A high-resolution large-area detector for quality assurance in radiotherapy.

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

Characterization of selected additive manufacturing materials for synchrotron monochromatic imaging and broad-beam radiotherapy at the Australian synchrotron-imaging and medical beamline.

Objective.This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline.Approach.Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities.Main results.Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments.Significance and conclusion.These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study.

3D-printed boluses for radiotherapy: influence of geometrical and printing parameters on dosimetric characterization and air gap evaluation.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry.

Multi-point calorimeter using distributed fiber Bragg gratings for small field dosimetry in radiotherapy.

BACKGROUND: The interest of using fiber Bragg gratings (FBGs) dosimeters in radiotherapy (RT) lies in their (i) microliter detection volume, (ii) customizable spatial resolution, (iii) multi-point dose measurement, (iv) real-time data acquisition and (v) insensitivity to Cherenkov light. These characteristics could prove very useful for characterizing dose distributions of small and nonstandard fields with high spatial resolution. PURPOSE: We developed a multi-point FBGs dosimeter customized for small field RT dosimetry with a spatial resolution of ∼ $\sim$ 1 mm. METHODS: The 3 cm-long multi-point dosimeter is made by embedding a 80 µ m $\umu{\rm {m}}$ silica fiber containing an array of thirty (30) co-located ∼ $\sim$ 1 mm-long fs-written FBGs inside a plastic cylinder with an UV curing optical adhesive. With its higher thermal expansion coefficient, the plastic cylinder increases the sensitivity of the dosimeter by stretching the fiber containing the FBGs when the temperature rises slightly due to radiation energy deposition. Irradiations (2000 MU at 600 MU/min) were performed with a Varian TrueBeam linear accelerator. RESULTS: The dose profile of a 2  × $ \times$ 2 cm 2 $^{2}$ 6 MV beam was measured with a mean relative difference of 1.8% (excluding the penumbra region). The measured output factors for a 6 MV beam are in general agreement with the expected values within the experimental uncertainty (except for the 2  × $\,\times $ 2 cm 2 $^{2}$ field). The detector response to different energy of photon and electron beams is within 5% of the mean response ( 0.068 ± 0.002 $0.068\pm 0.002$  pm/Gy). The calorimeter's post-irradiation thermal decay is in agreement with the theory. CONCLUSIONS: An energy-independent small field calorimeter that allows dose profile and output factor measurements for RT using FBGs was developed, which, to our knowledge, has never been done before. This type of detector could prove really useful for small field dosimetry, but also potentially for MRI-LINAC since FBGs are insensitive to magnetic fields and for FLASH since FBGs have been used to measure doses up to 100 kGy.

NTCP Calculations of Five Different Irradiation Techniques for the Treatment of Thymoma.

This study provided normal tissue complication probability (NTCP) calculations from photon radiotherapy techniques in eleven patients with thymoma. Five plans were created for each participant using three-dimensional conformal radiotherapy (3D-CRT), five-field intensity modulated radiotherapy (5F-IMRT), seven-field IMRT (7F-IMRT), and volumetric modulated arc therapy with full arcs (FA-VMAT) and partial arcs (PA-VMAT). The target coverage, homogeneity index and conformation number for the planning target volume (PTV) and dosimetric parameters for the organs-at-risk (OARs) were taken from the fifty-five generated plans. The patient-specific NTCP of the lungs, heart and esophagus was calculated with an in-house software tool using differential dose-volume histograms and the equivalent uniform dose model. The PTV dose metrics from 3D-CRT were inferior to those from IMRT and VMAT plans. The dose constraints for the OARs were met in all treatment plans. The NTCP range of the lungs, heart and esophagus was 0.34-0.49%, 0.03-0.06% and 0.08-0.10%, respectively. The NTCPs of the heart for the incidence of peridarditis from IMRT and VMAT were significantly smaller than those from conformal treatment (p < 0.05). The 7F-IMRT was significantly superior to FA-VMAT in reducing the NTCP of the lungs and the risk of pneumonitis (p = 0.001). Similar superiority of 5F-IMRT over PA-VMAT for lung protection was found (p = 0.009). The presented results may be employed in the selection of the appropriate irradiation technique for restricting the complications in the adjacent OARs.

