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1.
Br J Radiol ; 93(1107): 20180883, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30943055

RESUMO

OBJECTIVE: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: : Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: : Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: : This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.


Assuntos
Cordoma/terapia , Hipertermia Induzida/métodos , Terapia com Prótons/métodos , Sacro , Neoplasias da Coluna Vertebral/terapia , Idoso , Cordoma/diagnóstico por imagem , Cordoma/patologia , Terapia Combinada/métodos , Estudos de Viabilidade , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
2.
Br J Radiol ; 93(1107): 20190304, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31356107

RESUMO

Treatment planning is the process where the prescription of the radiation oncologist is translated into a deliverable treatment. With the complexity of contemporary radiotherapy, treatment planning cannot be performed without a computerized treatment planning system. Proton therapy (PT) enables highly conformal treatment plans with a minimum of dose to tissues outside the target volume, but to obtain the most optimal plan for the treatment, there are a multitude of parameters that need to be addressed. In this review areas of ongoing improvements and research in the field of PT treatment planning are identified and discussed. The main focus is on issues of immediate clinical and practical relevance to the PT community highlighting the needs for the near future but also in a longer perspective. We anticipate that the manual tasks performed by treatment planners in the future will involve a high degree of computational thinking, as many issues can be solved much better by e.g. scripting. More accurate and faster dose calculation algorithms are needed, automation for contouring and planning is required and practical tools to handle the variable biological efficiency in PT is urgently demanded just to mention a few of the expected improvements over the coming 10 years.


Assuntos
Algoritmos , Previsões , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Automação , Confiabilidade dos Dados , Humanos , Método de Monte Carlo , Determinação de Necessidades de Cuidados de Saúde , Órgãos em Risco/diagnóstico por imagem , Terapia com Prótons/tendências , Planejamento da Radioterapia Assistida por Computador/tendências , Radioterapia Conformacional/tendências , Eficiência Biológica Relativa , Fatores de Tempo
3.
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
4.
Int J Radiat Oncol Biol Phys ; 106(3): 597-603, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678633

RESUMO

PURPOSE: The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation. METHODS AND MATERIALS: Proton beams with linear energy transfer of 1.1 and 3.3 keV/µm irradiated human cancer and normal cells under a longitudinal (perpendicular) magnetic field of BL (BP) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field Dwo to the dose with the magnetic field Dw, R10 = Dwo/Dw, was determined for each cell line and magnetic field. RESULTS: For cancer cells exposed to the 1.1- (3.3-) keV/µm proton beams, R10s were increased to 1.10 ± 0.07 (1.11 ± 0.07) and 1.11 ± 0.07 (1.12 ± 0.07) by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, respectively. For normal cells, R10s were increased to 1.13 ± 0.06 (1.17 ± 0.06) and 1.17 ± 0.06 (1.30 ± 0.06) by the BLs. In contrast, R10s were not changed significantly from 1 by the perpendicular magnetic fields of BP = 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/µm proton beams. CONCLUSIONS: The biological effectiveness of proton beams was significantly enhanced by longitudinal magnetic fields of BL = 0.3 and 0.6 T, whereas the biological effectiveness was not altered by perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in magnetic resonance imaging guided proton therapy with a longitudinal magnetic field.


Assuntos
Transferência Linear de Energia , Campos Magnéticos , Terapia com Prótons/métodos , Eficiência Biológica Relativa , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Desenho de Equipamento , Humanos , Imagem por Ressonância Magnética Intervencionista , Radioterapia Guiada por Imagem
5.
Br J Radiol ; 93(1107): 20190583, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31696729

