The use of carbon fiber/polyetheretherketone (CF/PEEK) in pedicle screw fixation for spinal neoplasms-potential advantages in postoperative imaging and radiotherapy planning.

Background: Titanium pedicle screw fixation complicates postoperative care in patients with spinal neoplasms due to postoperative imaging artefacts and dose perturbation. This study aims to measure the benefits of using carbon fiber/polyetheretherketone (CF/PEEK) pedicle fixation compared to titanium in postoperative imaging, radiotherapy planning and delivery for spinal neoplasms treated with conventional external beam radiotherapy with a commercial treatment planning system. Methods: The properties of CF/PEEK pedicle fixation systems were compared to titanium in radiotherapy dose planning accuracy and postoperative computed tomography (CT) image quality. Dose profiles through the screw, tulip and longitudinal axis of the screw were acquired with radiochromic films and compared to a collapsed cone algorithm simulation, to measure dose agreement. The image quality of postoperative CTs were compared by defining four regions of interest around the vertebrae and screws in water phantom models and previous planning CTs, and comparing calculated artefact indexes (AIs). Results: CF/PEEK screws have non-inferior dosimetric prediction accuracy up to 50 mm beneath the screw for collapsed-cone algorithm planning systems. There is a statistically significant reduction in the absolute difference between calculated and measured dose at a depth of 2 mm beneath the screw. There is minimal attenuation with CF/PEEK relative to the surrounding dose, extending to 50 mm beneath the screw. There is a statistically significant improvement in CT imaging quality with reduced AIs in CF/PEEK fixation compared to titanium in both model and patient CT plans. Conclusions: CF/PEEK pedicle fixation can provide benefits in postoperative imaging and photon radiotherapy planning and delivery to patients with spinal neoplasms.

Commissioning of Aktina SRS cones and dosimetric validation of the RayStation photon Monte Carlo dose calculation algorithm.

Clinical implementation of SRS cones demands particular experimental care and dosimetric considerations in order to deliver precise and safe radiotherapy to patients. The purpose of this work was to present the commissioning data of recent Aktina cones combined with a 6MV flattened beam produced by an Elekta VersaHD linear accelerator. Additionally, the modelling process, and an assessment of dosimetric accuracy of the RayStation Monte Carlo dose calculation algorithm for cone based SRS was performed. There are currently no studies presenting beam data for this equipment and none that outlines the modelling parameters and validation of dose calculation using RayStation's photon Monte Carlo dose engine with cones. Beam data was measured using an SFD and a microDiamond and benchmarked against EBT3 film for cones of diameter 5-39 mm. Modelling was completed and validated within homogeneous and heterogeneous phantoms. End-to-end image-guided validation was performed using a StereoPHAN™ housing, an SRS MapCHECK and EBT3 film, and calculation time was investigated as a function of statistical uncertainty and field diameter. The TPS calculations agreed with measured data within their estimated uncertainties and clinical treatment plans could be calculated in under a minute. The data presented serves as a reference for others commissioning Aktina stereotactic cones and the modelling parameters serve similarly, while providing a starting point for those commissioning the same TPS algorithm for use with cones. It has been shown in this work that RayStation's Monte Carlo photon dose algorithm performs satisfactorily in the presence of SRS cones.

Nano X Image Guidance in radiation therapy: feasibility study protocol for cone beam computed tomography imaging with gravity-induced motion.

BACKGROUND: This paper describes the protocol for the Nano X Image Guidance (Nano X IG) trial, a single-institution, clinical imaging study. The Nano X is a prototype fixed-beam radiotherapy system developed to investigate the feasibility of a low-cost, compact radiotherapy system to increase global access to radiation therapy. This study aims to assess the feasibility of volumetric image guidance with cone beam computed tomography (CBCT) acquired during horizontal patient rotation on the Nano X radiotherapy system. METHODS: In the Nano X IG study, we will determine whether radiotherapy image guidance can be performed with the Nano X radiotherapy system where the patient is horizontally rotated while scan projections are acquired. We will acquire both conventional CBCT scans and Nano X CBCT scans for 30 patients aged 18 and above and receiving radiotherapy for head/neck or upper abdomen cancers. For each patient, a panel of experts will assess the image quality of Nano X CBCT scans against conventional CBCT scans. Each patient will receive two Nano X CBCT scans to determine the image quality reproducibility, the extent and reproducibility of patient motion and assess patient tolerance. DISCUSSION: Fixed-beam radiotherapy systems have the potential to help ease the current shortfall and increase global access to radiotherapy treatment. Advances in image guidance could facilitate fixed-beam radiotherapy using horizontal patient rotation. The efficacy of this radiotherapy approach is dependent on our ability to image and adapt to motion due to rotation and for patients to tolerate rotation during treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04488224. Registered on 27 July 2020.