Radiotherapy Infrastructure Shielding Calculations: software development for shielding calculations in a linear accelerator radiotherapy room.

This work aimed to develop and validate software that calculates the shielding thickness required for a radiotherapy room with a linear accelerator utilising geometric and dosimetric data. The software "Radiotherapy Infrastructure Shielding Calculations" (RISC) was developed using MATLAB programming. It does not require the installation of the MATLAB platform, and the user only needs to download and install the application, which displays a graphical user interface (GUI). The GUI includes empty cells to insert numerical values for several parameters to calculate the proper shielding thickness. The GUI comprises two main interfaces, one for the primary and one for the secondary barrier calculation. The interface of the primary barrier is divided into four tabs: (a) primary radiation, (b) patient scattered and leakage radiation, (c) IMRT techniques and (d) the shielding cost calculations. The interface of the secondary barrier includes three tabs: (a) patient scattered and leakage radiation, (b) IMRT techniques and (c) the shielding cost calculations. Each tab consists of two sections: one for input and one for output of the necessary data. The RISC is based on the methods and formulae of the NCRP 151 and calculates the primary and secondary barrier thickness for ordinary concrete with a density of 2.35 g/cm3 and the cost for a radiotherapy room with a linear accelerator that performs conventional or IMRT techniques. Calculations can be performed for photon energies of 4, 6, 10, 15, 18, 20, 25 and 30 MV of a dual-energy linear accelerator, while instantaneous dose rate (IDR) calculations are also performed. The RISC has been validated using all comparative examples of NCRP 151 and the calculations from shielding reports of the Varian IX linear accelerator at Methodist Hospital of Willowbrook and Elekta Infinity at the University Hospital of Patras. The RISC is accompanied by two text files: (a) "Terminology," extensively describing all parameters, and (b) "User's Manual," providing useful instructions to the user. The RISC is user-friendly, simple, fast and precise, providing accurate shielding calculations and quickly and easily reproducing different shielding scenarios for a radiotherapy room with a linear accelerator. Additionally, it could be used during the educational process of shielding calculations by graduate students or trainee medical physicists. As a future work, the RISC will be updated with new features such as skyshine radiation, door shielding, and other types of machines and shielding materials.

O odontólogo frente aos cuidados paliativos na oncologia / The dental surgeon facing palliative care in oncology: a literature review / El odontólogo ante los cuidados paliativos en oncología

Cuidados paliativos são um conjunto de procedimentos ofertados ao paciente por uma equipe multidisciplinar com objetivo de garantir bem-estar, autonomia,conforto e alívio de sintomas decorrentes de doença ou tratamento quando a cura é impossibilitada. O câncer representa uma das doenças que possuem chances de evoluir o paciente ao estágio terminal, momento em que cuidados paliativos são indicados e necessários. Dentro da equipe responsável, o cirurgião-dentista atua na prevenção, diagnóstico e tratamento de lesões expressas no sistema estomatognático que se manifestam estimuladas pelo câncer ou pelos tratamentos utilizados. O objetivo desta pesquisa é destacar a função do odontólogo dentro da equipe multidisciplinar paliativista para pacientes oncológicos. Trata-se de uma revisão bibliográfica sistemáticada literatura. Foram feitas buscas nas plataformas Biblioteca Virtual em Saúde (BVS) e Scientific Electronic Library Online (SciELO) e após aplicação dos critérios de inclusão e exclusão foram selecionados 14 artigos. A literatura evidencia que alterações orais estão relacionadas com o curso da neoplasia ou seu tratamento; as lesões mais descritas foram: mucosite, xerostomia, candidíase, cárie, periodontite e osteorradionecrose. Isso faz com que o paciente sofra limitações em realizar atividades básicas, alterando negativamente a sua qualidade de vida. A complexidade da manifestação oral pode interromper o tratamento antineoplásico. As medidas de enfrentamento mais empregadas para a saúde bucal do paciente oncológico são a laserterapia, bochechos com clorexidina 0,12%, instrução de higiene oral, uso de anti-inflamatórios, analgésicos e antifúngicos. A atuação do odontólogo na equipe multidisciplinar oncológica paliativista é indispensável para o controle das manifestações orais.

