Particle Therapy Research Articles

Evaluation of endocrinological sequelae following particle therapy performed on anterior skull base lesions in the adult population.

Radiotherapy has increasingly assumed a central role in the multidisciplinary treatment of skull base lesions. Unfortunately, it is often burdened by relevant radio-induced damage to the pituitary function and the surrounding structures and systems. Patients who were treated with radiotherapy around the sellar region especially have a high risk of developing radio-induced hypopituitarism. Particle therapy has the potential advantage of delivering a higher radiation dose to the target while potentially sparing the sellar region and pituitary function. The aim of this study is to evaluate the pituitary function in adult patients who have undergone hadron therapy for anterior skull base lesions involving or surrounding the pituitary gland. This is a retrospective, observational, and noncontrolled study. We evaluated pituitary and peripheral hormone levels in all patients referring to National Center for Oncological Hadrontherapy, Pavia, Italy for anterior skull base tumors. Furthermore, we performed a magnetic resonance imaging for every follow-up to evaluate potential tumoral growth. We evaluated 32 patients with different tumoral lesions with a mean follow-up of 27.9 months. The mean hadron therapy (HT) dose was 60 ± 14 Gray, with a mean dose per fraction of 2.3 ± 2.1 Gray. Six patients were treated with carbon ions and 26 with protons. Pituitary hormone alteration of some kind was reported for six patients. No patient experienced unexpected severe adverse events related to particle therapy. Particle radiotherapy performed on anterior skull base lesions has proved to cause limited damage to pituitary function in the adult population.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy

Objective. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP). Approach. Our model provides for selection of preferred ID parameters (I p ) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopic I p and macroscopic RTP. Selection of I p is demonstrated using published cell survival measurements for protons through argon, comparing results for nineteen I p : N k , k = 2, 3, …, 10, the number of ionizations in clusters of k or more per particle, and F k , k = 1, 2, …, 10, the number of clusters of k or more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation. Main results. The preferred I p were N 4 and F 5 for aerobic cells, N 5 and F 7 for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferred N k . Conversely, there was no significant difference for F 5 for aerobic cells and F 7 for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for these I p had the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert that I p exist that are more closely associated with biological effects than current LET-based approaches and microdosimetric RBE-based models used in particle RTP. However, more biological variables such as cell line and cycle phase, as well as ion beam pulse structure and rate still need investigation. Significance. Our model provides a practical means to select preferred I p from radiobiological data, and to convert I p to the macroscopic cluster dose for particle RTP.

Selecting Optimal Proton Pencil Beam Scanning Plan Parameters to Reduce Dose Discrepancy between Discrete Spot Plan and Continuous Scanning: A Proof-of-Concept Study.

Pencil beam scanning delivered with continuous scanning has several advantages over conventional discrete spot scanning. Such advantages include improved beam delivery efficiency and reduced beam delivery time. However, a move dose is delivered between consecutive spots with continuous scanning, and current treatment planning systems do not take this into account. Therefore, continuous scanning and discrete spot plans have an inherent dose discrepancy. Using the operating parameters of the state-of-the-art particle therapy system, we conducted a proof-of-concept study in which we systematically generated 28 plans for cubic targets with different combinations of plan parameters and simulated the dose discrepancies between continuous scanning and a planned one. A nomograph to guide the selection of plan parameters was developed to reduce the dose discrepancy. The effectiveness of the nomograph was evaluated with two clinical cases (one prostate and one liver). Plans with parameters guided by the nomograph decreased dose discrepancy than those used standard plan parameters. Specifically, the 2%/2 mm gamma passing rate increased from 96.3% to 100% for the prostate case and from 97.8% to 99.7% for the liver case. The CTV DVH root mean square error decreased from 2.2% to 0.2% for the prostate case and from 1.8% to 0.9% for the liver case. The decreased dose discrepancy may allow the relaxing of the delivery constraint for some cases, leading to greater benefits in continuous scanning. Further investigation is warranted.

A simple method to import CAD mesh format models in FLUKA.