Accurate and Fast Deep Learning Dose Prediction for a Preclinical Microbeam Radiation Therapy Study Using Low-Statistics Monte Carlo Simulations.

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.

FLASH radiotherapy with photon beams.

Ultra-high-dose rate "FLASH" radiotherapy (FLASH-RT) has been shown to drastically reduce normal tissue toxicities while being as efficacious as conventional dose rate radiotherapy to treat tumors. A large number of preclinical studies describing this so-called FLASH effect have led to the clinical translation of FLASH-RT using ultra-high-dose rate electron and proton beams. Although the vast majority of radiation therapy treatments are delivered using X-rays, few preclinical data using ultra-high-dose rate X-ray irradiation have been published. This review focuses on different methods that can be used to generate ultra-high-dose rate X-rays and their beam characteristics along with their effect on the biological tissues and the perspectives for the development of FLASH-RT with X-rays.

First extensive study of silver-doped lanthanum manganite nanoparticles for inducing selective chemotherapy and radio-toxicity enhancement.

Nanoparticles have a great potential to increase the therapeutic efficiency of several cancer therapies. This research examines the potential for silver-doped lanthanum manganite nanoparticles to enhance radiation therapy to target radioresistant brain cancer cells, and their potential in combinational therapy with magnetic hyperthermia. Magnetic and structural characterisation found all dopings of nanoparticles (NPs) to be pure and single phase with an average crystallite size of approximately 15 nm for undoped NPs and 20 nm for silver doped NPs. Additionally, neutron diffraction reveals that La0.9Ag0.1MnO3 (10%-LAGMO) NPs exhibit residual ferromagnetism at 300 K that is not present in lower doped NPs studied in this work, indicating that the Curie temperature may be manipulated according to silver doping. This radiobiological study reveals a completely cancer-cell selective treatment for LaMnO3, La0.975Ag0.025MnO3 and La0.95Ag0.05MnO3 (0, 2.5 and 5%-LAGMO) and also uncovers a potent combination of undoped lanthanum manganite with orthovoltage radiation. Cell viability assays and real time imaging results indicated that a concentration of 50 µg/mL of the aforementioned nanoparticles do not affect the growth of Madin-Darby Canine Kidney (MDCK) non-cancerous cells over time, but stimulate its metabolism for overgrowth, while being highly toxic to 9L gliosarcoma (9LGS). This is not the case for 10%-LAGMO nanoparticles, which were toxic to both non-cancerous and cancer cell lines. The nanoparticles also exhibited a level of toxicity that was regulated by the overproduction of free radicals, such as reactive oxygen species, amplified when silver ions are involved. With the aid of fluorescent imaging, the drastic effects of these reactive oxygen species were visualised, where nucleus cleavage (an apoptotic indicator) was identified as a major consequence. The genotoxic response of this effect for 9LGS and MDCK due to 10%-LAGMO NPs indicates that it is also causing DNA double strand breaks within the cell nucleus. Using 125 kVp orthovoltage radiation, in combination with an appropriate amount of NP-induced cell death, identified undoped lanthanum manganite as the most ideal treatment. Real-time imaging following the combination treatment of undoped lanthanum manganite nanoparticles and radiation, highlighted a hinderance of growth for 9LGS, while MDCK growth was boosted. The clonogenic assay following incubation with undoped lanthanum manganite nanoparticles combined with a relatively low dose of radiation (2 Gy) decreased the surviving fraction to an exceptionally low (0.6 ± 6.7)%. To our knowledge, these results present the first biological in-depth analysis on silver-doped lanthanum manganite as a brain cancer selective chemotherapeutic and radiation dose enhancer and as a result will propel its first in vivo investigation.

