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1.
Anticancer Res ; 41(2): 835-843, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517289

RESUMO

BACKGROUND/AIM: This study aimed to determine appropriate deformable image registration (DIR) algorithms for pancreatic cancer patients undergoing carbon ion radiotherapy (CIRT). PATIENTS AND METHODS: The performance of three types of DIR algorithms, including intensity-based DIR (iDIR), contour-based DIR (cDIR), and hybrid DIR (hDIR) were evaluated using seventy-one CT images from eight pancreatic cancer patients. Both the geometry of the CTV and subsequent dose warping discrepancies were evaluated using the dice similarity coefficient (DSC) and the difference in V95. RESULTS: cDIR and hDIR had superior performance than iDIR in both DSC and V95 (p<0.0001). iDIR caused accumulated dose to be underestimated by 5% in the median CTV V95 compared to the other methods. CONCLUSION: hDIR and cDIR can be utilized to assess the accumulated dose in CIRT for pancreatic cancer. iDIR can be considered when the obtained DSC is greater than 0.89.


Assuntos
Radioterapia com Íons Pesados/métodos , Neoplasias Pancreáticas/radioterapia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
Br J Radiol ; 93(1116): 20200247, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021102

RESUMO

In the UK, one in two people will develop cancer during their lifetimes and radiotherapy (RT) plays a key role in effective treatment. High energy proton beam therapy commenced in the UK National Health Service in 2018. Heavier charged particles have potential advantages over protons by delivering more dose in the Bragg peak, with a sharper penumbra, lower oxygen dependence and increased biological effectiveness. However, they also require more costly equipment including larger gantries to deliver the treatment. There are significant uncertainties in the modelling of relative biological effectiveness and the effects of the fragmentation tail which can deliver dose beyond the Bragg peak. These effects need to be carefully considered especially in relation to long-term outcomes.In 2019, a group of clinicians, clinical scientists, engineers, physical and life scientists from academia and industry, together with funding agency stakeholders, met to consider how the UK should address new technologies for RT, especially the use of heavier charged particles such as helium and carbon and new modes of delivery such as FLASH and spatially fractionated radiotherapy (SFRT).There was unanimous agreement that the UK should develop a facility for heavier charged particle therapy, perhaps constituting a new National Ion Research Centre to enable research using protons and heavier charged particles. Discussion followed on the scale and features, including which ions should be included, from protons through helium, boron, and lithium to carbon, and even oxygen. The consensus view was that any facility intended to treat patients must be located in a hospital setting while providing dedicated research space for physics, preclinical biology and clinical research with beam lines designed for both in vitro and in vivo research. The facility should to be able to investigate and deliver both ultra-high dose rate FLASH RT and SFRT (GRID, minibeams etc.). Discussion included a number of accelerator design options and whether gantries were required. Other potential collaborations might be exploited, including with space agencies, electronics and global communications industries and the nuclear industry.In preparation for clinical delivery, there may be opportunities to send patients overseas (for 12C or 4He ion therapy) using the model of the National Health Service (NHS) Proton Overseas Programme and to look at potential national clinical trials which include heavier ions, FLASH or SFRT. This could be accomplished under the auspices of NCRI CTRad (National Cancer Research Institute, Clinical and Translational Radiotherapy Research Working Group).The initiative should be a community approach, involving all interested parties with a vision that combines discovery science, a translational research capability and a clinical treatment facility. Barriers to the project and ways to overcome them were discussed. Finally, a set of different scenarios of features with different costs and timelines was constructed, with consideration given to the funding environment (prer-Covid-19) and need for cross-funder collaboration.


