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1.
J Appl Clin Med Phys ; 25(5): e14318, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38427776

RESUMO

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy. METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes (CTV) and organs at risk (OAR) were evaluated with respect to the planned dose using the reference (50th-percentile) parameter values. Correlation between CTV dose differences, and 18 different complexity metrics were evaluated using linear regression; R-squared values were used to determine the best metric. RESULTS: Perturbations to MLC offset and transmission parameters demonstrated the greatest changes in dose: up to 5.7% in CTVs and 16.7% for OARs. More complex clinical plans showed greater dose perturbation with atypical beam model parameters. The mean MLC Gap and Tongue & Groove index (TGi) complexity metrics best described the impact of TPS beam modeling variations on clinical dose delivery across all anatomical sites; similar, though not identical, trends between complexity and dose perturbation were observed among all sites. CONCLUSION: Extreme values for MLC offset and MLC transmission beam modeling parameters were found to most substantially impact the dose distribution of clinical plans and careful attention should be given to these beam modeling parameters. The mean MLC Gap and TGi complexity metrics were best suited to identifying clinical plans most sensitive to beam modeling errors; this could help provide focus for clinical QA in identifying unacceptable plans.


Assuntos
Neoplasias , Órgãos em Risco , Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação , Neoplasias/radioterapia , Aceleradores de Partículas/instrumentação , Algoritmos
2.
J Appl Clin Med Phys ; 24(6): e14040, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37191875

RESUMO

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Projetos Piloto , Japão , Credenciamento , Radiometria , Dosagem Radioterapêutica , Oncologia , Imagens de Fantasmas
3.
Acta Oncol ; 59(2): 141-148, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31746249

RESUMO

Background: The IAEA has developed and tested an on-site, end-to-end IMRT/VMAT dosimetry audit methodology for head and neck cases using an anthropomorphic phantom. The audit methodology is described, and the results of the international pilot testing are presented.Material and methods: The audit utilizes a specially designed, commercially available anthropomorphic phantom capable of accommodating a small volume ion chamber (IC) in four locations (three in planning target volumes (PTVs) and one in an organ at risk (OAR)) and a Gafchromic film in a coronal plane for the absorbed dose to water and two-dimensional dose distribution measurements, respectively. The audit consists of a pre-visit and on-site phases. The pre-visit phase is carried out remotely and includes a treatment planning task and a set of computational exercises. The on-site phase aims at comparing the treatment planning system (TPS) calculations with measurements in the anthropomorphic phantom following an end-to-end approach. Two main aspects were tested in the pilot study: feasibility of the planning constraints and the accuracy of IC and film results in comparison with TPS calculations. Treatment plan quality was scored from 0 to 100.Results: Forty-two treatment plans were submitted by 14 institutions from 10 countries, with 79% of them having a plan quality score over 90. Seventeen sets of IC measurement results were collected, and the average measured to calculated dose ratio was 0.988 ± 0.016 for PTVs and 1.020 ± 0.029 for OAR. For 13 film measurement results, the average gamma passing rate was 94.1% using criteria of 3%/3 mm, 20% threshold and global gamma.Conclusions: The audit methodology was proved to be feasible and ready to be adopted by national dosimetry audit networks for local implementation.


Assuntos
Auditoria Médica/métodos , Radiometria/normas , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/normas , Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Agências Internacionais , Auditoria Médica/normas , Imagens de Fantasmas , Projetos Piloto , Garantia da Qualidade dos Cuidados de Saúde , Radiometria/instrumentação , Dosagem Radioterapêutica
4.
Am J Physiol Cell Physiol ; 308(10): C803-12, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25980014

RESUMO

Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the brain circumventricular subfornical organ (SFO) mediate the central hypertensive actions of Angiotensin II (ANG II). However, the downstream signaling events remain unclear. Here we tested the hypothesis that angiotensin type 1a receptors (AT1aR), ER stress, and ROS induce activation of the transcription factor nuclear factor-κB (NF-κB) during ANG II-dependent hypertension. To spatiotemporally track NF-κB activity in the SFO throughout the development of ANG II-dependent hypertension, we used SFO-targeted adenoviral delivery and longitudinal bioluminescence imaging in mice. During low-dose infusion of ANG II, bioluminescence imaging revealed a prehypertensive surge in NF-κB activity in the SFO at a time point prior to a significant rise in arterial blood pressure. SFO-targeted ablation of AT1aR, inhibition of ER stress, or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase in SFO NF-κB. These findings highlight the utility of bioluminescence imaging to longitudinally track transcription factor activation during the development of ANG II-dependent hypertension and reveal an AT1aR-, ER stress-, and ROS-dependent prehypertensive surge in NF-κB activity in the SFO. Furthermore, the increase in NF-κB activity before a rise in arterial blood pressure suggests a causal role for SFO NF-κB in the development of ANG II-dependent hypertension.