The adaptation and investigation of cone-beam CT reconstruction algorithms for horizontal rotation fixed-gantry scans of rabbits.

Fixed-gantry radiation therapy has been proposed as a low-cost alternative to the conventional rotating-gantry radiation therapy, that may help meet the rising global treatment demand. Fixed-gantry systems require gravitational motion compensated reconstruction algorithms to produce cone-beam CT (CBCT) images of sufficient quality for image guidance. The aim of this work was to adapt and investigate five CBCT reconstruction algorithms for fixed-gantry CBCT images. The five algorithms investigated were Feldkamp-Davis-Kress (FDK), prior image constrained compressed sensing (PICCS), gravitational motion compensated FDK (GMCFDK), motion compensated PICCS (MCPICCS) (a novel CBCT reconstruction algorithm) and simultaneous motion estimation and iterative reconstruction (SMEIR). Fixed-gantry and rotating-gantry CBCT scans were acquired of 3 rabbits, with the rotating-gantry scans used as a reference. Projections were sorted into rotation bins, based on the angle of rotation of the rabbit during image acquisition. The algorithms were compared using the structural similarity index measure root mean square error, and reconstruction time. Evaluation of the reconstructed volumes showed that, when compared with the reference rotating-gantry volume, the conventional FDK algorithm did not accurately reconstruct fixed-gantry CBCT scans. Whilst the PICCS reconstruction algorithm reduced some motion artefacts, the motion estimation reconstruction methods (GMCFDK, MCPICCS and SMEIR) were able to greatly reduce the effect of motion artefacts on the reconstructed volumes. This finding was verified quantitatively, with GMCFDK, MCPICCS and SMEIR reconstructions having RMSE 17%-19% lower and SSIM 1% higher than a conventional FDK. However, all motion compensated fixed-gantry CBCT reconstructions had a 56%-61% higher RMSE and 1.5% lower SSIM than FDK reconstructions of conventional rotating-gantry CBCT scans. The results show that motion compensation is required to reduce motion artefacts for fixed-gantry CBCT reconstructions. This paper further demonstrates the feasibility of fixed-gantry CBCT scans, and the ability of CBCT reconstruction algorithms to compensate for motion due to horizontal rotation.

Advances in modelling gold nanoparticle radiosensitization using new Geant4-DNA physics models.

Gold nanoparticles have demonstrated significant radiosensitization of cancer treatment with x-ray radiotherapy. To understand the mechanisms at the basis of nanoparticle radiosensitization, Monte Carlo simulations are used to investigate the dose enhancement, given a certain nanoparticle concentration and distribution in the biological medium. Earlier studies have ordinarily used condensed history physics models to predict nanoscale dose enhancement with nanoparticles. This study uses Geant4-DNA complemented with novel track structure physics models to accurately describe electron interactions in gold and to calculate the dose surrounding gold nanoparticle structures at nanoscale level. The computed dose in silico due to a clinical kilovoltage beam and the presence of gold nanoparticles was related to in vitro brain cancer cell survival using the local effect model. The comparison of the simulation results with radiobiological experimental measurements shows that Geant4-DNA and local effect model can be used to predict cell survival in silico in the case of x-ray kilovoltage beams.

Thulium oxide nanoparticles as radioenhancers for the treatment of metastatic cutaneous squamous cell carcinoma.

Metastases from cutaneous squamous cell carcinoma (cSCC) occur in 2%-5% of cases. Surgery is the standard treatment, often combined with adjuvant radiotherapy. Concurrent carboplatin treatment with post-operative radiotherapy may be prescribed, although it has not shown benefit in recent clinical trials in high-risk cSCC patients. The novel high-Z nanoparticle thulium (III) oxide has been shown to enhance radiation dose delivery to brain tumors by specific uptake of these nanoparticles into the cancerous tissue. As the dose-enhancement capacity of thulium oxide nanoparticles following radiotherapy against metastatic cSCC cells is unknown, its efficacy as a radiosensitizer was evaluated, with and without carboplatin. Novel and validated human patient-derived cell lines of metastatic cSCC were used. The sensitivity of the cells to radiation was investigated using short-term proliferation assays as well as clonogenic survival as the radiobiological endpoint. Briefly, cells were irradiated with 125 kVp orthovoltage x-rays (0-6 Gy) with and without thulium oxide nanoparticles (99.9% trace metals basis; 50 µg ml-1) or low dose carboplatin pre-sensitization. Cellular uptake of the nanoparticles was first confirmed by microscopy and found to have no impact on short-term cell survival for the cSCC cells, highlighting the biocompatibility of thulium oxide nanoparticles. Clonogenic cell survival assays confirmed radio-sensitization when exposed to thulium nanoparticles, with the cell sensitivity increasing by a factor of 1.24 (calculated at the 10% survival fraction) for the irradiated cSCC cells. The combination of carboplatin with thulium oxide nanoparticles with irradiation did not result in significant further reductions in survival compared to nanoparticles alone. This is the first study to provide in vitro data demonstrating the independent radiosensitization effect of high-Z nanoparticles against metastatic cSCC with or without carboplatin. Further preclinical investigations with radiotherapy plus high-Z nanoparticles for the management of metastatic cSCC are warranted.