Monte Carlo (MC) code FLUKA possesses widespread usage and accuracy in the simulation of particle beam radiotherapy. However, the conversion from computer-aided design (CAD) mesh format models to FLUKA readable geometries could not be implemented directly and conveniently. A simple method was required to be developed. The present study proposed a simple method to voxelize CAD mesh format files by using a Python-based script and establishing geometric models in FLUKA. Five geometric models including cube, sphere, cone, ridge filter (RGF), and 1D-Ripple Filter (1D-RiFi) were created and exported as CAD mesh format files (.stl). An open-source Python-based script was used to convert them into voxels by endowing X, Y, and Z (following the Cartesian coordinates system) of solid materials in the three-dimensional (3D) grid. A FLUKA (4-2.2, CERN) predefined routine was used to establish the voxelized geometry model (VGM), while Flair (3.2-1, CERN) was used to build the direct geometry model (DGM) in FLUKA for comparison purposes. Uniform carbon ion radiation fields 8×8cm3 and 4×4cm3 were generated to transport through the five pairs of models, 2D and 3D dose distributions were compared. The integral depth dose (IDD) in water of three different energy levels of carbon ion beams transported through 1D-RiFis were also simulated and compared. Moreover, the volume between CAD mesh and VGMs, as well as the computing speed between FLUKA DGMs and VGMs were simultaneously recorded. The volume differences between VGMs and CAD mesh models were not more than 0.6%. The maximum mean point-to-point deviation of IDD distribution was 0.7%±0.51% (mean±standard deviation). The 3D dose Gamma-index passing rates were never lower than 97% with criteria of 1%-1mm. The difference in computing CPU time was 2.89%±0.22 on average. The present study proposed and verified a Python-based method for converting CAD mesh format files into VGMs and establishing them in FLUKA simply as well as accurately.

Experimental Determination of the Charge Carrier Transport Models for Improving the Simulation of the HR GaAs:Cr Detectors' Response.

The response of Timepix3 detectors with 300 µm and 500 µm thick HR GaAs:Cr sensors was studied with particle beams at the Danish Centre for Particle Therapy in Aarhus, Denmark. Therefore, the detectors were irradiated at different angles with protons of 240 MeV. The precise per-pixel time and energy measurements were exploited in order to determine the charge carrier transport properties. Using the tracks left by the penetrating charged particles hitting the sensor at the grazing angle, we were able to determine the charge collection efficiency, the charge carrier drift times across the sensor thickness, the dependency of the electron, and for the first time, the hole drift velocity on the electric field. Moreover, extracting the dependence of the charge cloud size on the interaction depth for different bias voltages, it was possible to determine the dependence of the diffusion coefficient on the applied bias voltage. A good agreement was found with the previously reported values for n-type GaAs. The measurements were conducted for different detector assemblies to estimate the systematic differences between them, and to generalize the results. The experimental findings were implemented into the Allpix Squared simulation framework and validated by a comparison of the measurement and simulation for the 241Am γ-ray source.

The efficacy of boron neutron capture therapy with folate receptor targeted novel boron carrier in F98 rat brain tumor models.

21 Background: Boron neutron capture therapy (BNCT) is a particle therapy that can be targeted at the cellular level. The most commonly used boron carrier in clinical BNCT is boronophenylalanine (BPA), which is taken up into the tumor cell via L type amino acid transporter (LAT-1). The development of new boron carrier is an important issue, because BNCT using BPA is sometimes ineffective. Focusing on folate receptors that are highly expressed in malignant gliomas, PBC-IP which contained the pteroyl group was developed. The efficacy of BNCT with this drug was evaluated. The efficacy of BNCT using PBC-IP in the F98 rat brain tumor model has been evaluated. Methods: F98 rat glioma cells were used in the in vitro cellular uptake experiment.F98 rat glioma cells were exposed to BPA, sodium borocaptate (BSH), and PBC-IP. F98 rat brain tumor models were used in biodistribution experiment and neutron irradiation experiment. PBC-IP was administered by Convection enhanced delivery (CED). Results: In vitro cellular uptake experiment showed the boron concentration of PBC-IP was much higher than that of BPA and BSH. In vivo biodistribution experiment showed that boron concentration in the tumor using PBC-IP CED was the highest at 3 hours after the termination of 24 h administration. In the in vivo neutron irradiation experiment, significantly difference was observed between BNCT BPA group and combination BNCT (BPA + PBC-IP) group. In addition, long time survivors were observed in BNCT using PBC-IP groups, which were not observed in BNCT BPA groups. Conclusions: This study showed that PBC-IP in combination with BPA may provide the multi-targeted neutron capture therapy, this is because the mechanism of tumor accumulation of PBC-IP is different from that of BPA. In addition, therapeutic strategies targeting folate receptors may be useful, and further research is warranted.