Assuntos
Angiotensina II/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Hipertensão/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Órgão Subfornical/efeitos dos fármacos , Animais , Retículo Endoplasmático/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/induzido quimicamente , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
5.
Radiother Oncol ; : 110581, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395670

RESUMO

BACKGROUND AND PURPOSE: Reducing motion is vital in treating hepatobiliary (HPB) and pancreatic malignancies. Abdominal compression (AC) and breath-hold (BH) techniques aim to minimise respiratory motion, yet their adoption remains limited, and practices vary. This review examines the impact of AC and BH on motion, set-up errors, and patient tolerability in HPB and pancreatic patients. MATERIALS AND METHODS: This systematic review, conducted using PRISMA and PICOS criteria, includes publications from January 2015 to February 2023. Eligible studies focused on AC and BH interventions in adults with HPB and pancreatic malignancies. Endpoints examined motion, set-up errors, intra-fraction errors, and patient tolerability. Due to study heterogeneity, Synthesis Without Meta-Analysis was used, and a 5 mm threshold assessed the impact of motion mitigation. RESULTS: In forty studies, 14 explored AC and 26 BH, with 20 on HPB, 13 on pancreatic, and 7 on mixed cohorts. Six studied pre-treatment, 22 inter/intra-fraction errors, and 12 both. Six AC pre-treatment studies showed > 5 mm motion, and 4 BH and 2 AC studies reported > 5 mm inter-fraction errors. Compression studies commonly investigated the arch and belt, and DIBH was the predominant BH technique. No studies compared AC and BH. There was variation in the techniques, and several studies did not follow standardised error reporting. Patient experience and tolerability were under-reported. CONCLUSION: The results indicate that AC effectively reduces motion, but its effectiveness may vary. BH can immobilise motion; however, it can be inconsistent between fractions. The review underscores the need for larger, standardised studies and emphasizes the importance of considering the patient's perspective for tailored treatments.

6.
Med Phys ; 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39466302

RESUMO

BACKGROUND: The Joint AAPM-ESTRO TG-360 is developing a quantitative framework to evaluate treatment verification systems used for patient-specific quality assurance (PSQA). A subgroup was commissioned to determine which potential failure modes had the greatest risk to treatment quality and safety, and therefore should be evaluated as part of the PSQA verification. PURPOSE: To create an extensive database of potential radiotherapy failure modes that should be detected by PSQA and to determine their relative importance for maximizing treatment quality. METHODS: The subgroup consisted of eight physicists from seven countries, including representatives from three international quality assurance groups. We collected error reports from RO-ILS, SAFRON, AAPM TG publications, and other literature, including international audits. We focused on the subset of failure modes that impact whether the planned dose matches the dose received by the patient. We performed a failure-mode-and-effects analysis (FMEA), estimating the severity (S), occurrence (O), and detectability (D) of each failure mode. Detectability was scored assuming that PSQA was not done but other routine clinical QA was performed, which allowed us to see the importance of PSQA for detecting each specific failure mode. We analyzed the risk priority number (RPN = O*S*D), O*S, and severity rankings to determine the priority of each failure mode. RESULTS: We collected 394 error reports, which we categorized into 33 failure modes that underwent FMEA. Five failure modes were in the top ranks for both RPN and O*S analysis: four involving treatment planning system (TPS) commissioning and one regarding patient model errors. The highest-ranking RPN failure modes were: TPS algorithm limitations, TPS commissioning errors [multileaf collimator (MLC) modeling, output factor, percent-depth-dose/tissue-maximum-ratio (PDD/TMR), off-axis factor], and patient weight variation. The highest O*S failure modes were similar, with the addition of external patient position variation and incorrect linear accelerator isocenter and cGy/monitor units calibration. RPN and O*S analyses prioritized failure modes that impacted multiple patients with high occurrence and detectability scores, while severity analysis gave higher priority to single-patient modes with high severity scores. The highest-ranking severity modes were MLC sequence deletion, collision, and TPS isocenter incorrect. CONCLUSION: We have developed a list of failure modes critical to be detected during PSQA and ranked them in order of importance. The top failure modes emphasize the importance of utilizing a variety of treatment verification systems for PSQA, from secondary dose calculation through in-vivo dosimetry, in order to detect all possible errors. For failure modes in the top quartile, PSQA is critical. Without adequate PSQA, these errors may go undetected unless caught by an external audit. This analysis can be useful for optimizing PSQA workflows and for designing evaluations of treatment verification systems, and will be used by the Joint AAPM-ESTRO TG-360 to determine an appropriate validation strategy.

