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1.
Radiother Oncol ; 198: 110414, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38942120

RESUMO

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.


Assuntos
Neoplasias Infratentoriais , Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Terapia com Prótons/métodos , Neoplasias Infratentoriais/radioterapia , Europa (Continente) , Criança , Planejamento da Radioterapia Assistida por Computador/métodos , Pré-Escolar , Masculino , Feminino , Órgãos em Risco/efeitos da radiação , Tronco Encefálico/efeitos da radiação
2.
Radiother Oncol ; 196: 110293, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38653379

RESUMO

The evidence for the value of particle therapy (PT) is still sparse. While randomized trials remain a cornerstone for robust comparisons with photon-based radiotherapy, data registries collecting real-world data can play a crucial role in building evidence for new developments. This Perspective describes how the European Particle Therapy Network (EPTN) is actively working on establishing a prospective data registry encompassing all patients undergoing PT in European centers. Several obstacles and hurdles are discussed, for instance harmonization of nomenclature and structure of technical and dosimetric data and data protection issues. A preferred approach is the adoption of a federated data registry model with transparent and agile governance to meet European requirements for data protection, transfer, and processing. Funding of the registry, especially for operation after the initial setup process, remains a major challenge.


Assuntos
Sistema de Registros , Humanos , Europa (Continente) , Estudos Prospectivos , Neoplasias/radioterapia , Terapia com Prótons
3.
Phys Med ; 118: 103301, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38290179

RESUMO

PURPOSE: The aim of this work is to investigate the feasibility of the Jagiellonian Positron Emission Tomography (J-PET) scanner for intra-treatment proton beam range monitoring. METHODS: The Monte Carlo simulation studies with GATE and PET image reconstruction with CASToR were performed in order to compare six J-PET scanner geometries. We simulated proton irradiation of a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out Bragg Peak (SOBP) of various ranges. The sensitivity and precision of each scanner were calculated, and considering the setup's cost-effectiveness, we indicated potentially optimal geometries for the J-PET scanner prototype dedicated to the proton beam range assessment. RESULTS: The investigations indicate that the double-layer cylindrical and triple-layer double-head configurations are the most promising for clinical application. We found that the scanner sensitivity is of the order of 10-5 coincidences per primary proton, while the precision of the range assessment for both SPB and SOBP irradiation plans was found below 1 mm. Among the scanners with the same number of detector modules, the best results are found for the triple-layer dual-head geometry. The results indicate that the double-layer cylindrical and triple-layer double-head configurations are the most promising for the clinical application, CONCLUSIONS:: We performed simulation studies demonstrating that the feasibility of the J-PET detector for PET-based proton beam therapy range monitoring is possible with reasonable sensitivity and precision enabling its pre-clinical tests in the clinical proton therapy environment. Considering the sensitivity, precision and cost-effectiveness, the double-layer cylindrical and triple-layer dual-head J-PET geometry configurations seem promising for future clinical application.


Assuntos
Terapia com Prótons , Prótons , Estudos de Viabilidade , Tomografia por Emissão de Pósitrons , Terapia com Prótons/métodos , Imagens de Fantasmas , Método de Monte Carlo
5.
Radiat Prot Dosimetry ; 199(14): 1616-1619, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37721070

RESUMO

Quality control of therapeutic photon beams in the form of postal dose audits based on passive dosemeters is widely used in photon radiotherapy. On the other hand, no standardised dosimetry audit programme for proton centres has been established in Europe so far. We evaluated alanine/EPR dosimetry systems developed at the Istituto Superiore di Sanità (Italy), the Hasselt Universiteit (Belgium) and the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences (Poland) for their applicability as a potential tool for routine mailed dose audits of passively scattered therapeutic proton beams. The evaluation was carried out in the form of an intercomparison. Dosemeters were irradiated in the 70 MeV proton beam at ocular proton therapy facility in the Cyclotron Centre Bronowice at the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences in Krakow. A very good agreement was found between the dose measured by three laboratories and the delivered dose determined with an ionisation chamber. This, together with the inherent properties of alanine, such as non-destructive readout, tissue equivalence, weak energy dependence, dose rate independence and insignificant fading, makes alanine a good candidate for a dosemeter used in postal auditing in proton ocular radiotherapy.


