Ion-beam radiotherapy is a growing cancer treatment modality because it offers a superior dose distribution in the patient compared with conventional radiotherapy using X-rays. Thanks to their versatility, application-specific integrated circuits (ASIC) increasingly gain interest for research into ion imaging and ion-beam characterisation. Timepix3 is a hybrid semiconductor pixel detector, which offers nanosecond time binning as well as dead-time-free and noise-free data-driven readout at a pixel pitch of 55µm × 55µm. In this work, a novel 4-chip Timepix3 mini-tracker (quad module) was characterised in a therapeutic proton beam. The quad module has two detection layers equipped with two Timepix3 chips each, which are stacked like a particle telescope at a distance of 20.3mm. In a detection layer, two Timepix3 chips share the same sensitive silicon sensor. The surface area of the silicon sensor is approximately 28mm × 14mm. Apart from the pixels at the chip edges and the masked pixels, the quad module showed a uniform counting response to the mono-energetic proton irradiation without noticeable defects. The measurement accuracy of the energy deposition was found to be better than 1% at 340keV. The synchronisation between the four chips of the quad module showed systematic delays of up to 25ns. When these delays are corrected, the time resolution of the quad module is (1.17 ± 0.03)ns. The time resolution could be further improved with the implementation of a time-walk correction. It is concluded that the quad module fulfils the requirements to be used as a charged-particle tracker in ion-beam radiotherapy. Future testing will focus on the radiation hardness, dose-rate dependence and response to high-LET radiation.

Objective . In this contribution we present a special Fano test for charged particles in presence of magnetic fields in the MC code TOol for PArticle Simulation (TOPAS), as well as the determination of magnetic field correction factors k B for Farmer-type ionization chambers using proton beams. Approach . Customized C++ extensions for TOPAS were implemented to model the special Fano tests in presence of magnetic fields for electrons and protons. The Geant4-specific transport parameters, DRoverR and finalRange, were investigated to optimize passing rate and computation time. The k B was determined for the Farmer-type PTW 30013 ionization chamber, and 5 custom built ionization chambers with same geometry but varying inner radius, testing magnetic flux density ranging from 0 to 1.0 T and two proton beam energies of 157.43 and 221.05 MeV. Main results . Using the investigated parameters, TOPAS passed the Fano test within 0.39 ± 0.15% and 0.82 ± 0.42%, respectively for electrons and protons. The chamber response ( k B,M,Q ) gives a maximum at different magnetic flux densities depending of the chamber size, 1.0043 at 1.0 T for the smallest chamber and 1.0051 at 0.2 T for the largest chamber. The local dose difference c B remained ≤ 0.1% for both tested energies. The magnetic field correction factor k B , for the chamber PTW 30013, varied from 0.9946 to 1.0036 for both tested energies. Significance . The developed extension for the special Fano test in TOPAS MC code with the adjusted transport parameters, can accurately transport electron and proton particles in magnetic field. This makes TOPAS a valuable tool for the determination of k B . The ionization chambers we tested showed that k B remains small (≤0.72%). To the best of our knowledge, this is the first calculations of k B for proton beams. This work represents a significant step forward in the development of MRgPT and protocols for proton dosimetry in presence of magnetic field.

Purpose/Objective(s)Differentiation between radiation-induced lung fibrosis (RILF) and tumor local recurrence (LR) remains challenging in SBRT treated NSCLC patients. We aimed to integrate spatially and time-resolved 4D radiomics with dosiomics biomarkers to develop a novel robust multi-omics classifier of LR vs RILF.Materials/Methods210 NSCLC patients (101/48% T1-2N0M0, 109/52% T1-3N1/xM0/x) treated with SBRT (median dose 60 Gy/8 fractions) between 2009 and 2019 were identified. Image-based quantitative features were extracted from the SBRT planning and follow-up (FU) CTs at the time point of diagnosis of LR/RILF or a matched time point for CTs without LR/RILF (radiomics) and from dose distributions (dosiomics). The region of interest was the planning target volume plus a 10mm margin (PTV+10mm). Time-dependent alterations of the radiomics features in FU CTs were integrated (delta-radiomics). To identify relevant features associated with RILF or LR, resampling (iterations = 1000) of feature selection methods were applied. An ensemble classifier comprising random forests, neural networks, and logistic regression was then trained. The area under the ROC curve (AUC) with a 70%/30% training/testing split and a 5-fold cross-validated AUC on the entire cohort were calculated for performance assessment at CT FU.ResultsOut of the 210, 36 patients (17%) were reported with LR and 44 (21%) with RILF. The median FU time was 19 months (range, 5-87). 20 LR and 23 RILF FU CTs, both with median time after SBRT of 15 months, were identified. 53 patients with matching clinical characteristics without LR/RILF (none), at matched FU time points (median time after SBRT: 17 months), were additionally selected, resulting in a cohort of 96 patients (20/21% LR, 23/24% RILF, 53/55% none). Discrimination of RILF versus LC using 4D radiomics features was achieved with a testing and 5-fold AUC of 0.82 [95%CI 0.79 0.86] and 0.85 [0.83 0.88]. The addition of a dosiomics feature improved performance to 0.85 [0.82 0.87] and 0.88 [0.85 0.91]. The PTV+10mm-based classifier includes 4 textural features (2 delta-radiomics, 1 radiomics from the FU CT and 1 dosiomics). A non-significant correlation was found between the significant features and tumor volume before RT (Spearman's r <0.1, p<0.05).ConclusionOur data indicate that integrative omics by combining radiotherapy volume and dose constraints with spatially and time-resolved radiomics may provide a novel mean for better discrimination of tumor recurrence vs RILF after SBRT.

An experimental campaign was carried out at the NASA Space Radiation Laboratory to perform an additional, independent dosimetric characterization of the beams of protons, helium and carbon ions for radiobiological experiments. The campaign was undertaken by the request and with the support from the National Cancer Institute, U.S. In this initial phase, the goals were to obtain a first assessment of the dosimetric reproducibility of the beam control system, including analysis of spatial homogeneity and evaluation of ion beam contamination. They should facilitate the design of further experimental campaigns for beam characterization for radiobiological experiments. Measurements included reference dosimetry with comparison of in-house and external ionization chambers and electrometers, lateral-dose profile measurements in air, depth-dose profile in a water tank, evaluation of water equivalent thickness of a HDPE binary range shifter and estimation of impurities of the investigated helium-ion beam. The experiments and results are presented.

The dosimetric advantages of ion therapy come at the cost of an increased sensitivity to range inaccuracies in the treatment planning and delivery stages. This prompts the development of imaging techniques capable of an accurate assessment of the relative stopping power (RSP). We investigate carbon-ion imaging based on a prototype integration-mode detector working as a range telescope. Experiments were conducted at the Heidelberg Ion-Beam Therapy Center with active pencil beam scanning. The aim of this article is to experimentally operate the imaging system in low-dose regimes. Therefore, an adjustment of the synchronization mechanism between beam delivery and data acquisition was required. Different from the previous studies, this article investigates unexplored dosimetric scenarios and faced the related technological challenges. Radiographic and tomographic images of two tissue-equivalent phantoms were acquired and the image quality was evaluated. Relying on dedicated signal processing to solve the range mixing problem, the tomographic images showed an RSP accuracy of better than 0.6%. This article evaluates the imaging performance with low-dose exposure, focusing on the technological requirements and pointing out the current limitations. Hence, this article supports the development of upgraded integration-mode ion imaging systems for reducing range uncertainties in particle therapy.