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BACKGROUND AND PURPOSE: This study quantifies intrafraction motion in surface-guided radiotherapy (SGRT) for breast cancer and considers the need for individualized intrafraction motion measures when calculating Planning Target Volume (PTV) margins. METHODS: SGRT was used to assess intrafraction motion in consecutive patients according to (1) site irradiated (whole breast (WB)/chest wall (CW) versus WB/CWâ¯+â¯regional lymph nodes) and (2) the use of deep inspiration breath hold (DIBH) versus free-breathing (FB). Intrafraction motion variation was evaluated throughout the treatment course for all cases. Associations between intrafraction motion and patient specific characteristics were explored. The usefulness of individualised intrafraction motion measures for PTV margin determination was considered. RESULTS: 102 patients undergoing 1360 fractions were included. On a population level, average intrafraction motion was less than 0.4mm and 0.2 degrees for translational and rotational directions, respectively, with 95th percentiles < 1.2mm and 0.6 degrees. No clinically meaningful differences in intrafraction motion were observed according to site irradiated or the use of DIBH. Consistency in intrafraction motion was noted for all patients throughout the treatment course. No clinically meaningful associations were found between intrafraction motion and patient specific characteristics such as age, seroma volume, PTV volume, and mean body volume. CONCLUSION: Intrafractional deviations with SGRT, using manufacturer-recommended ROIs, are minimal, do not vary substantially for different treatment techniques or patient specific characteristics, and remain constant throughout the treatment course. A universal intrafraction motion measure may be sufficient for calculating PTV margins. Further validation studies are needed to evaluate the impact of ROI size and coverage.
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BACKGROUND: The Relative Biological Effectiveness (RBE) of kilovoltage photon beams has been previously investigated in vitro and in silico using analytical methods. The estimated values range from 1.03 to 1.82 depending on the methodology and beam energies examined. PURPOSE: The focus of this work was to independently estimate RBE values for a range of clinically used kilovoltage beams (70-200 kVp) while investigating the suitability of using TOPAS-nBio for this task. METHODS: Previously validated spectra of clinical beams were used to generate secondary electron spectra at several depths in a water tank phantom via TOPAS Monte Carlo (MC) simulations. Cell geometry was irradiated with the secondary electrons in TOPAS-nBio MC simulations. The deposited dose and the calculated number of DNA strand breaks were used to estimate RBE values. RESULTS: Monoenergetic secondary electron simulations revealed the highest direct and indirect double strand break yield at approximately 20 keV. The average RBE value for the kilovoltage beams was calculated to be 1.14. CONCLUSIONS: TOPAS-nBio was successfully used to estimate the RBE values for a range of clinical radiotherapy beams. The calculated value was in agreement with previous estimates, providing confidence in its clinical use in the future.
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Quebras de DNA de Cadeia Dupla , Método de Monte Carlo , Eficiência Biológica Relativa , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Humanos , Elétrons , Dosagem Radioterapêutica , Fótons , Simulação por Computador , Imagens de FantasmasRESUMO
PURPOSE: Accepted conformity metrics in stereotactic ablative body radiotherapy (SABR) have significant limitations. This work aimed to develop a spatial assessment methodology that improves and automates checks of dose prescription and dose gradient from planning target volume (PTV) edge. METHODS: A Python-based script was developed to determine linear distances from the PTV edge to specified isodose, every 15 degrees on all axial slices and along the central axis in the coronal plane. A new "Internal PTV contour" distance metric is introduced as a size and shape indicator. 134 previously treated SABR patients stratified by anatomical site and PTV volume were analysed to establish baselines and tolerances for automation acceptability. RESULTS: In the axial plane, median distance (MD) from PTV edge to the 100 % isodose was 0.13 mm (range: -0.67 to 0.53 mm), and for the 90 % isodose was 2.37 mm (1.36 to 3.40 mm). Lung and non-Lung dose gradient criteria was established by fitting a second order polynomial to the MD as a function of "Internal PTV contour". This resulted in acceptability criteria of MD + 1 mm for 80 % isodose and MD + 2 mm for the 50 % isodose. For the coronal plane, MD to the 100 % isodose was 0.49 mm (-1.24 to 2.14 mm) and for the 90 % was 1.73 mm (-0.49 to 4.13 mm). CONCLUSIONS: Our in-house script enables a high-quality spatial assessment of PTV dose coverage and gradient, with the new 'Internal PTV contour' distance metric correlating well with dose gradient.