Toward personalized synchrotron microbeam radiation therapy.

Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer.

Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an EpCAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM-, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term CTC cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets.

Technical advances in x-ray microbeam radiation therapy.

In the last 25 years microbeam radiation therapy (MRT) has emerged as a promising alternative to conventional radiation therapy at large, third generation synchrotrons. In MRT, a multi-slit collimator modulates a kilovoltage x-ray beam on a micrometer scale, creating peak dose areas with unconventionally high doses of several hundred Grays separated by low dose valley regions, where the dose remains well below the tissue tolerance level. Pre-clinical evidence demonstrates that such beam geometries lead to substantially reduced damage to normal tissue at equal tumour control rates and hence drastically increase the therapeutic window. Although the mechanisms behind MRT are still to be elucidated, previous studies indicate that immune response, tumour microenvironment, and the microvasculature may play a crucial role. Beyond tumour therapy, MRT has also been suggested as a microsurgical tool in neurological disorders and as a primer for drug delivery. The physical properties of MRT demand innovative medical physics and engineering solutions for safe treatment delivery. This article reviews technical developments in MRT and discusses existing solutions for dosimetric validation, reliable treatment planning and safety. Instrumentation at synchrotron facilities, including beam production, collimators and patient positioning systems, is also discussed. Specific solutions reviewed in this article include: dosimetry techniques that can cope with high spatial resolution, low photon energies and extremely high dose rates of up to 15 000 Gy s-1, dose calculation algorithms-apart from pure Monte Carlo Simulations-to overcome the challenge of small voxel sizes and a wide dynamic dose-range, and the use of dose-enhancing nanoparticles to combat the limited penetrability of a kilovoltage energy spectrum. Finally, concepts for alternative compact microbeam sources are presented, such as inverse Compton scattering set-ups and carbon nanotube x-ray tubes, that may facilitate the transfer of MRT into a hospital-based clinical environment. Intensive research in recent years has resulted in practical solutions to most of the technical challenges in MRT. Treatment planning, dosimetry and patient safety systems at synchrotrons have matured to a point that first veterinary and clinical studies in MRT are within reach. Should these studies confirm the promising results of pre-clinical studies, the authors are confident that MRT will become an effective new radiotherapy option for certain patients.

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

Dosimetric validation of the Theragenics AgX-100® I-125 seed for ROPES eye plaque brachytherapy.

With the discontinued distribution of the I-125 Oncura Onco seed (model 6711), the Theragenics AgX100® I-125 seeds were considered as a suitable alternative for eye plaque brachytherapy as their physical properties matched the requirements for use with the ROPES eye plaques. The purpose of this study aims at validating the dosimetry of the AgX-100 loaded ROPES plaques (11 mm diameter, 15 mm diameter with flange, 15 mm diameter with notch, 18 mm diameter) and assess the differences with the discontinued I-125 6711 model. To independently verify the plaque dosimetry, the brachytherapy module of RADCALC® version 6.2.3.6 was commissioned for the new AgX-100 I-125 seed using the published AAPM TG43 data from the literature. Experimental dosimetry verification was performed using EBT3 Gafchromic™ film and TLD-100 micro-cubes in a specially designed Solid Water® phantom. Both RADCALC® and film confirmed the dosimetry calculated by Plaque Simulator (PS) version 6.4.6 The dose calculated by PS agrees with RADCALC® to within 2% for depths of 1-15 mm for the 4 available ROPES plaques. The dosimetric measurements agreed with the calculations of PS for clinically relevant depths (4 mm to 6 mm) within the evaluated uncertainties of 4.7% and 7.2% for EBT3 film and TLDs respectively. The AgX-100 I-125 seed was a suitable replacement for the 6711 I-125 seed. Due to the introduction of the stainless-steel backscatter factor in PS v6.4.6, the department has decided to report both the homogenous dose and heterogeneity corrected dose for each eye plaque patient.