Assuntos
Terapia com Prótons , Prótons , Olho , Radiometria , Alanina
6.
Phys Med Biol ; 68(10)2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37011632

RESUMO

Objective.Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field consisting of low- and high-linear energy transfer (LET) components, the latter of which is characterized by an increased ionization density on the microscopic scale associated with increased biological effectiveness. Prediction of the yield and LET of primary and secondary charged particles at a certain depth in the patient is performed by Monte Carlo simulations but is difficult to verify experimentally.Approach.Here, the results of measurements performed with Timepix detector in the mixed radiation field produced by a therapeutic proton beam in water are presented and compared to Monte Carlo simulations. The unique capability of the detector to perform high-resolution single particle tracking and identification enhanced by artificial intelligence allowed to resolve the particle type and measure the deposited energy of each particle comprising the mixed radiation field. Based on the collected data, biologically important physics parameters, the LET of single protons and dose-averaged LET, were computed.Main results.An accuracy over 95% was achieved for proton recognition with a developed neural network model. For recognized protons, the measured LET spectra generally agree with the results of Monte Carlo simulations. The mean difference between dose-averaged LET values obtained from measurements and simulations is 17%. We observed a broad spectrum of LET values ranging from a fraction of keVµm-1to about 10 keVµm-1for most of the measurements performed in the mixed radiation fields.Significance.It has been demonstrated that the introduced measurement method provides experimental data for validation of LETDor LET spectra in any treatment planning system. The simplicity and accessibility of the presented methodology make it easy to be translated into a clinical routine in any proton therapy facility.


Assuntos
Terapia com Prótons , Humanos , Terapia com Prótons/métodos , Prótons , Inteligência Artificial , Transferência Linear de Energia , Dosagem Radioterapêutica , Método de Monte Carlo , Radiometria
7.
Phys Med Biol ; 67(24)2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36541512

RESUMO

Objective.Verification of delivered proton therapy treatments is essential for reaping the many benefits of the modality, with the most widely proposedin vivoverification technique being the imaging of positron emitting isotopes generated in the patient during treatment using positron emission tomography (PET). The purpose of this work is to reduce the computational resources and time required for simulation of patient activation during proton therapy using the GPU accelerated Monte Carlo code FRED, and to validate the predicted activity against the widely used Monte Carlo code GATE.Approach.We implement a continuous scoring approach for the production of positron emitting isotopes within FRED version 5.59.9. We simulate treatment plans delivered to 95 head and neck patients at Centrum Cyklotronowe Bronowice using this GPU implementation, and verify the accuracy using the Monte Carlo toolkit GATE version 9.0.Main results.We report an average reduction in computational time by a factor of 50 when using a local system with 2 GPUs as opposed to a large compute cluster utilising between 200 to 700 CPU threads, enabling simulation of patient activity within an average of 2.9 min as opposed to 146 min. All simulated plans are in good agreement across the two Monte Carlo codes. The two codes agree within a maximum of 0.95σon a voxel-by-voxel basis for the prediction of 7 different isotopes across 472 simulated fields delivered to 95 patients, with the average deviation over all fields being 6.4 × 10-3σ.Significance.The implementation of activation calculations in the GPU accelerated Monte Carlo code FRED provides fast and reliable simulation of patient activation following proton therapy, allowing for research and development of clinical applications of range verification for this treatment modality using PET to proceed at a rapid pace.


Assuntos
Terapia com Prótons , Humanos , Elétrons , Prótons , Tomografia por Emissão de Pósitrons/métodos , Isótopos , Método de Monte Carlo , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica
8.
Radiat Prot Dosimetry ; 198(19): 1471-1475, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36138419

RESUMO

The Maastro Proton Therapy Centre is the first European facility housing the Mevion S250i Hyperscan synchrocyclotron. The proximity of the accelerator to the patient, the presence of an active pencil beam delivery system downstream of a passive energy degrader and the pulsed structure of the beam make the Mevion stray neutron field unique amongst proton therapy facilities. This paper reviews the results of a rem-counter intercomparison experiment promoted by the European Radiation Dosimetry Group at Maastro and compares them with those at other proton therapy facilities. The Maastro neutron H*(10) in the room (100-200 µSv/Gy at about 2 m from the isocentre) is in line with accelerators using purely passive or wobbling beam delivery modalities, even though Maastro shows a dose gradient peaked near the accelerator. Unlike synchrotron- and cyclotron-based facilities, the pulsed beam at Maastro requires the employment of rem-counters specifically designed to withstand pulsed neutron fields.


