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1.
Radiologe ; 60(11): 1038-1046, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33025131

RESUMO

CLINICAL/METHODICAL ISSUE: Oral cavity malignancies are the most common tumors in the field of ear, nose and throat medicine or otorhinolaryngology worldwide. It comprises a heterogeneous group of tumors, the knowledge of which is necessary to meet the different requirements of diagnostics and therapy. STANDARD RADIOLOGICAL METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), sonography (US), nuclear medical procedures (NUK). PERFORMANCE: The above-mentioned diagnostics are used in a complementary manner. ACHIEVEMENTS: Early diagnosis of the tumor improves staging and thus the patient's therapy and prognosis. PRACTICAL RECOMMENDATIONS: The radiologist plays an important role in the interdisciplinary treatment of malignant tumors of the oral cavity. Despite great progress in radiotherapy, oncology and immunotherapy, surgery still plays an important role in the treatment of malignant diseases of the oral cavity.


Assuntos
Neoplasias Bucais , Tomografia Computadorizada por Raios X , Humanos , Imageamento por Ressonância Magnética , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Estadiamento de Neoplasias , Prognóstico
3.
Br J Cancer ; 110(11): 2655-61, 2014 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-24786603

RESUMO

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Sorafenibe , Temozolomida , Resultado do Tratamento
4.
Phys Med Biol ; 69(16)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39025113

RESUMO

Objective.Online adaptive radiation therapy requires fast and automated contouring of daily scans for treatment plan re-optimization. However, automated contouring is imperfect and introduces contour uncertainties. This work aims at developing and comparing robust optimization strategies accounting for such uncertainties.Approach.A deep-learning method was used to predict the uncertainty of deformable image registration, and to generate a finite set of daily contour samples. Ten optimization strategies were compared: two baseline methods, five methods that convert contour samples into voxel-wise probabilities, and three methods accounting explicitly for contour samples as scenarios in robust optimization. Target coverage and organ-at-risk (OAR) sparing were evaluated robustly for simplified proton therapy plans for five head-and-neck cancer patients.Results.We found that explicitly including target contour uncertainty in robust optimization provides robust target coverage with better OAR sparing than the baseline methods, without increasing the optimization time. Although OAR doses first increased when increasing target robustness, this effect could be prevented by additionally including robustness to OAR contour uncertainty. Compared to the probability-based methods, the scenario-based methods spared the OARs more, but increased integral dose and required more computation time.Significance.This work proposed efficient and beneficial strategies to mitigate contour uncertainty in treatment plan optimization. This facilitates the adoption of automatic contouring in online adaptive radiation therapy and, more generally, enables mitigation also of other sources of contour uncertainty in treatment planning.


Assuntos
Neoplasias de Cabeça e Pescoço , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Incerteza , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos
5.
Phys Med Biol ; 69(15)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38986481

RESUMO

Objective. Predicting potential deformations of patients can improve radiotherapy treatment planning. Here, we introduce new deep-learning models that predict likely anatomical changes during radiotherapy for head and neck cancer patients.Approach. Denoising diffusion probabilistic models (DDPMs) were developed to generate fraction-specific anatomical changes based on a reference cone-beam CT (CBCT), the fraction number and the dose distribution delivered. Three distinct DDPMs were developed: (1) theimage modelwas trained to directly generate likely future CBCTs, (2) the deformable vector field (DVF) model was trained to generate DVFs that deform a reference CBCT and (3) thehybrid modelwas trained similarly to the DVF model, but without relying on an external deformable registration algorithm. The models were trained on 9 patients with longitudinal CBCT images (224 CBCTs) and evaluated on 5 patients (152 CBCTs).Results. The generated images mainly exhibited random positioning shifts and small anatomical changes for early fractions. For later fractions, all models predicted weight losses in accordance with the training data. The distributions of volume and position changes of the body, esophagus, and parotids generated with the image and hybrid models were more similar to the ground truth distribution than the DVF model, evident from the lower Wasserstein distance achieved with the image (0.33) and hybrid model (0.30) compared to the DVF model (0.36). Generating several images for the same fraction did not yield the expected variability since the ground truth anatomical changes were only in 76% of the fractions within the 95% bounds predicted with the best model. Using the generated images for robust optimization of simplified proton therapy plans improved the worst-case clinical target volume V95 with 7% compared to optimizing with 3 mm set-up robustness while maintaining a similar integral dose.Significance. The newly developed DDPMs generate distributions similar to the real anatomical changes and have the potential to be used for robust anatomical optimization.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Neoplasias de Cabeça e Pescoço , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Difusão
6.
Radiother Oncol ; 190: 109953, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37839557

