Luke Wang, Eliza Chung, Cameron Wellard, Allison Barraclough, Belinda A Campbell, Geoffrey Chong, Pietro R Di Ciaccio, Gareth P Gregory, Greg Hapgood, Anna M Johnston, Constantine Tam, Stephen Opat, Erica M Wood, Zoe K McQuilten, Eliza A Hawkes
{"title":"Definitions and use of tumor bulk in phase 3 lymphoma trials: a comprehensive literature review.","authors":"Luke Wang, Eliza Chung, Cameron Wellard, Allison Barraclough, Belinda A Campbell, Geoffrey Chong, Pietro R Di Ciaccio, Gareth P Gregory, Greg Hapgood, Anna M Johnston, Constantine Tam, Stephen Opat, Erica M Wood, Zoe K McQuilten, Eliza A Hawkes","doi":"10.1182/bloodadvances.2024015072","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Tumor \"bulk\" has historically been considered an important prognostic marker and a clinical tool to guide treatment in patients with lymphoma. However, its use and definitions in trial designs vary significantly, and it is unclear how this has influenced the relevance of bulk in contemporary practice. This comprehensive literature review evaluated the definitions, applications, and prognostic impact of bulk in phase 3 randomized trials in 4 major lymphoma subtypes. Overall, 87 studies were identified across follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), and Hodgkin lymphoma (HL) with a wide range of bulk thresholds used (5 cm, 6 cm, 7 cm, 7.5 cm, 10 cm, and >1/3 mediastinal mass ratio [MMR]). The most common threshold was as follows: FL, 7 cm (58%); DLBCL, 7.5 cm and 10 cm (44% each); PTCL, 7.5 cm (66%); and HL, one-third MMR (91%). Bulk threshold was used by trials to determine eligibility (66%), stratification (24%), as a prognostic risk factor (37%), and as a decision tool for risk-adapted treatment, for example, radiotherapy (29%); however, bulk definitions used for these varied both between, and within, lymphoma subtypes and even within single trials in 25%. Furthermore, 32 studies incorporated bulk in prognostic analyses with only 5 showing significance for differential survival outcomes. Our analysis demonstrates high inconsistency in thresholds defining tumor bulk and use of bulk in phase 3 lymphoma trials across eligibility, stratification, therapeutic risk adaptation, and prognostication. This highlights an urgent need for international consensus on definitions of bulk within trials to improve its prognostic and predictive values and refine its application in clinical practice.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2275-2284"},"PeriodicalIF":7.4000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood advances","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/bloodadvances.2024015072","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Tumor "bulk" has historically been considered an important prognostic marker and a clinical tool to guide treatment in patients with lymphoma. However, its use and definitions in trial designs vary significantly, and it is unclear how this has influenced the relevance of bulk in contemporary practice. This comprehensive literature review evaluated the definitions, applications, and prognostic impact of bulk in phase 3 randomized trials in 4 major lymphoma subtypes. Overall, 87 studies were identified across follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), and Hodgkin lymphoma (HL) with a wide range of bulk thresholds used (5 cm, 6 cm, 7 cm, 7.5 cm, 10 cm, and >1/3 mediastinal mass ratio [MMR]). The most common threshold was as follows: FL, 7 cm (58%); DLBCL, 7.5 cm and 10 cm (44% each); PTCL, 7.5 cm (66%); and HL, one-third MMR (91%). Bulk threshold was used by trials to determine eligibility (66%), stratification (24%), as a prognostic risk factor (37%), and as a decision tool for risk-adapted treatment, for example, radiotherapy (29%); however, bulk definitions used for these varied both between, and within, lymphoma subtypes and even within single trials in 25%. Furthermore, 32 studies incorporated bulk in prognostic analyses with only 5 showing significance for differential survival outcomes. Our analysis demonstrates high inconsistency in thresholds defining tumor bulk and use of bulk in phase 3 lymphoma trials across eligibility, stratification, therapeutic risk adaptation, and prognostication. This highlights an urgent need for international consensus on definitions of bulk within trials to improve its prognostic and predictive values and refine its application in clinical practice.
期刊介绍：
Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016.
Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.
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