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We introduce an approach for global fitting of the recently publishedhigh-throughput and high accuracy clonogenic cell-survival data for therapeuticscanned proton beams. Our fitting procedure accounts for the correlationbetween the cell-survival, the absorbed (physical) dose and the proton linearenergy transfer (LET). The fitting polynomials and constraints have beenconstructed upon generalization of the microdosimetric kinetic model (gMKM)adapted to account for the low energy and high lineal-energy spectrum of thebeam where the current radiobiological models may underestimate the reportedrelative biological effectiveness (RBE). The parameters ({\alpha},\b{eta}) ofthe linear-quadratic (LQ) model calculated by the presented method reveal asmooth transition from low to high LETs which is an advantage of the currentmethod over methods previously employed to fit the same clonogenic data.Finally, the presented approach provides insight into underlying microscopicmechanisms which, with future study, may help to elucidate radiobiologicalresponses along the Bragg curve and resolve discrepancies between experimentaldata and current RBE models.

A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data