RESUMO

BACKGROUND AND PURPOSE: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study. MATERIALS AND METHODS: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. RESULTS: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. CONCLUSION: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.


Assuntos
Produtos Biológicos , Neoplasias , Terapia com Prótons , Humanos , Animais , Camundongos , Prótons , Elétrons , Dosagem Radioterapêutica , Radiometria
7.
Phys Med Biol ; 68(10)2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37084737

RESUMO

Background.At the Center for Proton Therapy at the Paul Scherrer Institute (PSI) the delivery of proton radiation is controlled via gas-based ionization chambers: the beam is turned off when a certain amount of preset charge has been collected. At low dose rates the charge collection efficiency in these detectors is unity, at ultra-high dose rates it is less due to induced charge recombination effects. If not corrected, the latter would lead to an overdosage.Purpose.In the scope of this work, we developed a novel approach to anin situcharge recombination correction for our dose defining detectors, when irradiated with a proton beam at ultra-high dose rates. This approach is based on the Two-Voltage-Method.Methods.We have translated this method to two separate devices operated simultaneously at different conditions. By doing so, the charge collection losses can be corrected directly and without the need for empirical correction values. This approach has been tested at ultra-high dose rates; proton beam was delivered by the COMET cyclotron to Gantry 1 at PSI.Results.We were able to correct the charge losses caused by recombination effects at local beam currents of approximately 700 nA (i.e. instantaneous dose rate of 3600 Gy s-1at isocenter). The corrected collected charges in our gaseous detectors were compared against recombination-free measurements with a Faraday cup. The ratio of both quantities shows no significant dose rate dependence within their respective combined uncertainties.Conclusions. Correcting recombination effects in our gas-based detectors with the novel method greatly eases the handling of Gantry 1 as 'FLASH test bench'. Not only is the application of a preset dose more accurate compared to using an empirical correction curve, also the re-determination of empirical correction curves in the case of a beam phase space change can be omitted.


Assuntos
Terapia com Prótons , Prótons , Radiometria/métodos , Terapia com Prótons/métodos , Ciclotrons , Radiação Ionizante
8.
Phys Med Biol ; 68(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37820691

RESUMO

Objective.Online adaptive radiotherapy aims to fully leverage the advantages of highly conformal therapy by reducing anatomical and set-up uncertainty, thereby alleviating the need for robust treatments. This requires extensive automation, among which is the use of deformable image registration (DIR) for contour propagation and dose accumulation. However, inconsistencies in DIR solutions between different algorithms have caused distrust, hampering its direct clinical use. This work aims to enable the clinical use of DIR by developing deep learning methods to predict DIR uncertainty and propagating it into clinically usable metrics.Approach.Supervised and unsupervised neural networks were trained to predict the Gaussian uncertainty of a given deformable vector field (DVF). Since both methods rely on different assumptions, their predictions differ and were further merged into a combined model. The resulting normally distributed DVFs can be directly sampled to propagate the uncertainty into contour and accumulated dose uncertainty.Main results.The unsupervised and combined models can accurately predict the uncertainty in the manually annotated landmarks on the DIRLAB dataset. Furthermore, for 5 patients with lung cancer, the propagation of the predicted DVF uncertainty into contour uncertainty yielded for both methods anexpected calibration errorof less than 3%. Additionally, theprobabilisticly accumulated dose volume histograms(DVH) encompass well the accumulated proton therapy doses using 5 different DIR algorithms. It was additionally shown that the unsupervised model can be used for different DIR algorithms without the need for retraining.Significance.Our work presents first-of-a-kind deep learning methods to predict the uncertainty of the DIR process. The methods are fast, yield high-quality uncertainty estimates and are useable for different algorithms and applications. This allows clinics to use DIR uncertainty in their workflows without the need to change their DIR implementation.


