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Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management.
EBioMedicine 2019; 47:163-169E

Abstract

BACKGROUND

Utilizing the linear quadratic model and the radiosensitivity index (RSI), we have derived an expression for the genomically adjusted radiation dose (GARD) to model radiation dose effect. We hypothesize GARD is associated with local recurrence and can be used to optimize individual triple negative breast cancer (TNBC) radiation dose.

METHODS

TN patients from two independent datasets were assessed. The first cohort consisted of 58 patients treated at 5 European centers with breast conservation surgery followed by adjuvant radiotherapy (RT). The second dataset consisted of 55 patients treated with adjuvant radiation therapy.

FINDINGS

In cohort 1, multivariable analysis revealed that as a dichotomous variable (HR: 2.5 95% CI 1-7.1; p = .05), GARD was associated with local control. This was confirmed in the second independent dataset where GARD was the only significant factor associated with local control (HR: 4.4 95% CI 1.1-29.5; p = .04). We utilized GARD to calculate an individualized radiation dose for each TN patient in cohort 2 by determining the physical dose required to achieve the GARD target value (GARD ≥ 21). While 7% of patients were optimized with a dose of 30 Gy, 91% of patients would be optimized with 70 Gy.

INTERPRETATION

GARD is associated with local control following whole breast or post-mastectomy radiotherapy (RT) in TN patients. By modeling RT dose effect with GARD, we demonstrate that no single dose is optimal for all patients and propose the first dose range to optimize RT at an individual patient level in TNBC.

Authors+Show Affiliations

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Case Western Reserve University, Department of Radiation Oncology, Cleveland, OH 44106, USA.Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Morton Plant Hospital, Clearwater, FL 33756, USA.Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.Cleveland Clinic, Department of Radiation Oncology, Cleveland, OH 44195, USA.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address: Roberto.diaz@moffitt.org.Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address: javier.torresroca@moffitt.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31416721

Citation

Ahmed, Kamran A., et al. "Utilizing the Genomically Adjusted Radiation Dose (GARD) to Personalize Adjuvant Radiotherapy in Triple Negative Breast Cancer Management." EBioMedicine, vol. 47, 2019, pp. 163-169.
Ahmed KA, Liveringhouse CL, Mills MN, et al. Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management. EBioMedicine. 2019;47:163-169.
Ahmed, K. A., Liveringhouse, C. L., Mills, M. N., Figura, N. B., Grass, G. D., Washington, I. R., ... Torres-Roca, J. F. (2019). Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management. EBioMedicine, 47, pp. 163-169. doi:10.1016/j.ebiom.2019.08.019.
Ahmed KA, et al. Utilizing the Genomically Adjusted Radiation Dose (GARD) to Personalize Adjuvant Radiotherapy in Triple Negative Breast Cancer Management. EBioMedicine. 2019;47:163-169. PubMed PMID: 31416721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management. AU - Ahmed,Kamran A, AU - Liveringhouse,Casey L, AU - Mills,Matthew N, AU - Figura,Nicholas B, AU - Grass,G Daniel, AU - Washington,Iman R, AU - Harris,Eleanor E, AU - Czerniecki,Brian J, AU - Blumencranz,Peter W, AU - Eschrich,Steven A, AU - Scott,Jacob G, AU - Diaz,Roberto, AU - Torres-Roca,Javier F, Y1 - 2019/08/12/ PY - 2019/06/27/received PY - 2019/08/01/revised PY - 2019/08/07/accepted PY - 2019/8/17/pubmed PY - 2019/8/17/medline PY - 2019/8/17/entrez KW - Breast cancer KW - Genomically adjusted radiation dose KW - Personalized radiotherapy KW - Radiotherapy SP - 163 EP - 169 JF - EBioMedicine JO - EBioMedicine VL - 47 N2 - BACKGROUND: Utilizing the linear quadratic model and the radiosensitivity index (RSI), we have derived an expression for the genomically adjusted radiation dose (GARD) to model radiation dose effect. We hypothesize GARD is associated with local recurrence and can be used to optimize individual triple negative breast cancer (TNBC) radiation dose. METHODS: TN patients from two independent datasets were assessed. The first cohort consisted of 58 patients treated at 5 European centers with breast conservation surgery followed by adjuvant radiotherapy (RT). The second dataset consisted of 55 patients treated with adjuvant radiation therapy. FINDINGS: In cohort 1, multivariable analysis revealed that as a dichotomous variable (HR: 2.5 95% CI 1-7.1; p = .05), GARD was associated with local control. This was confirmed in the second independent dataset where GARD was the only significant factor associated with local control (HR: 4.4 95% CI 1.1-29.5; p = .04). We utilized GARD to calculate an individualized radiation dose for each TN patient in cohort 2 by determining the physical dose required to achieve the GARD target value (GARD ≥ 21). While 7% of patients were optimized with a dose of 30 Gy, 91% of patients would be optimized with 70 Gy. INTERPRETATION: GARD is associated with local control following whole breast or post-mastectomy radiotherapy (RT) in TN patients. By modeling RT dose effect with GARD, we demonstrate that no single dose is optimal for all patients and propose the first dose range to optimize RT at an individual patient level in TNBC. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/31416721/Utilizing_the_genomically_adjusted_radiation_dose_(GARD)_to_personalize_adjuvant_radiotherapy_in_triple_negative_breast_cancer_management L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(19)30537-7 DB - PRIME DP - Unbound Medicine ER -