Knopf, Antje
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Publication Possible association of dose rate and the development of late visual toxicity for patients with intracranial tumours treated with pencil beam scanned proton therapy(BioMed Central, 17.06.2024) Meijers, Arturs; Daartz, Juliane; Knopf, Antje; Van Heerden, Michelle; Bizzocchi, Nicola; Vazquez, Miriam Varela; Bachtiary, Barbara; Pica, Alessia; Shih, Helen A.; Weber, Damien CharlesBackground and purpose Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities. Materials and methods Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated. Results For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases. Conclusions Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.01A - Beitrag in wissenschaftlicher ZeitschriftPublication Organ motion in particle therapy and the role of imaging(IOP Publishing, 06/2024) Paganelli, Chiara; Molinelli, Silvia; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeOrgan motion is one of the main challenges to account for in particle therapy to plan and deliver an accurate treatment. In this chapter, we will explain the concept of organ motion in terms of inter- and intra-fraction variations. The current inter- and intra-fraction motion compensation techniques demanding for imaging will be also reported.04A - Beitrag SammelbandPublication Conclusions and future perspectives of imaging in particle therapy(IOP Publishing, 06/2024) Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeIn this chapter, we will consolidate the concluding remarks presented throughout the preceding chapters, with a specific emphasis on the technical and methodological advancements in image-guided particle therapy, as well as elucidating the future trajectory of this field.04A - Beitrag SammelbandPublication Treatment verification in particle therapy(IOP Publishing, 01.06.2024) Gianoli, Chiara; De Simoni, M.; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeTo make the most of the physical and biological potentials of Particle Therapy (PT), it would be extremely desirable to verify dose deposition in vivo. In this chapter, we describe and compare in vivo range verification methods currently being proposed, developed or clinically implemented, including PET and prompt gamma imaging. The potential of other emerging techniques for indirect treatment verification will be also cited.04A - Beitrag SammelbandPublication Integration of imaging in clinical protocols of particle therapy(IOP Publishing, 06/2024) Trnkova, P.; Bolsi, Alessandra; Knopf, Antje; Hoffmann, A.; Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje04A - Beitrag SammelbandPublication Imaging in article therapy. Current practice and future trends(IOP Publishing, 06/2024) Paganelli, Chiara; Gianoli, Chiara; Knopf, Antje; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeThe benefits of particle therapy (PT), stemming from its physical and radiobiological advantages, necessitate the use of dedicated imaging technologies and approaches to ensure precise treatment planning and delivery. This book endeavors to establish a fundamental understanding of imaging within the context of PT, alongside exploring current research and clinical perspectives on its role. The focus is directed towards examining near-room, in-room, and in-beam technologies, both those already in clinical use and those in the developmental stage, which play pivotal roles in treatment planning, delivery, and verification processes, enabling adjustments either offline or online. Concurrently, the text addresses methodological solutions derived from these imaging modalities to effectively address challenges such as range uncertainties, anatomical variations, and biological properties, thereby enhancing the accuracy of treatment modeling and adaptation.03 - SammelbandPublication Artificial intelligence to generate synthetic CT for adaptive particle therapy(IOP Publishing, 06/2024) Thummerer, Adrian; Zaffino, Paolo; Spadea, Maria Francesca; Knopf, Antje; Maspero, Matteo; Paganelli, Chiara; Gianoli, Chiara; Knopf, AntjeRecently, Artificial Intelligence (AI) methods for the generation of synthetic computed tomography (sCT) have received significant research attention as an alternative to classical ones (e.g. bulk density assignment, atlas based virtual CT). We present here an overview of these methods for particle therapy (PT) applications, including strategies to replace CT in magnetic resonance imaging (MRI)-based treatment planning and to facilitate cone beam CT (CBCT)-based image-guided adaptive PT.04A - Beitrag SammelbandPublication Technical note: development of a simulation framework, enabling the investigation of locally tuned single energy proton radiography(IOP Publishing, 07.02.2024) Lundberg, Måns; Meijers, Arturs; Souris, Kevin; Deffet, Sylvain; Weber, Damien C; Lomax, Antony; Knopf, AntjeRange uncertainties remain a limitation for the confined dose distribution that proton therapy can offer. The uncertainty stems from the ambiguity when translating CT Hounsfield Units (HU) into proton stopping powers. Proton Radiography (PR) can be used to verify the proton range. Specifically, PR can be used as a quality-control tool for CBCT-based synthetic CTs. An essential part of the work illustrating the potential of PR has been conducted using multi-layer ionization chamber (MLIC) detectors and mono-energetic PR. Due to the dimensions of commercially available MLICs, clinical adoption is cumbersome. Here, we present a simulation framework exploring locally-tuned single energy (LTSE) proton radiography and corresponding potential compact PR detector designs. Based on a planning CT data set, the presented framework models the water equivalent thickness. Subsequently, it analyses the proton energies required to pass through the geometry within a defined ROI. In the final step, an LTSE PR is simulated using the MCsquare Monte Carlo code. In an anatomical head phantom, we illustrate that LTSE PR allows for a significantly shorter longitudinal dimension of MLICs. We compared PR simulations for two exemplary 30 × 30 mm2proton fields passing the phantom at a 90° angle at an anterior and a posterior location in an iso-centric setup. The longitudinal distance over which all spots per field range out is significantly reduced for LTSE PR compared to mono-energetic PR. In addition, we illustrate the difference in shape of integral depth dose (IDD) when using constrained PR energies. Finally, we demonstrate the accordance of simulated and experimentally acquired IDDs for an LTSE PR acquisition. As the next steps, the framework will be used to investigate the sensitivity of LTSE PR to various sources of errors. Furthermore, we will use the framework to systematically explore the dimensions of an optimized MLIC design for daily clinical use.01A - Beitrag in wissenschaftlicher ZeitschriftPublication A review of the clinical introduction of 4D particle therapy research concepts(Elsevier, 01/2024) Knäusl, Barbara; Belotti, Gabriele; Bertholet, Jenny; Daartz, Juliane; Flampouri, Stella; Hoogeman, Mischa; Knopf, Antje; Lin, Haibo; Moerman, Astrid; Paganelli, Chiara; Rucinski, Antoni; Schulte, Reinhard; Shimizu, Shing; Stützer, Kristin; Zhang, Xiaodong; Zhang, Ye; Czerska, KatarzynaBackground and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.01A - Beitrag in wissenschaftlicher ZeitschriftPublication A survey of practice patterns for real-time intrafractional motion-management in particle therapy(Elsevier, 26.04.2023) Zhang, Ye; Trnkova, Petra; Toshito, Toshiyuki; Heijmen, Ben; Richter, Christian; Aznar, Marianne; Albertini, Francesca; Bolsi, Alexandra; Daartz, Juliane; Bertholet, Jenny; Knopf, Antje01A - Beitrag in wissenschaftlicher Zeitschrift