Assuntos
Aprendizado Profundo , Humanos , Incerteza , Redes Neurais de Computação , Algoritmos , Planejamento da Radioterapia Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos
9.
Phys Med Biol ; 68(9)2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37019120

RESUMO

Objective.fast and accurate contouring of daily 3D images is a prerequisite for online adaptive radiotherapy. Current automatic techniques rely either on contour propagation with registration or deep learning (DL) based segmentation with convolutional neural networks (CNNs). Registration lacks general knowledge about the appearance of organs and traditional methods are slow. CNNs lack patient-specific details and do not leverage the known contours on the planning computed tomography (CT). This works aims to incorporate patient-specific information into CNNs to improve their segmentation accuracy.Approach.patient-specific information is incorporated into CNNs by retraining them solely on the planning CT. The resulting patient-specific CNNs are compared to general CNNs and rigid and deformable registration for contouring of organs-at-risk and target volumes in the thorax and head-and-neck regions.Results.patient-specific fine-tuning of CNNs significantly improves contour accuracy compared to standard CNNs. The method further outperforms rigid registration and a commercial DL segmentation software and yields similar contour quality as deformable registration (DIR). It is additionally 7-10 times faster than DIR.Significance.patient-specific CNNs are a fast and accurate contouring technique, enhancing the benefits of adaptive radiotherapy.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Neoplasias de Cabeça e Pescoço , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Algoritmos , Planejamento da Radioterapia Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
10.
Phys Med Biol ; 68(17)2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37385266

RESUMO

Objective.Anatomical and daily set-up uncertainties impede high precision delivery of proton therapy. With online adaptation, the daily plan is reoptimized on an image taken shortly before the treatment, reducing these uncertainties and, hence, allowing a more accurate delivery. This reoptimization requires target and organs-at-risk (OAR) contours on the daily image, which need to be delineated automatically since manual contouring is too slow. Whereas multiple methods for autocontouring exist, none of them are fully accurate, which affects the daily dose. This work aims to quantify the magnitude of this dosimetric effect for four contouring techniques.Approach.Plans reoptimized on automatic contours are compared with plans reoptimized on manual contours. The methods include rigid and deformable registration (DIR), deep-learning based segmentation and patient-specific segmentation.Main results.It was found that independently of the contouring method, the dosimetric influence of usingautomaticOARcontoursis small (<5% prescribed dose in most cases), with DIR yielding the best results. Contrarily, the dosimetric effect of using theautomatic target contourwas larger (>5% prescribed dose in most cases), indicating that manual verification of that contour remains necessary. However, when compared to non-adaptive therapy, the dose differences caused by automatically contouring the target were small and target coverage was improved, especially for DIR.Significance.The results show that manual adjustment of OARs is rarely necessary and that several autocontouring techniques are directly usable. Contrarily, manual adjustment of the target is important. This allows prioritizing tasks during time-critical online adaptive proton therapy and therefore supports its further clinical implementation.