Development and commissioning of a full-size prototype fixed-beam radiotherapy system with horizontal patient rotation.

PURPOSE: Compared to conventional linacs with rotating gantries, a fixed-beam radiotherapy system could be smaller, more robust and more cost-effective. In this work, we developed and commissioned a prototype x-ray radiotherapy system utilizing a fixed vertical radiation beam and horizontal patient rotation. METHODS: The prototype system consists of an Elekta Synergy linac with gantry fixed at 0° and a custom-built patient rotation system (PRS). The PRS was designed to immobilize patients and safely rotate them about the horizontal axis. The interlocks and emergency stops of the linac and PRS were connected. Custom software was developed to monitor the system status, control the motion of the PRS and modify treatment plans for the fixed-beam configuration. Following installation, the prototype system was commissioned for three-dimensional (3D) conformal therapy based on guidelines specified in AAPM TG-45 and TG-142, with modifications for the fixed-beam geometry made where necessary. RESULTS: The system and control software was tested in a variety of machine states and executed motion, stop and beam gating commands as expected. Interlocks and emergency stops of the linac and PRS were found to correctly stop PRS motion and both kV and MV radiation beams when triggered. For 3D conformal treatments, the prototype system met all AAPM TG-45 and TG-142 specifications for geometric and dosimetric accuracy. Motion of the PRS was within 0.6 ± 0.3 mm and 0.10° ± 0.07° of input values for translation and rotation respectively. The axis of rotation of the PRS was coincident with the radiation beam axis to less than 1 mm. End-to-end treatment verification for 6 MV conformal treatments showed less than 2% difference between planned and delivered dose for all fields. CONCLUSION: In this work, we have developed and commissioned a radiotherapy system that utilizes a fixed vertical radiation beam and horizontal patient rotation. This system is a proof-of-concept prototype for a fixed-beam treatment system without a rotating gantry. Fixed-beam systems that are smaller and more cost-effective could help in improving global access to radiotherapy.

First in vitro evidence of modulated electro-hyperthermia treatment performance in combination with megavoltage radiation by clonogenic assay.

Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in the treatment of cancer. It is a variation that relies on a particular form of enhanced selectivity to enable more effective cancerous cell death yet maintaining the integrity of healthy non-cancerous cells. It is yet to successfully make the major step into the wider medical community despite several encouraging trials. In this study, we investigate mEHT from an in vitro perspective. We demonstrate a supra-additive effect on 9 L gliosarcoma cells when exposed to mEHT in combination with MV X-ray radiation. The supra-additive effect is hypothesized to be induced by the mEHT mechanism that in turn causes apoptosis, membrane damage and an increase in rate of cell growth. This proves to be extremely advantageous in the case of the aggressive 9 L cell line as it is known to be radioresistant. However, the universal success of this multimodal treatment does not appear to be positive for all cell lines and requires further research. Due to the fundamental approach taken in this research, our results also provide a new prospect for mEHT to be a tool for sterilizing otherwise radioresistant cancers.

Cone-beam CT reconstruction with gravity-induced motion.

