Omission of Radiation Therapy is Associated with Inferior Disease Control in High Risk Early-Stage Hodgkin Lymphoma:

Early-stage classical Hodgkin lymphoma (HL) is highly curable, yet optimal frontline treatment remains contested. Combined modality therapy (CMT) with chemotherapy followed by radiotherapy (RT) has been the standard, but concern over RT-associated toxicities has driven adoption of chemotherapy-alone approaches despite randomized trials failing to demonstrate noninferiority with RT omission. We analyzed 810 adult patients treated across eight academic centers for stage I/II HL between 1/2012 and 1/2022, comparing outcomes with CMT and chemotherapy alone. Primary endpoints were progression-free (PFS) and overall survival (OS); propensity-score matching was conducted to homogenize baseline characteristics between the groups, and subgroup analyses were conducted to identify clinical features associated with differential benefit. Among 480 propensity-matched patients, five-year OS was 98.6% with CMT versus 97.3% with chemotherapy alone (p=0.620); five-year PFS was 87.2% vs 81.4% (p=0.053). CMT conferred significantly superior PFS in patients with bulky disease (91.8% vs 73.0%; HR 3.77; p=0.005) and interim (iPET)-positive disease (Deauville score (DS)≥4; 74.9% vs 51.9%; HR 2.97; p=0.020). iPET response was the strongest independent predictor of both progression (HR 7.02) and mortality (HR 6.97), with PFS declining markedly across DS groups (DS1-2: 92.2%; DS3: 79.4%; DS4-5: 46.4%). Among iPET-positive patients, those receiving unplanned consolidative RT required less salvage therapy than those managed with chemotherapy escalation alone (29.0% vs. 45.2%; p=0.037). Late toxicities were more frequent with CMT, though 69% of second malignancies occurred outside the RT field. These findings support risk-adapted, biomarker-driven treatment selection and the need for prospective trials incorporating modern RT techniques and iPET-adapted algorithms.

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Journal
Blood Advances
Published
2026-10-28
DOI
https://doi.org/10.1182/bloodadvances.2026021839
Primary Topic
Lymphoma Diagnosis and Treatment
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article
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article

Omission of Radiation Therapy is Associated with Inferior Disease Control in High Risk Early-Stage Hodgkin Lymphoma:

Jordan S. Carter, Jakub Svoboda, Joachim Yahalom, Tatyana A. Feldman et al.
Blood Advances
Lymphoma Diagnosis and Treatment
article

Omission of Radiation Therapy is Associated with Inferior Disease Control in High Risk Early-Stage Hodgkin Lymphoma:

Jordan S. Carter, Jakub Svoboda, Joachim Yahalom, Tatyana A. Feldman, Elise A. Chong, Stefan Klaus Barta, Brandon S. Imber, Boyu Hu, Meryl D. Colton, Nikita Dave, Maria Katerina Alfaro, Daniel Jeffrey Landsburg, Beatrice Fregonese, Joanna Meehan Rhodes, Abhiraj Saxena, Alison J. Moskowitz, Michael Roderick Cook, Michael Joseph Lariviere, Emily B. Tomasulo, Harper Hubbeling, Rachel L. Koch, Nicole Birrer, Behzad Amoozgar, Stephen J. Schuster, Carrie Ho, Sunita Dwivedy Nasta, Nirav Niranjan Shah, John Peter Plastaras, Zachary AK Frosch, Ashley Dunton, Colin J Thomas, Reid M. Muenzen, Amelia Mantione, Alexandra Danielle Dreyfuss
article en

Abstract

Early-stage classical Hodgkin lymphoma (HL) is highly curable, yet optimal frontline treatment remains contested. Combined modality therapy (CMT) with chemotherapy followed by radiotherapy (RT) has been the standard, but concern over RT-associated toxicities has driven adoption of chemotherapy-alone approaches despite randomized trials failing to demonstrate noninferiority with RT omission. We analyzed 810 adult patients treated across eight academic centers for stage I/II HL between 1/2012 and 1/2022, comparing outcomes with CMT and chemotherapy alone. Primary endpoints were progression-free (PFS) and overall survival (OS); propensity-score matching was conducted to homogenize baseline characteristics between the groups, and subgroup analyses were conducted to identify clinical features associated with differential benefit. Among 480 propensity-matched patients, five-year OS was 98.6% with CMT versus 97.3% with chemotherapy alone (p=0.620); five-year PFS was 87.2% vs 81.4% (p=0.053). CMT conferred significantly superior PFS in patients with bulky disease (91.8% vs 73.0%; HR 3.77; p=0.005) and interim (iPET)-positive disease (Deauville score (DS)≥4; 74.9% vs 51.9%; HR 2.97; p=0.020). iPET response was the strongest independent predictor of both progression (HR 7.02) and mortality (HR 6.97), with PFS declining markedly across DS groups (DS1-2: 92.2%; DS3: 79.4%; DS4-5: 46.4%). Among iPET-positive patients, those receiving unplanned consolidative RT required less salvage therapy than those managed with chemotherapy escalation alone (29.0% vs. 45.2%; p=0.037). Late toxicities were more frequent with CMT, though 69% of second malignancies occurred outside the RT field. These findings support risk-adapted, biomarker-driven treatment selection and the need for prospective trials incorporating modern RT techniques and iPET-adapted algorithms.

Blood Advances
Rutgers, The State University of New Jersey (US), Fox Chase Cancer Center (US), Hackensack University Medical Center (US), Memorial Sloan Kettering Cancer Center (US), University of Miami (US), University of California, San Francisco (US), Medical College of Wisconsin (US), University of Utah (US), Hospital of the University of Pennsylvania (US), Huntsman Cancer Institute (US), UCSF Helen Diller Family Comprehensive Cancer Center (US), Abramson Cancer Center (US), Rutgers Cancer Institute (US), Medical College of Wisconsin Cancer Center (US), Drexel University (US), University of Pennsylvania (US)
Good health and well-being
Openalex Percentile: Top 13%
Lymphoma Diagnosis and Treatment
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