Definitions and use of tumor bulk in phase 3 lymphoma trials: a comprehensive literature review

Luke Wang ^1,2, Eliza Chung ¹, Cameron Wellard ¹

¹School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
²Department of Haematology, Eastern Health, Melbourne, Australia.
³Department of Haematology, Fiona Stanley Hospital, Perth, Australia.
⁴Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁵The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
⁶Department of Clinical Pathology, The University of Melbourne, Parkville, Australia.
⁷Ballarat Regional Integrated Cancer Centre, Ballarat, Australia.
⁸Department of Haematology, Canberra Hospital, Canberra, Australia.
⁹College of Health and Medicine, Australian National University, Canberra, Australia.
¹⁰School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.
¹¹Monash Health, Melbourne, Australia.
¹²Princess Alexandra Hospital, Brisbane, Australia.
¹³School of Medicine, The University of Queensland, Brisbane, Australia.
¹⁴Royal Hobert Hospital, Hobart, Australia.
¹⁵University of Tasmania, Hobart, Australia.
¹⁶Alfred Health, Melbourne, Australia.
¹⁷Monash University, Melbourne, Australia.
¹⁸Olivia Newton-John Cancer Research Institute at Austin Health, Melbourne, Australia.

⁰School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Blood Advances +

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January 18, 2025

View abstract on PubMed

Summary

Tumor bulk is inconsistently defined and applied in lymphoma clinical trials. This lack of consensus hinders its prognostic value and requires international standardization for better patient care.

Area Of Science

Hematology
Oncology
Clinical Trials

Background

Tumor bulk has been a historical prognostic marker in lymphoma.
Definitions and applications of tumor bulk in clinical trials lack standardization.
Contemporary relevance of tumor bulk requires re-evaluation due to varying definitions.

Purpose Of The Study

To comprehensively review definitions, applications, and prognostic impact of tumor bulk in phase 3 lymphoma trials.
To evaluate inconsistencies in tumor bulk thresholds and their use across major lymphoma subtypes.
To identify the need for international consensus on tumor bulk definitions in clinical practice.

Main Methods

Literature review of 87 phase 3 randomized trials in follicular lymphoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, and Hodgkin lymphoma.
Analysis of reported tumor bulk thresholds (e.g., 5-10 cm, mediastinal mass ratio).
Evaluation of tumor bulk's role in trial eligibility, stratification, risk adaptation, and prognostication.

Main Results

Wide range of bulk thresholds (5-10 cm, >1/3 MMR) were used across lymphoma subtypes.
Inconsistent application of bulk definitions for eligibility, stratification, and treatment decisions.
Only 5 out of 32 studies incorporating bulk in prognostic analyses found significant differential survival outcomes.

Conclusions

Significant inconsistencies exist in defining and utilizing tumor bulk in phase 3 lymphoma trials.
Current variations in bulk definitions impede its prognostic and predictive value.
An urgent need for international consensus on tumor bulk definitions is highlighted to refine its clinical application.

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