL remains unclear. In this study we analyzed the survival effect of different treatment modalities along with clinical variables in two cohorts of patients with stage I DLBCL involving either the tonsils or the neck lymph nodes (LN).
METHODS: This is a retrospective analysis of patients with stage I DLBCL with primary involvement of the tonsil or neck lymph nodes derived from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 with follow up through 2017. We concentrated our analysis on patients with Ann Arbor stage I and treated with chemotherapy and/or radiotherapy. We excluded cases without histologic confirmation, untreated, incomplete survival data or unknown cause of death. The major end-points of this study were overall survival (OS) and lymphoma-specific survival (LSS). Kaplan-Meier and log-rank test were used in the OS analysis with Cox proportional hazard regression model to assess predictors of OS. LSS was evaluated using competing risk analysis. The Fine and Gray subdistribution hazard model was used to assess the effect of demographic and treatment related variables on the risk of lymphoma-specific death. We reported subdistribution hazard ratios (SHR) with corresponding 95% confidence intervals.
RESULTS: 1978 (tonsil: 311 and neck LN: 1667) patients with DLBCL met the inclusion criteria. Overall, most patients were ≥ 60 years (n=1130, 57.1%), male (n=1101, 55.7%), white (n=1631, 82.5%), non-Hispanic (n=1775, 89.7%), and treated with chemotherapy (n=935, 47.3%) followed by chemotherapy/radiotherapy (n=929, 47%). Patients &lt;60 years (48.9% vs 41.8%; P=0.019), non-White race (21.9% vs 16.7%; P=0.029) and Hispanic origin (14.1% vs 9.5%; P=0.013) were more common in DLBCL in tonsil compared to neck LN.
Patients with tonsil DLBCL exhibited longer median OS compared to neck LN (16.2 vs. 14.2 years; P=0.033) (Figure 1A). In patients with tonsil DLBCL, consolidation with radiation did not lead to longer median 5-year OS (83.9%, 95%CI 76.7-89% vs 81.8%, 95%CI 74.1-87.4%; P=0.523) or LSS (HR=0.73, 95%CI 0.37-1.42; P=0.350) compared to chemotherapy (Figure 1B and Table 1). Contrary, patients with neck LN demonstrated better OS (5-year OS 82.6%, 95% 79.7-85.1 vs 72.2% 95%CI 68.9-75.2%; P&lt;0.001) and LSS (HR=0.55, 95%CI 1.51-3.14; P&lt;0.001) if they received consolidation with radiotherapy compared to chemotherapy only (Figure 1C and Table 2).
CONCLUSION: Based on our analysis consolidation with radiotherapy does not improve OS or LSS in patients with stage I tonsil DLBCL treated with chemotherapy. Conversely, consolidation with radiation significantly improves survival in patients with localized LN DLBCL.
Figure 1 Figure 1.

Disclosures
Lossos: NCI: Research Funding; Seattle Genetics: Consultancy; Stanford University: Patents & Royalties; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member.