Assuntos
Terapia com Prótons , Humanos , Terapia com Prótons/métodos , Doses de Radiação , Nêutrons , Radiometria/métodos , Ciclotrons , Dosagem Radioterapêutica
9.
Front Oncol ; 12: 904563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957900

RESUMO

Since 2010, EURADOS Working Group 9 (Radiation Dosimetry in Radiotherapy) has been involved in the investigation of secondary and scattered radiation doses in X-ray and proton therapy, especially in the case of pediatric patients. The main goal of this paper is to analyze and compare out-of-field neutron and non-neutron organ doses inside 5- and 10-year-old pediatric anthropomorphic phantoms for the treatment of a 5-cm-diameter brain tumor. Proton irradiations were carried out at the Cyclotron Centre Bronowice in IFJ PAN Krakow Poland using a pencil beam scanning technique (PBS) at a gantry with a dedicated scanning nozzle (IBA Proton Therapy System, Proteus 235). Thermoluminescent and radiophotoluminescent dosimeters were used for non-neutron dose measurements while secondary neutrons were measured with track-etched detectors. Out-of-field doses measured using intensity-modulated proton therapy (IMPT) were compared with previous measurements performed within a WG9 for three different photon radiotherapy techniques: 1) intensity-modulated radiation therapy (IMRT), 2) three-dimensional conformal radiation therapy (3D CDRT) performed on a Varian Clinac 2300 linear accelerator (LINAC) in the Centre of Oncology, Krakow, Poland, and 3) Gamma Knife surgery performed on the Leksell Gamma Knife (GK) at the University Hospital Centre Zagreb, Croatia. Phantoms and detectors used in experiments as well as the target location were the same for both photon and proton modalities. The total organ dose equivalent expressed as the sum of neutron and non-neutron components in IMPT was found to be significantly lower (two to three orders of magnitude) in comparison with the different photon radiotherapy techniques for the same delivered tumor dose. For IMPT, neutron doses are lower than non-neutron doses close to the target but become larger than non-neutron doses further away from the target. Results of WG9 studies have provided out-of-field dose levels required for an extensive set of radiotherapy techniques, including proton therapy, and involving a complete description of organ doses of pediatric patients. Such studies are needed for validating mathematical models and Monte Carlo simulation tools for out-of-field dosimetry which is essential for dedicated epidemiological studies which evaluate the risk of second cancers and other late effects for pediatric patients treated with radiotherapy.

10.
Radiat Oncol ; 17(1): 50, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264184

RESUMO

BACKGROUND: Variable relative biological effectiveness (vRBE) in proton therapy might significantly modify the prediction of RBE-weighted dose delivered to a patient during proton therapy. In this study we will present a method to quantify the biological range extension of the proton beam, which results from the application of vRBE approach in RBE-weighted dose calculation. METHODS AND MATERIALS: The treatment plans of 95 patients (brain and skull base patients) were used for RBE-weighted dose calculation with constant and the McNamara RBE model. For this purpose the Monte Carlo tool FRED was used. The RBE-weighted dose distributions were analysed using indices from dose-volume histograms. We used the volumes receiving at least 95% of the prescribed dose (V95) to estimate the biological range extension resulting from vRBE approach. RESULTS: The vRBE model shows higher median value of relative deposited dose and D95 in the planning target volume by around 1% for brain patients and 4% for skull base patients. The maximum doses in organs at risk calculated with vRBE was up to 14 Gy above dose limit. The mean biological range extension was greater than 0.4 cm. DISCUSSION: Our method of estimation of biological range extension is insensitive for dose inhomogeneities and can be easily used for different proton plans with intensity-modulated proton therapy (IMPT) optimization. Using volumes instead of dose profiles, which is the common method, is more universal. However it was tested only for IMPT plans on fields arranged around the tumor area. CONCLUSIONS: Adopting a vRBE model results in an increase in dose and an extension of the beam range, which is especially disadvantageous in cancers close to organs at risk. Our results support the need to re-optimization of proton treatment plans when considering vRBE.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias da Base do Crânio/radioterapia , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Método de Monte Carlo , Estadiamento de Neoplasias , Órgãos em Risco , Polônia , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Neoplasias da Base do Crânio/patologia , Tomografia Computadorizada por Raios X
11.
Phys Med Biol ; 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35259730