Future Perspective: Carbon Ion Radiotherapy for Head and Neck and Skull Base Malignancies.

Head and neck and base of skull malignancies are challenging for surgical and radiotherapy treatment due to the density of sensitive tissues. Carbon ion radiotherapy (CIRT) is a form of heavy particle therapy that uses accelerated carbon ions to treat malignancies that may be radioresistant or in challenging anatomic locations. CIRT has an increased biological effectiveness (ie, increased cell killing) at the end of the range of the carbon beam (ie, within the target tissue) but not in the entrance dose. This increased biological effectiveness can overcome the effects of radioresistant tumors, tissue hypoxia, and the need for radiotherapy fractionation.

Calibration method and performance of a time-of-flight detector to measure absolute beam energy in proton therapy.

The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles' penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi-layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid-state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50μm active thickness, and single particle detection capability) and time-of-flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self-calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self-calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1mm. The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring.

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

Objective. This work investigates the use of Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) detectors to determine both the dose and the radiation quality in light ion beams. The radiation quality is here expressed through either the linear energy transfer (LET) or the closely related metric Q eff, which depends on the particle’s speed and effective charge. The derived LET and Q eff values are applied to improve the dosimetry in light ion beams. Approach. OSL detectors were irradiated in mono-energetic 1H-, 4He-, 12C-, and 16O-ion beams. The OSL signal is associated with two emission bands that were separated using a pulsed stimulation technique and subjected to automatic corrections based on reference irradiations. Each emission band was investigated independently for dosimetry, and the ratio of the two emission intensities was parameterized as a function of fluence- and dose-averaged LET, as well as Q eff. The determined radiation quality was subsequently applied to correct the dose for ionization quenching. Main results. For both materials, the Q eff determinations in 1H- and 4He-ion beams are within 5 % of the Monte Carlo simulated values. Using the determined radiation quality metrics to correct the nonlinear (ionization quenched) detector response leads to doses within 2 % of the reference doses. Significance. Al2O3:C and Al2O3:C,Mg OSL detectors are applicable for dosimetry and radiation quality estimations in 1H- and 4He-ions. Only Al2O3:C,Mg shows promising results for dosimetry in 12C-ions. Across both materials and the investigated ions, the estimated Q eff values were less sensitive to the ion types than the estimated LET values were. The reduced uncertainties suggest new possibilities for simultaneously estimating the physical and biological dose in particle therapy with OSL detectors.

Uncertainty in the range of the protons and C-ions in particle therapy due to a hydration level of a human body model

Cancer treatment with protons and carbon ions relies on the property of the accelerated charged particles to deposit most of their energy in the vicinity of their range (around the Bragg peak). The level of hydration in a cancer patient's body may vary within hours. Some patients may be heavy to moderately dehydrated, and some may be well and even excessively hydrated. In this research, we aim to estimate the uncertainty of the protons and C-ion ranges because of the different hydration levels of the human body. For the study of the impact of body hydration level on the particle's ranges, we have designed a new phantom model – a homogeneous mixture of an Average HUuman BOdy constituting elements (AHUBO) in three states of hydration: normal (n), dehydrated (d), and excessively hydrated (e) by applying corresponding recalibration in the “atomic-stoichiometry model” due to the water sufficiency/deficiency. The purpose of the study is to estimate the shift in the ranges depending on the hydration level, possibly suggest particle beam energy adjustments to overcome the range uncertainties, to deliver the prescribed dose to the tumour while sparing the healthy tissue. Herein we present the results of the FLUKA-Flair simulations of the therapeutic range of energies of protons (50–105 MeV) and C-ions (30–210 MeV) respectively, into an AHUBO head phantom model at three levels of hydration (normal, dehydrated, and excessively hydrated). The range uncertainty was estimated via the shifts of the Bragg-peaks position for the three different hydration levels. The estimations showed that the range uncertainty (ΔR) due to body hydration for the maximum energy in the range for protons at 105 MeV is about 0.04 mm and for C-ions at 190 MeV/u is about 0.06 mm.