RESUMO

OBJECTIVE: To identify a subgroup of lung cancer plans where the analytical dose calculation (ADC) algorithm may be clinically acceptable compared to Monte Carlo (MC) dose calculation in intensity modulated proton therapy (IMPT). METHODS: Robust-optimised IMPT plans were generated for 20 patients to a dose of 70 Gy (relative biological effectiveness) in 35 fractions in Raystation. For each case, four plans were generated: three with ADC optimisation using the pencil beam (PB) algorithm followed by a final dose calculation with the following algorithms: PB (PB-PB), MC (PB-MC) and MC normalised to prescription dose (PB-MC scaled). A fourth plan was generated where MC optimisation and final dose calculation was performed (MC-MC). Dose comparison and γ analysis (PB-PB vs PB-MC) at two dose thresholds were performed: 20% (D20) and 99% (D99) with PB-PB plans as reference. RESULTS: Overestimation of the dose to 99% and mean dose of the clinical target volume was observed in all PB-MC compared to PB-PB plans (median: 3.7 Gy(RBE) (5%) (range: 2.3 to 6.9 Gy(RBE)) and 1.8 Gy(RBE) (3%) (0.5 to 4.6 Gy(RBE))). PB-MC scaled plans resulted in significantly higher CTVD2 compared to PB-PB (median difference: -4 Gy(RBE) (-6%) (-5.3 to -2.4 Gy(RBE)), p ≤ .001). The overall median γ pass rates (3%-3 mm) at D20 and D99 were 93.2% (range:62.2-97.5%) and 71.3 (15.4-92.0%). On multivariate analysis, presence of mediastinal disease and absence of range shifters were significantly associated with high γ pass rates. Median D20 and D99 pass rates with these predictors were 96.0% (95.3-97.5%) and 85.4% (75.1-92.0%). MC-MC achieved similar target coverage and doses to OAR compared to PB-PB plans. CONCLUSION: In the presence of mediastinal involvement and absence of range shifters Raystation ADC may be clinically acceptable in lung IMPT. Otherwise, MC algorithm would be recommended to ensure accuracy of treatment plans. ADVANCES IN KNOWLEDGE: Although MC algorithm is more accurate compared to ADC in lung IMPT, ADC may be clinically acceptable where there is mediastinal involvement and absence of range shifters.


Assuntos
Algoritmos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Tomografia Computadorizada Quadridimensional , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias do Mediastino/radioterapia , Análise Multivariada , Órgãos em Risco/efeitos da radiação , Eficiência Biológica Relativa , Incerteza
6.
Br J Radiol ; 93(1107): 20190494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31687835

RESUMO

Clinical parameters and empirical evidence are the primary determinants for current treatment planning in radiation oncology. Personalized medicine in radiation oncology is only at the very beginning to take the genetic background of a tumor entity into consideration to define an individual treatment regimen, the total dose or the combination with a specific anticancer agent. Likewise, stratification of patients towards proton radiotherapy is linked to its physical advantageous energy deposition at the tumor site with minimal healthy tissue being co-irradiated distal to the target volume. Hence, the fact that photon and proton irradiation also induce different qualities of DNA damages, which require differential DNA damage repair mechanisms has been completely neglected so far. These subtle differences could be efficiently exploited in a personalized treatment approach and could be integrated into personalized treatment planning. A differential requirement of the two major DNA double-strand break repair pathways, homologous recombination and non-homologous end joining, was recently identified in response to proton and photon irradiation, respectively, and subsequently influence the mode of ionizing radiation-induced cell death and susceptibility of tumor cells with defects in DNA repair machineries to either quality of ionizing radiation.This review focuses on the differential DNA-damage responses and subsequent biological processes induced by photon and proton irradiation in dependence of the genetic background and discusses their impact on the unicellular level and in the tumor microenvironment and their implications for combined treatment modalities.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA/fisiologia , Fótons/uso terapêutico , Medicina de Precisão , Terapia com Prótons , Eficiência Biológica Relativa , Absorção de Radiação , Animais , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral/efeitos da radiação , Terapia Combinada , Reparo do DNA por Junção de Extremidades , Humanos , Transferência Linear de Energia , Neoplasias/genética , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Tolerância a Radiação/genética , Radiação Ionizante , Microambiente Tumoral
7.
Br J Radiol ; 93(1107): 20190334, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31738081

RESUMO

Dose in proton radiotherapy is generally prescribed by scaling the physical proton dose by a constant value of 1.1. Relative biological effectiveness (RBE) is defined as the ratio of doses required by two radiation modalities to cause the same level of biological effect. The adoption of an RBE of 1.1. assumes that the biological efficacy of protons is similar to photons, allowing decades of clinical dose prescriptions from photon treatments and protocols to be utilized in proton therapy. There is, however, emerging experimental evidence that indicates that proton RBE varies based on technical, tissue and patient factors. The notion that a single scaling factor may be used to equate the effects of photons and protons across all biological endpoints and doses is too simplistic and raises concern for treatment planning decisions. Here, we review the models that have been developed to better predict RBE variations in tissue based on experimental data as well as using a mechanistic approach.


