Purpose: Proton radiotherapy has been booming since the new millennium. Contemporary proton dosimetry is to use Relative Biological Effectiveness (RBE=1.1) factor to convert reference photon dose to perspective proton dose regardless treatment strategies. This shortcut simplifies proton dosimetry into an add-on to the existing photon dosimetry, causing dose uncertainties in fractionated strategies. As a direct-ionization modality, protons essentially differ from X-rays/γ-rays in cell-killing mechanism. In this study, we intended to establish direct proton dosimetry for fractionated treatment strategies.
Methods: Unlike X-rays/γ-rays, the cellular survival percentage for proton is a straight line in logarithm scale against dose, hence escalation doses remain a straight line. Different fractional strategies are mathematically equivalent if they have the same escalated doses, regardless of number of fractions or fractional dose in each strategy. This dose invariance feature is essential for fractionation themes in proton dosimetry. In X-rays/γ-rays dosimetry, biological effective dose (BED) is used to compare 2 conventional fractionation (CF) themes, but the endpoints are different due to approximation with LQ modeling. In proton dosimetry, the endpoint is identical (mono-endpoint), and no approximation is needed.
Results: We evaluated dose uncertainties and deviation of endpoint of using fixed RBE=1.1 in all fractionated themes, referencing to direct proton dosimetry. For CF the dose uncertainties are minimal. For hyper-fractionation, the real RBE>1.1, hence using fixed RBE will overdose. For hypo-fractionation, SBRT and SRS, the real RBE<1.1, hence using fixed RBE will be under-dosed, and the uncertainties increase with decrease of number of fractions for same endpoint.
Conclusion: We established an independent proton dosimetry with high precision based on radiobiological nature, in which dose invariance and mono-endpoint are 2 essential features. We evaluate dose uncertainties for all fractionated themes using fixed RBE=1.1. For its accuracy, proton dosimetry could be used as the primary reference in radiotherapy, rather than vice versa.