TY - JOUR
T1 - Maximum Tumor Diameter is Associated with Relapse Risk in Limited-Stage Hodgkin Lymphoma
T2 - An International Study
AU - Phillips, Elizabeth H
AU - Counsell, Nicholas
AU - Illidge, Tim M
AU - André, Marc
AU - Aurer, Igor
AU - Fiaccadori, Valeria
AU - Fortpied, Catherine
AU - Neven, Anouk
AU - Federico, Massimo
AU - Barrington, Sally F
AU - Raemaekers, John M
AU - Radford, John
N1 - © 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2025/5/13
Y1 - 2025/5/13
N2 - Tumor bulk is an established prognostic factor in Hodgkin lymphoma (HL), but most patients with limited-stage (LS) HL do not have "bulk" by standard definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with relapse risk in LS-HL patients achieving positron emission tomography negativity (PET-) after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We aimed to externally validate these findings in the H10 trial. Stage I/IIA HL patients, without mediastinal bulk, who achieved PET- with ABVD were included. Patients received 3 ABVD plus radiotherapy (n = 208) or 3 ABVD alone (n = 211) in RAPID, and 3 to 4 ABVD plus radiotherapy (n = 556) or 4 to 6 ABVD alone (n = 303) in H10. MTD was strongly associated with event-free survival (relapse or HL-related death) in H10 (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.07-1.38; P = .003), a similar effect to that seen in RAPID (HR, 1.19; 95% CI, 1.02-1.39; P = .02), giving an estimated 21% risk increase per centimeter MTD (HRpooled, 1.21; 95% CI, 1.09-1.33; P < .001). Effect sizes were similar for patients treated with ABVD alone and ABVD plus radiotherapy, with no differential effect (pinteraction = 0.97). Treatment modality and MTD were independent risk factors; patients with higher MTD receiving chemotherapy alone had the greatest relapse risk. This international validation study confirms MTD is strongly associated with relapse risk in patients with LS-HL achieving PET- and informs decision-making around risk-adapted application of radiotherapy. The trials were registered at www.clinicaltrials.gov as #NCT00943423 and #NCT00433433.
AB - Tumor bulk is an established prognostic factor in Hodgkin lymphoma (HL), but most patients with limited-stage (LS) HL do not have "bulk" by standard definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with relapse risk in LS-HL patients achieving positron emission tomography negativity (PET-) after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We aimed to externally validate these findings in the H10 trial. Stage I/IIA HL patients, without mediastinal bulk, who achieved PET- with ABVD were included. Patients received 3 ABVD plus radiotherapy (n = 208) or 3 ABVD alone (n = 211) in RAPID, and 3 to 4 ABVD plus radiotherapy (n = 556) or 4 to 6 ABVD alone (n = 303) in H10. MTD was strongly associated with event-free survival (relapse or HL-related death) in H10 (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.07-1.38; P = .003), a similar effect to that seen in RAPID (HR, 1.19; 95% CI, 1.02-1.39; P = .02), giving an estimated 21% risk increase per centimeter MTD (HRpooled, 1.21; 95% CI, 1.09-1.33; P < .001). Effect sizes were similar for patients treated with ABVD alone and ABVD plus radiotherapy, with no differential effect (pinteraction = 0.97). Treatment modality and MTD were independent risk factors; patients with higher MTD receiving chemotherapy alone had the greatest relapse risk. This international validation study confirms MTD is strongly associated with relapse risk in patients with LS-HL achieving PET- and informs decision-making around risk-adapted application of radiotherapy. The trials were registered at www.clinicaltrials.gov as #NCT00943423 and #NCT00433433.
KW - Adolescent
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Bleomycin/therapeutic use
KW - Dacarbazine/therapeutic use
KW - Doxorubicin/therapeutic use
KW - Female
KW - Hodgkin Disease/pathology
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Neoplasm Staging
KW - Positron-Emission Tomography
KW - Prognosis
KW - Recurrence
KW - Risk Factors
KW - Tumor Burden
KW - Vinblastine/therapeutic use
KW - Young Adult
UR - https://pubmed.ncbi.nlm.nih.gov/39774828/
U2 - 10.1182/bloodadvances.2024015140
DO - 10.1182/bloodadvances.2024015140
M3 - Article
C2 - 39774828
SN - 2473-9529
VL - 9
SP - 2266
EP - 2274
JO - Blood advances
JF - Blood advances
IS - 9
ER -