Assuntos
Terapia com Prótons , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Radiometria , Órgãos em Risco
11.
Phys Med Biol ; 68(11)2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37172608

RESUMO

Objective.4D dose reconstruction in proton therapy with pencil beam scanning (PBS) typically relies on a single pre-treatment 4DCT (p4DCT). However, breathing motion during the fractionated treatment can vary considerably in both amplitude and frequency. We present a novel 4D dose reconstruction method combining delivery log files with patient-specific motion models, to account for the dosimetric effect of intra- and inter-fractional breathing variability.Approach.Correlation between an external breathing surrogate and anatomical deformations of the p4DCT is established using principal component analysis. Using motion trajectories of a surface marker acquired during the dose delivery by an optical tracking system, deformable motion fields are retrospectively reconstructed and used to generate time-resolved synthetic 4DCTs ('5DCTs') by warping a reference CT. For three abdominal/thoracic patients, treated with respiratory gating and rescanning, example fraction doses were reconstructed using the resulting 5DCTs and delivery log files. The motion model was validated beforehand using leave-one-out cross-validation (LOOCV) with subsequent 4D dose evaluations. Moreover, besides fractional motion, fractional anatomical changes were incorporated as proof of concept.Main results.For motion model validation, the comparison of 4D dose distributions for the original 4DCT and predicted LOOCV resulted in 3%/3 mm gamma pass rates above 96.2%. Prospective gating simulations on the p4DCT can overestimate the target dose coverage V95%by up to 2.1% compared to 4D dose reconstruction based on observed surrogate trajectories. Nevertheless, for the studied clinical cases treated with respiratory-gating and rescanning, an acceptable target coverage was maintained with V95%remaining above 98.8% for all studied fractions. For these gated treatments, larger dosimetric differences occurred due to CT changes than due to breathing variations.Significance.To gain a better estimate of the delivered dose, a retrospective 4D dose reconstruction workflow based on motion data acquired during PBS proton treatments was implemented and validated, thus considering both intra- and inter-fractional motion and anatomy changes.


Assuntos
Neoplasias Pulmonares , Terapia com Prótons , Humanos , Terapia com Prótons/métodos , Estudos Retrospectivos , Estudos Prospectivos , Tomografia Computadorizada Quadridimensional/métodos , Movimento (Física) , Carmustina , Planejamento da Radioterapia Assistida por Computador/métodos
12.
bioRxiv ; 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37131769

RESUMO

Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (± 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

13.
Phys Med Biol ; 68(1)2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36571234

RESUMO

Objective.4D dose calculation (4DDC) for pencil beam scanned (PBS) proton therapy is typically based on phase-sorting of individual pencil beams onto phases of a single breathing cycle 4DCT. Understanding the dosimetric limitations and uncertainties of this approach is essential, especially for the realistic treatment scenario with irregular free breathing motion.Approach.For three liver and three lung cancer patient CTs, the deformable multi-cycle motion from 4DMRIs was used to generate six synthetic 4DCT(MRI)s, providing irregular motion (11/15 cycles for liver/lung; tumor amplitudes ∼4-18 mm). 4DDCs for two-field plans were performed, with the temporal resolution of the pencil beam delivery (4-200 ms) or with 8 phases per breathing cycle (500-1000 ms). For the phase-sorting approach, the tumor center motion was used to determine the phase assignment of each spot. The dose was calculated either using the full free breathing motion or individually repeating each single cycle. Additionally, the use of an irregular surrogate signal prior to 4DDC on a repeated cycle was simulated. The CTV volume with absolute dose differences >5% (Vdosediff>5%) and differences in CTVV95%andD5%-D95%compared to the free breathing scenario were evaluated.Main results.Compared to 4DDC considering the full free breathing motion with finer spot-wise temporal resolution, 4DDC based on a repeated single 4DCT resulted inVdosediff>5%of on average 34%, which resulted in an overestimation ofV95%up to 24%. However, surrogate based phase-sorting prior to 4DDC on a single cycle 4DCT, reduced the averageVdosediff>5%to 16% (overestimationV95%up to 19%). The 4DDC results were greatly influenced by the choice of reference cycle (Vdosediff>5%up to 55%) and differences due to temporal resolution were much smaller (Vdosediff>5%up to 10%).Significance.It is important to properly consider motion irregularity in 4D dosimetric evaluations of PBS proton treatments, as 4DDC based on a single 4DCT can lead to an underestimation of motion effects.


