A Biological-Driven Approach to Explore Dose-Escalated Ultra-Hypofractionation in Breast Cancer Radiotherapy

To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model.