7.
Phys Imaging Radiat Oncol ; 29: 100543, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38390588

RESUMO

Background and purpose: Multi-leaf collimators (MLCs) with tilted leaf sides have a complex transmission behaviour that is not easily matched by radiotherapy treatment planning systems (TPSs). We sought to develop an MLC model that can accurately match test fields and clinically relevant plans at different centres. Materials and methods: Two new MLC models were developed and evaluated within a research version of a commercial TPS. Prototype I used adjusted-constant transmissions and Prototype II used variable transmissions at the tongue-and-groove and leaf-tip regions. Three different centres evaluated these prototypes for a tilted MLC and compared them with their initial MLC model using test fields and patient-specific quality-assurance measurements of clinically relevant plans. For the latter, gamma passing rates (GPR) at 2 %/2mm were recorded. Results: For the prototypes the same set of MLC parameters could be used at all centres, with only a slight adjustment of the offset parameter. For centres A and C, average GPR were >95 % and within 0.5 % GPR difference between the standard, and prototype models. In center B, prototypes I and II improved the agreement in clinically relevant plans, with an increase in GPR of 2.3 % ± 0.8 % and 3.0 ± 0.8 %, respectively. Conclusions: The prototype MLC models were either similar or superior to the initial MLC model, and simpler to configure because fewer trade-offs were required. Prototype I performed comparably to the more sophisticated Prototype II and its configuration can be easily standardized, which can be useful to reduce variability and improve safety in clinical practice.

8.
Med Phys ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316455

RESUMO

BACKGROUND: In 2021, a Technical Meeting was hosted by the International Atomic Energy Agency (IAEA) where it was recommended that a standardized method for assessing the accuracy of film dose calculations should be established. PURPOSE: To design an audit that evaluates the accuracy of film dosimetry processes. To propose a framework for identifying out-of-tolerance results and to perform an international pilot study to test the audit design. METHODS: Six members of an international Dosimetry Audit Network (DAN) developed an audit for radiochromic film dosimetry. A single host center provided the materials to each participating DAN member to conduct the audits. Materials included: (1) a set of two irradiated audit films (10 Sq: 10 cm × 10 cm, 15 Sq: 15 cm × 15 cm), (2) a reference calibration film set, and (3) a blank sheet of film. The participants were blinded to the dose and tasked with producing dose maps using their standard film dosimetry process. Average Region-Of-Interest (ROI: 2 cm × 2 cm) dose was measured from the dose maps and compared to the known dose. In the audit, all participants used their local scanning and software protocols. Film calibration was performed in two distinct ways: (1) using a calibration film set which was provided by the host center and (2) using a calibration film set which was locally irradiated. Several variations of the audit were also performed to examine how scanning and software processing can affect film dosimetry results. In the first variation of the audit (VariantA), a set of film scans was processed using five different software solutions. In the second variation of the audit (VariantB), all films were scanned on the same scanner and processed using two in-house software solutions. RESULTS: Taking one film scan from each participant, the standard deviations (1σ) (SD) in the dose returned from the host calibration and returned from the local calibration were ±7.2% and ±6.5% respectively, with variations from -12.4% to 12.9% of the known dose. The larger dose variations in the data set were attributed to the corrections applied for variations in scanner brightness during processing and incorrectly assigned calibration doses. When the raw image data set was processed by an expert user of each software solution (VariantA) the SDs were ±2.7% and ±3.7% for in-house and vendor-based software, respectively. When the films were scanned on a single scanner and processed with the two in-house software solutions (VariantB) the results had a SD of ±2.3%. CONCLUSIONS: An audit has been designed and tested for radiotherapy film dosimetry at an international level. A framework for diagnosing issues within a film dosimetry process has been proposed that could be used to audit centers that use film as a dosimeter. Incorporating quality assurance throughout the film process is important in obtaining accurate and consistent film dosimetry. A better understanding of vendor-based software systems is necessary for users to process accurate and consistent film dosimetry.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39362313

