Radiotherapy delivery with ultra-high dose rates (UHDR) has consistently produced normal tissue sparing while maintaining efficacy for tumour control in preclinical studies, known as the FLASH effect. Modified clinical electron linacs have been used for pre-clinical studies at reduced source-surface distance (SSD) and novel intra-operative devices are becoming available. In this context, we modified a clinical linac to deliver 16 MeV UHDR electron beams with an isocentric setup. The first Varian TrueBeam (SN 1001) was clinically operative between 2009-2022, it was then decommissioned and converted into a research platform. The 18 MeV electron beam was converted into the experimental 16 MeV UHDR. Modifications were performed by Varian and included a software patch, thinner scattering foil and beam tuning. The dose rate, beam characteristics and reproducibility were measured with electron applicators at SSD = 100 cm. The dose per pulse at isocenter was up to 1.28 Gy/pulse, corresponding to average and instantaneous dose rates up to 256 Gy/s and 3⋅10⁵ Gy/s, respectively. Beam characteristics were equivalent between 16 MeV UHDR and conventional for field sizes up to 10x10cm² and an overall beam reproducibility within ± 2.5% was measured. We report on the first technical conversion of a Varian TrueBeam to produce 16 MeV UHDR electron beams. This research platform will allow isocenter experiments and deliveries with conventional setups up to field sizes of 10x10 cm² within a hospital environment, reducing the gap between preclinical and clinical electron FLASH investigations.

The aim of this study was to quantify anatomical changes of parotids and submandibular glands and evaluate potential dosimetric advantages during weekly adaptive MR-guided radiotherapy (MRgRT) for the definitive treatment of head and neck cancer (HNC). The data and plans of 12 patients treated with bilateral intensity-modulated radiotherapy for HNC using MR-linac, with weekly offline adaptations, were prospectively evaluated. The positional and volumetric changes of the salivary glands were analyzed by manual segmentation in weekly MRI images and the dosimetric impact of these anatomical changes on the adapted treatment plans was assessed. The mean volume change in parotid and submandibular gland volume was −31.9% (p < 0.0001) and −29.7% (p < 0.0001) after five weeks, respectively. The volume change was significantly correlated with the cumulative dose for the respective gland at the time of volume measurement. Inter-parotid distance changed by −5.4% (6.5 mm) on average after five weeks (p = 0.0005). The distance became significantly smaller only in the left-right direction. The inter-submandibular gland distance changed by 0.7 mm (p = 0.38). This study demonstrated significant changes in salivary gland volumes and position following daily MR guidance and weekly plan adaptation. Ongoing clinical trials will provide data on the clinical impact of these changes and novel MR-based adaptation strategies.

Radiomics supposes an alternative non-invasive tumor characterization tool, which has experienced increased interest with the advent of more powerful computers and more sophisticated machine learning algorithms. Nonetheless, the incorporation of radiomics in cancer clinical-decision support systems still necessitates a thorough analysis of its relationship with tumor biology. Herein, we present a systematic review focusing on the clinical evidence of radiomics as a surrogate method for tumor molecular profile characterization. An extensive literature review was conducted in PubMed, including papers on radiomics and a selected set of clinically relevant and commonly used tumor molecular markers. We summarized our findings based on different cancer entities, additionally evaluating the effect of different modalities for the prediction of biomarkers at each tumor site. Results suggest the existence of an association between the studied biomarkers and radiomics from different modalities and different tumor sites, even though a larger number of multi-center studies are required to further validate the reported outcomes.

The physical range uncertainty limits the exploitation of the full potential of charged particle therapy. In this work, we face this issue aiming to measure the absolute Bragg peak position in the target. We investigate p, ⁴ He, ¹² C and ¹⁶ O beams accelerated at the Heidelberg Ion-Beam Therapy Center. The residual range of the primary ¹² C ions is correlated to the energy spectrum of the prompt gamma radiation. The prompt gamma spectroscopy method was demonstrated for proton beams accelerated by cyclotrons and is developed here for the first time for heavier ions accelerated by a synchrotron. We develop a detector system that includes (i) a spectroscopic unit based on cerium(III) bromide and bismuth germanium oxide scintillating crystals, (ii) a beam trigger based on an array of scintillating fibers and (iii) a data acquisition system based on a FlashADC. We test the system in two different scenarios. In the first series of experiments, we detect and identify 19 independent spectral lines over a wide gamma energy spectrum in the presence of the four ion species for different targets, including a water target with a titanium insert. In the second series of experiments, we introduce a collimator aiming to relate the spectral information to the range of the primary particles. We perform extensive measurements for a ¹² C beam and demonstrate submillimetric precision for the measurement of its Bragg peak position in the experimental setup. The features of the energy and time spectra for gamma radiation induced by p, ⁴ He and ¹⁶ O are investigated upstream and downstream from the Bragg peak position. We conclude the analysis by extrapolating the required future developments, which would be needed to achieve range verification with a 2 mm accuracy during a single fraction delivery of D = 2 G y physical dose.

The requirement of computed tomography (CT) for radiotherapy planning may be bypassed by synthetic CT (sCT) generated from magnetic resonance (MR), which has recently led to the clinical introduction of MR-only radiotherapy for specific sites. Further developments are required for abdominal sCT, mostly due to the presence of mobile air pockets affecting the dose calculation. In this study we aimed to overcome this limitation for abdominal sCT at a low field (0.35 T) hybrid MR-Linac. A retrospective analysis was conducted enrolling 168 patients corresponding to 215 MR-CT pairs. After the exclusion criteria, 152 volumetric images were used to train the cycle-consistent generative adversarial network (CycleGAN) and 34 to test the sCT. Image similarity metrics and dose recalculation analysis were performed. The generated sCT faithfully reproduced the original CT and the location of the air pockets agreed with the MR scan. The dose calculation did not require manual bulk density overrides and the mean deviations of the dose-volume histogram dosimetric points were within 1 % of the CT, without any outlier above 2 %. The mean gamma passing rates were above 99 % for the 2 %/ 2 mm analysis and no cases below 95 % were observed. This study presented the implementation of CycleGAN to perform sCT generation in the abdominal region for a low field hybrid MR-Linac. The sCT was shown to correctly allocate the electron density for the mobile air pockets and the dosimetric analysis demonstrated the potential for future implementation of MR-only radiotherapy in the abdomen.