Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Time-resolved dosimetry with pencil-beam scanning for quality assurance/quality control in particle therapy.

This study aimed to measure dose in a scanning carbon beam-irradiation field with high sampling rate that is sufficient for identifying spots and verifying the characteristics of the scanning beam that cannot generally be derived from the dose. To identify the spot, which is the smallest control unit of beam information during irradiation, effecting measurements with a sampling time of 10 µs or shorter is necessary. The provided dose within a specific time is referred to as time-resolved dose (TRD). We designed a circuit for time-resolved dosimetry using a fast-data acquisition unit (SL1000, Yokogawa Electric Co.), which can measure 100 000 samples per second. Moreover, we used converters to enable a connection between an ionization chamber (IC) and the SL1000. TRD was measured successfully using point irradiation and two-dimensional irradiation patterns in a scanned carbon beam. Based on the moving time of the spot obtained from the position monitor, the dose delivered to the IC from each spot position (spot dose) was interpreted. The spot dose, displacement of the chamber from the beam's center axis, and beam size were derived using TRD and position monitor outputs, which were measured concurrent with TRD. Spot dose up to a radius of 8 mm area from the IC's center were observed. Using the spot-dose equations and simulation, we show that the spot dose of each position varies depending on the beam size and displacement of the IC's center from the beam's center axis. We devise an interpretation method for the characteristics that may apply to quality assurance, such as the verification of the trend for the beam axis and isocenter to coincide, as well as beam-size verification.

Study on the RBE estimation for carbon beam scanning irradiation using a solid-state microdosimeter.

PURPOSE: The purpose of this study was to study the field size effect on the estimated Relative Biological Effectiveness (RBE) for carbon scanning beam irradiation. METHODS: A silicon-on-insulator (SOI) microdosimeter system developed by the Centre for Medical Radiation Physics, University of Wollongong, Australia, was used for lineal-energy measurements (microdosimetric quantity). The RBE values were derived based on the modified microdosimetric kinetic model (MKM) at different depths in a water phantom in the scanning carbon beam for various scanned areas. RESULTS: Our study shows that the difference in RBE values derived from the SOI microdosimeter measurements with the MKM model and from the Treatment Planning System (TPS). The difference of the RBE values is within 6.5 % at the peak point of the spread-out Bragg Peak (SOBP) region. Compared to the spot-beam, RBE values obtained in the scanned-beam with a larger scanned area of 1.0 × 1.0 cm2 have better agreement with which estimated by the TPS. CONCLUSIONS: This study shows the possibility of using the SOI microdosimeter system as a quality assurance (QA) tool for RBE evaluation in carbon-pencil beam scanning radiotherapy.

Analysis of Neutron Production in Passively Scattered Ion-Beam Therapy.

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety.

Metformin enhances the radiosensitivity of human liver cancer cells to γ-rays and carbon ion beams.

The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt. Thus, metformin effectively enhanced the therapeutic effect of radiation with a wide range of LET, in particular carbon ion beams and it may be useful for increasing the clinical efficacy of carbon ion beams.