Assuntos
Modelos Teóricos , Neoplasias/radioterapia , Terapia com Prótons/métodos , Lesões por Radiação , Eficiência Biológica Relativa , Algoritmos , Animais , Linhagem Celular Tumoral , DNA/efeitos da radiação , Reparo do DNA , Humanos , Modelos Biológicos , Método de Monte Carlo , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Planejamento da Radioterapia Assistida por Computador
8.
Br J Radiol ; 93(1107): 20190469, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860338

RESUMO

Proton arc therapy (PAT) has been proposed as a possible evolution for proton therapy. This commentary uses dosimetric and cancer risk evaluations from earlier studies to compare PAT with intensity modulated proton therapy. It is concluded that, although PAT may not produce better physical dose distributions than intensity modulated proton therapy, the radiobiological considerations associated with particular PAT techniques could offer the possibility of an increased therapeutic index.


Assuntos
Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Índice Terapêutico , Humanos , Neoplasias Pulmonares/radioterapia , Órgãos em Risco/efeitos da radiação , Hipofracionamento da Dose de Radiação , Radiobiologia , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Incerteza
9.
Br J Radiol ; 93(1107): 20190873, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31860337

RESUMO

The UK has an important role in the evaluation of proton beam therapy (PBT) and takes its place on the world stage with the opening of the first National Health Service (NHS) PBT centre in Manchester in 2018, and the second in London coming in 2020. Systematic evaluation of the role of PBT is a key objective. By September 2019, 108 patients had started treatment, 60 paediatric, 19 teenagers and young adults and 29 adults. Obtaining robust outcome data is vital, if we are to understand the strengths and weaknesses of current treatment approaches. This is important in demonstrating when PBT will provide an advantage and when it will not, and in quantifying the magnitude of benefit.The UK also has an important part to play in translational PBT research, and building a research capability has always been the vision. We are perfectly placed to perform translational pre-clinical biological and physical experiments in the dedicated research room in Manchester. The nature of DNA damage from proton irradiation is considerably different from X-rays and this needs to be more fully explored. A better understanding is needed of the relative biological effectiveness (RBE) of protons, especially at the end of the Bragg peak, and of the effects on tumour and normal tissue of PBT combined with conventional chemotherapy, targeted drugs and immunomodulatory agents. These experiments can be enhanced by deterministic mathematical models of the molecular and cellular processes of DNA damage response. The fashion of ultra-high dose rate FLASH irradiation also needs to be explored.


Assuntos
Institutos de Câncer/estatística & dados numéricos , Terapia com Prótons/estatística & dados numéricos , Medicina Estatal/estatística & dados numéricos , Adolescente , Adulto , Institutos de Câncer/provisão & distribução , Fortalecimento Institucional , Criança , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Dano ao DNA , Inglaterra , Humanos , Modelos Teóricos , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Avaliação de Programas e Projetos de Saúde , Terapia com Prótons/efeitos adversos , Radioterapia (Especialidade)/educação , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Pesquisa , Pesquisa Médica Translacional , Resultado do Tratamento , Incerteza , Adulto Jovem
10.
Br J Radiol ; 93(1107): 20190412, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31868525

RESUMO

Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is low, concerns were raised about late effects like secondary cancer caused by dose depositions far away from the treated area. This is especially true for neutrons and therefore the stray dose contribution from neutrons in proton therapy is still being investigated. The higher biological effectiveness of neutrons compared to photons is the main cause of these concerns. The gold-standard in neutron dosimetry is measurements, but performing neutron measurements is challenging. Different approaches have been taken to overcome these difficulties, for instance with newly developed neutron detectors. Monte Carlo simulations is another common technique to assess the dose from secondary neutrons. Measurements and simulations are used to develop analytical models for fast neutron dose estimations. This article tries to summarize the developments in the different aspects of neutron dose in proton therapy since 2017. In general, low neutron doses have been reported, especially in active proton therapy. Although the published biological effectiveness of neutrons relative to photons regarding cancer induction is higher, it is unlikely that the neutron dose has a large impact on the second cancer risk of proton therapy patients.