Assuntos
Neoplasias Pulmonares , Terapia com Prótons , Humanos , Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada Quadridimensional/métodos , Movimento (Física) , Terapia com Prótons/métodos , Respiração , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia
14.
Phys Med ; 104: 101-111, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36395638

RESUMO

PURPOSE: To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. METHODS: At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of âˆ¼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. RESULTS: The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. CONCLUSIONS: Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.


Assuntos
Prótons , Reprodutibilidade dos Testes
15.
Ann Oncol ; 22(1): 156-164, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20587509

RESUMO

BACKGROUND: this study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. PATIENTS AND METHODS: data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. RESULTS: sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. CONCLUSIONS: combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.


Assuntos
Linfoma não Hodgkin/terapia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , Adulto Jovem
16.
Dis Esophagus ; 24(4): 258-64, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21073624

RESUMO

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The aims of this retrospective study were to analyze the epidemiology, clinical characteristics, and treatment outcomes of these patients. Between 1994 and 2004, 24 patients with SCCE from several centers were reviewed for data on demographics, presenting symptoms, diagnosis, disease stage, type of treatment, and outcome. SCCE occurs in the sixth decade: median age (interquartile range [IQR]): 65 (59-69) years with a male predominance (63%). The most common complaining symptoms were rapidly progressive dysphagia (79%), weight loss (54%), and retrosternal/epigastric pain (46%). The tumor arises primarily in the middle (52%) or in the lower (35%) third of the esophagus. History of tobacco and alcohol exposure was present in 90% and 70% of case, respectively. Extensive disease was present in 13 cases (54%) at initial diagnosis. The overall median survival (IQR) was 11 (8-20) months for all 24 patients, and the 2-year overall survival was 25.1%. Four patients were alive more than 2 years after treatment. Chemotherapy increased the survival compared with symptomatic management in extensive disease (median survival [IQR]: 9.5 [6-14] vs. 6 [4-7] months, P= 0.05). In limited disease, concurrent chemo-radiotherapy was more effective than non-concurrent treatment (median survival [IQR]: 36 [14-93] vs. 11 [9-15] months, P= 0.04). Two patients were treated by surgery and chemoradiation therapy with a survival of 35 and 66 months. Chemotherapy is the cornerstone of treatment of SCCE in all stage. For limited disease SCCE, concurrent chemo-radiotherapy is the primary choice compared with sequential approach. The role of surgery was not assessable in our study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Idoso , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/radioterapia , Terapia Combinada , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Phys Med Biol ; 66(12)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33906166

RESUMO

Recently, proton therapy treatments delivered with ultra-high dose rates have been of high scientific interest, and the Faraday cup (FC) is a promising dosimetry tool for such experiments. Different institutes use different FC designs, and either a high voltage guard ring, or the combination of an electric and a magnetic field is employed to minimize the effect of secondary electrons. The authors first investigate these different approaches for beam energies of 70, 150, 230 and 250 MeV, magnetic fields between 0 and 24 mT and voltages between -1000 and 1000 V. When applying a magnetic field, the measured signal is independent of the guard ring voltage, indicating that this setting minimizes the effect of secondary electrons on the reading of the FC. Without magnetic field, applying the negative voltage however decreases the signal by an energy dependent factor up to 1.3% for the lowest energy tested and 0.4% for the highest energy, showing an energy dependent response. Next, the study demonstrates the application of the FC up to ultra-high dose rates. FC measurements with cyclotron currents up to 800 nA (dose rates of up to approximately 1000 Gy s-1) show that the FC is indeed dose rate independent. Then, the FC is applied to commission the primary gantry monitor for high dose rates. Finally, short-term reproducibility of the monitor calibration is quantified within single days, showing a standard deviation of 0.1% (one sigma). In conclusion, the FC is a promising, dose rate independent tool for dosimetry up to ultra-high dose rates. Caution is however necessary when using a FC without magnetic field, as a guard ring with high voltage alone can introduce an energy dependent signal offset.


