A higher therapeutic index might be achieved in carbon therapy when used in combination with Minibeam Radiation Therapy (CMBRT). Nevertheless, the biochemical effects underlying CMBRT are not profoundly known. This work aims to study the nature of these effects by employing synchrotron-based Fourier Transform Infrared microspectroscopy (SR-FTIRM).
Cancer cell irradiations (LM8 mouse...
Background: the biology underlying proton minibeam radiation therapy (pMBRT) is not fully known yet. Therefore, this study reports on the in vivo biochemical mechanisms following pMBRT irradiations using Fourier Transform Infrared Microspectroscopy (FTIRM). This technique can reveal details of the biochemical structure of the main biomolecules and their possible modifications by measuring...
Glioblastoma multiforme is the most common malignant brain tumor with a very poor prognosis. High infiltration rates, uncontrolled cell growth, and a strong ability to develop therapy resistance are components of the aggressive nature of this type of cancer. Despite multimodal treatment, the tumor often recurs within 1-2 cm of the primary tumor.
In this study, the migration behavior of U87...
The existence of severe hypoxia in locally advanced tumors is well characterized. In terms of particle minibeam applications, few studies have considered the dose that may be required to completely sterilize tumor tissue that falls within the peak dose volumes. Instead, peak doses are mostly decided at random and dictated by valley dose treatment goals or anatomic constraints depending on...
Purpose: The clinical translation of proton minibeam radiation therapy (pMBRT) is non-trivial, for which the proper treatment planning technique remains an open question: on one hand, the uniform target dose is desirable for anti-tumor efficacy and the easy acceptance of pMBRT as a standalone treatment modality; on the other hand, high peak-to-valley dose ratio (PVDR) is also desirable in...
Minibeam therapy faces challenges in preserving deep-seated normal tissue due to the lateral spreading of minibeams caused by small-angle scattering. Unlike proton minibeams, helium or carbon minibeams experience less spreading, potentially reducing side effects. Studies with proton beams indicate that reaching full therapeutic potential of minibeam therapy requires high beam brightness....
The primary aim of radical radiotherapy is to effectively treat tumors while minimizing damage to normal tissues. Hadron therapy, utilizing heavy particles such as protons, alpha particles, and carbon ions, provides a unique advantage over conventional photon therapy, which can be increased by the use of spatial fractionation. The focus of this research project is to further enhance the effect...
Proton minibeam therapy (pMBT) using sub-millimeter beams spaced a few millimeters apart has demonstrated the ability to reduce side effects in normal tissues and possible increase of the therapeutic ratio. Preclinical studies also indicate that FLASH irradiation, delivering ultra-high dose rates (>40 Gy/s), minimizes tissue toxicity while maintaining effective tumor control. However,...
Proton minibeam radiation therapy (pMBT) and FLASH radiotherapy (FLASH-RT) have attracted the interest of scientists due to the better sparing of healthy tissue compared to conventional modalities. Combining these methods may lead to further reduction of the induced side effects. In this proof-of-principle study, the feasibility of designing a ridge filter (RF) for the FLASH application of...
Automated detection and tracking of living cells in microscopy recordings by deep learning algorithms may considerably speed up and facilitate evaluation compared to manual post-processing. However, the performance of such algorithms on individual sets of cell data and their generalizability differ significantly. One approach is to use a deep learning object detection model, which identifies...
In collaboration with the Helmholtz Zentrum Berlin (HZB) a new pMBT facility, called MINIBEE, is currently under construction. The facility will include a small animal radiation research platform (SARRP) for positioning small animals or in vitro samples, X-ray irradiation, onboard CT-imaging, and treatment planning. Additionally, there will be a microscope that enables imaging of samples...
Healthy tissue toxicity limitations of neon beams may be overcome by combining such ions with the remarkable normal tissue sparing that spatially fractionated radiotherapies provide. The present study explores the biochemical effects involved at a single-cell level in neon minibeam radiation therapy (NeMBRT) using synchrotron-based Fourier transform infrared microspectroscopy (SR-FTIRM). This...
Radiotherapy is one of three methods used to fight against cancer along with surgery and chemotherapy, and has currently attracted a lot of scientific interest particularly due to novel techniques, like Proton Minibeam Radiotherapy (pMBT) and FLASH therapy. The latter can deliver an ultra-high dose rate of radiation to the target (>40 Gy/s). From a biological aspect, the main target of...
LhARA (Laser-hybrid Accelerator for Radiobiological Applications) is conceived as a novel, uniquely flexible facility dedicated to the study of the biological response to ionising radiation. The design for LhARA offers versatility, allowing for the production of spatially fractionated radiation therapy (SFRT) at the in-vitro and in-vivo end stations.
Background
SFRT aims to minimise...