Assuntos
Fracionamento da Dose de Radiação , Radioterapia com Íons Pesados/métodos , Neoplasias/radioterapia , Humanos , Reino Unido
3.
Br J Radiol ; 93(1115): 20200172, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021811

RESUMO

OBJECTIVE: Particle radiobiology has contributed new understanding of radiation safety and underlying mechanisms of action to radiation oncology for the treatment of cancer, and to planning of radiation protection for space travel. This manuscript will highlight the significance of precise physical and biologically effective dosimetry to this translational research for the benefit of human health.This review provides a brief snapshot of the evolving scientific basis for, and the complex current global status, and remaining challenges of hadron therapy for the treatment of cancer. The need for particle radiobiology for risk planning in return missions to the Moon, and exploratory deep-space missions to Mars and beyond are also discussed. METHODS: Key lessons learned are summarized from an impressive collective literature published by an international cadre of multidisciplinary experts in particle physics, radiation chemistry, medical physics of imaging and treatment planning, molecular, cellular, tissue radiobiology, biology of microgravity and other stressors, theoretical modeling of biophysical data, and clinical results with accelerator-produced particle beams. RESULTS: Research pioneers, many of whom were Nobel laureates, led the world in the discovery of ionizing radiations originating from the Earth and the Cosmos. Six radiation pioneers led the way to hadron therapy and the study of charged particles encountered in outer space travel. Worldwide about 250,000 patients have been treated for cancer, or other lesions such as arteriovenous malformations in the brain between 1954 and 2019 with charged particle radiotherapy, also known as hadron therapy. The majority of these patients (213,000) were treated with proton beams, but approximately 32,000 were treated with carbon ion radiotherapy. There are 3500 patients who have been treated with helium, pions, neon or other ions. There are currently 82 facilities operating to provide ion beam clinical treatments. Of these, only 13 facilities located in Asia and Europe are providing carbon ion beams for preclinical, clinical, and space research. There are also numerous particle physics accelerators worldwide capable of producing ion beams for research, but not currently focused on treating patients with ion beam therapy but are potentially available for preclinical and space research. Approximately, more than 550 individuals have traveled into Lower Earth Orbit (LEO) and beyond and returned to Earth. CONCLUSION: Charged particle therapy with controlled beams of protons and carbon ions have significantly impacted targeted cancer therapy, eradicated tumors while sparing normal tissue toxicities, and reduced human suffering. These modalities still require further optimization and technical refinements to reduce cost but should be made available to everyone in need worldwide. The exploration of our Universe in space travel poses the potential risk of exposure to uncontrolled charged particles. However, approaches to shield and provide countermeasures to these potential radiation hazards in LEO have allowed an amazing number of discoveries currently without significant life-threatening medical consequences. More basic research with components of the Galactic Cosmic Radiation field are still required to assure safety involving space radiations and combined stressors with microgravity for exploratory deep space travel. ADVANCES IN KNOWLEDGE: The collective knowledge garnered from the wealth of available published evidence obtained prior to particle radiation therapy, or to space flight, and the additional data gleaned from implementing both endeavors has provided many opportunities for heavy ions to promote human health.


Assuntos
Radioterapia com Íons Pesados , Neoplasias/radioterapia , Institutos de Câncer/provisão & distribução , Feminino , Radioterapia com Íons Pesados/história , Radioterapia com Íons Pesados/métodos , Radioterapia com Íons Pesados/estatística & dados numéricos , Íons Pesados/história , História do Século XIX , História do Século XX , Humanos , Malformações Arteriovenosas Intracranianas/história , Malformações Arteriovenosas Intracranianas/radioterapia , Íons/história , Masculino , Neônio/história , Neônio/uso terapêutico , Neoplasias Induzidas por Radiação/prevenção & controle , Nêutrons/história , Nêutrons/uso terapêutico , Prêmio Nobel , Aceleradores de Partículas , Prótons/história , Exposição à Radiação , Proteção Radiológica , Radiobiologia/história , Voo Espacial
4.
PLoS One ; 15(6): e0234471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520972

RESUMO

Abdominal spacers are useful for maintaining the distance between the target tumors and surrounding tissues, such as the gastrointestinal tract, in patients treated with carbon ion radiotherapy. Surgical intervention to remove the spacers is sometimes necessary because of abdominal infections triggered by long-term spacer placement or intestinal perforation. Therefore, spacers that do not require surgical removal and provide effective drainage against abdominal infections are urgently needed. This study aimed to develop a spacer that could be removed non-surgically and one that provides the therapeutic effect of drainage in patients who receive carbon ion radiotherapy for abdominal tumors. A novel fan-shaped spacer was constructed from a film drain that was folded along the trigger line. Simple withdrawal of the trigger line caused the film drain to fold and the holding lines to become free. We performed laparoscopy-assisted insertion with pneumoperitoneum and blind removal of the spacer fourteen times using a porcine model. Saline in the abdominal cavity was effectively aspirated using the spacer. Our novel fan-shaped spacer could be removed safely without surgery and was able to drain fluid effectively from the abdominal cavity.