Palliative care comprises a set of procedures offered by a multidisciplinary team to patients who cannot be cured, aiming to restore and ensure well-being, autonomy, independence, comfort and relief from symptoms resulting from illness or treatments. Cancer commonly leads the patient to the terminal stage, and at this stage palliative care is indicated and necessary. Composing the multidisciplinary team, the dentist works in the prevention, diagnosis and treatment of injuries that arise in the stomatognathic system, which manifest themselves due to cancer or its treatments. The objective of this research was to highlight the work of the dentist in the multidisciplinary team of palliative care for cancer patients. This is a systematic bibliographic review of the literature, with an integrative character. Study searches were performed in the Virtual Health Library (VHL) and Scientific Electronic Library Online (SciELO). After applying the inclusion and exclusion criteria, 14 articles were selected. Results showed that oral alterations are completely related to the development of the neoplasm or its treatment; the most described lesions were: mucositis, xerostomia, candidiasis, osteoradionecrosis, radiation caries and periodontitis. These injuries make the patient suffer limitations to perform basic activities, such as eating or communicating, negatively altering their quality of life. The complexity of the oral manifestation can determine the interruption of the anticancer treatment. The most used coping measures for the oral healthof cancer patients are: low- potency laser therapy, mouthwash with 0.12% chlorhexidine, instructionin oral hygiene and use of anti-inflammatory, analgesic and antifungal drugs. The role of dentists in the multidisciplinary palliative oncology team is essential for the control of oral lesions.

Los cuidados paliativos son un conjunto de procedimientos ofrecidos al paciente por un equipo multidisciplinar con el objetivo de garantizar el bienestar, la autonomía, el confort y el alivio de los síntomas derivados de la enfermedad o del tratamiento cuando la curación es imposible. El cáncer representa una de las enfermedades que tienen posibilidades de evolucionar al paciente hasta la fase terminal, momento en el que los cuidados paliativos son indicados y necesarios. Dentro del equipo responsable, el cirujano dentista actúa en la prevención, diagnóstico y tratamiento de las lesiones expresadas en el sistema estomatognático que se manifiestan estimuladas por el cáncer o por los tratamientos utilizados. El objetivo de esta investigación es destacar la función del odontólogo dentro del equipo paliativo multidisciplinar para pacientes oncológicos. Se trata de una revisión bibliográfica sistemática. Se realizaron búsquedas en las plataformas Virtual Health Library (BVS) y Scientific Electronic Library Online (SciELO) y tras aplicar los criterios de inclusión y exclusión, se seleccionaron 14 artículos. La literatura muestra que las alteraciones orales están relacionadas con el curso del cáncer o su tratamiento; las lesiones más comúnmente descritas fueron: mucositis, xerostomía, candidiasis, caries, periodontitis y osteorradionecrosis. Esto hace que el paciente sufra limitaciones para realizar actividades básicas, alterando negativamente su calidad de vida. La complejidad de la manifestación oral puede interrumpir el tratamiento antineoplásico. Las medidas de afrontamiento más utilizadas para la salud bucodental de los pacientes con cáncer son la terapia láser, los enjuagues bucales con clorhexidina al 0,12%, las instrucciones de higiene bucodental y el uso de fármacos antiinflamatorios, analgésicos y antifúngicos. La actuación del odontólogo en el equipo multidisciplinar de oncología paliativa es fundamental para el control de las manifestaciones orales.

Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device.

The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y ß-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and ß), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

Estimativa da necessidade de radioterapia externa no Brasil baseada em critérios epidemiológicos / Optimal utilization of radiotherapy in Brazil according to local epidemiological data

