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Cancers
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Steps towards the Clinics in Spatially Fractionated Radiation Therapy
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Steps towards the Clinics in Spatially Fractionated Radiation Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 10 September 2024 | Viewed by 5635

Special Issue Editor

Dr. Stefan Bartzsch

E-Mail Website
Guest Editor
Klinikum rechts der Isar der, Technischen Universität München, Munich, Germany
Interests: radiation therapy; microbeam radiation

Special Issue Information

Dear Colleagues,

Despite the technical optimization of radiation oncology, treatment outcomes for certain cancer types remain dismal, and there is a need for disruptive new techniques. Spatially fractionated radiation therapies (SFRTs), such as proton minibeams and X-ray microbeams, are a development of recent years that may lead to a paradigm change in radiation oncology. SFRTs are characterized by extremely inhomogeneous fields with doses of up to several 100 Gy in the peak regions. The extreme demands on technology, patient safety, and dosimetry have for a long time prevented clinical translation, and after decades of research there are still open biomedical questions.

Today, technology has matured and compact radiation sources have been developed, and the first clinical trials seem to be in reach. This Special Issue is dedicated to the remaining open questions on the way of SFRTs to the clinics, looking at radiation technology, dosimetry, treatment planning, outcome modeling, and preclinical studies. Related original research articles or reviews are welcome.

Dr. Stefan Bartzsch
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbeams
  • minibeams
  • spatially fractionated radiation therapy
  • dosimetry
  • treatment planning
  • radiation sources
  • synchrotrons
  • high dose rates
  • preclinical studies
  • veterinary trials

Published Papers (4 papers)