Background and Objectives: The 18 MeV medical cyclotron at Bern University Hospital (Inselspital) is designed for routine radiopharmaceutical production. It is equipped with a Beam Transfer Line (BTL), accessible in a separate bunker, for research in medical applications of particle physics. In an effort to make pre-clinical proton therapy studies more accessible to research groups, the BTL...
Preclinical and clinical studies have shown that radiation delivery at ultra-high dose rate (UHDR, > 40 Gy/s) and sufficiently high total dose elicits the FLASH effect that maintains anti-tumor efficacy and spares normal tissue as compared with conventional dose rate (0.05 Gy/s), used in RT clinical practice. The 22 MeV electron PITZ beam delivers radiation at both UHDR up to unique 10^14 Gy/s...
After 25 years of successful research in the nuclear and radiation physics and biology domain, the KVI-CART research center in Groningen has been re-focussed and re-established as the open access UMCG PARticle Therapy Research Center (PARTREC). Using the superconducting cyclotron AGOR and being embedded within the University Medical Center Groningen, it operates in synergy with the clinical...
roton minibeam radiation therapy (pMBRT) is a novel therapeutic approach offering great promise for the treatment of radioresistant tumors based on the spatial fractionation of the dose. pMBRT applies a high dose modulation consisting of high doses (peaks) deposited in the paths of millimetric planar beams and low doses (valleys) in the rest of the tissue. This distinct dose delivery leads to...
The radiation biology research at the UMCG PARTREC accelerator facility was pivotal in providing pre-clinical evidence for introduction of proton therapy as a cancer treatment modality in the Netherlands. UMCG PARTREC (formerly known as KVI-CART) operates the unique superconducting cyclotron AGOR that provides customizable ion beams of all stable elements, that are employed for a wide range of...
The main parameters for minibeams that seem to affect the magnitude of the sparing effect are the peak/valley dose ratio, the FWHM and the distance between peaks. The quantitative dependencies of the minibeam effect on these parameters are not yet fully understood. Therefore, a systematic investigation of the variations of the biological effects in vitro and in vivo (small animals) as a...
Purpose:
Microbeam and minibeam radiotherapy are the most extreme forms of spatially fractionated photon radiotherapy. Both techniques may improve cancer treatment substantially because they preclinically demonstrated high dose tolerances of normal tissue at similar tumor control rates as conventional radiotherapy. However, until now, suitable clinical treatment facilities are lacking, which...
Using TRS-398, primary standard level dose measurements for calibrating ionisation chambers are currently realised in a 60Co beam. The upcoming UK IPEM Code of Practice for Proton Radiotherapy will provide a new protocol for the direct calibration of ionization chambers in a proton beam using the NPL Primary Standard Portable Calorimeter (PSPC) reducing the uncertainty on reference absorbed...
This work presents the realization and complete characterization of a low energy electron mini-beam flash beam. This beam can vary the Flash parameters (Dose per pulse, average dose rate, intra-pulse dose rate) and the mini-beam parameters (Peak-to-Valley Dose Ratio (PVDR), FWHM and center-to-center (ctc) distance) independently from one and another. We utilize the Triode-Gun equipped...
An experimental campaign was conducted at Institut Curie, France, to perform dosimetry with the Primary Standard Proton Calorimeter (PSPC) developed by the National Physical Laboratory (NPL), UK, in proton minibeams. The minibeams were produced using a collimator with 400µm wide slits of 5cm length and 4mm separation. Dosimetry was also performed with EBT3 radiochromic film and PTW Roos...
Spatially fractionated radiation therapy (SFRT) has shown promise in increasing the therapeutic window compared to conventional irradiation techniques. However, which dose parameter best correlates highly modulated dose distributions with cellular and clinical endpoints remains unresolved. The aim of this work was to determine the predictive value of several physical and biological dose...
The Centre for Accelerator Science (CAS) of the Australian Nuclear Science and Technology Organisation (ANSTO) is a national state-of-art facility for applied accelerator science, equipped with 10 MV Van de Graaff ANTARES [1] accelerator to accelerate mono-energetic ions, such as proton up to 10 MeV (ideally 20 MeV), light and heavy ions up to 120 MeV.
The Heavy Ion Nuclear Microprobes...
Particle minibeam radiation therapy (PMBT) is a novel therapeutic approach offering great promise for
the treatment of radioresistant tumors based on the spatial fractionation of the dose and the combination
with particle therapy. PMBT offers a high dose modulation consisting of high doses (peaks) deposited in
the paths of millimetric planar beams and low doses (valleys) in the rest of the...
CNAO is one of the four centres in Europe, and six worldwide, offering treatment of tumours with both protons and carbon ions. Since its start in September 2011 almost 4500 patients have been treated. In addition to clinical activity, CNAO performs research as an institutional mission. In this framework a room dedicated to experimental activities is available and open also to external...
