Re-evaluating the α/β ratio in 2026: A systematic review and quantitative reappraisal in the era of molecular radiobiology.

Abstract

The linear-quadratic (LQ) model and its derived ratio, α/β, have served as the cornerstone of radiotherapy dose-fractionation decisions. The period from 2015 to 2026 has witnessed a substantial re-evaluation of this paradigm, driven by the clinical success of hypofractionation in prostate and breast cancer, stereotactic body radiation therapy (SBRT), and radiogenomics. A systematic review with narrative synthesis was conducted to evaluate quantitative estimates of α/β derived from clinical and preclinical studies over the last decade, updating classical assumptions using modern trial data. Extensive Phase III data in prostate cancer consistently define an α/β of 1.2 to 2.0 Gy. Microscopic models in breast cancer align with an α/β of ∼2.7 Gy. Conversely, lung SBRT data present a high modeled α/β driven by hypoxia artifacts. Genomic integration via the Genomic Adjusted Radiation Dose (GARD) reveals that α/β operates as a dynamic, patient-specific phenotype. In the molecular era, static α/β assumptions must be integrated with disease-specific kinetics, microenvironmental data, and genomic intrinsic radiosensitivity.