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Neoplasias Pulmonares , Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radiocirurgia/métodos , Neoplasias Pulmonares/radioterapia , Algoritmos , Radioterapia de Intensidade Modulada/métodosRESUMO
Background and purpose: Hypo-fractionated lung Stereotactic Ablative Body Radiotherapy (SABR) has often been avoided when tumours are close to the chest wall. Our strategic objective was the reduction of fraction number, while maintaining target biological effective dose coverage without increasing chest wall toxicity (CWT) predictors. Materials and methods: Twenty previously treated lung SABR patients were stratified into four cohorts according to distance from PTV to the chest wall, <1 cm, <0.5 cm, overlapping up to 0.5 cm and 1.0 cm. For each patient, four plans were created; a chest wall optimised plan for 54 Gy in 3 fractions, the clinical plan re-prescribed for 55 Gy in 5, 48 Gy in 3 and 45 Gy in 3 fractions. Results: For a PTV distance of 0.5-0.0 cm, a reduction of the median (range) Dmax from 55.7 (57.5-54.1) Gy to 40.0 (37.1-42.0 Gy) Gy was observed for the chest wall optimised plans. The median V30Gy decreased from 18.9 (9.7-25.6) cm3 to 3.1 (1.8-4.5) cm3. For a PTV overlap of up to 0.5 cm, the Dmax reduced from 66.5 (64.1-70) Gy to 53.2 (50.6-55.1) Gy. The V30Gy decreased from 21.5 (16.5-29.5) cm3 to 14.9 (11.3-20.2) cm3. For the cohort with up to 1.0 cm overlap, there was a reduction in Dmax values of 9.9 Gy. The V30Gy for clinical plans, at 66.8 (18.7-188.8) cm3, decreased to 55.3 (15.5-149) cm3. Conclusion: When PTVs are within 0.5 cm of chest wall, lung SABR dose heterogeneity can be used to reduce fraction number without increasing CWT predictors.
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Kilovoltage radiotherapy dose calculations are generally performed with manual point dose calculations based on water dosimetry. Tissue heterogeneities, irregular surfaces, and introduction of lead cutouts for treatment are either not taken into account or crudely approximated in manual calculations. Full Monte Carlo (MC) simulations can account for these limitations but require a validated treatment unit model, accurately segmented patient tissues and a treatment planning interface (TPI) to facilitate the simulation setup and result analysis. EGSnrc was used in this work to create a model of Xstrahl kilovoltage unit extending the range of energies, applicators, and validation parameters previously published. The novel functionality of the Python-based framework developed in this work allowed beam modification using custom lead cutouts and shields, commonly present in kilovoltage treatments, as well as absolute dose normalization using the output of the unit. 3D user-friendly planning interface of the developed framework facilitated non-co-planar beam setups for CT phantom MC simulations in DOSXYZnrc. The MC models of 49 clinical beams showed good agreement with measured and reference data, to within 2% for percentage depth dose curves, 4% for beam profiles at various depths, 2% for backscatter factors, 0.5 mm of absorber material for half-value layers, and 3% for output factors. End-to-end testing of the framework using custom lead cutouts resulted in good agreement to within 3% of absolute dose distribution between simulations and EBT3 GafChromic film measurements. Gamma analysis demonstrated poor agreement at the field edges which was attributed to the limitations of simulating smooth cutout shapes. Dose simulated in a heterogeneous phantom agreed to within 7% with measured values converted using the ratio of mass energy absorption coefficients of appropriate tissues and air.
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Radiometria , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiometria/métodos , Simulação por Computador , Planejamento da Radioterapia Assistida por Computador/métodos , Imagens de Fantasmas , Método de Monte Carlo , Dosagem RadioterapêuticaRESUMO
Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR. Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test. Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference (P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference (P = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm3) when using MR LAVA for contouring in comparison to CT. Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases.