Assuntos
Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Nêutrons/efeitos adversos , Terapia com Prótons/métodos , Humanos , Método de Monte Carlo , Fótons/uso terapêutico , Terapia com Prótons/efeitos adversos , Radiometria/instrumentação , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa
11.
Int J Radiat Oncol Biol Phys ; 106(1): 82-89, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580927

RESUMO

PURPOSE: To investigate the efficacy and safety of proton beam therapy (PBT) for the treatment of stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Six hundred sixty-nine patients with 682 tumors histologically or clinically diagnosed stage I NSCLC according to the seventh edition of Union for International Cancer Control who received passive-scattering PBT from April 2004 and December 2013 in Japan were retrospectively reviewed to analyze survival, local control, and toxicities. RESULTS: Of 669 patients, 486 (72.6%) were men, with a median age of 76 years (range, 42-94 years). NSCLC was histologically confirmed in 440 patients (65.7%). Clinical T stages included T1a (n = 265; 38.9%), T1b (n = 216; 31.7%), and T2a (n = 201; 29.4%). The total irradiation doses of PBT ranged from 74.4 to 131.3 biological effective dose GyE (median, 109.6 biological effective dose GyE). The median follow-up period was 38.2 months (range, 0.6-154.5 months) for all patients. The 3-year overall survival and progression-free survival rates for all patients were 79.5% and 64.1%, respectively. For patients with stage IA tumors, the 3-year overall survival and progression-free survival rates were 82.8% and 70.6%, respectively, and the corresponding rates for patients with stage IB tumors were 70.8% and 47.3%, respectively. The 3-year local progression-free rates for all, stage IA, and stage IB patients were 89.8%, 93.5%, and 79.4%, respectively. The incidence of grade 2, 3, 4, and 5 pneumonitis was 9.8%, 1.0%, 0%, and 0.7%, respectively. The incidence of grade ≥3 dermatitis was 0.4%. No grade 4 or severe adverse events, other than pneumonitis, were observed. CONCLUSIONS: PBT appears to yield acceptable survival rates, with a low rate of toxicities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Terapia com Prótons/efeitos adversos , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/patologia , Radiodermatite/epidemiologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Taxa de Sobrevida
12.
Int J Radiat Oncol Biol Phys ; 106(1): 167-173, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586664

RESUMO

PURPOSE: The adenoid cystic carcinoma (ACC), Erbitux, and Particle Therapy (ACCEPT) phase 1/2 trial (NCT01192087) evaluated a combined-modality approach (concurrent cetuximab and intensity modulated radiation therapy with carbon ion boost) for newly diagnosed nonmetastatic head and neck ACC. METHODS AND MATERIALS: Twenty-three patients with ACC were enrolled between June 2012 and June 2017 after initial diagnosis or postoperatively. All received a 400 mg/m2 cetuximab loading dose a week before radiation therapy, followed by weekly 250 mg/m2 doses starting on the first day of radiation therapy. The carbon ion radiation therapy boost was 24 Gy (relative biological effectiveness) in 8 daily fractions, followed by intensity modulated radiation therapy (54 Gy). The primary endpoint was safety and feasibility (defined based on Common Terminology Criteria for Adverse Events grade ≥3 events). Secondary endpoints included local and distant relapse, disease-free survival, and overall survival. RESULTS: Disease was most commonly in the paranasal sinuses (30%), palate (17%), and nasopharynx (17%). Nine (39%) patients underwent surgery (R1: 22%, R2: 78%). Median follow-up was 38.5 months. No patients experienced grade 4 to 5 events. Rates of grade 3 rash and radiation dermatitis were 17% and 22%, respectively. Grade 2 and 3 mucositis and dysgeusia occurred in 43% and 48% and in 9% and 0%, respectively. Grade 2 to 3 dysphagia and xerostomia were present in 43% and 4% and in 26% and 0%, respectively. At last follow-up, 5 (22%) patients experienced in-field relapse and 6 (26%) developed distant metastases. The 3-year disease-free survival was 67%, and median overall survival was 54 months. CONCLUSIONS: Outcomes of this trial were satisfactory. Although the trial did not meet the predefined criteria of feasibility owing to the comparatively high rates of grade 3 dermatitis, numbers are comparable to existing data on cetuximab + radiation therapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Adenoide Cístico/terapia , Cetuximab/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Radioterapia com Íons Pesados , Radioterapia de Intensidade Modulada , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Adenoide Cístico/patologia , Cetuximab/administração & dosagem , Quimiorradioterapia/efeitos adversos , Terapia Combinada/métodos , Transtornos de Deglutição/etiologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Esquema de Medicação , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Radioterapia com Íons Pesados/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Radiodermatite/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Eficiência Biológica Relativa , Xerostomia/etiologia
13.
Int J Radiat Oncol Biol Phys ; 106(1): 194-205, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610250

RESUMO

PURPOSE: To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing. METHODS AND MATERIALS: The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICRC-p treatments using a murine glioma cell line (GL261) was performed. RESULTS: CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/ß)x assignment and RBE modeling, the CICRC-p treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUDHe. For both CICRC-p and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICRC-p treatment in heterogenous settings. CONCLUSIONS: Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings.