RESUMO

PURPOSE: The Imaging Radiation Oncology Core (IROC) head and neck (H&N) phantom is used to credential institutions for intensity modulated radiation therapy delivery for all anatomic sites where delivery of modulated therapy is a primary challenge. This study evaluated how appropriate the use of this phantom is for varied clinical anatomy by evaluating how closely the IROC H&N phantom described clinical dose errors from beam modeling compared with various anatomic sites. METHODS AND MATERIALS: The multileaf collimator (MLC) offset, transmission, percent depth dose, and 7 additional beam modeling parameters for a Varian accelerator were modified in RayStation to match community data at the 2.5th, 25th, 50th, 75th, and 97.5th percentile levels. Modifications were evaluated on 25 H&N phantom cases and 25 clinical cases (H&N, prostate, lung, mesothelioma, and brain), generating 2000 plan perturbations. Differences in mean dose delivered to clinical target volumes and maximum dose to organs at risk were compared between phantom and clinical plans to assess the relationship between dose deviations in phantom versus clinical target volumes and as a function of 18 different complexity metrics. RESULTS: Perturbations to MLC offset and transmission parameters demonstrated the greatest impact on dose accuracy for phantom and clinical plans (for all anatomic sites). The phantom demonstrated equivalent or greater sensitivity to these parameter perturbations compared with clinical sites, largely aligning with treatment complexity. The mean MLC gap best described the impact of errors in treatment planning system beam modeling parameters in phantom plans and clinical plans from various anatomic sites. CONCLUSIONS: When compared across various anatomic sites, the IROC H&N credentialing phantom exhibited similar or greater sensitivity to errors in the treatment planning system. As such, it is a suitable surrogate device for assessing institutional performance across various anatomic sites. If an institution successfully irradiates the phantom, that result confers confidence that intensity modulated radiation therapy to a wide range of anatomic sites can be successfully delivered by the institution.

10.
Radiother Oncol ; 197: 110366, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38830537

RESUMO

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Irradiação Corporal Total , Humanos , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/normas , Irradiação Corporal Total/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Dosagem Radioterapêutica , Transplante de Células-Tronco Hematopoéticas/métodos , Órgãos em Risco/efeitos da radiação
11.
Exp Physiol ; 98(2): 415-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22962286

RESUMO

In the present study, we used atomic force microscopy (AFM) to examine the ligand-binding properties of α7-containing nicotinic acetylcholine receptors (nAChRs) expressed on neurons from the ventral respiratory group. We also determined the effect of acute and prolonged exposure to nicotine on the binding probability of nAChRs. Neurons from neonatal (postnatal day 5-10) and juvenile rats (3-4 weeks old) were cultured. Internalization of Alexa Fluor 488-conjugated substance P was used to identify respiratory neurons that expressed the neurokinin-1 receptor (NK1-R), a recognized marker of ventral respiratory group neurons. To assess functional changes in nAChRs, AFM probes conjugated with anti-α7 subunit nAChR antibody were used to interact cyclically with the surface of the soma of NK1-R-positive neurons. Measurements were made of the frequency of antibody adhesion to the α7 receptor subunit and of the detachment forces between the membrane-attached receptor and the AFM probe tip. Addition of α-bungarotoxin (a specific antagonist of α7 subunit-containing nAChRs) to the cell bath produced a 69% reduction in binding to the α7 subunit (P < 0.05, n = 10), supporting specificity of binding. Acute exposure to nicotine (1 µM added to culture media) produced an 80% reduction in nAChR antibody binding to the α7 subunit (P < 0.05, n = 9). Prolonged incubation (72 h) of the cell culture in nicotine significantly reduced α7 binding in a concentration-dependent manner. Collectively, these findings demonstrate that AFM is a sensitive tool for assessment of functional changes in nAChRs expressed on the surface of living NK1-R-expressing medullary neurons. Moreover, these data demonstrate that nicotine exposure decreases the binding probability of α7 subunit-containing nAChRs.