A wealth of preclinical evidence is demonstrating superior tumour control and less side effects for SFRT. Particularly, the normal tissue tolerance towards extremely high peak doses is the promoting argument for SFRT. However, recent research is showing that peak dose is not the determining factor for toxicity or tumour control. The many parameters required to define the radiation field are a...
Contact: Elisabeth Bodenstein - Beamline Scientist elisabeth.bodenstein@oncoray.de
Jörg Pawelke - Core Facility Manager joerg.pawelke@oncoray.de
An innovative proton facility is at the heart of the OncoRay research building. While cancer patients are being treated in the clinical part, scientists can concurrently conduct research in the experimental area of the University Proton Therapy...
The Proton Therapy Research Centre (PTRC) at the TRIUMF particle accelerator center in Vancouver, British Columbia, Canada, conducts pre-clinical and dosimetry research with the proton therapy beam line that clinically treated ocular cancer between 1995 and 2018. Extracted proton energies between 116 MeV and 70 MeV are available, with most of the work being conducted at the former treatment...
An R&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ) [1]. This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of 6 to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1...
Particle radiation research is crucial for advancing our understanding of radiobiology and its applications in medicine. As an evolving field, it focuses on studying the interactions of charged particles, such as protons and heavy ions, with biological tissues. This research provides insights into the effects of particle radiation on cells, DNA, and tissues, enabling us to develop safer and...
Compared to classic proton therapy, proton minibeam radiation therapy (pMBT) further spares normal tissue. To fully study this potential with small animal experiments focused minibeams with a σ of 50 μm , a beam current of 1 nA and approx. 4 cm proton range (water) is needed. The MiniBEE located at the Helmholtz-Zentrum Berlin, is designed to fullfill all requirements of researchers for...
Abstract: The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium‐7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of...
Charged particles, characterized by superior relative biological effectiveness (RBE) and more targeted depth dose deposition as compared with photons, have the potential to significantly enhance the therapeutic index of minibeam radiation therapy (MBRT). Proton minibeam radiation therapy has emerged as a compelling technique, showcasing remarkable normal tissue sparing for both skin and brain...
A research version of the RayStation treatment planning system dedicated to particle therapy related explorations has been developed. It provides, for research purposes (ie. non-clinical use), the following features not available in clinical releases of the RayStation system:
• Scorers: Trackends, LETd, LETt, Qefft,Qeffd, dose components, 10+ RBE models (McNamara, RMF, DDK…), dose rate,...
Particle therapy has many advantages over conventional photon therapy, particularly for treating deep-seated solid tumours due to its greater conformal energy deposition achieved in the form of the Bragg peak (BP). The benefits of spatially fractionated radiation fields leading to increased healthy tissue dose tolerance have been demonstrated with high intensity photon microbeam studies. The...
The goal of the ERC-funded project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology) has been to realize an innovative portable system to enable precision image-guided small animal proton irradiation at existing beamlines of clinical proton therapy facilities. The modular SIRMIO system combines a dedicated beamline consisting of passive and...
The capacity to automate treatment planning tasks is demanded from the user community. Main motivation is to save time and to ensure consistency in treatments and followup. Going forward, we see that clinic specific configurable automation is one of several prerequisites for bringing adaptive therapy into routine clinical use. The latter need applies both for typical treatment planning system...
The capacity to automate treatment planning tasks is demanded from the user community. Main motivation is to save time and to ensure consistency in treatments and followup. Going forward, we see that clinic specific configurable automation is one of several prerequisites for bringing adaptive therapy into routine clinical use. The latter need applies both for typical treatment planning system...
Preclinical studies comparing proton minibeams (pMB) with proton broad-beams (pBB) have demonstrated that pMB can improve the sparing of healthy tissues while there are also indications for an increase in therapeutic index. Minibeams can be generated either via collimation, a method easier to apply regarding technical purposes, or via magnetic focusing, which even though it is more...
Contact: experimente@mit-marburg.de | matthias.witt@mit-marburg.de | matthias.witt@lse.thm.de
Physical beam properties at MIT
The Marburg Ion Beam Therapy Center (MIT) is one of four European Hadron Therapy Centers that offer raster scanning for both proton and carbon ions. The synchrotron-based accelerator provides protons in the energy range of 48.08 MeV to 221.07 MeV and carbon ions from...
The University of Washington (UW) Medical Center operates a Scanditronix MC50 multi-particle, variable energy cyclotron for fast neutron therapy patient care, radioisotope production, radiation-effects testing of electronic devices, and translational in vitro and in vivo research. The cyclotron is located within the UW Radiation Oncology Department and has four beamlines. The first beamline is...