Fixed-gantry cone-beam computed tomography (CBCT), where the imaging hardware is fixed while the subject is continuously rotated 360° in the horizontal position, has implications for building compact and affordable fixed-gantry linear accelerators (linacs). Fixed-gantry imaging with a rotating subject presents a challenging image reconstruction problem where the gravity-induced motion is coupled to the subject's rotation angle. This study is the first to investigate the feasibility of fixed-gantry CBCT using imaging data of three live rabbits in an ethics-approved study. A novel data-driven motion correction method that combines partial-view reconstruction and motion compensation was developed to overcome this challenge. Fixed-gantry CBCT scans of three live rabbits were acquired on a standard radiotherapy system with the imaging beam fixed and the rabbits continuously rotated using an in-house programmable rotation cradle. The reconstructed images of the thoracic region were validated against conventional CBCT scans acquired at different cradle rotation angles. Results showed that gravity-induced motion caused severe motion blur in all of the cases if unaccounted for. The proposed motion correction method yielded clinically usable image quality with <1 mm gravity-induced motion blur for rabbits that were securely immobilized on the rotation cradle. Shapes of the anatomic structures were correctly reconstructed with <0.5 mm accuracy. Translational motion accounted for the majority of gravity-induced motion. The motion-corrected reconstruction represented the time-averaged location of the thoracic region over a 360° rotation. The feasibility of fixed-gantry CBCT has been demonstrated. Future work involves the validation of imaging accuracy for human subjects, which will be useful for emerging compact fixed-gantry radiotherapy systems.

"Characterization of ELEKTA SRS cone collimator using high spatial resolution monolithic silicon detector array".

PURPOSE: To investigate the accuracy of the dosimetry of radiation fields produced by small ELEKTA cone collimators used for stereotactic radiosurgery treatments (SRS) using commercially available detectors EBT3 GafchromicTM film, IBA Stereotactic diode (SFD), and the recently developed detector DUO, which is a monolithic silicon orthogonal linear diode array detector. METHODS: These three detectors were used for the measurement of beam profiles, output factors, and percentage depth dose for SRS cone collimators with cone sizes ranging from 5 to 50 mm diameter. The measurements were performed at 10 cm depth and 90 cm SSD. RESULTS: The SRS cone beam profiles measured with DUO, EBT3 film, and IBA SFD agreed well, results being in agreement within ±0.5 mm in the FWHM, and ±0.7 mm in the penumbra region. The output factor measured by DUO with 0.5 mm air gap above agrees within ±1% with EBT3. The OF measured by IBA SFD (corrected for the over-response) agreed with both EBT3 and DUO within ±2%. All three detectors agree within ±2% for PDD measurements for all SRS cones. CONCLUSIONS: The characteristics of the ELEKTA SRS cone collimator have been evaluated by using a monolithic silicon high spatial resolution detector DUO, EBT3, and IBA SFD diode. The DUO detector is suitable for fast real-time quality assurance dosimetry in small radiation fields typical for SRS/SRT. This has been demonstrated by its good agreement of measured doses with EBT 3 films.

A CBCT study of the gravity-induced movement in rotating rabbits.

Fixed-beam radiotherapy systems with subjects rotating about a longitudinal (horizontal) axis are subject to gravity-induced motion. Limited reports on the degree of this motion, and any deformation, has been reported previously. The purpose of this study is to quantify the degree of anatomical motion caused by rotating a subject around a longitudinal axis, using cone-beam CT (CBCT). In the current study, a purpose-made longitudinal rotating was aligned to a Varian TrueBeam kV imaging system. CBCT images of three live rabbits were acquired at fixed rotational offsets of the cradle. Rigid and deformable image registrations back to the original position were used to quantify the motion experienced by the subjects under rotation. In the rotation offset CBCTs, the mean magnitude of rigid translations was 5.7 ± 2.7 mm across all rabbits and all rotations. The translation motion was reproducible between multiple rotations within 2.1 mm, 1.1 mm, and 2.8 mm difference for rabbit 1, 2, and 3, respectively. The magnitude of the mean and absolute maximum deformation vectors were 0.2 ± 0.1 mm and 5.4 ± 2.0 mm respectively, indicating small residual deformations after rigid registration. In the non-rotated rabbit 4DCBCT, respiratory diaphragm motion up to 5 mm was observed, and the variation in respiratory motion as measured from a series of 4DCBCT scans acquired at each rotation position was small. The principle motion of the rotated subjects was rigid translational motion. The deformation of the anatomy under rotation was found to be similar in scale to normal respiratory motion. This indicates imaging and treatment of rotated subjects with fixed-beam systems can use rigid registration as the primary mode of motion estimation. While the scaling of deformation from rabbits to humans is uncertain, these proof-of-principle results indicate promise for fixed-beam treatment systems.

Semiconductor real-time quality assurance dosimetry in brachytherapy.

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.