Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called “indirect” damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our under-standing of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Purpose In all recent protocols for the reference dosimetry of clinical proton beams, ionization chamber perturbation factors are assumed to be unity. In this work, such factors were computed using the FLUKA Monte Carlo code for three ionization chamber types, with particular attention to the influence of nuclear interactions. Methods The accuracy of the transport algorithms implemented in FLUKA was first evaluated by performing a Fano cavity test. Ionization chamber perturbation factors were computed for the PTW‐34001 Roos® and the PTW‐34070 and PTW‐34073 Bragg peak® chambers for proton beams of 60–250 MeV using the same transport parameters that were needed to pass the Fano test. Results FLUKA was found to pass the Fano test within 0.15%. Ionization chamber simulation results show that the presence of the air cavity and the wall results in dose perturbations of the order of 0.6% and 0.8%, respectively. The perturbation factors are shown to be energy dependent and nuclear interactions must be taken into account for accurate calculation of the ionization chamber's response. Conclusion Ionization chamber perturbations can amount to 1% in high‐energy proton beams and therefore need to be considered in dosimetry procedures.

The interest in proton and ion-beam therapy has increased substantially in recent years, leading the Bureau International des Poids et Mesures to recommend that a new quantity be defined to account for the biological effect of treatment modalities used in the radiotherapy. In response, we have begun work on the design of a new microbolometer based on the inductive superconducting transition-edge detector (ISTED) designed at the National Physical Laboratory. Our work aims to expand the use of the ISTED from its current use as an infra-red detector to the measurement of energy deposition of photons, hadrons and ions by incorporating a tissue-equivalent absorber. We present here the work carried out till date, including the detection of single visible photons, with an energy resolution of 0.2 eV and a time response of a few microseconds, using a 15-µm Superconducting QUantum Interference Device operating at 9 K. We also describe thermal computational modelling carried out for a simple ISTED absorber. Finally, we discuss the work currently in progress and that to be carried out before the detector is realised.