Characterisation of the HollandPTC R&D proton beamline for physics and radiobiology studies.

HollandPTC is an independent outpatient center for proton therapy, scientific research, and education. Patients with different types of cancer are treated with Intensity Modulated Proton Therapy (IMPT). Additionally, the HollandPTC R&D consortium conducts scientific research into the added value and improvements of proton therapy.

Enhanced radiosensitivity of head and neck cancer cells to proton therapy via hyperthermia-induced homologous recombination deficiency.

Background And Purpose: Radiotherapy induces tumor cell killing by generating DNA double strand breaks (DSBs). The effectiveness of radiotherapy is significantly influenced by the repair of DSBs, which counteracts this lethal effect. Current investigations are focused on determining whether non-homologous end joining (NHEJ) or homologous recombination is the predominant repair pathway following proton and photon radiation.

Development of patient-specific pre-treatment verification procedure for FLASH proton therapy based on time resolved film dosimetry.

Background: Pre-clinical studies demonstrate that delivering a high dose at a high dose rate result in less toxicity while maintaining tumor control, known as the FLASH effect. In proton therapy, clinical trials have started using 250 MeV transmission beams and more trials are foreseen. A novel aspect of FLASH treatments, compared to conventional radiotherapy, is the importance of dose rate next to dose and geometry.

Novel Bragg peak characterization method using proton flux measurements on plastic scintillators.

. Bragg peak measurements play a key role in the beam quality assurance in proton therapy. Used as base data for the treatment planning softwares, the accuracy of the data is crucial when defining the range of the protons in the patient.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life.

radiation sensitivity assessment for individual head and neck cancer patients using deep learning-based automated nuclei and DNA damage foci detection.

Introduction: Tumor biopsy tissue response to irradiation is potentially an interesting biomarker for tumor response, therefore, for treatment personalization. Tumor response can be characterized by DNA damage response, expressed by the large-scale presence of DNA damage foci in tumor nuclei. Currently, characterizing tumor nuclei and DNA damage foci is a manual process that takes hours per patient and is subjective to inter-observer variability, which is not feasible in for clinical decision making.

Micro-Vessels-Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma-Endothelial Cells Co-Culture Models.

Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. While X-ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can damage cancer cells while sparing the surrounding healthy tissue. However, the effects of protons on in vitro GBM models at the cellular level, especially when co-cultured with endothelial cells, the building blocks of brain micro-vessels, are still unexplored.

A Geant4 based simulation platform of the HollandPTC R&D proton beamline for radiobiological studies.

A Geant4 based simulation platform of the Holland Proton Therapy Centre (HollandPTC, Netherlands) R&D beamline (G4HPTC-R&D) was developed to enable the planning, optimisation and advanced dosimetry for radiobiological studies. It implemented a six parameter non-symmetrical Gaussian pencil beam surrogate model to simulate the R&D beamline in both a pencil beam and passively scattered field configuration. Three different experimental proton datasets (70 MeV, 150 MeV, and 240 MeV) of the pencil beam envelope evolution in free air and depth-dose profiles in water were used to develop a set of individual parameter surrogate functions to enable the modelling of the non-symmetrical Gaussian pencil beam properties with only the ProBeam isochronous cyclotron mean extraction proton energy as input.

A hybrid multi-particle approach to range assessment-based treatment verification in particle therapy.

Particle therapy (PT) used for cancer treatment can spare healthy tissue and reduce treatment toxicity. However, full exploitation of the dosimetric advantages of PT is not yet possible due to range uncertainties, warranting development of range-monitoring techniques. This study proposes a novel range-monitoring technique introducing the yet unexplored concept of simultaneous detection and imaging of fast neutrons and prompt-gamma rays produced in beam-tissue interactions.

Analytic prediction of droplet vaporization events to estimate the precision of ultrasound-based proton range verification.

Background: The safety and efficacy of proton therapy is currently hampered by range uncertainties. The combination of ultrasound imaging with injectable radiation-sensitive superheated nanodroplets was recently proposed for in vivo range verification. The proton range can be estimated from the distribution of nanodroplet vaporization events, which is stochastically related to the stopping distribution of protons, as nanodroplets are vaporized by protons reaching their maximal LET at the end of their range.

Evaluation of Proton-Induced DNA Damage in 3D-Engineered Glioblastoma Microenvironments.

Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. For this reason, besides clinical and preclinical studies, novel models for the assessment of cancer response to drugs and radiation are being developed. In such context, three-dimensional (3D)-engineered cellular microenvironments, compared to unrealistic two-dimensional (2D) monolayer cell culture, provide a model closer to the configuration.

Acoustic Modulation Enables Proton Detection With Nanodroplets at Body Temperature.

Superheated nanodroplet (ND) vaporization by proton radiation was recently demonstrated, opening the door to ultrasound-based in vivo proton range verification. However, at body temperature and physiological pressures, perfluorobutane nanodroplets (PFB-NDs), which offer a good compromise between stability and radiation sensitivity, are not directly sensitive to primary protons. Instead, they are vaporized by infrequent secondary particles, which limits the precision for range verification.

Spatiotemporal Distribution of Nanodroplet Vaporization in a Proton Beam Using Real-Time Ultrasound Imaging for Range Verification.

The potential of proton therapy to improve the conformity of the delivered dose to the tumor volume is currently limited by range uncertainties. Injectable superheated nanodroplets have recently been proposed for ultrasound-based in vivo range verification, as these vaporize into echogenic microbubbles on proton irradiation. In previous studies, offline ultrasound images of phantoms with dispersed nanodroplets were acquired after irradiation, relating the induced vaporization profiles to the proton range.

