Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer managementResearch in context
Kamran A. Ahmed,
Casey L. Liveringhouse,
Matthew N. Mills,
Nicholas B. Figura,
G. Daniel Grass,
Iman R. Washington,
Eleanor E. Harris,
Brian J. Czerniecki,
Peter W. Blumencranz,
Steven A. Eschrich,
Jacob G. Scott,
Roberto Diaz,
Javier F. Torres-Roca
Affiliations
Kamran A. Ahmed
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Casey L. Liveringhouse
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Matthew N. Mills
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Nicholas B. Figura
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
G. Daniel Grass
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Iman R. Washington
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Eleanor E. Harris
Case Western Reserve University, Department of Radiation Oncology, Cleveland, OH 44106, USA
Brian J. Czerniecki
Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Peter W. Blumencranz
Morton Plant Hospital, Clearwater, FL 33756, USA
Steven A. Eschrich
Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Jacob G. Scott
Cleveland Clinic, Department of Radiation Oncology, Cleveland, OH 44195, USA
Roberto Diaz
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Corresponding authors at: H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, 12902 Magnolia Dr., Tampa, FL 33612, USA.
Javier F. Torres-Roca
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; Corresponding authors at: H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, 12902 Magnolia Dr., Tampa, FL 33612, USA.
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. Keywords: Genomically adjusted radiation dose, Personalized radiotherapy, Radiotherapy, Breast cancer