RESUMO

Objective Proton therapy is gaining popularity because of the improved dose delivery over conventional radiation therapy. The secondary dose to healthy tissues is dominated by secondary neutrons. Commercial rem-counters are valuable instruments for the on-line assessment of neutron ambient dose equivalent (H*(10)). In general, however, a priori knowledge of the type of facility and of the radiation field is required for the proper choice of any survey meter. The novel Mevion S250i Hyperscan synchrocyclotron mounts the accelerator directly on the gantry. It provides a scanned 227 MeV proton beam, delivered in pulses with a pulse width of 10 µs at 750 Hz frequency, which is afterwards degraded in energy by a range shifter modulator system. This environment is particularly challenging for commercial rem-counters; therefore, we tested the reliability of some of the most widespread rem-counters to understand their limits in the Mevion S250i stray neutron field. Approach This work, promoted by the European Radiation Dosimetry Group (EURADOS), describes a rem-counter intercomparison at the Maastro Proton Therapy centre in the Netherlands, which houses the novel Mevion S250i Hyperscan system. Several rem-counters were employed in the intercomparison (LUPIN, LINUS, WENDI-II, LB6411, NM2B-458, NM2B-495Pb), which included simulation of a patient treatment protocol employing a water tank phantom. The outcomes of the experiment were compared with models and data from the literature. Main results We found that only the LUPIN allowed for a correct assessment of H*(10) within a 20% uncertainty. All other rem-counters underestimated the reference H*(10) by factors from 2 to more than 10, depending on the detector model and on the neutron dose per pulse. In pulsed fields, the neutron dose per pulse is a fundamental parameter, while the average neutron dose rate is a secondary quantity. An average 150-200 µSv/GyRBE neutron H*(10) at various positions around the phantom and at distances between 186 cm and 300 cm from it was measured per unit therapeutic dose delivered to the target. Significance Our results are partially in line with results obtained at similar Mevion facilities employing passive energy modulation. Comparisons with facilities employing active energy modulation confirmed that the neutron H*(10) can increase up to more than a factor of 10 when passive energy modulation is employed. The challenging environment of the Mevion stray neutron field requires the use of specific rem-counters sensitive to high-energy neutrons (up to a few hundred MeV) and specifically designed to withstand pulsed neutron fields.

12.
Med Phys ; 49(4): 2672-2683, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35090187

RESUMO

PURPOSE: Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary. The purpose of this study is to evaluate and compare out-of-field doses in pediatric CSI treatment using conventional and advanced photon radiotherapy (RT) and advanced proton therapy. To our knowledge, it is the first such comparison based on in-phantom measurements. Additionally, for out-of-field doses during photon RT in this and other studies, comparisons were made using analytical modeling. METHODS: In order to describe the out-of-field doses absorbed in a pediatric patient during actual clinical treatment, an anthropomorphic phantom, which mimics the 10-year-old child, was used. Photon 3D-conformal RT (3D-CRT) and two advanced, highly conformal techniques: photon volumetric-modulated arc therapy (VMAT) and active pencil beam scanning (PBS) proton RT were used for CSI treatment. Radiophotoluminescent and poly-allyl-diglycol-carbonate nuclear track detectors were used for photon and neutron dosimetry in the phantom, respectively. Out-of-field doses from neutrons were expressed in terms of dose equivalent. A two-Gaussian model was implemented for out-of-field doses during photon RT. RESULTS: The mean VMAT photon doses per target dose to all organs in this study were under 50% of the target dose (i.e., <500 mGy/Gy), while the mean 3D-CRT photon dose to oesophagus, gall bladder, and thyroid, exceeded that value. However, for 3D-CRT, better sparing was achieved for eyes and lungs. The mean PBS photon doses for all organs were up to three orders of magnitude lower compared to VMAT and 3D-CRT and exceeded 10 mGy/Gy only for the oesophagus, intestine, and lungs. The mean neutron dose equivalent during PBS for eight organs of interest (thyroid, breasts, lungs, liver, stomach, gall bladder, bladder, prostate) ranged from 1.2 mSv/Gy for bladder to 23.1 mSv/Gy for breasts. Comparison of out-of-field doses in this and other phantom studies found in the literature showed that a simple and fast two-Gaussian model for out-of-field doses as a function of distance from the field edge can be applied in a CSI using photon RT techniques. CONCLUSIONS: PBS is the most promising technique for out-of-field dose reduction in comparison to photon techniques. Among photon techniques, VMAT is a preferred choice for most of out-of-field organs and especially for the thyroid, while doses for eyes, breasts, and lungs are lower for 3D-CRT. For organs outside the field edge, a simple analytical model can be helpful for clinicians involved in treatment planning using photon RT but also for retrospective data analysis for cancer risk estimates and epidemiology in general.