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Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis.
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Efeito Espectador , Lesões por Radiação , Masculino , Humanos , Efeito Espectador/efeitos da radiação , Quebras de DNA de Cadeia Dupla , Sobrevivência Celular/efeitos da radiação , Linhagem CelularRESUMO
On Friday, May 14, 2021, the Health Service Executive, the organization providing public health services in the Republic of Ireland, was the victim of a significant cyberattack on its information technology systems. All systems were subsequently shut down to prevent further damage and to allow cybersecurity experts to investigate the attack. As a result, oncology services were severely disrupted, with the cessation of radiation therapy treatments in all public radiation therapy departments. Ireland has 5 large public and 6 smaller private radiation therapy centers in total. Because of the widespread adoption of electronic medical records in radiation therapy departments, it wasn't possible to retrieve patient details of those who were undergoing radiation therapy at the time of the cyberattack. In total, 513 patients nationally had their radiation therapy interrupted. A national radiation therapy cyberattack response team was formed immediately to oversee the response to the attack. The immediate concerns were radiation therapy emergencies and category 1 patients where gaps in treatment would have an adverse effect on outcome. Communication with patients and the public was also established as a priority and agreements were reached with the private sector for the treatment of patients affected by the cyberattack. The national media was used to alert patients of the need to communicate with their radiation therapy department. Dedicated phone lines were established. Locally, radiation therapy departments held daily crisis meetings with key staff members, including information technology personnel. Individual centers employed different technologies for treatment planning and data storage, so local solutions to the cyberattack to reestablish radiation therapy for patients were developed. In addition, national documentation on prioritization of patients to resume treatment was produced and a national approach was made to compensate for gaps in treatment caused by the attack. All 5 centers had reestablished radiation therapy by May 30, although there has been a long aftermath to the cyberattack. In this article, we provide an overview of the effects of the cyberattack on our national radiation therapy service and our strategy to resume patient treatment in a timely fashion.
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On May 14, 2021, the Health Service Executive (HSE) of Ireland experienced a major ransomware cyberattack. The HSE initially took down all of its information technology systems to protect its core systems. All Internet connections within the HSE were unavailable from 7 am for approximetely three weeks which had a major effect on the radiation oncology service nationally within the public service. St. Luke's Radiation Oncology Network (SLRON) is a complex, 3-center radiation oncology service, and it is the largest in the country; with 14 linear accelerators, it is one of the largest radiation centers in Europe. This article details the response of SLRON to the outage resultant from the cyberattack. Although the outage affected all patient services, including laboratory, diagnostic imaging, and inpatient care, the article primarily focuses on our response to get the radiation oncology service restarted as quickly as possible and details the steps we took to reinstate our systems safely, how we prioritized patient treatments, and how we communicated with patients, staff, and the public without having access to standard communication pathways. All decisions were risk assessed and were made with the best resources available to us at the time to maximize the outcome for our patients and mitigate significant delays. The risk remains ongoing, and the onerous task of uploading backlogs and reconciling patient records is a continuing risk.
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AIMS: To retrospectively evaluate the quality of fit of 3D printed bolus over four different treatment sites to determine whether certain sites favor a 3D printed approach and if the quality of fit changes over the course of treatment. MATERIALS AND METHODS: A retrospective analysis of the first 60 cases treated using 3D printed bolus in our radiotherapy center was undertaken. All boluses were printed using flexible thermoplastic polyurethane (TPU) material. We developed a system of rating the quality of fit using four quality categories. The analysis of 60 patients consisted of a review of a total 627 treatment fractions for head and neck (H&N), scalp, pelvis, and extremity treatment sites. RESULTS: Out of 627 fractions evaluated, 75.1% were rated either "good" or "excellent", 20.6% were rated as "acceptable" and 4.3% were rated "poor". H&N, scalp, and extremity treatment regions were found to favor a 3D printed approach. However, pelvis cases had a higher proportion of "acceptable" and "poor" ratings. Trend analysis showed no notable change in the quality of 3D printed bolus fit over the course of treatment, except for pelvis cases which tended to change categories more than other treatment sites. CONCLUSION: This evaluation demonstrates that 3D printed bolus, created using semi-flexible materials such as TPU, is an effective and practical bolus choice for radiotherapy. In particular, using a 3D printed approach for H&N, scalp, and extremities was found to have a highly conformal fit.