Interaction of therapeuticC ions with bone-like targets: physical characterization and dosimetric effect at material interfaces.

Carbon therapy is a promising treatment option for cancer. The physical and biological properties of carbon ions can theoretically allow for the delivery of curative doses to the tumor, while simultaneously limiting risks of toxicity to adjacent healthy structures. The treatment effectiveness can be further improved by decreasing the uncertainties stemming from several sources, including the modeling of tissue heterogeneity.

Relative stopping power measurements and prosthesis artifacts reduction in proton CT.

We present a set-up for proton computed tomography (pCT), composed of a microstrip silicon tracker and a YAG:Ce calorimeter, able to directly measure the relative stopping power (RSP) maps to be used in hadron therapy. The system, tested with an electron density phantom at the Trento proton Therapy Center, is able to correlate measured and expected RSP with discrepancies of the order of 1% or less. Furthermore, pCT tomographies of an anthropomorphous head phantom taken with our device, when compared with x-ray CT images of the same object, evidence a significant reduction of artifacts induced by titanium spinal bone prosthesis and tungsten dental filling.

Microdosimetric measurements as a tool to assess potential in-field and out-of-field toxicity regions in proton therapy.

Relative biological effectiveness (RBE) variations are thought to be one of the primary causes of unexpected normal-tissue toxicities during tumor treatments with charged particles. Unlike carbon therapy, where treatment planning is optimized on the basis of the RBE-weighted dose, a constant RBE value of 1.1 is currently used in proton therapy.

Measurement of PET isotope production cross sections for protons and carbon ions on carbon and oxygen targets for applications in particle therapy range verification.

Measured cross sections for the production of the PET isotopes [Formula: see text], [Formula: see text] and [Formula: see text] from carbon and oxygen targets induced by protons (40-220 [Formula: see text]) and carbon ions (65-430 [Formula: see text]) are presented. These data were obtained via activation measurements of irradiated graphite and beryllium oxide targets using a set of three scintillators coupled by a coincidence logic. The measured cross sections are relevant for the PET particle range verification method where accurate predictions of the [Formula: see text] emitter distribution produced by therapeutic beams in the patient tissue are required.

A new facility for proton radiobiology at the Trento proton therapy centre: Design and implementation.

We present a new facility dedicated to radiobiology research, which has been implemented at the Trento Proton Therapy Centre (Italy). A dual-ring double scattering system was designed to produce irradiation fields of two sizes (i.e.

STUDY FOR A PASSIVE SCATTERING LINE DEDICATED TO RADIOBIOLOGY EXPERIMENTS AT THE TRENTO PROTON THERAPY CENTER.

The recent worldwide spread of Proton Therapy centers paves the way to new opportunities for basic and applied research related to the use of accelerated proton beams. Clinical centers make use of proton beam energies up to about 230 MeV. This represents an interesting energy range for a large spectrum of applications, including detector testing, radiation shielding and space research.

Experimental Assessment of Lithium Hydride's Space Radiation Shielding Performance and Monte Carlo Benchmarking.

The harmful effects of space radiation pose a serious health risk to astronauts participating in future long-term missions. Such radiation effects must be considered in the design phase of space vessels as well as in mission planning. Crew radioprotection during long periods in deep space (e.

Accelerator-Based Tests of Shielding Effectiveness of Different Materials and Multilayers using High-Energy Light and Heavy Ions.

The roadmap for space exploration foresees longer journeys and further excursions outside low-Earth orbit as well as the establishment of permanent outposts on other celestial bodies, such as the Moon or Mars. The design of spacecrafts and habitats depends heavily on the mission scenario and must consider the radiation protection properties of the structural components as well as dedicated shielding. In fact, short- and long-term effects caused by exposure to cosmic radiation are now considered among the main health risks of space travel.

Benchmarking Geant4 hadronic models for prompt-γ monitoring in carbon ion therapy.

Purpose: The real-time monitoring of the spread-out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt-γ produced by the interactions of the C ion beam with a polymethyl methacrylate (PMMA) target.

Fragmentation of 120 and 200 MeV uHe ions in water and PMMA targets.

Recently, the use of He particles in cancer radiotherapy has been reconsidered as they potentially represent a good compromise between protons and C ions. The first step to achieve this goal is the development of a dedicated treatment planning system, for which basic physics information such as the characterization of the beam lateral scattering and fragmentation cross sections are required. In the present work, the attenuation of He primary particles and the build-up of secondary charged fragments at various depths in water and polymethyl methacrylate were investigated experimentally for 120 and 200 MeV u beams delivered by the synchrotron at the Heidelberg Ion-Beam Therapy Center, Heidelberg.

Secondary radiation measurements for particle therapy applications: nuclear fragmentation produced by He ion beams in a PMMA target.

Nowadays there is a growing interest in particle therapy treatments exploiting light ion beams against tumors due to their enhanced relative biological effectiveness and high space selectivity. In particular promising results are obtained by the use of He projectiles. Unlike the treatments performed using protons, the beam ions can undergo a fragmentation process when interacting with the atomic nuclei in the patient body.

Helium ions for radiotherapy? Physical and biological verifications of a novel treatment modality.

Purpose: Modern facilities for actively scanned ion beam radiotherapy allow in principle the use of helium beams, which could present specific advantages, especially for pediatric tumors. In order to assess the potential use of these beams for radiotherapy, i.e.