PURPOSE: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS: Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS: Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.

Arthur JE Child Comprehensive Cancer Centre Calgary Alberta Canada

Clinical Biostatistics Fred Hutchinson Cancer Research Center Seattle Washington

Department of Radiation Medicine OHSU Portland Oregon

Department of Radiation Oncology British Columbia Cancer Vancouver Centre Vancouver Canada

Department of Radiation Oncology H Lee Moffitt Cancer Center and Research Institute Tampa Florida

Department of Radiation Oncology Massachusetts General Hospital Boston Massachusetts

Department of Radiation Oncology MDACC Houston Texas

Department of Radiation Oncology Stanford University School of Medicine Stanford California

Department of Radiation Oncology University of Pennsylvania Philadelphia Pennsylvania

Department of Radiation Oncology University of Pennsylvania Philadelphia Pennsylvania; Merck Rahway New Jersey

Department of Radiation Oncology University of Washington Seattle Washington; Radiation Oncology Divisioin Fred Hutchinson Cancer Center Seattle Washington

Department of Radiation Oncology University of Washington Seattle Washington; Radiation Oncology Divisioin Fred Hutchinson Cancer Center Seattle Washington; Radiation Oncology Duke Cancer Institute Durham North Carolina

Division of Hematology Oncology Hospital of the University of Pennsylvania Philadelphia Pennsylvania

Proton Therapy Center Czech Budinova Praha Cezech Republic

Radiation Oncology Department Cedars Sinai Los Angeles California

Radiation Oncology Duke Cancer Institute Durham North Carolina

UT Southwestern Medical Center Dallas Texas

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