A Monte Carlo study of high-LET particle production in proton boron therapy

We simulate the production of high-LET particles from different boron nuclear reactions in proton therapy. This study is motivated by neutron capture-enhanced particle therapy (NCEPT) (Safavi-Naeini et al. in Sci Rep 8(1):1–13, 2018) and the recently proposed proton boron capture therapy (PBCT) (Cirrone et al. in Sci Rep 8(1):1–15, 2018), where both therapy types suggest to utilize the production of high-LET particle for enhancing the RBE of the treatment. From Monte Carlo simulations performed in TOPAS (Perl et al. in Med Phys 39(11):6818–6837, 2012), we find that NCEPT reaction is the more prominent reaction of the two with a factor of 4000 pm 700 more particles produced. The reason for this is the relative high fluence of thermal and epithermal neutrons (neutrons < 1 hbox { keV}) present in clinical relevant proton fields. The creation of these neutrons is shown to be highly influenced by the target phantom and proton field size. By varying the field and phantom size, it was found that the fluence of low-energy neutrons can increase/decrease two orders of magnitude.

MR-guided ion therapy: Detector response in magnetic fields during carbon ion irradiation.

Combining carbon ion therapy with on-bed MR imaging has the potential to bring particle therapy to a new level of precision. However, the introduction of magnetic fields brings challenges for dosimetry and quality assurance. For protons, a small, but significant change in detector response was shown in the presence of magnetic fields previously. For carbon ion beams, so far no such experiments have beenperformed. To investigate the influence of external magnetic fields on the response of air-filled ionizationchambers. Four commercially available ionization chambers, three thimble type (Farmer, Semiflex, and PinPoint), and a plane parallel (Bragg peak) detector were investigated. Detectors were aligned in water such that their effective point of measurement was located at 2 cm depth. Irradiations were performed using square fields for carbon ions of 186.1, 272.5, and 402.8MeV/u employing magnetic field strengths of 0, 0.25, 0.5, and 1 T. In addition, the detector response for protons and carbon ions was compared taking into account the secondary electron spectra and employing protons of 252.7 MeV forcomparison. For all four detectors, a statistically significant change in detector response, dependent on the magnetic field strength, was found. The effect was more pronounced for higher energies. The highest effects were found at 0.5 T for the PinPoint detector with a change in detector response of 1.1%. The response of different detector types appeared to be related to the cavity diameter. For proton and carbon ion irradiation with similar secondary electron spectra, the change in detector response was larger for carbon ions compared toprotons. A small, but significant dependence of the detector response was found for carbon ion irradiation in a magnetic field. The effect was found to be larger for smaller cavity diameters and at medium magnetic field strengths. Changes in detector response were more pronounced for carbon ions compared toprotons.

Study of particle acceleration by Laguerre–Gaussian ultra intense laser plasma interactions

In this work, simulations of multi-petawatt lasers in the range of ∼0.2 PW–∼100 PW with varying Laguerre–Gaussian (LG) azimuthal modes as well as linearly polarized (LP) and circularly polarized (CP) laser beams striking near critical density targets were studied by using three-dimensional particle in cell (PIC) codes. Particle acceleration mechanisms have a dependence on laser polarization and it affects the energy gained by the particles. It is known that laser pulses can be polarized helically by applying the LG distribution function to the fundamental Gaussian laser profile. In this study, differently polarized laser beams with varying powers were employed to study laser driven particle acceleration and compares accelerated charged particles’ energy spectra and angular distribution. It is seen that LG laser beams can accelerate higher energetic particles due to higher conversion efficiency compared to LP and CP laser beams. It is also seen that LG laser beams can collimate ions with a narrower spread compared to LP and CP beams. Furthermore, ions can have a smaller divergence angle with increasing azimuthal mode index when the laser is LG polarized. We also studied the energy deposition of these particles in a water cell obtained by the PIC codes for different laser parameters by using Geant4 Monte Carlo simulations which suggests that LG laser beam can be useful for the future hadron therapy applications.

