Prediction of normal tissue complication probability for rat spinal cord tolerance following ion irradiations.

Currently, treatment planning in cancer hadrontherapy relies on dose-volume criteria and physical quantities constraints. However, incorporating biologically related models of tumor control probability and of normal tissue complication probability (NTCP) would help further minimizing adverse tissue reactions, and would allow achieving a more patient-specific strategy. The aim of this work was therefore the development of a mechanistic approach to predict NTCP for late tissue reactions following ion irradiation.

Radiation exposure of astronauts following an intense solar particle event: analysis and comparison of doses in male and female voxel phantoms.

According to NASA's plans, a human travel to the Moon is planned by the end of 2025 with the Artemis II mission, and humans should land on the Moon again in 2026. Exposure to space radiation is one of the main risks for the crew members; while for these short missions the doses from galactic cosmic rays would be relatively low, the possible occurrence of an intense solar particle event (SPE) represents a major concern, especially considering that in 2025 the Sun activity will be at its peak. Quantifying the amount and the effects of such exposure is therefore crucial, to identify shielding conditions that allow respecting the dose limits established by the various space agencies.

Radiation Damage in Biomolecules and Cells 3.0.

Ionizing radiation is widely used in medicine, not only as a diagnostic tool but also as a therapeutic agent, since about half of cancer patients are treated with ionizing radiation, while most of them are irradiated with X-rays [...

Radiation Damage in Biomolecules and Cells 2.0.

It is well known that ionizing radiation, when it hits living cells, causes a plethora of different damage types at different levels [...

A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits.

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer.

The innovative Mn for positron emission tomography (PET) imaging: Production cross section modeling and dosimetric evaluation.

Background: Manganese is a paramagnetic element suitable for magnetic resonance imaging (MRI) of neuronal function. However, high concentrations of Mn can be neurotoxic. Mn may be a valid alternative as positron emission tomography (PET) imaging agent, to obtain information similar to that delivered by MRI but using trace levels of Mn , thus reducing its toxicity.

First application of the BIANCA biophysical model to carbon-ion patient cases.

The main objective of this work consists of applying, for the first time, the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the RBE calculation for C-ion cancer patients, and comparing the outcomes with those obtained by the LEM I model, which is applied in clinics. Indeed, the continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The relative biological effectiveness (RBE) of heavy ions is higher than that of protons, with a significant variation along the beam path.

Radiobiological damage by space radiation: extension of the BIANCA model to heavy ions up to iron, and pilot application to cosmic ray exposure.

Space research seems to be object of a renewed interest, also considering that human missions to the Moon, and possibly Mars, are being planned. Among the risks affecting such missions, astronauts' exposure to space radiation is a major concern. In this work, the question of the evaluation of biological damage by Galactic Cosmic Rays (GCR) was addressed by a biophysical model called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), which simulates the induction of cell death and chromosome aberrations by different ions.

Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model.

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells.

Radiation Damage in Biomolecules and Cells.

Ionizing radiation is widely used in medicine, both as a diagnostic tool and as a therapeutic agent [...

In Vivo Validation of the BIANCA Biophysical Model: Benchmarking against Rat Spinal Cord RBE Data.

(1) Background: Cancer ion therapy is constantly growing thanks to its increased precision and, for heavy ions, its increased biological effectiveness (RBE) with respect to conventional photon therapy. The complex dependence of RBE on many factors demands biophysical modeling. Up to now, only the Local Effect Model (LEM), the Microdosimetric Kinetic Model (MKM), and the "mixed-beam" model are used in clinics.

PREDICTING BIOLOGICAL EFFECTS ALONG HADRONTHERAPY DOSE PROFILES BY THE BIANCA BIOPHYSICAL MODEL.

