Cytogenetic biodosimetry for radiotherapy: anthropomorphic phantom-based dose-response calibration and in vivo evaluation

OBJECTIVES: Cytogenetic biodosimetry has limited applicability in radiobiological monitoring of radiotherapy due to methodological constraints. To address this problem, we developed and evaluated an inverse biodosimetry approach that included cytogenetic dose-response curve (DRC) construction using an anthropomorphic tissue-equivalent phantom. METHODS: Peripheral blood from a healthy donor was irradiated in vitro with 6 MV linac photons inside a RANDO phantom, reproducing dose distributions of a single radiotherapy fraction for glioblastoma or breast cancer with planned target volume doses 2.0 and 2.67 Gy, respectively. The resulting DRC for dicentric plus centric ring (Dic+CR) yield was fitted to the linear-quadratic model. Its applicability was explored using individual dose-volume data from 12 radiotherapy patients (5 glioblastoma, 7 breast cancer) to calculate expected Dic+CR yields, which were compared with aberration yields observed after the first treatment fraction. RESULTS: The phantom-based DRC showed good agreement with the linear-quadratic model across the investigated dose range. Expected Dic+CR yields calculated from patient-specific dose-volume data were of the same order of magnitude as the observed yields but were lower in 10 of 12 patients. The association between expected and observed yields was positive but not statistically significant (r = 0.39, p = 0.21). CONCLUSIONS: The proof-of-concept for inverse cytogenetic biodosimetry using phantom-based DRC in radiotherapy patients was achieved. Further studies in larger patient cohorts are required to evaluate the influence of in vivo-specific biological factors. ADVANCES IN KNOWLEDGE: This is the first study integrating an phantom-based cytogenetic DRC with patient-specific dose-volume data for chromosomal biodosimetry in radiotherapy context.