Assuntos
Neoplasias Abdominais/radioterapia , Cateteres , Drenagem/métodos , Radioterapia com Íons Pesados/métodos , Abdome/fisiopatologia , Neoplasias Abdominais/cirurgia , Animais , Drenagem/instrumentação , Suínos
5.
Oncology ; 98(8): 513-519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32408297

RESUMO

Background and summary: Among all vulvar cancers, primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a very rare tumor characterized by a slow growth, a high local aggressiveness, and a remarkable recurrence rate. Due to its rarity, treatment remains a challenge for oncologists and gynecological surgeons. Key message: The present paper reports clinical, radiological, and histological features of ACC of Bartholin's gland and reviews the literature data on the treatment options with a particular focus on the potential role of particle radiation therapy.


Assuntos
Glândulas Vestibulares Maiores/patologia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/radioterapia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/radioterapia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/tratamento farmacológico , Feminino , Radioterapia com Íons Pesados/métodos , Humanos , Recidiva Local de Neoplasia , Prognóstico , Doenças Raras/diagnóstico , Doenças Raras/patologia , Doenças Raras/radioterapia , Fatores de Risco , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/tratamento farmacológico
6.
Phys Med Biol ; 65(16): 165001, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32422621

RESUMO

The commissioning and operation of a particle therapy centre requires an extensive set of detectors for measuring various parameters of the treatment beam. Among the key devices are detectors for beam range quality assurance. In this work, a novel range telescope based on a plastic scintillator and read out by a large-scale CMOS sensor is presented. The detector is made of a stack of 49 plastic scintillator sheets with a thickness of 2-3 mm and an active area of 100 × 100 mm2, resulting in a total physical stack thickness of 124.2 mm. This compact design avoids optical artefacts that are common in other scintillation detectors. The range of a proton beam is reconstructed using a novel Bragg curve model that incorporates scintillator quenching effects. Measurements to characterise the performance of the detector were carried out at the Heidelberger Ionenstrahl-Therapiezentrum (HIT, Heidelberg, GER) and the Clatterbridge Cancer Centre (CCC, Bebington, UK). The maximum difference between the measured range and the reference range was found to be 0.41 mm at a proton beam range of 310 mm and was dominated by detector alignment uncertainties. With the new detector prototype, the water-equivalent thickness of PMMA degrader blocks has been reconstructed within ± 0.1 mm. An evaluation of the radiation hardness proves that the range reconstruction algorithm is robust following the deposition of 6,300 Gy peak dose into the detector. Furthermore, small variations in the beam spot size and transverse beam position are shown to have a negligible effect on the range reconstruction accuracy. The potential for range measurements of ion beams is also investigated.


Assuntos
Algoritmos , Radioterapia com Íons Pesados/métodos , Plásticos , Monitoramento de Radiação/métodos , Contagem de Cintilação/instrumentação , Telescópios/estatística & dados numéricos , Humanos
7.
Breast Cancer Res Treat ; 181(2): 291-296, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32318954