The BIANCA biophysical model of cell death and chromosome aberrations was further refined and applied to predict the biological effectiveness along Spread-Out Bragg Peaks used in hadrontherapy. The simulation outcomes were compared with in vitro survival data on protons, He-ions and C-ions over a wide LET range, and the particle- and LET-dependence of the DNA Cluster Lesions (CLs) yields used as input parameters was investigated. For each particle type, the CL yield was found to increase with LET in a linear-quadratic fashion; fitting the CL yields allowed to predict cell death and chromosome aberrations in principle at any depth along a longitudinal proton dose profile used at CNAO.

Analysis of Radiation-Induced Chromosomal Aberrations on a Cell-by-Cell Basis after Alpha-Particle Microbeam Irradiation: Experimental Data and Simulations.

There is a continued need for further clarification of various aspects of radiation-induced chromosomal aberration, including its correlation with radiation track structure. As part of the EMRP joint research project, Biologically Weighted Quantities in Radiotherapy (BioQuaRT), we performed experimental and theoretical analyses on chromosomal aberrations in Chinese hamster ovary cells (CHO-K1) exposed to α particles with final energies of 5.5 and 17.

BIANCA, a biophysical model of cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy.

An upgraded version of the BIANCA II biophysical model, which describes more realistically interphase chromosome organization and the link between chromosome aberrations and cell death, was applied to V79 and AG01522 cells exposed to protons, C-ions and He-ions over a wide LET interval (0.6-502 keV µm), as well as proton-irradiated U87 cells. The model assumes that (i) ionizing radiation induces DNA 'cluster lesions' (CLs), where by definition each CL produces two independent chromosome fragments; (ii) fragment (distance-dependent) mis-rejoining, or un-rejoining, produces chromosome aberrations; (iii) some aberrations lead to cell death.

Proximity effects in chromosome aberration induction: Dependence on radiation quality, cell type and dose.

It is widely accepted that, in chromosome-aberration induction, the (mis-)rejoining probability of two chromosome fragments depends on their initial distance, r. However, several aspects of these "proximity effects" need to be clarified, also considering that they can vary with radiation quality, cell type and dose. A previous work performed by the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model has suggested that, in human lymphocytes and fibroblasts exposed to low-LET radiation, an exponential function of the form exp(-r/r), which is consistent with free-end (confined) diffusion, describes proximity effects better than a Gaussian function.

Proximity effects in chromosome aberration induction by low-LET ionizing radiation.

Although chromosome aberrations are known to derive from distance-dependent mis-rejoining of chromosome fragments, evaluating whether a certain model describes such "proximity effects" better than another one is complicated by the fact that different approaches have often been tested under different conditions. Herein, a biophysical model ("BIANCA", i.e.

Calculating Variations in Biological Effectiveness for a 62 MeV Proton Beam.

A biophysical model of radiation-induced cell death and chromosome aberrations [called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA)] was further developed and applied to therapeutic protons. The model assumes a pivotal role of DNA cluster damage, which can lead to clonogenic cell death following three main steps: (i) a DNA "cluster lesion" (CL) produces two independent chromosome fragments; (ii) fragment mis-rejoining within a threshold distance d gives rise to chromosome aberrations; (iii) certain aberration types (dicentrics, rings, and large deletions) lead to clonogenic inactivation. The yield of CLs and the probability, f, that a chromosome fragment remains un-rejoined even if other fragment(s) are present within d, were adjustable parameters.

The BIANCA model/code of radiation-induced cell death: application to human cells exposed to different radiation types.

This paper presents a biophysical model of radiation-induced cell death, implemented as a Monte Carlo code called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), based on the assumption that some chromosome aberrations (dicentrics, rings, and large deletions, called ‘‘lethal aberrations’’) lead to clonogenic inactivation. In turn, chromosome aberrations are assumed to derive from clustered, and thus severe, DNA lesions (called ‘‘cluster lesions,’’ or CL) interacting at the micrometer scale; the CL yield and the threshold distance governing CL interaction are the only model parameters. After a pilot study on V79 hamster cells exposed to protons and carbon ions, in the present work the model was extended and applied to AG1522 human cells exposed to photons, He ions, and heavier ions including carbon and neon.