Revisiting fractionation in prostate carbon ion therapy: first comparative analysis of biologically effective dose using mMKM with diverse parameters.

BACKGROUND

Carbon ion radiotherapy (CIRT) for prostate cancer has evolved from conventional regimens [66 Gy(RBE)/20 fractions (66G20), 63 Gy(RBE)/20 fractions (63G20)] toward hypofractionated schedules [57.6 Gy(RBE)/16 fractions (57.6G16), 51.6 Gy(RBE)/12 fractions (51.6G12), and 40 Gy(RBE)/4 fractions (40G4)]. Whether these are biologically equivalent remains unclear. To our knowledge, this is the first study to systematically evaluate the biological effects of these regimens using the modified microdosimetric kinetic model (mMKM) across diverse parameter settings.

METHODS

Biologically effective dose (BED) was calculated using four approaches: (1) photon linear-quadratic (LQ) model (2), modified microdosimetric kinetic model (mMKM) with human salivary gland parameters and fixed RBE of 2.41 (3), mMKM3.1, and (4) mMKM with varied domain radius (0.2–0.5 μm) and α/β (1.5–10 Gy). Tumor control probability (TCP) was further estimated based on a reanalysis of the Ion Prostate Irradiation trial.

RESULTS

Photon LQ analysis suggested near-equivalent BEDs for 63G20, 57.6G16, and 51.6G12 (~ 200 Gy and ~ 130 Gy for α/β = 1.5 and 3 Gy), with 40G4 markedly higher. In contrast, all mMKM-based methods showed progressive BED reductions with hypofractionation versus 63G20 (–16.8% to − 11.3% for 51.6G12; − 30.4% to − 5.2% for 40G4). TCP decreased by 15.5% for 51.6G12 and 28.7% for 40G4. mMKM also yielded higher effective α/β values for CIRT, reflecting reduced fractionation sensitivity.

CONCLUSIONS

mMKM-based modeling challenges the assumption of dose equivalence in hypofractionated prostate CIRT, suggesting potential underdosing risks. This parameter-sensitive analysis underscores the need for biologically robust models to refine dose prescription and optimize outcomes in particle therapy. CLINICAL TRIAL NUMBER: Not applicable.