RESUMO

PURPOSE: Breast cancer is the most commonly diagnosed cancer in women, with many efforts aimed at reducing acute and late toxicity given the generally favorable clinical outcomes with the current standard of care. Carbon ion radiation therapy is an emerging technique that may reduce dose to adjacent organs at risk while allowing dose escalation to the target. Given the efficacy of the standard treatments for breast cancer, there have been few prospective studies to date investigating carbon ion radiation therapy in breast cancer. METHODS: PubMed/Medline, Ebsco, Cochrane, and Scopus were systematically reviewed using the search terms "carbon ion" and "breast" in November 2019. Out of the 76 articles screened, 26 articles were included. RESULTS: This comprehensive review describes the physical and biological properties of carbon ion radiation therapy, with an emphasis on how these properties can be applied in the setting of breast cancer. Studies investigating the role of carbon ion radiation therapy in early stage breast cancers are reviewed. Additionally, the use of carbon ion radiation therapy in locally advanced disease, recurrent disease, and radiation-induced angiosarcoma are discussed. CONCLUSION: Although the data is limited, the early clinical results are promising. Further clinical trials are needed, especially in the setting of locally advanced and recurrent disease, to fully define the potential role of carbon ion radiation therapy in the treatment of breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia com Íons Pesados/métodos , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico
8.
Phys Med Biol ; 65(12): 125002, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32320970

RESUMO

Radiochromic films are useful as dosimeters in high-precision radiotherapy owing to their high spatial resolution. However, when a particle beam is measured using a radiochromic film, the dose cannot be estimated accurately because the film darkness varies with variations in linear energy transfer (LET). This paper proposes a novel method for estimating the LET and the dose based on the film darkness. In this method, after a high-LET particle beam, such as a carbon-ion beam, was incident on the film, the film was digitized and its net optical density was determined. Further, the non-linearity of the film response curve between the dose and the darkness, depending on LET, was used. Then, calibration curves were created using 290 MeV u-1 mono energetic carbon-ion beams. We used LETs of 20, 50, 100, and 150 keV µm-1 and a physical dose of 2-14 Gy. The calibration curves were approximated for each LET using a quadratic function. The correlations between the coefficients of the quadratic function and the LET were also obtained. To verify the proposed method, the films were irradiated under 12 different conditions corresponding to various depths and doses. Four depths of -2, -5, -10, and -20 mm with respect to the Bragg peak, and three different preset values were used for the film measurements. The films were analyzed in four groups, where each group comprised films irradiated at the same depth. The LETs obtained from the film analysis, ordered from the upstream of the beam, were 20, 41, 56, and 97 keV µm-1, and the doses for the lowest preset value were 3.95, 4.07, 4.03, and 3.99 Gy for the four groups. The LETs obtained from the film analysis increased toward the Bragg peak, and the doses measured in the ionization chamber were almost equal to 4 Gy.


Assuntos
Dosimetria Fotográfica/métodos , Transferência Linear de Energia , Calibragem , Carbono/uso terapêutico , Radioterapia com Íons Pesados/métodos
9.
Cancer Radiother ; 24(5): 429-436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32247687

RESUMO

Imaging is critical to each step of precision radiation therapy, i.e. planning, setup, delivery and assessment of response. Hadrontherapy can be considered to deliver more precise dose distribution that may better spare normal tissues from intermediate low doses of radiation. In addition, hadrontherapy using high linear energy transfer ions may also be used for dose escalation on biological target volumes defined by functional imaging. However, the physical characteristics of hadrontherapy also make it more demanding in terms of imaging accuracy and image-based dose calculation. Some of the developments needed in imaging are specific to hadrontherapy. The current review addresses current status of imaging in proton therapy and the drawbacks of photon-based imaging for hadrons. It also addresses requirements in hadrontherapy planning with respect to multimodal imaging for proper target and organ at risk definition as well as to target putative radioresistant areas such as hypoxic ones, and with respect to dose calculation using dual energy CT, MR-proton therapy, proton radiography. Imaging modalities, such as those used in photon-based radiotherapy (intensity modulated and stereotactic radiotherapy), are somewhat already implemented or should be reaching "routine" hadrontherapy (at least proton therapy) practice in planning, repositioning and response evaluation optimizable within the next five years. Online monitoring imaging by PET, as currently developed for hadrontherapy, is already available. Its spatiotemporal limits restrict its use but similar to prompt gamma detection, represents an area of active research for the next 5 to 10 years. Because of the more demanding and specific dose deposit characteristics, developments image-guided hadrontherapy, such as specific proton imaging using tomography or ionoacoustics, as well as delivery with MR-proton therapy, may take another 10 years to reach the clinics in specific applications. Other aspects are briefly described such as range monitoring. Finally, the potential of imaging normal tissue changes and challenges to assess tumour response are discussed.


