Abstract
The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy.
Highlights
ResultsMore than 50% of cancer patients receive radiotherapy in their course of disease
The quality control further consisted of a tissue equivalent water phantom-based physical dosimetry, which is currently employed for dose verification of patient plans [4]
The analysis indicated that the number of initial radiation induced foci (RIF) at early time point (0.5 hour post-irradiation) was lower in the cells irradiated with low LETd beams in comparison to the cells irradiated with higher LETd (12C and 16O)
Summary
ResultsMore than 50% of cancer patients receive radiotherapy in their course of disease. In addition to precision and physical characteristics, specific biological properties of different ion species (e.g. helium-, carbon-, neon-, silicon- or argon ions) to circumvent tumor radioresistance mechanisms, were postulated by pioneering experiments conducted at Lawrence Berkeley Laboratory [2]. After implementation of cutting-edge technological approaches, such as raster scanning method, the Heidelberg Ion-Beam therapy Center (HIT) provides the opportunity for a back to back comparison of four promising radiation qualities, i.e., proton (1H), helium(4H), carbon- (12C) and oxygen ions (16O). Based on currently mostly advanced physical planning models in-silico, Monte Carlo (MC) simulations [3] of prescribed dose for each ion source were conducted. The quality control further consisted of a tissue equivalent water phantom-based physical dosimetry, which is currently employed for dose verification of patient plans [4]. The prescribed physical dose was correlated with clonogenic cell survival as the gold standard radiobiological readout [5]
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