Abstract
The presence of a single large disease site or so-called tumor ‘bulk’ in lymphoma has been variably associated with outcomes and influenced management decisions. However, challenges arise in using bulk as a prognosticator due to varied definitions across different lymphoma subtypes but also within studies of each subtype, increased utility of positron emission tomography (PET) in decisionmaking and recent incorporation of novel therapies. We analyzed data from the Australasian Lymphoma Registry regarding presence and influence of bulk on outcomes and treatment decisions in six key subtypes: diffuse large B-cell (DLBCL), follicular, marginal zone, T-cell, Hodgkin (HL) and Burkitt lymphoma (BL). Of the 5090 eligible patients identified between 2016-2025, 88% had documented information on the presence of bulk (registry definition >5cm). Patients with bulk were more likely to receive systemic chemotherapy alone, and less likely to have localized treatment alone (radiotherapy and/or surgery), compared to those without bulk. Bulk was associated with inferior overall survival (OS) in DLBCL patients, and superior OS in HL patients, in the univariate analyses. Exploratory analysis using disease-specific bulk definitions from clinicians practising in Australia and New Zealand showed inferior progression-free survival in DLBCL (bulk >7.5cm) and OS in BL patients (bulk >10cm), but not other subtypes. We demonstrated real-world evidence of management heterogeneity for patients with bulk, with potential prognostic implications. International standardization of the definition of bulk is urged for uniform utility in PET-based and molecular prognostication across clinical studies. Trial registration at the Australian New Zealand Clinical Trials Registry: ANZCTRN12617000050358.
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