Assuntos
Radioterapia com Íons Pesados/métodos , Imagem Multimodal/métodos , Neoplasias/radioterapia , Órgãos em Risco/diagnóstico por imagem , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Transferência Linear de Energia , Neoplasias/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Radioterapia/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos
10.
Rev Sci Instrum ; 91(2): 023309, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113412

RESUMO

The National Institute of Radiological Sciences has investigated multiple-ion therapy using energetic beams of helium, carbon, oxygen, and neon ions, to improve treatment outcomes of refractory cancer. For this therapy, it is necessary to ensure the helium-ion beam purity to avoid irradiation by unwanted ions. Here, we develop a measurement method for monitoring beam purity. This method can measure the charge number of the ions in a high-purity beam using an ionization chamber and Faraday cup. In addition, it can be used to detect the contamination of the clinical helium-ion beam. We perform beam experiments to evaluate our beam-purity monitoring method and predict that our method is capable of detecting contamination below 1%.


Assuntos
Radioterapia com Íons Pesados/métodos , Humanos , Controle de Qualidade
11.
Phys Med Biol ; 65(12): 125006, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32176873

RESUMO

In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.


Assuntos
Radioisótopos de Carbono/uso terapêutico , Radioterapia com Íons Pesados/métodos , Radioisótopos de Oxigênio/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Humanos , Método de Monte Carlo , Movimento (Física) , Imagens de Fantasmas , Eficiência Biológica Relativa
12.
Phys Med Biol ; 65(12): 125007, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32182606

RESUMO

We investigate the effects of an increase in the production of secondary electrons when a ß - source commonly used in internal radionuclide therapy, 67Cu, is radiolabelled to a super-paramagnetic iron oxide nanoparticle (SPION), with specific emphasis on the role of SPION cluster size and geometry. A positive relationship is found between the degree to which the nanoparticles are clustered and the associated radio-enhancement effects, with cluster population size playing a major role, as well as SPION separation within a cluster and the distance between clusters. Our simulation results indicate that SPIONs labelled with 67Cu can induce a nonlinear amplification in the number of secondary electrons produced of up to 4% in bulk, with localised regions of nearer inter-SPION separation producing an increase of over 400% for a 20 nm average SPION separation. Such variation in enhancement due to local concentration effects may help identify clinical strategies that enhance efficacy for a given radiation dosage, or achieve equal efficacy with reduced radiation dosage.


Assuntos
Partículas beta/uso terapêutico , Radioisótopos de Cobre/uso terapêutico , Radioterapia com Íons Pesados/métodos , Nanopartículas Metálicas/uso terapêutico , Humanos , Método de Monte Carlo
13.
Eur J Radiol ; 126: 108933, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171109

RESUMO

PURPOSE: To evaluate if baseline ADC from DWI sequences could predict response to treatment in patients with sacral chordoma not suitable for surgery treated with carbon ion radiotherapy (CIRT) alone compared with volume changes. METHODS: Fifty-nine patients with sacral chordoma not suitable for surgery underwent one cycle of CIRT alone and a minimum of 12-months follow-up. All patients underwent MRI before treatment (baseline), every three months in the first two years after treatment, and every six months afterwards. For each MRI, lesion volume was obtained and median, kurtosis, and skewness ADC were analyzed within the whole lesion volume. Volume changes between baseline and the last available follow-up were used to divide patients with partial response, progression of disease and stable disease (PR, PD, and SD). RESULTS: Ten patients were excluded since DWI sequences from baseline MRI were not available. ADC maps obtained from baseline DWI examinations of 50 lesions in the remaining 49 patients were considered. Seven lesions were categorized as PD, 30 PR, and 13 SD. PD showed significantly higher median ADC values at baseline (p = 0.003) compared with both PR and SD (1665vs1253vs1263 *10-6 mm²/s), and more negative skewness values (-0.26vs0.26vs0.08), although not significantly different (p = 0.16). CONCLUSIONS: Preliminary results suggest that baseline ADC could predict response to treatment with CIRT, particularly to detect potential non-responder patients.


