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Multicenter Study
. 2019 Sep:47:163-169.
doi: 10.1016/j.ebiom.2019.08.019. Epub 2019 Aug 12.

Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management

Kamran A Ahmed  1 , Casey L Liveringhouse  1 , Matthew N Mills  1 , Nicholas B Figura  1 , G Daniel Grass  1 , Iman R Washington  1 , Eleanor E Harris  2 , Brian J Czerniecki  3 , Peter W Blumencranz  4 , Steven A Eschrich  5 , Jacob G Scott  6 , Roberto Diaz  7 , Javier F Torres-Roca  8
Affiliations
Multicenter Study

Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management

Kamran A Ahmed et al. EBioMedicine. 2019 Sep.

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.

Keywords: Breast cancer; Genomically adjusted radiation dose; Personalized radiotherapy; Radiotherapy.

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Conflict of interest statement

Steven A. Eschrich PhD and Javier F. Torres-Roca MD report stock and leadership in Cvergenx, Inc. and royalty and patents on RSI. Javier F. Torres-Roca MD and Jacob G. Scott MD PhD report royalty and patents on GARD.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curve for local control in triple negative patients (cohort 1) according to GARD high (≥23.2) and GARD low (<23.2) categories.
Fig. 2
Fig. 2
Kaplan-Meier curve for local control in triple negative patients (cohort 2) according to GARD high (≥21) and GARD low (<21) categories.
Fig. 3
Fig. 3
Model for the percentage of triple negative patients in cohort 2 achieving GARD high with doses between 30 and 70 Gy.
See this image and copyright information in PMC

References

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