Minimum data elements for the Australian Particle Therapy Clinical Quality Registry.

Construction of the first Australian particle therapy (PT) centre is underway. Establishment of a national registry, to be known as the Australian Particle Therapy Clinical Quality Registry (ASPIRE), has been identified as a mandatory requirement for PT treatment to be reimbursed by the Australian Medicare Benefits Schedule. This study aimed to determine a consensus set of Minimum Data Elements (MDEs) for ASPIRE. A modified Delphi and expert consensus process was completed. Stage 1 compiled currently operational English-language international PT registries. Stage 2 listed the MDEs included in each of these four registries. Those included in three or four registries were automatically included as a potential MDE for ASPIRE. Stage 3 interrogated the remaining data items, and involved three rounds - an online survey to a panel of experts, followed by a live poll session of PT-interested participants, and finally a virtual discussion forum of the original expert panel. One hundred and twenty-three different MDEs were identified across the four international registries. The multi-staged Delphi and expert consensus process resulted in a total of 27 essential MDEs for ASPIRE; 14 patient factors, four tumour factors and nine treatment factors. The MDEs provide the core mandatory data items for the national PT registry. Registry data collection for PT is paramount in the ongoing global effort to accumulate more robust clinical evidence regarding PT patient and tumour outcomes, quantifying the magnitude of clinical benefit and justifying the relatively higher costs of PT investment.

Virtual 4DCT generated from 4DMRI in gated particle therapy: phantom validation and application to lung cancer patients

Objective. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved. To support the clinical practice based on 4D computed tomography (CT), 4D magnetic resonance imaging (MRI) acquisitions can be exploited. The purpose of this study was to validate a method for virtual 4DCT generation from 4DMRI data for lung cancers on a porcine lung phantom, and to apply it to lung cancer patients in PT. Approach. Deformable image registration was used to register each respiratory phase of the 4DMRI to a reference phase. Then, a static 3DCT was registered to this reference MR image set, and the virtual 4DCT was generated by warping the registered CT according to previously obtained deformation fields. The method was validated on a physical phantom for which a ground truth 4DCT was available and tested on lung tumor patients, treated with gated PT at end-exhale, by comparing the virtual 4DCT with a re-evaluation 4DCT. The geometric and dosimetric evaluation was performed for both proton and carbon ion treatment plans. Main results. The phantom validation exhibited a geometrical accuracy within the maximum resolution of the MRI and mean dose deviations, with respect to the prescription dose, up to 3.2% for target D 95%, with a mean gamma pass rate of 98%. For patients, the virtual and re-evaluation 4DCTs showed good correspondence, with errors on target D 95% up to 2% within the gating window. For one patient, dose variations up to 10% at end-exhale were observed due to relevant inter-fraction anatomo-pathological changes that occurred between the planning and re-evaluation CTs. Significance. Results obtained on phantom data showed that the virtual 4DCT method was accurate, allowing its application on patient data for testing within a clinical scenario.

Influence of the background in Compton camera images for proton therapy treatment monitoring

Objective. Background events are one of the most relevant contributions to image degradation in Compton camera imaging for hadron therapy treatment monitoring. A study of the background and its contribution to image degradation is important to define future strategies to reduce the background in the system. Approach. In this simulation study, the percentage of different kinds of events and their contribution to the reconstructed image in a two-layer Compton camera have been evaluated. To this end, GATE v8.2 simulations of a proton beam impinging on a PMMA phantom have been carried out, for different proton beam energies and at different beam intensities. Main results. For a simulated Compton camera made of Lanthanum (III) Bromide monolithic crystals, coincidences caused by neutrons arriving from the phantom are the most common type of background produced by secondary radiations in the Compton camera, causing between 13% and 33% of the detected coincidences, depending on the beam energy. Results also show that random coincidences are a significant cause of image degradation at high beam intensities, and their influence in the reconstructed images is studied for values of the time coincidence windows from 500 ps to 100 ns. Significance. Results indicate the timing capabilities required to retrieve the fall-off position with good precision. Still, the noise observed in the image when no randoms are considered make us consider further background rejection methods.