Assuntos
Neoplasias Encefálicas/radioterapia , Carcinoma Adenoide Cístico/radioterapia , Cordoma/radioterapia , Glioma/radioterapia , Radioterapia com Íons Pesados/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias da Coluna Vertebral/radioterapia , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Carbono/uso terapêutico , Carcinoma Adenoide Cístico/diagnóstico por imagem , Linhagem Celular Tumoral , Cordoma/diagnóstico por imagem , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Glioma/diagnóstico por imagem , Hélio/uso terapêutico , Humanos , Transferência Linear de Energia , Camundongos , Órgãos em Risco , Imagens de Fantasmas , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Sacro , Neoplasias da Coluna Vertebral/diagnóstico por imagem
14.
Int J Mol Sci ; 20(19)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591311

RESUMO

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.


Assuntos
Ciclina D1/genética , Tolerância a Radiação , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Ciclina D1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Células MCF-7 , Terapia com Prótons , Eficiência Biológica Relativa , Transdução de Sinais/efeitos da radiação , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/radioterapia , Raios X
15.
Br J Radiol ; 92(1104): 20190672, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31603350

RESUMO

OBJECTIVE: This paper considers aspects of radiobiology and cell and tissue kinetics applicable to legal disputations concerned with diagnostic and treatment onset delays. METHODS: Various models for tumour volume changes with time are reviewed for estimating volume ranges at earlier times, using ranges of kinetic parameters. Statistical cure probability methods, using Poisson statistics with allowances for parameter heterogeneity, are also described to estimate the significance of treatment delays, as well as biological effective dose (BED) estimations of radiation effectiveness. RESULTS: The use of growth curves, based on parameters in the literature but with extended ranges, can identify a window of earlier times when such tumour volumes would be amenable to a cure based on the literature for curability with stage (and dimensions). Also, where tumour dimensions are not available in a post-operative setting, higher cure probabilities can be achieved if treatment had been given at earlier times. CONCLUSION: The use of radiobiological modelling can provide useful insights, with quantitative assessments of probable prior conditions and future outcomes, and thus be of assistance to a Court in deciding the most correct judgement. ADVANCES IN KNOWLEDGE: This study collates prior knowledge about aspects of radiobiology that can be useful in the accumulation of sufficient proof within medicolegal claims involving diagnostic and treatment days.


Assuntos
Diagnóstico Tardio/legislação & jurisprudência , Neoplasias/diagnóstico , Neoplasias/radioterapia , Radiobiologia/legislação & jurisprudência , Tempo para o Tratamento/legislação & jurisprudência , Algoritmos , Biomarcadores Tumorais/análise , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Estadiamento de Neoplasias , Neoplasias/patologia , Distribuição de Poisson , Resolução de Problemas , Prognóstico , Radioterapia (Especialidade)/legislação & jurisprudência , Radioterapia (Especialidade)/métodos , Radiobiologia/métodos , Eficiência Biológica Relativa , Fatores de Tempo , Carga Tumoral/fisiologia
17.
Radiat Res ; 192(6): 662-665, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31560639

RESUMO

Previously reported studies have revealed that the application of a magnetic field longitudinal to a carbon-ion beam enhances its biological effectiveness. Here we investigated how timing of the magnetic field application with respect to beam irradiation influenced this effect. Human cancer cells were exposed to carbon-ion beams with linear energy transfer (LET) of 12 and 50 keV/µm. The longitudinal magnetic field of 0.3 T was applied to the cells just before, during or immediately after the beam irradiation. The effects of the timing on the biological effectiveness were evaluated by cell survival. The biological effectiveness increased only if the magnetic field was applied during beam irradiation for both LETs.


Assuntos
Carbono/química , Sobrevivência Celular/efeitos da radiação , Radioterapia com Íons Pesados/métodos , Íons Pesados , Transferência Linear de Energia , Campos Magnéticos , Calibragem , Linhagem Celular Tumoral , Dano ao DNA , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Humanos , Íons , Eficiência Biológica Relativa , Reprodutibilidade dos Testes
18.
Technol Cancer Res Treat ; 18: 1533033819871309, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495269

RESUMO

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness = 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness = 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.