Assuntos
Neoplasias Cerebelares , Radiação Cranioespinal , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Neoplasias Cerebelares/radioterapia , Criança , Radiação Cranioespinal/efeitos adversos , Radiação Cranioespinal/métodos , Humanos , Masculino , Órgãos em Risco/efeitos da radiação , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
13.
Radiother Oncol ; 163: 143-149, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34461183

RESUMO

PURPOSE: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. METHODS: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. RESULTS: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. CONCLUSIONS: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.


Assuntos
Terapia com Prótons , Neoplasias da Base do Crânio , Encéfalo/diagnóstico por imagem , Humanos , Método de Monte Carlo , Necrose/etiologia , Terapia com Prótons/efeitos adversos , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/radioterapia
14.
Phys Med ; 82: 54-63, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33588228

RESUMO

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.


Assuntos
Inteligência Artificial , Tomografia Computadorizada Quadridimensional , Humanos , Japão , Polônia , Planejamento da Radioterapia Assistida por Computador
15.
Int J Nanomedicine ; 14: 7249-7262, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564877

RESUMO

BACKGROUND: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. METHOD: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. RESULTS: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. CONCLUSION: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.


Assuntos
Alginatos/farmacologia , Alginatos/toxicidade , Curcumina/farmacologia , Curcumina/toxicidade , Micelas , Testes de Toxicidade , Alginatos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Materiais Biocompatíveis/química , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Citocinas/sangue , Feminino , Humanos , Hidrodinâmica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Especificidade de Órgãos
16.
Acta Oncol ; 58(12): 1720-1730, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31393203

RESUMO

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Cooperação Internacional , Órgãos em Risco , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Tronco Encefálico/efeitos da radiação , Cóclea/efeitos da radiação , Europa (Continente) , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Laringe/efeitos da radiação , Neoplasias Nasais/diagnóstico por imagem , Neoplasias Nasais/radioterapia , Nervo Óptico/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/radioterapia , Glândula Parótida/efeitos da radiação , Fótons/uso terapêutico , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X , Carga Tumoral
17.
Phys Med ; 46: 67-74, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29519411

RESUMO

PURPOSE: The feasibility of setting-up generic, hospital-independent dose alert levels to initiate vigilance on possible skin injuries in interventional procedures was studied for three high-dose procedures (chemoembolization (TACE) of the liver, neuro-embolization (NE) and percutaneous coronary intervention (PCI)) in 9 European countries. METHODS: Gafchromic® films and thermoluminescent dosimeters (TLD) were used to determine the Maximum Skin Dose (MSD). Correlation of the online dose indicators (fluoroscopy time, kerma- or dose-area product (KAP or DAP) and cumulative air kerma at interventional reference point (Ka,r)) with MSD was evaluated and used to establish the alert levels corresponding to a MSD of 2 Gy and 5 Gy. The uncertainties of alert levels in terms of DAP and Ka,r, and uncertainty of MSD were calculated. RESULTS: About 20-30% of all MSD values exceeded 2 Gy while only 2-6% exceeded 5 Gy. The correlations suggest that both DAP and Ka,r can be used as a dose indicator for alert levels (Pearson correlation coefficient p mostly >0.8), while fluoroscopy time is not suitable (p mostly <0.6). Generic alert levels based on DAP (Gy cm2) were suggested for MSD of both 2 Gy and 5 Gy (for 5 Gy: TACE 750, PCI 250 and NE 400). The suggested levels are close to the lowest values published in several other studies. The uncertainty of the MSD was estimated to be around 10-15% and of hospital-specific skin dose alert levels about 20-30% (with coverage factor k = 1). CONCLUSIONS: The generic alert levels are feasible for some cases but should be used with caution, only as the first approximation, while hospital-specific alert levels are preferred as the final approach.