Assuntos
Cordoma/diagnóstico por imagem , Cordoma/radioterapia , Imagem de Difusão por Ressonância Magnética/métodos , Radioterapia com Íons Pesados/métodos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Resultado do Tratamento
14.
Phys Med Biol ; 65(9): 095007, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32028273

RESUMO

Accurate beam range prediction during clinical treatment planning is key to improve targeted dose delivery in proton and heavy ion therapy. A substantial source of beam range uncertainty is the prediction of ion stopping power ratio (SPR) relative to water from an empirical calibration based on conventional x-ray computed tomography (CT) used in clinical practice today. The aim of this study was to investigate the potential of a novel spectral CT imaging technique based on a dual-layer detector-based approach to improve the SPR prediction for particle therapy treatment planning, an improvement that would minimize the beam range uncertainty and allow for reduced safety margins in the patient. Using calibrated and validated maps of electron density and effective atomic number from spectral CT data, predicted SPR values in tissue substitutes were within a mean accuracy of 0.6% compared to measured SPR and showed substantially better agreement with measured data compared to standard CT-number-to-SPR calibration. The accuracy of SPR was not affected by CT acquisition settings, reconstruction parameters, phantom size, and type. Additionally, various spectral CT conversion algorithms were compared to determine the most accurate prediction method. Dosimetric validation of the developed method using a half-head anthropomorphic phantom in a routine-like setting indicated that SPR prediction with dual-layer spectral CT outperforms the clinical single-energy CT standard with a range prediction improvement of 1 mm. This study demonstrated in homogeneous and heterogeneous phantoms that spectral CT is feasible for particle therapy planning to improve range estimates for high-precision particle therapy.


Assuntos
Algoritmos , Cabeça/diagnóstico por imagem , Radioterapia com Íons Pesados/métodos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Calibragem , Humanos , Radiometria/métodos , Incerteza
15.
BMC Cancer ; 20(1): 75, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000716

RESUMO

BACKGROUND: Carbon ion Radiotherapy for prostate cancer is widely used, however reports are limited from single institute or short follow up. We performed a prospective observational study (GUNMA0702) to evaluate the feasibility and efficacy of carbon ion radiotherapy for localized and locally advanced prostate cancer. METHODS: Between June 2010 and August 2013, 304 patients with localized prostate cancer were treated, with a median follow-up duration of 60 months. All patients received carbon ion radiotherapy with 57.6 Gy (RBE) in 16 fractions over 4 weeks. Hormonal therapy was given according to the risk group. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0 by the National Cancer Institute. RESULTS: The overall 5-year biochemical relapse-free rate was 92.7%, with rates of 91.7, 93.4, and 92.0% in low-risk, intermediate-risk, and high-risk patients, respectively. The 5-year local control and overall survival rates were 98.4 and 96.6%, respectively. Acute grade 3 or greater toxicity was not observed. Late grade 2 and grade 3 genitourinary and gastrointestinal toxicity rates were 9 and 0.3%, and 0.3, and 0%, respectively. CONCLUSIONS: The present protocol of carbon ion radiotherapy for prostate cancer provided low genitourinary and gastrointestinal toxicity with good biochemical control within 5 years. TRIAL REGISTRATION: University Medical Information Network Clinical Trial Registry number: UMIN000003827.


Assuntos
Radioterapia com Íons Pesados/métodos , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Radioterapia com Íons Pesados/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Próstata/patologia , Hipofracionamento da Dose de Radiação , Análise de Sobrevida , Resultado do Tratamento
16.
Phys Med Biol ; 65(5): 055002, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31962302