Assuntos
Microscopia de Força Atômica , Neurônios/metabolismo , Receptores da Neurocinina-1/metabolismo , Receptores Nicotínicos/metabolismo , Centro Respiratório/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Bungarotoxinas/metabolismo , Bungarotoxinas/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Corantes Fluorescentes/metabolismo , Ligantes , Masculino , Neurônios/efeitos dos fármacos , Nicotina/metabolismo , Nicotina/farmacologia , Agonistas Nicotínicos/metabolismo , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/metabolismo , Antagonistas Nicotínicos/farmacologia , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/efeitos dos fármacos , Centro Respiratório/citologia , Centro Respiratório/efeitos dos fármacos , Substância P/análogos & derivados , Substância P/metabolismo , Fatores de Tempo , Receptor Nicotínico de Acetilcolina alfa7
12.
J Appl Clin Med Phys ; 14(6): 4460, 2013 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-24257288

RESUMO

Quality assurance (QA) for intensity- and volumetric-modulated radiotherapy (IMRT and VMAT) has evolved substantially. In recent years, various commercial 2D and 3D ionization chamber or diode detector arrays have become available, allowing for absolute verification with near real time results, allowing for streamlined QA. However, detector arrays are limited by their resolution, giving rise to concerns about their sensitivity to errors. Understanding the limitations of these devices is therefore critical. In this study, the sensitivity and resolution of the PTW 2D-ARRAY seven29 and OCTAVIUS II phantom combination was comprehensively characterized for use in dynamic sliding window IMRT and RapidArc verification. Measurement comparisons were made between single acquisition and a multiple merged acquisition techniques to improve the effective resolution of the 2D-ARRAY, as well as comparisons against GAFCHROMIC EBT2 film and electronic portal imaging dosimetry (EPID). The sensitivity and resolution of the 2D-ARRAY was tested using two gantry angle 0° modulated test fields. Deliberate multileaf collimator (MLC) errors of 1, 2, and 5 mm and collimator rotation errors were inserted into IMRT and RapidArc plans for pelvis and head & neck sites, to test sensitivity to errors. The radiobiological impact of these errors was assessed to determine the gamma index passing criteria to be used with the 2D-ARRAY to detect clinically relevant errors. For gamma index distributions, it was found that the 2D-ARRAY in single acquisition mode was comparable to multiple acquisition modes, as well as film and EPID. It was found that the commonly used gamma index criteria of 3% dose difference or 3 mm distance to agreement may potentially mask clinically relevant errors. Gamma index criteria of 3%/2 mm with a passing threshold of 98%, or 2%/2 mm with a passing threshold of 95%, were found to be more sensitive. We suggest that the gamma index passing thresholds may be used for guidance, but also should be combined with a visual inspection of the gamma index distribution and calculation of the dose difference to assess whether there may be a clinical impact in failed regions.


Assuntos
Imagens de Fantasmas , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Algoritmos , Calibragem , Simulação por Computador , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X
13.
Lancet Oncol ; 13(1): 43-54, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22169269

RESUMO

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy. METHODS: We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923. FINDINGS: 153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5-61·3), six (4·3%; 95% CI 1·6-9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2-8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2-5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5-6·2) of 138 men, three (2·2%; 0·5-6·3) of 137, and none (0·0%; 97·5% CI 0·0-2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years. INTERPRETATION: Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years. FUNDING: Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada , Idoso , Idoso de 80 Anos ou mais , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Reino Unido
14.
Br J Radiol ; 96(1144): 20220650, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36475820

RESUMO

The use of volumetric arc therapy and inverse planning has been in routine use in radiotherapy for two decades. However, use in total body irradiation (TBI) has been more recent and few guidelines exist as to how to plan or verify. This has led to heterogeneous approaches. The goal of this review is to provide an overview of current advanced planning and dosimetry verification protocols used in optimised conformal TBI as a basis for investigating the need for greater standardisation in TBI.


Assuntos
Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Irradiação Corporal Total/métodos
15.
Phys Med ; 114: 103136, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37769414

RESUMO

This study aimed to validate a bespoke 3D-printed phantom for use in quality assurance (QA) of a 6 degrees-of-freedom (6DoF) treatment couch. A novel phantom design comprising a main body with internal cube structures, was fabricated at five centres using Polylactic Acid (PLA) material, with an additional phantom produced incorporating a PLA-stone hybrid material. Correctional setup shifts were determined using image registration by 3D-3D matching of high HU cube structures between obtained cone-beam computer tomography (CBCT) images to reference CTs, containing cubes with fabricated rotational offsets of 3.5°, 1.5° and -2.5° in rotation, pitch, and roll, respectively. Average rotational setup shifts were obtained for each phantom. The reproducibility of 3D-printing was probed by comparing the internal cube size as well as Hounsfield Units between each of the uniquely produced phantoms. For the five PLA phantoms, the average rot, pitch and roll correctional differences from the fabricated offsets were -0.3 ± 0.2°, -0.2 ± 0.5° and 0.2 ± 0.3° respectively, and for the PLA hybrid these differences were -0.09 ± 0.14°, 0.30 ± 0.00° and 0.03 ± 0.10°. There was found to be no statistically significant difference in average cube size between the five PLA printed phantoms, with the significant difference (P < 0.05) in HU of one phantom compared to the others attributed to setup choice and material density. This work demonstrated the capability producing a novel 3D-printed 6DoF couch QA phantom design, at multiple centres, with each unique model capable of sub-degree couch correction.