Accelerating 4D image reconstruction for magnetic resonance-guided radiotherapy.

Physiological motion impacts the dose delivered to tumours and vital organs in external beam radiotherapy and particularly in particle therapy. The excellent soft-tissue demarcation of 4D magnetic resonance imaging (4D-MRI) could inform on intra-fractional motion, but long image reconstruction times hinder its use in online treatment adaptation. Here we employ techniques from high-performance computing to reduce 4D-MRI reconstruction times below two minutes to facilitate their use in MR-guided radiotherapy. Four patients with pancreatic adenocarcinoma were scanned with a radial stack-of-stars gradient echo sequence on a 1.5T MR-Linac. Fast parallelised open-source implementations of the extra-dimensional golden-angle radial sparse parallel algorithm were developed for central processing unit (CPU) and graphics processing unit (GPU) architectures. We assessed the impact of architecture, oversampling and respiratory binning strategy on 4D-MRI reconstruction time and compared images using the structural similarity (SSIM) index against a MATLAB reference implementation. Scaling and bottlenecks for the different architectures were studied using multi-GPU systems. All reconstructed 4D-MRI were identical to the reference implementation (SSIM 0.99). Images reconstructed with overlapping respiratory bins were sharper at the cost of longer reconstruction times. The CPU +GPU implementation was over 17 times faster than the reference implementation, reconstructing images in 60 1 s and hyper-scaled using multiple GPUs. Respiratory-resolved 4D-MRI reconstruction times can be reduced using high-performance computing methods for online workflows in MR-guided radiotherapy with potential applications in particle therapy.

Hi'CT: a pixel sensor-based device for ion tomography

Carbon ions, commonly referred to as particle therapy, have become increasingly popular in the last decade. Accurately predicting the range of ions in tissues is important for the precise delivery of doses in heavy-ion radiotherapy. Range uncertainty is currently the largest contributor to dose uncertainty in normal tissues, leading to the use of safety margins in treatment planning. One potential method is the direct relative stopping measurement (RSP) with ions. Heavy-ion CT (Hi′CT), a compact segmented full digital tomography detector using monolithic active pixel sensors, was designed and evaluated using a 430 MeV/u high-energy carbon ion pencil beam in Geant4. The precise position of the individual carbon ion track can be recorded and reconstructed using a 30 μm × 30 μm small pixel pitch size. Two types of customized image reconstruction algorithms were developed, and their performances were evaluated using three different modules of CATPHAN 600-series phantoms. The RSP measurement accuracy of the tracking algorithm for different types of materials in the CTP404 module was less than 1%. In terms of spatial resolution, the tracking algorithm could achieve a 20% modulation transfer function normalization value of CTP528 imaging results at 5 lp/cm, which is significantly better than that of the fast imaging algorithm (3 lp/cm). The density resolution obtained using the tracking algorithm of the customized CTP515 was approximately 10.5%. In conclusion, a compact digital Hi'CT system was designed, and its nominal performance was evaluated in a simulation. The RSP resolution and image quality provide potential feasibility for scanning most parts of an adult body or pediatric patient, particularly for head and neck tumor treatment.

Intensity-modulated radiotherapy for the management of primary and recurrent chordomas: a retrospective long-term follow-up study.

Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy. 57 patients (age, 11.8-81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7-82.5) in 22-36 fractions. LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5-24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC. Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible.

Neurotoxicity from Old and New Radiation Treatments for Brain Tumors.

Research regarding the mechanisms of brain damage following radiation treatments for brain tumors has increased over the years, thus providing a deeper insight into the pathobiological mechanisms and suggesting new approaches to minimize this damage. This review has discussed the different factors that are known to influence the risk of damage to the brain (mainly cognitive disturbances) from radiation. These include patient and tumor characteristics, the use of whole-brain radiotherapy versus particle therapy (protons, carbon ions), and stereotactic radiotherapy in various modalities. Additionally, biological mechanisms behind neuroprotection have been elucidated.