Assuntos
Fluoroscopia/efeitos adversos , Pele/efeitos da radiação , Cirurgia Assistida por Computador , Estudos de Viabilidade , Humanos , Dosimetria Termoluminescente
19.
Radiat Prot Dosimetry ; 180(1-4): 355-359, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29149320

RESUMO

We developed a radiation detector based on an organic scintillator for spectrometry and dosimetry of out-of-field secondary neutrons from clinical proton beams. The detector consists of an EJ-299-34 crystalline organic scintillator, coupled by fiber optic cable to a silicon photomultiplier (SiPM). Proof of concept measurements were taken with 137Cs and 252Cf, and corresponding simulations were performed in MCNPX-PoliMi. Despite its small size, the detector is able to discriminate between neutron and gamma-rays via pulse shape discrimination. We simulated the response function of the detector to monoenergetic neutrons in the 100 keV-0 MeV range using MCNPX-PoliMi. The measured unfolded 252Cf neutron spectrum is in good agreement with the theoretical Watt fission spectrum. We determined the ambient dose equivalent by folding the spectrum with the fluence-to-ambient dose conversion coefficient, with a 1.4% deviation from theory. Some preliminary proton beam experiments were preformed at the Bronowice Cyclotron Center patient treatment facility using a clinically relevant proton pencil beam for brain tumor and craino-spinal treatment directed at a child phantom.


Assuntos
Neoplasias Encefálicas/radioterapia , Califórnio/análise , Radioisótopos de Césio/análise , Nêutrons , Imagens de Fantasmas , Contagem de Cintilação/instrumentação , Criança , Pré-Escolar , Simulação por Computador , Humanos , Dosagem Radioterapêutica
20.
Med Pr ; 68(6): 735-741, 2017 Oct 17.
Artigo em Polonês | MEDLINE | ID: mdl-28857089

RESUMO

BACKGROUND: One of the numerous sub-areas of interventional radiology is the use of X-rays in gastroenterology. X-ray fluoroscopy is applied in therapeutic procedures, including endoscopic retrograde cholangiopancreatography (ERCP) that is frequently performed. The ERCP procedure is aimed at imaging the pancreatic duct and biliary tracts. MATERIAL AND METHODS: In this paper radiation risk to the gastrenterologist performing ERCP procedures was investigated. The procedures were performed by a single gastroenterologist in the ERCP Laboratory, University Clinical Hospital Military Memorial Medical Academy - Central Veterans' Hospital in Lódz, Poland. The study comprised 2 series of measurements, one taken during the procedures with continuous fluoroscopy mode, the other during procedures with fluoroscopy in pulsed mode at a frequency of 3 pulses/s. Exposure parameters, anatomical data of patient and dose equivalents for the eyes, skin of the hand and the effective dose for whole body of the gastroenterologist were recorded during each procedure. RESULTS: The collected data cover 70 ERCP procedures - 40 procedures were controlled by continuous fluoroscopy and 30 by pulsed fluoroscopy. The results reveal that pulsed fluoroscopy makes it possible to reduce doses received by the gastroeneterologist from 45% to 60% compared to continuous fluoroscopy. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography procedures can cause radiation risk to the gastroenterologist performing them. The use of continuous fluoroscopy can result in achieving an equivalent dose to eye lens nearly 20 mSv per year, i.e., the decreased annual limit recommended by the International Commission on Radiological Protection (ICRP). Med Pr 2017;68(6):735-741.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Corpo Clínico Hospitalar , Exposição Ocupacional/efeitos adversos , Doses de Radiação , Proteção Radiológica/normas , Serviço Hospitalar de Radiologia/normas , Feminino , Gastroenterologistas/normas , Humanos , Masculino , Exposição Ocupacional/análise , Polônia , Monitoramento de Radiação/métodos , Radiologia Intervencionista/normas , Padrões de Referência
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