Optimizing heart and lung sparing in synchronous bilateral breast cancer radiotherapy: a dosimetric and radiobiological analysis of three different fractionation schedules

This study aimed to compare and evaluate ultra-hypofractionation (UHF), hypofractionation (HF), and conventional fractionation (CF) schedules in synchronous bilateral breast cancer radiotherapy (SBBC), focusing on dosimetric parameters impact on lungs, Heart and associated NTCP values. A retrospective analysis was conducted on five patients with SBBC. Three fractionation schedules were evaluated UHF: 26Gy/5, HF: 40.05Gy/15 and CF 50Gy/25. Treatment plans were generated for each schedule using VMAT planning techniques with dual isocenter. Dosimetric parameters were evaluated using the Kruskal-Wallis H-test. Normal tissue complication probability (NTCP) was assessed using Poisson-LQ and Lyman-Kutcher-Berman models. Biological Effective Dose (BED) and Equivalent Dose in 2 Gy fractions (EQD2) were calculated for radiobiological comparisons. Correlations between dose-volume parameters and NTCP values were analyzed. Significant reductions were observed in V105CC, Homogeneity Index, and Body D2CC for the right PTV from CF to UHF (p<0.05). OAR dose-volume parameters demonstrated a parabolic variation (x2) with prescribed dose, with all evaluated parameters showing statistically significant differences across fractionation schedules (p<0.01). Strong positive correlations were observed between dose-volume parameters across fractionation schedules (r=0.989-1.0 for lung parameters). Dose-volume parameters strongly correlated with NTCP values for lung-related endpoints (r > 0.985, p < 0.001). NTCP models revealed decreased risks with UHF compared to CF and HF, with grade ≥2 radiation pneumonitis probabilities ranging from 2.69-6.80% and symptomatic fibrosis probabilities from 22.45-38.91%, both increasing from UHF to CF. BED and EQD2 calculations demonstrated higher biological effectiveness for late-responding tissues in CF, while effects on tumor control were more consistent across fractionation schemes. UHF demonstrates superior OAR sparing and reduced NTCP compared to HF and CF, while maintaining comparable tumor control probability. These findings support the potential of UHF as a safe and effective approach in SBBC radiotherapy, offering improved normal tissue protection without compromising treatment efficacy. (author)