RESUMO

Recently, it has been proposed that a mixed helium/carbon beam could be used for online monitoring in carbon ion beam therapy. Fully stripped, the two ion species exhibit approximately the same mass/charge ratio and hence could potentially be accelerated simultaneously in a synchrotron to the same energy per nucleon. At the same energy per nucleon, helium ions have about three times the range of carbon ions, which could allow for simultaneous use of the carbon ion beam for treatment and the helium ion beam for imaging. In this work, measurements and simulations of PMMA phantoms as well as anthropomorphic phantoms irradiated sequentially with a helium ion and a carbon ion beam at equal energy per nucleon are presented. The range of the primary helium ion beam and the fragment tail of the carbon ion beam exiting the phantoms were detected using a novel range telescope made of thin plastic scintillator sheets read out by a flat-panel CMOS sensor. A 10:1 carbon to helium mixing ratio is used, generating a helium signal well above the carbon fragment background while adding little to the dose delivered to the patient. The range modulation of a narrow air gap of 1 mm thickness in the PMMA phantom that affects less than a quarter of the particles in a pencil beam were detected, demonstrating the achievable relative sensitivity of the presented method. Using two anthropomorphic pelvis phantoms it is shown that small rotations of the phantom as well as simulated bowel gas movements cause detectable changes in the helium/carbon beam exiting the phantom. The future prospects and limitations of the helium/carbon mixing as well as its technical feasibility are discussed.


Assuntos
Radioterapia com Íons Pesados/métodos , Hélio/uso terapêutico , Carbono/uso terapêutico , Radioterapia com Íons Pesados/instrumentação , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Telescópios
17.
Br J Radiol ; 93(1107): 20190224, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31317768

RESUMO

The combination of radiotherapy and immunotherapy is one of the most promising strategies for cancer treatment. Recent clinical results support the pre-clinical experiments pointing to a benefit for the combined treatment in metastatic patients. Charged particle therapy (using protons or heavier ions) is considered one of the most advanced radiotherapy techniques, but its cost remains higher than conventional X-ray therapy. The most important question to be addressed to justify a more widespread use of particle therapy is whether they can be more effective than X-rays in combination with immunotherapy. Protons and heavy ions have physical advantages compared to X-rays that lead to a reduced damage to the immune cells, that are required for an effective immune response. Moreover, densely ionizing radiation may have biological advantages, due to different cell death pathways and release of cytokine mediators of inflammation. We will discuss results in esophageal cancer patients showing that charged particles can reduce the damage to blood lymphocytes compared to X-rays, and preliminary in vitro studies pointing to an increased release of immune-stimulating cytokines after heavy ion exposure. Pre-clinical and clinical studies are ongoing to test these hypotheses.


Assuntos
Neoplasias Esofágicas/radioterapia , Radioterapia com Íons Pesados/métodos , Terapia com Prótons/métodos , Radioimunoterapia/métodos , Morte Celular , Citocinas/metabolismo , DNA/efeitos da radiação , Dano ao DNA , Neoplasias Esofágicas/imunologia , Humanos , Imunoterapia/economia , Mediadores da Inflamação/metabolismo , Linfócitos/efeitos da radiação , Linfopenia/etiologia , Raios X/efeitos adversos
18.
Br J Radiol ; 93(1107): 20190291, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31437004

RESUMO

Hypofractionated radiotherapy is attractive concerning patient burden and therapy costs, but many aspects play a role when it comes to assess its safety. While exploited for conventional photon therapy and carbon ion therapy, hypofractionation with protons is only rarely applied. One reason for this is uncertainty in the described dose, mainly due to the relative biological effectiveness (RBE), which is small for protons, but not negligible. RBE is generally dose-dependent, and for higher doses as used in hypofractionation, a thorough RBE evaluation is needed. This review article focuses on the RBE variability in protons and associated issues or implications for hypofractionation.