Esta tese teve como objetivo estimar a necessidade de radioterapia no Brasil a partir de dados epidemiológicos locais. O estudo foi desenvolvido em duas etapas que consistiram na estimativa de casos incidentes e, posteriormente, na classificação dos casos registrados nos Registros Hospitalares de Câncer (RHC) para integrar as árvores de decisão para o emprego do tratamento radioterápico conforme evidências e diretrizes clínicas de tratamento. As estimativas de casos incidentes em 2018 foram calculadas a partir de dados de Registros de Câncer de Base Populacional (RCBP) selecionados de acordo com critérios internacionais de qualidade e de dados corrigidos para causas mal definidas e não específicas na causa básica dos óbitos registrados no Sistema de Informação de Mortalidade (SIM) no período de 2007 a 2016. Foram calculadas razões de incidência/mortalidade (I/M) anuais para cada topografia, estratificadas por sexo e faixa etária nos RCBP selecionados. As razões I/M para 2018 foram estimadas para as regiões brasileiras a partir de modelos multiníveis de Poisson a partir de uma abordagem longitudinal com efeito aleatório no RCBP. As razões estimadas foram aplicadas ao número de óbitos ocorridos em 2018 por tipo de câncer, também corrigido para causas mal definidas e não específicas na causa básica, registrados no SIM. As distribuições dos dados por estadiamento obtidas a partir do RHC foram combinadas às frequências relativas por tipo de câncer incidente e aos dados das árvores de decisão do projeto Collaboration for Cancer Outcomes Research and Evaluation (CCORE) para uso da radioterapia. As estimativas de necessidade foram calculadas por tipo de câncer e para o conjunto das neoplasias, exceto pele não melanoma. Foram realizadas análises de sensibilidade para avaliar a relevância dos dados locais na estimativa de necessidade. O número necessário de equipamentos de radioterapia para atender os casos que se beneficiariam do tratamento em algum momento no curso da doença foi calculado e a análise da cobertura da oferta foi realizada. Para o Brasil, em 2018, foram estimados 506.462 casos novos de câncer, exceto pele não melanoma. Diferenças regionais nas razões I/M e no padrão de casos incidentes foram identificadas, podendo estar relacionadas a fatores socioeconômicos. Foi estimado que 53,55% dos casos novos no Brasil teriam necessidade de tratamento radioterápico. A maior necessidade de radioterapia foi identificada para o Norte: 55,32%, com um peso expressivo do câncer do colo do útero, tanto pela incidência como pelo número de casos em estágios avançados, para os quais a radioterapia é considerada tratamento de escolha. Para atender aos casos com necessidade de radioterapia no Brasil, foram estimados 497 equipamentos de radioterapia externa, sendo o déficit estimado em 114 para 2018 no país. Os maiores déficits foram observados para o Norte e para a rede assistencial do SUS. Em conclusão, o emprego de parâmetros internacionais não se mostrou adequado para a realidade brasileira. O planejamento de recursos para a assistência oncológica no Brasil demanda estimativas confiáveis baseadas nas necessidades locais para que as inequidades não sejam ainda mais agravadas.

This thesis aimed to estimate the need for radiotherapy in Brazil based on local epidemiological data. The study was developed in two stages which consisted of estimating incident cases and, later, classifying the cases registered in the Hospital Cancer Registries (RHC) to integrate decision trees for the use of radiotherapy according to evidence and clinical treatment guidelines. The estimates of incident cases in 2018 were calculated based on data from Population-Based Cancer Registries (RCBP) selected according to international quality criteria and from data corrected for ill-defined and non-specific causes in the underlying cause of deaths recorded in the System of Mortality Information (SIM) from 2007 to 2016. Annual incidence/mortality ratios (I/M) were calculated for each topography, stratified by sex and age group in the selected RCBP. The I/M ratios for 2018 were estimated for Brazilian regions using multilevel Poisson models from a longitudinal approach with random effect on the RCBP. The estimated reasons were applied to the number of deaths that occurred in 2018 by type of cancer, also corrected for ill-defined and non-specific causes in the underlying cause, recorded in the SIM. The staging data distributions obtained from the RHC were combined with the relative frequencies by type of incident cancer and data from the Collaboration for Cancer Outcomes Research and Evaluation (CCORE) project decision trees for radiotherapy use. Optimal utilization rates were estimated by type of cancer and for the set of tumors, except for non-melanoma skin. Sensitivity analyzes were performed to assess the relevance of local data in estimating the need. The number of radiotherapy equipment needed to attend to cases that would benefit from treatment at some point in the course of the disease was calculated and the analysis of the offer coverage was performed. For Brazil, in 2018, 506,462 new cases of cancer were estimated, except for non-melanoma skin. Regional differences in I/M ratios and in the pattern of incident cases were identified, which may be related to socioeconomic factors. It was estimated that 53.55% of new cases in Brazil would need radiotherapy. The greatest need for radiotherapy was identified for the North: 55.32%, with an expressive weight of cervical cancer, both in terms of incidence and the number of cases in advanced stages, for which radiotherapy is considered the treatment of choice. To meet the need for radiotherapy in Brazil, 497 external radiotherapy equipment were estimated, with an estimated deficit of 114 for 2018 in the country. The greatest deficits were observed for the North and for the SUS care network. In conclusion, the use of international parameters was not adequate for the Brazilian reality. The planning of resources for cancer care in Brazil requires reliable estimates based on local needs so that inequities are not further aggravated.

Theranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis.

Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500-1,700 nm) window modified by catalase, arginine-glycine-aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.

Development of a new poly-ε-caprolactone with low melting point for creating a thermoset mask used in radiation therapy.

This study aimed to develop a poly-ε-caprolactone (PCL) material that has a low melting point while maintaining the deformation ability. The new PCL (abbreviated as 4b45/2b20) was fabricated by mixing two types of PCL with different molecular weights, numbers of branches, and physical properties. To investigate the melting point, crystallization temperature, elastic modulus, and elongation at break for 4b45/2b20 and three commercially available masks, differential scanning calorimetry and tensile tests were performed. The melting point of 4b45/2b20 was 46.0 °C, and that of the commercially available masks was approximately 56.0 °C (55.7 °C-56.5 °C). The elastic modulus at 60 °C of 4b45/2b20 was significantly lower than the commercially available masks (1.1 ± 0.3 MPa and 46.3 ± 5.4 MPa, p = 0.0357). In addition, the elongation at break of 4b45/2b20 were significantly larger than the commercially available masks (275.2 ± 25.0% and 216.0 ± 15.2%, p = 0.0347). The crystallization temperature of 4b45/2b20 (22.1 °C) was clinically acceptable and no significant difference was found in the elastic modulus at 23 °C (253.7 ± 24.3 MPa and 282.0 ± 44.3 MPa, p = 0.4). As a shape memory-based thermoset material, 4b45/2b20 has a low melting point and large deformation ability. In addition, the crystallization temperature and strength are within the clinically acceptable standards. Because masks made using the new PCL material are formed with less pressure on the face than commercially available masks, it is a promising material for making a radiotherapy mask that can reduce the burden on patients.

Compare of Interfractional Setup Reproducibility Between Vacuum-Lock Bag and Thermoplastic Mask in Radiotherapy for Breast Cancer.

Background: This study aimed to analyze the difference of setup reproducibility between Vacuum-lock bag and Thermoplastic mask in the radiotherapy for breast cancer. Methods: A total of 100 invasive breast carcinoma patients were collected, among whom 50 patients were immobilized with Vacuum-lock bag (VB group), and the other 50 patients were immobilized with Thermoplastic mask (TM group). Set up reproducibility in different axes and comfort levels between two groups at three treatment progress points during the radiation therapy were collected and analyzed. Results: The linear regression model showed that fixed device was an independent factor of radiotherapy setup error (SE). Further subgroup analysis based on different axes showed that the SE caused by the fixed device was obvious in all directions. The comfort level in the VB group was significantly larger than that in the TM group at the beginning of treatment, reduced as the treatment progress going on, and finally disappeared within three weeks. Conclusions: Thermoplastic mask could significantly reduce positioning errors in the radiotherapy of breast cancer. Although more discomfort was found in the TM group, it could be eliminated as the treatment progresses.

Towards high spatial resolution tissue-equivalent dosimetry for microbeam radiation therapy using organic semiconductors.