Assuntos
Radiocirurgia , Radioterapia Guiada por Imagem , Reprodutibilidade dos Testes , Radiocirurgia/métodos , Imagens de Fantasmas , Impressão Tridimensional , Poliésteres
16.
Radiother Oncol ; 182: 109494, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36708923

RESUMO

BACKGROUND AND PURPOSE: The Global Clinical Trials RTQA Harmonization Group (GHG) set out to evaluate and prioritize clinical trial quality assurance. METHODS: The GHG compiled a list of radiotherapy quality assurance (QA) tests performed for proton and photon therapy clinical trials. These tests were compared between modalities to assess whether there was a need for different types of assessments per modality. A failure modes and effects analysis (FMEA) was performed to assess the risk of each QA failure. RESULTS: The risk analysis showed that proton and photon therapy shared four out of five of their highest-risk failures (end-to-end anthropomorphic phantom test, phantom tests using respiratory motion, pre-treatment patient plan review of contouring/outlining, and on-treatment/post-treatment patient plan review of dosimetric coverage). While similar trends were observed, proton therapy had higher risk failures, driven by higher severity scores. A sub-analysis of occurrence × severity scores identified high-risk scores to prioritize for improvements in RTQA detectability. A novel severity scaler was introduced to account for the number of patients affected by each failure. This scaler did not substantially alter the ranking of tests, but it elevated the QA program evaluation to the top 20th percentile. This is the first FMEA performed for clinical trial quality assurance. CONCLUSION: The identification of high-risk errors associated with clinical trials is valuable to prioritize and reduce errors in radiotherapy and improve the quality of trial data and outcomes, and can be applied to optimize clinical radiotherapy QA.


Assuntos
Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Prótons , Humanos , Fótons/uso terapêutico , Radiometria , Medição de Risco
17.
Radiother Oncol ; 186: 109775, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37385376

RESUMO

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Imagens de Fantasmas , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos
18.
J Neurosci ; 31(34): 12318-29, 2011 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-21865474

RESUMO

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular function in vivo and regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for baroreflex control of sympathetic outflow, produced dose-dependent increases in mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In contrast, immunoneutralization of endogenous BDNF (anti-BDNF), or microinjection of K252a alone, decreased MAP, HR, and LSNA. The effects of anti-BDNF were abolished by blockade of ionotropic glutamate receptors, indicating a role for glutamate signaling in the response to BDNF. In vitro, BDNF reduced the amplitude of miniature EPSCs as well as solitary tract (TS) evoked EPSC amplitude and action potential discharge (APD) in second-order nTS neurons. BDNF effects on EPSCs were independent of GABAergic signaling and abolished by AMPA receptor blockade. In contrast, K252a increased spontaneous EPSC frequency and TS evoked EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing current into second-order neurons, indicating reduced intrinsic neuronal excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role in regulating cardiovascular function, likely via modulation of primary afferent glutamatergic excitatory transmission and neural activity.


Assuntos
Vias Autônomas/fisiologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Neurônios/fisiologia , Núcleo Solitário/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley
19.
Am J Physiol Regul Integr Comp Physiol ; 302(10): R1219-32, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22403798

RESUMO

Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia (n = 4, 21% O(2)) or acute hypoxia (12, 10, or 8% O(2); n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O(2) was similar whether arterial pressure was allowed to decrease (-13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O(2). Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.


Assuntos
Hipóxia/fisiopatologia , Neurônios/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Núcleo Solitário/fisiologia , Animais , Pressão Sanguínea/fisiologia , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/fisiologia , Masculino , Bulbo/citologia , Bulbo/fisiologia , Neurônios/citologia , Núcleo Hipotalâmico Paraventricular/citologia , Fenótipo , Proteínas Proto-Oncogênicas c-fos/fisiologia , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/citologia
20.
Lancet Oncol ; 12(2): 127-36, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21236730

RESUMO

BACKGROUND: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. METHODS: We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. FINDINGS: 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival. INTERPRETATION: Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. FUNDING: Cancer Research UK (CRUK/03/005).


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Glândula Parótida , Radioterapia de Intensidade Modulada/métodos , Xerostomia/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
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