Assuntos
Condrossarcoma/radioterapia , Transferência Linear de Energia , Radiografia , Raios X/efeitos adversos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Condrossarcoma/patologia , Dano ao DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Radiação Ionizante , Eficiência Biológica Relativa
19.
Phys Med ; 64: 132-144, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515012

RESUMO

PURPOSE: To develop a user-friendly program for biological modeling to analyze radiation-induced responses at the scales of the cell population and organ. METHODS: The program offers five established cell population surviving fraction (SF) models to estimate the SF and the relative biological effectiveness (RBE) from clonogenic assay data, and two established models to calculate the normal tissue complication probability (NTCP) and tumor control probability (TCP) from radiation treatment plans. Users can also verify the results with multiple types of quantitative analyses and graphical representation tools. RESULTS: Users can verify the estimated SF, model parameters, RBE, and the respective uncertainties in the calculations of the SF and RBE modes. The qualities of the treatment plans can also be compared with at most three rival plans in terms of the NTCP, TCP, uncomplicated TCP (UCP), and user-dependent weight-based UCP (UUCP), in the calculation of the NTCP and TCP modes. Based on the validation study on accuracy and speed, the averaged mean relative errors (MREs) of the estimated parameters for all tested cell lines were not higher than 0.3% in each of the studied SF models, and the averaged MREs of the calculated NTCP and TCP for all tested treatment plans were not higher than 0.1%. The computation times for SF, RBE, NTCP, and TCP were less than 1.5 s. CONCLUSIONS: The dose response analysis program can provide a trustworthy and convenient environment for researchers to analyze radiation-induced biological effects.


Assuntos
Modelos Teóricos , Eficiência Biológica Relativa , Calibragem , Probabilidade , Fatores de Tempo
20.
Radiat Res ; 192(4): 380-387, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390313

RESUMO

When assessing radiation-related risk among the atomic bomb survivors, choices in modeling approach can have an important impact on the results, which are then used to inform radiation protection standards throughout the world. The atomic bombings of Hiroshima and Nagasaki produced a mixed-field radiation exposure from two sources: neutrons and gamma rays. Neutrons are more densely ionizing and cause greater biological damage per unit absorbed dose, resulting in greater relative biological effectiveness (RBE) than gamma rays. To account for this, a combined weighted dose is typically calculated as the sum of the gamma-ray dose and 10 times the neutron dose in the Radiation Effects Research Foundation's reports of mortality, solid cancer incidence and other outcomes. In addition, the colon, which is often chosen as the whole-body representative organ in these analyses, is relatively deep in the body and therefore its dose calculation involves heavy body shielding of neutrons and a low neutron/gamma-ray ratio. With added follow-up and recently updated doses, we used a data-driven approach to determine the best-fitting neutron RBE for a range of organs of varying depth. Aggregated person-year tables of solid cancer incidence (1958-2009) from the Life Span Study were created with separate neutron and gamma-ray DS02R1 doses for several organs including breast, brain, thyroid, bone marrow, lung, liver and colon. Typical excess relative risk models estimating the linear effect of radiation dose were fitted using a range of neutron weights (1-250) to calculate combined dose for each organ, and model deviances were compared to assess fit. Furthermore, models using separate terms for gamma-ray and neutron dose were also examined, wherein the ratio of the neutron/gamma-ray linear terms indicated the best estimate of the RBE. The best-fitting RBE value for the traditional weighted colon dose was 80 [95% confidence interval (CI): 20-190], while the RBEs for other organs using weighted doses ranged from 25 to 60, with the best-fitting weights and confidence interval widths both incrementally increasing with greater depth of organ. Models using separate neutron- and gamma-ray-dose terms gave similar results to weighted linear combinations, with a neutron/gamma-ray term ratio of 79.9 (95% CI: 18.8-192.3) for colon. These results indicated that the traditionally modeled RBE of 10 may underestimate the effect of neutrons across the full dose range, although these updated estimates still have fairly wide confidence bounds. Furthermore, the colon is among the deepest of organs and may not be the best choice as a single surrogate organ dose, as it may minimize the role of the neutrons. Future work with more refined organ doses could shed more light on RBE-related information available in the Life Span Study data.


Assuntos
Nêutrons/efeitos adversos , Armas Nucleares , Eficiência Biológica Relativa , Sobreviventes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Raios gama , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Adulto Jovem
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