Spatially fractionated ultra-high-dose-rate beams used during microbeam radiation therapy (MRT) have been shown to increase the differential response between normal and tumour tissue. Quality assurance of MRT requires a dosimeter that possesses tissue equivalence, high radiation tolerance and spatial resolution. This is currently an unsolved challenge. This work explored the use of a 500 nm thick organic semiconductor for MRT dosimetry on the Imaging and Medical Beamline at the Australian Synchrotron. Three beam filters were used to irradiate the device with peak energies of 48, 76 and 88 keV with respective dose rates of 3668, 500 and 209 Gy s-1. The response of the device stabilized to 30% efficiency after an irradiation dose of 30 kGy, with a 0.5% variation at doses of 35 kGy and higher. The calibration factor after pre-irradiation was determined to be 1.02 ±â€…0.005 µGy per count across all three X-ray energy spectra, demonstrating the unique advantage of using tissue-equivalent materials for dosimetry. The percentage depth dose curve was within ±5% of the PTW microDiamond detector. The broad beam was fractionated into 50 microbeams (50 µm FHWM and 400 µm centre-to-centre distance). For each beam filter, the FWHMs of all 50 microbeams were measured to be 51 ±â€…1.4, 53 ±â€…1.4 and 69 ±â€…1.9 µm, for the highest to lowest dose rate, respectively. The variation in response suggested the photodetector possessed dose-rate dependence. However, its ability to reconstruct the microbeam profile was affected by the presence of additional dose peaks adjacent to the one generated by the X-ray microbeam. Geant4 simulations proved that the additional peaks were due to optical photons generated in the barrier film coupled to the sensitive volume. The simulations also confirmed that the amplitude of the additional peak in comparison with the microbeam decreased for spectra with lower peak energies, as observed in the experimental data. The material packaging can be optimized during fabrication by solution processing onto a flexible substrate with a non-fluorescent barrier film. With these improvements, organic photodetectors show promising prospects as a cost-effective high spatial resolution tissue-equivalent flexible dosimeter for synchrotron radiation fields.

Megavolt bremsstrahlung measurements from linear induction accelerators demonstrate possible use as a FLASH radiotherapy source to reduce acute toxicity.

Recent studies indicate better efficacy and healthy tissue sparing with high dose-rate FLASH radiotherapy (FLASH-RT) cancer treatment. This technique delivers a prompt high radiation dose rather than fractional doses over time. While some suggest thresholds of > 40 Gy s-1 with a maximal effect at > 100 Gy s-1, accumulated evidence shows that instantaneous dose-rate and irradiation time are critical. Mechanisms are still debated, but toxicity is minimized while inducing apoptosis in malignant tissue. Delivery technologies to date show that a capability gap exists with clinic scale, broad area, deep penetrating, high dose rate systems. Based on these trends, if FLASH-RT is adopted, it may become a dominant approach except in the least technologically advanced countries. The linear induction accelerator (LIA) developed for high instantaneous and high average dose-rate, species independent charged particle acceleration, has yet to be considered for this application. We review the status of LIA technology, explore the physics of bremsstrahlung-converter-target interactions and our work on stabilizing the electron beam. While the gradient of the LIA is low, we present our preliminary work to improve the gradient by an order of magnitude, presenting a point design for a multibeam FLASH-RT system using a single accelerator for application to conformal FLASH-RT.

3D-printed individualized tooth-borne tissue retraction devices compared to conventional dental splints for head and neck cancer radiotherapy: a randomized controlled trial.

BACKGROUND: Despite modern treatment techniques, radiotherapy (RT) in patients with head and neck cancer (HNC) may be associated with high rates of acute and late treatment-related toxicity. The most effective approach to reduce sequelae after RT is to avoid as best as possible healthy tissues and organs at risk from the radiation target volume. Even small geometric changes can lead to a significant dose reduction in normal tissue and better treatment tolerability. The major objective of the current study is to investigate 3D printed, tooth-borne tissue retraction devices (TRDs) compared to conventional dental splints for head and neck RT. METHODS: In the current two-arm randomized controlled phase II trial, a maximum of 34 patients with HNC will be enrolled. Patients will receive either TRDs or conventional dental splints (randomization ratio 1:1) for the RT. The definition of the target volume, modality, total dose, fractionation, and imaging guidance is not study-specific. The primary endpoint of the study is the rate of acute radiation-induced oral mucositis after RT. The quality of life, local control and overall survival 12 months after RT are the secondary endpoints. Also, patient-reported outcomes and dental status, as well as RT plan comparisons and robustness analyzes, will be assessed as exploratory endpoints. Finally, mesenchymal stem cells, derived from the patients' gingiva, will be tested in vitro for regenerative and radioprotective properties. DISCUSSION: The preliminary clinical application of TRD showed a high potential for reducing acute and late toxicity of RT in patients with HNC. The current randomized study is the first to prospectively investigate the clinical tolerability and efficacy of TRDs for radiation treatment of head and neck tumors. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04454697; July 1st 2020; https://clinicaltrials.gov/ct2/show/record/NCT04454697 .