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Research

14 pages, 6937 KiB  
Article
In Vivo Microbeam Radiation Therapy at a Conventional Small Animal Irradiator
by Mabroor Ahmed, Sandra Bicher, Stephanie Elisabeth Combs, Rainer Lindner, Susanne Raulefs, Thomas E. Schmid, Suzana Spasova, Jessica Stolz, Jan Jakob Wilkens, Johanna Winter and Stefan Bartzsch
Cancers 2024, 16(3), 581; https://doi.org/10.3390/cancers16030581 - 30 Jan 2024
Viewed by 870
Abstract
Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal [...] Read more.
Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT. Full article
(This article belongs to the Special Issue Steps towards the Clinics in Spatially Fractionated Radiation Therapy)
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13 pages, 1697 KiB  
Article
The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model
by Felix Jaekel, Jason Paino, Elette Engels, Mitzi Klein, Micah Barnes, Daniel Häusermann, Christopher Hall, Gang Zheng, Hongxin Wang, Guido Hildebrandt, Michael Lerch and Elisabeth Schültke
Cancers 2023, 15(9), 2470; https://doi.org/10.3390/cancers15092470 - 26 Apr 2023
Viewed by 1136
Abstract
Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as [...] Read more.
Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450–800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size. Full article
(This article belongs to the Special Issue Steps towards the Clinics in Spatially Fractionated Radiation Therapy)
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17 pages, 6241 KiB  
Article
Accurate and Fast Deep Learning Dose Prediction for a Preclinical Microbeam Radiation Therapy Study Using Low-Statistics Monte Carlo Simulations
by Florian Mentzel, Jason Paino, Micah Barnes, Matthew Cameron, Stéphanie Corde, Elette Engels, Kevin Kröninger, Michael Lerch, Olaf Nackenhorst, Anatoly Rosenfeld, Moeava Tehei, Ah Chung Tsoi, Sarah Vogel, Jens Weingarten, Markus Hagenbuchner and Susanna Guatelli
Cancers 2023, 15(7), 2137; https://doi.org/10.3390/cancers15072137 - 04 Apr 2023
Cited by 1 | Viewed by 1638
Abstract
Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumor diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Monte Carlo (MC) simulations are one of the most used methods at the Imaging [...] Read more.
Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumor diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Monte Carlo (MC) simulations are one of the most used methods at the Imaging and Medical Beamline, Australian Synchrotron to calculate the dose in MRT preclinical studies. The steep dose gradients associated with the 50μm-wide coplanar beamlets present a significant challenge for precise MC simulation of the dose deposition of an MRT irradiation treatment field in a short time frame. The long computation times inhibit the ability to perform dose optimization in treatment planning or apply online image-adaptive radiotherapy techniques to MRT. Much research has been conducted on fast dose estimation methods for clinically available treatments. However, such methods, including GPU Monte Carlo implementations and machine learning (ML) models, are unavailable for novel and emerging cancer radiotherapy options such as MRT. In this work, the successful application of a fast and accurate ML dose prediction model for a preclinical MRT rodent study is presented for the first time. The ML model predicts the peak doses in the path of the microbeams and the valley doses between them, delivered to the tumor target in rat patients. A CT imaging dataset is used to generate digital phantoms for each patient. Augmented variations of the digital phantoms are used to simulate with Geant4 the energy depositions of an MRT beam inside the phantoms with 15% (high-noise) and 2% (low-noise) statistical uncertainty. The high-noise MC simulation data are used to train the ML model to predict the energy depositions in the digital phantoms. The low-noise MC simulations data are used to test the predictive power of the ML model. The predictions of the ML model show an agreement within 3% with low-noise MC simulations for at least 77.6% of all predicted voxels (at least 95.9% of voxels containing tumor) in the case of the valley dose prediction and for at least 93.9% of all predicted voxels (100.0% of voxels containing tumor) in the case of the peak dose prediction. The successful use of high-noise MC simulations for the training, which are much faster to produce, accelerates the production of the training data of the ML model and encourages transfer of the ML model to different treatment modalities for other future applications in novel radiation cancer therapies. Full article
(This article belongs to the Special Issue Steps towards the Clinics in Spatially Fractionated Radiation Therapy)
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16 pages, 2735 KiB  
Article
Longitudinally Heterogeneous Tumor Dose Optimizes Proton Broadbeam, Interlaced Minibeam, and FLASH Therapy
by Matthias Sammer, Aikaterini Rousseti, Stefanie Girst, Judith Reindl and Günther Dollinger
Cancers 2022, 14(20), 5162; https://doi.org/10.3390/cancers14205162 - 21 Oct 2022
Cited by 2 | Viewed by 1403
Abstract
The prerequisite of any radiation therapy modality (X-ray, electron, proton, and heavy ion) is meant to meet at least a minimum prescribed dose at any location in the tumor for the best tumor control. In addition, there is also an upper dose limit [...] Read more.
The prerequisite of any radiation therapy modality (X-ray, electron, proton, and heavy ion) is meant to meet at least a minimum prescribed dose at any location in the tumor for the best tumor control. In addition, there is also an upper dose limit within the tumor according to the International Commission on Radiation Units (ICRU) recommendations in order to spare healthy tissue as well as possible. However, healthy tissue may profit from the lower side effects when waving this upper dose limit and allowing a larger heterogeneous dose deposition in the tumor, but maintaining the prescribed minimum dose level, particularly in proton minibeam therapy. Methods: Three different longitudinally heterogeneous proton irradiation modes and a standard spread-out Bragg peak (SOBP) irradiation mode are simulated for their depth-dose curves under the constraint of maintaining a minimum prescribed dose anywhere in the tumor region. Symmetric dose distributions of two opposing directions are overlaid in a 25 cm-thick water phantom containing a 5 cm-thick tumor region. Interlaced planar minibeam dose distributions are compared to those of a broadbeam using the same longitudinal dose profiles. Results and Conclusion: All longitudinally heterogeneous proton irradiation modes show a dose reduction in the healthy tissue compared to the common SOBP mode in the case of broad proton beams. The proton minibeam cases show eventually a much larger mean cell survival and thus a further reduced equivalent uniform dose (EUD) in the healthy tissue than any broadbeam case. In fact, the irradiation mode using only one proton energy from each side shows better sparing capabilities in the healthy tissue than the common spread-out Bragg peak irradiation mode with the option of a better dose fall-off at the tumor edges and an easier technical realization, particularly in view of proton minibeam irradiation at ultra-high dose rates larger than ~10 Gy/s (so-called FLASH irradiation modes). Full article
(This article belongs to the Special Issue Steps towards the Clinics in Spatially Fractionated Radiation Therapy)
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