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Impact of Myc-Altered Pathology on Radiation Therapy Efficacy Among Patients With Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Study by ILROG

YD. Tseng, P. Stevenson, B. Nguyen, DC. Li, DY. Lee, I. Paydar, J. Nakashima, A. Balogh, R. Ravella, AB. Barbour, C. Post, H. Ababneh, CC. Pinnix, LK. Ballas, MS. Binkley, K. Dedeckova, RT. Hoppe, C. Patel, N. Nabavizadeh, CR. Kelsey, KA. Kumar,...

. 2025 ; 121 (5) : 1237-1247. [pub] 20241115

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, multicentrická studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc25009392

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.

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$a 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.
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$a Stevenson, Phil $u Clinical Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington
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$a Nguyen, Bachviet $u Department of Radiation Oncology, British Columbia Cancer, Vancouver Centre, Vancouver, Canada
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$a Li, Davey C $u Department of Radiation Oncology, British Columbia Cancer, Vancouver Centre, Vancouver, Canada
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$a Lee, Daniel Y $u Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
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$a Paydar, Ima $u Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; Merck, Rahway, New Jersey
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$a Nakashima, Justyn $u Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
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$a Balogh, Alex $u Arthur JE Child Comprehensive Cancer Centre, Calgary, Alberta, Canada
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$a Ravella, Revathi $u UT Southwestern Medical Center, Dallas, Texas
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$a Barbour, Andrew B $u Department of Radiation Oncology, University of Washington, Seattle, Washington; Radiation Oncology Divisioin, Fred Hutchinson Cancer Center, Seattle, Washington; Radiation Oncology, Duke Cancer Institute, Durham, North Carolina
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$a Post, Carl $u Department of Radiation Medicine, OHSU, Portland, Oregon
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$a Ababneh, Hazim $u Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
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$a Pinnix, Chelsea C $u Department of Radiation Oncology, MDACC, Houston, Texas
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$a Ballas, Leslie K $u Radiation Oncology Department, Cedars-Sinai, Los Angeles, California
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$a Binkley, Michael S $u Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
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$a Dedeckova, Katerina $u Proton Therapy Center Czech, Budinova, Praha, Cezech Republic
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$a Hoppe, Richard T $u Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
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$a Patel, Chirayu $u Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
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$a Nabavizadeh, Nima $u Department of Radiation Medicine, OHSU, Portland, Oregon
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$a Kelsey, Christopher R $u Radiation Oncology, Duke Cancer Institute, Durham, North Carolina
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$a Kumar, Kiran A $u UT Southwestern Medical Center, Dallas, Texas
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$a Landsburg, Daniel $u Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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$a Figura, Nicholas B $u Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
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$a Lo, Andrea C $u Department of Radiation Oncology, British Columbia Cancer, Vancouver Centre, Vancouver, Canada
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$a Plastaras, John P $u Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
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