Assuntos
Terapia com Prótons , Calibragem , Prótons , Radiometria , Reprodutibilidade dos Testes
18.
Clin Oncol (R Coll Radiol) ; 33(12): e578-e585, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34340918

RESUMO

AIMS: Sacral chordomas are locally aggressive, radio-resistant tumours. Proton therapy has the potential to deliver high radiation doses, which may improve the therapeutic ratio when compared with conventional radiotherapy. We assessed tumour control and radiation-induced toxicity in a cohort of sacral chordoma patients treated with definitive or postoperative pencil beam scanning proton therapy. METHODS AND MATERIALS: Sixty patients with histologically proven sacral chordoma treated between November 1997 and October 2018 at the Paul Scherrer Institute with postoperative (n = 50) or definitive proton therapy (n = 10) were retrospectively analysed. Only 10 (17%) patients received combined photon radiotherapy and proton therapy. Survival rates were calculated using the Kaplan-Meier actuarial method. The Log-rank test was used to compare different functions for local control, freedom from distant recurrence and overall survival. Acute and late toxicity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: The median follow-up was 48 months (range 4-186). Local recurrence occurred in 20 (33%) patients. The 4-year local control, freedom from distant recurrence and overall survival rates were 77%, 89% and 85%, respectively. On univariate analysis, subtotal resection/biopsy (P = 0.02), tumour extension restricted to bone (P = 0.01) and gross tumour volume >130 ml (P = 0.04) were significant predictors for local recurrence. On multivariate analysis, tumour extension restricted to bone (P = 0.004) and gross total resection (P = 0.02) remained independent favourable prognostic factors for local recurrence. Twenty-four (40%), 28 (47%) and eight (11%) patients experienced acute grade 1, 2 and 3 toxicities, respectively. The 4-year late toxicity-free survival was 91%. Two patients developed secondary malignancies to the bladder 3-7 years after proton therapy. CONCLUSIONS: Our data indicate that pencil beam scanning proton therapy for sacral chordomas is both safe and effective. Gross total resection, tumour volume <130 ml and tumour restricted to the bone are favourable prognostic factors for local tumour control.


Assuntos
Cordoma , Terapia com Prótons , Neoplasias da Coluna Vertebral , Cordoma/radioterapia , Humanos , Recidiva Local de Neoplasia/radioterapia , Terapia com Prótons/efeitos adversos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/radioterapia , Carga Tumoral
19.
Radiat Oncol ; 16(1): 81, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933118

RESUMO

INTRODUCTION: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). MATERIALS AND METHODS: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). RESULTS: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). CONCLUSIONS: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.


Assuntos
Benchmarking/métodos , Neoplasias Hipofaríngeas/radioterapia , Órgãos em Risco/efeitos da radiação , Neoplasias Orofaríngeas/radioterapia , Garantia da Qualidade dos Cuidados de Saúde/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Supraglotite/radioterapia , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Hipofaríngeas/patologia , Variações Dependentes do Observador , Neoplasias Orofaríngeas/patologia , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Supraglotite/patologia
20.
Cancer Radiother ; 24(6-7): 687-690, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32753239

RESUMO

Proton therapy is delivered to selected cancer patients presenting with rare tumours, for which a dose escalation paradigm and/or a reduced dose-bath to the organs at risk is pursued. It is a costly treatment with an additional cost factor of 2-3 when compared to photon radiotherapy. Notwithstanding the 180'000 patients treated with protons, scars robust clinical evidence is available to justify the administration of this treatment modality. The European Particle Therapy Network (EPTN) was created in 2015 to answer the critical European needs for cooperation among protons and carbon ions centres in the framework of clinical research networks. EPTN with other European groups will launch a number of prospective clinical trials that could be practice changing if positive. Alternative way to generate clinical data could be provided by alternative methodologies, such as the Dutch model-based approach, or could be provided by European infrastructure projects.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/tendências , Pesquisa Biomédica , Europa (Continente) , Previsões , Humanos
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