Assuntos
Terapia com Prótons/métodos , Hipofracionamento da Dose de Radiação , Eficiência Biológica Relativa , Radioterapia com Íons Pesados/métodos , Humanos , Terapia com Prótons/estatística & dados numéricos , Radiobiologia , Resultado do Tratamento , Incerteza
19.
Int J Radiat Biol ; 96(2): 172-178, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31633435

RESUMO

Purpose: Accumulated damage in neural stem cells (NSCs) during brain tumor radiotherapy causes cognitive dysfunction to the patients. Carbon-ion radiotherapy can reduce undesired irradiation of normal tissues more efficiently than conventional photon radiotherapy. This study elucidates the responses of NSCs to carbon-ion radiation.Methods: Human NSCs and glioblastoma A-172 cells were irradiated with carbon-ion radiation and γ-rays, which have different linear-energy-transfer (LET) values of 108 and 0.2 keV/µm, respectively. After irradiation, growth rates were measured, apoptotic cells were detected by flow cytometry, and DNA synthesizing cells were immunocytochemically visualized.Results: Growth rates of NSCs and A-172 cells were decreased after irradiation. The percentages of apoptotic cells were remarkably increased in NSCs but not in A-172 cells. In contrast, the fractions of DNA synthesizing A-172 cells were decreased in a dose-dependent manner. These results indicate that apoptosis induction and DNA synthesis inhibition contribute to the growth inhibition of NSCs and glioblastoma cells, respectively. In addition, high-LET carbon ions induced more profound effects than low-LET γ-rays.Conclusions: Apoptosis is an important clinical target to protect NSCs during brain tumor radiotherapy using carbon-ion radiation as well as conventional X-rays.


Assuntos
Apoptose/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Raios gama , Glioblastoma/radioterapia , Radioterapia com Íons Pesados/métodos , Células-Tronco Neurais/efeitos da radiação , Biomarcadores/metabolismo , Carbono , Divisão Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , DNA/efeitos da radiação , Dano ao DNA , Relação Dose-Resposta à Radiação , Humanos , Imuno-Histoquímica , Íons , Transferência Linear de Energia , Nestina/metabolismo , Fótons , Fatores de Transcrição SOXB1/metabolismo
20.
Int J Radiat Biol ; 96(2): 179-186, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31633439

RESUMO

Purpose: We studied lethal and mutagenic bystander effects in normal human fibroblasts irradiated with low-energy-carbon ions.Materials and methods: After cells reached confluence, cells were irradiated with initial energies of 6 MeV/n carbon ions. The residual energy and LET value were 4.6 MeV/n and 309 keV/µm. The doses used for survival and mutational studies were 0.082 and 0.16 Gy. Irradiation was carried out using 4 different irradiation conditions and plating conditions: (1) The entire cell area on the Mylar film was irradiated (We abbreviate as 'all irradiation'); (2) Irradiated and unirradiated cells were pooled in a 1:1 ratio and plated as a single culture until the plating for lethal and mutagenic experiments (We abbreviate as 'mixed population'); (3) Only half of the area on the Mylar film were irradiated using an ion-beam stopper (We abbreviate as 'half irradiation'); and (4) Only half of the area of the cells were irradiated, and a specific inhibitor of gap junctions was added to the culture (We abbreviate as 'half irradiation with inhibitor'). Cell samples were analyzed for lethal and mutagenic bystander effects, including a PCR evaluation of the mutation spectrum.Results: The surviving fraction of all irradiation was the same as the half irradiation case. The surviving fractions of both mixed population and the half irradiation with inhibitor were the same level and higher than those of all irradiation and half irradiation. The mutation frequencies at the HPRT (the hypoxanthine-guanine phosphoribosyl transferase) locus of all irradiation and half irradiation were at the same level and were higher than those of mixed population and half irradiation with inhibitor, respectively.Conclusion: There is evidence that the bystander effects for both lethality and mutagenicity occurred in the unirradiated half of the cells, in which only half of the cells were irradiated with the carbon ions. These results suggest that the bystander cellular effects via gap-junction-mediated cell-cell communication are induced by high-LET-carbon ions.


Assuntos
Efeito Espectador/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Fibroblastos/efeitos da radiação , Junções Comunicantes/efeitos da radiação , Radioterapia com Íons Pesados/métodos , Mutagênese , Carbono/química , Técnicas de Cultura de Células , Dano ao DNA , Relação Dose-Resposta à Radiação , Íons Pesados , Humanos , Hipoxantina Fosforribosiltransferase/genética , Íons , Transferência Linear de Energia , Mutagênicos , Mutação
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