Development of a compact X-band linear accelerator system mounted on an O-arm rotating gantry for radiation therapy.

A compact X-band linear accelerator (LINAC) system equipped with a small and lightweight magnetron was constructed to develop a high-precision image-guided radiotherapy system. The developed LINAC system was installed in an O-ring gantry where cone-beam computed tomography (CBCT) was embedded. When the O-arm gantry is rotated, an x-ray beam is stably generated, which resulted from the stable transmission of radio frequency power into the X-band LINAC system. Quality assurance (QA) tests, including mechanical and dosimetry checks, were carried out to ensure safety and operation performance according to the American Association of Physicists in Medicine's TG-51, 142, an international standard protocol established by accredited institutions. In addition, delivery QA of the radiotherapy planning system was conducted to verify intensity-modulated radiotherapy techniques. Therefore, it was demonstrated that the developed X-band LINAC system mounted on the O-arm gantry proved to be valid and reliable for potential use in CBCT image-guided radiation therapy.

The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose.

PURPOSE: γH2AX biodosimetry has been proposed as an alternative dosimetry method for microbeam radiation therapy (MRT) because conventional dosimeters, such as ionization chambers, lack the spatial resolution required to accurately measure the MRT valley dose. Here we investigated whether γH2AX biodosimetry should be used to measure the biological valley dose of MRT-irradiated mammalian cells. MATERIALS AND METHODS: We irradiated human skin fibroblasts and mouse skin flaps with synchrotron MRT and broad beam (BB) radiation. BB doses of 1-5 Gy were used to generate a calibration curve in order to estimate the biological MRT valley dose using the γH2AX assay. RESULTS: Our key finding was that MRT induced a non-linear dose response compared to BB, where doses 2-3 times greater showed the same level of DNA DSB damage in the valley in cell and tissue studies. This indicates that γH2AX may not be an appropriate biodosimeter to estimate the biological valley doses of MRT-irradiated samples. We also established foci yields of 5.9 ± 0.04 and 27.4 ± 2.5  foci/cell/Gy in mouse skin tissue and human fibroblasts respectively, induced by BB. Using Monte Carlo simulations, a linear dose response was seen in cell and tissue studies and produced predicted peak-to-valley dose ratios (PVDRs) of ∼30 and ∼107 for human fibroblasts and mouse skin tissue respectively. CONCLUSIONS: Our report highlights novel MRT radiobiology, attempts to explain why γH2AX may not be an appropriate biodosimeter and suggests further studies aimed at revealing the biological and cellular communication mechanisms that drive the normal tissue sparing effect, which is characteristic of MRT.

McKesson® lubricating jelly and Aquasonic® ultrasound gel can be used as bolus materials for radiation therapy.

Bolus materials are commonly used for both human and veterinary radiation therapy (RT). Commercially available bolus materials often leave an air gap between the bolus and the skin which can lead to underdosing of the tumor. This prospective exploratory study evaluated the 6 MV X-ray and electron beam (6, 9, and 12 MeV) attenuating properties for two alternative bolus materials: McKesson lubricating jelly® (MLJ) and Aquasonic 100 Ultrasound gel® (AUG). The results comparing MLJ and water for 12 MeV and 9 MeV electron beams showed <3% difference, however, no other significant differences in radiation dose between water and MLJ nor AUG were seen. Findings demonstrated that both AUG and MLJ have radiation dose attenuating properties similar to water and supported use of these materials as alternative bolus materials for veterinary radiation therapy applications.