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Impressão Tridimensional , Planejamento da Radioterapia Assistida por Computador , Humanos , Dosagem Radioterapêutica , Estudos Retrospectivos , Couro CabeludoRESUMO
The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.
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Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Choque Térmico/genética , Proteínas Mitocondriais/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Antígeno Nuclear de Célula em Proliferação/genética , Neoplasias da Próstata/genética , Tolerância a Radiação/genética , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Estudos de Casos e Controles , Cromossomos/efeitos da radiação , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Doses de Radiação , Tolerância a Radiação/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto JovemRESUMO
PURPOSE: Radiation therapy plans are assessed using dose volume metrics derived from clinical toxicity and outcome data. In this study, plans for patients with locally advanced non-small cell lung cancer (LA-NSCLC) are examined in the context of the implementation of the Acuros XB (AXB) dose calculation algorithm focussing on the impact on common metrics. METHODS: Volumetric modulated arc therapy (VMAT) plans were generated for twenty patients, using the Analytical Anisotropic Algorithm (AAA) and recalculated with AXB for both dose to water (Dw) and dose to medium (Dm). Standard dose volume histogram (DVH) metrics for both targets and organs-at-risk (OARs) were extracted, in addition to tumour control probability (TCP) for targets. RESULTS: Mean dose to the planning target volume (PTV) was not clinically different between the algorithms (within ±1.1 Gy) but differences were seen in the minimum dose, D99% and D98% as well as for conformity and homogeneity metrics. A difference in TCP was seen for AXBDm plans versus both AXBDw and AAA plans. No clinically relevant differences were seen in the lung metrics. For point doses to spinal cord and oesophagus, the AXBDm values were lower than AXBDw, by up to 1.0 Gy. CONCLUSION: Normalisation of plans to the mean/median dose to the target does not need to be adjusted when moving from AAA to AXB. OAR point doses may decrease by up to 1 Gy with AXBDm, which can be accounted for in clinical planning. Other OAR metrics do not need to be adjusted.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Algoritmos , Benchmarking , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Probabilidade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
The Irish Association of Physicists in Medicine (IAPM) is an association of medical physicists in Ireland. The IAPM was founded in 2010 with the merger of the Association of Physical Scientists in Medicine (APSM) and the Irish Radiotherapy Physics Group (IRPG). The 10th Annual Scientific Meeting of the IAPM was held in Dublin on 23rd March 2019. This editorial summarises the proceedings of the day including invited speakers, diagnostic imaging and radiotherapy sessions, the Young Investigator Grant, the Early Careers bursary, joint session and poster presentations. A special issue of Physica Medica was dedicated to the event featuring a number of research papers.
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Genetic and epigenetic profile changes associated with individual radiation sensitivity are well documented and have led to enhanced understanding of the mechanisms of the radiation-induced DNA damage response. However, the search continues to identify reliable biomarkers of individual radiation sensitivity. Herein, we report on a multi-biomarker approach using traditional cytogenetic biomarkers, DNA damage biomarkers and transcriptional microRNA (miR) biomarkers coupled with their potential gene targets to identify radiosensitivity in ataxia-telangiectasia mutated (ATM)-deficient lymphoblastoid cell lines (LCL); ATM-proficient cell lines were used as controls. Cells were 0.05 and 0.5 Gy irradiated, using a linear accelerator, with sham-irradiated cells as controls. At 1 h postirradiation, cells were fixed for γ-H2AX analysis as a measurement of DNA damage, and cytogenetic analysis using the G2 chromosomal sensitivity assay, G-banding and FISH techniques. RNA was also isolated for genetic profiling by microRNA (miR) and RT-PCR analysis. A panel of 752 miR were analyzed, and potential target genes, phosphatase and tensin homolog (PTEN) and cyclin D1 (CCND1), were measured. The cytogenetic assays revealed that although the control cell line had functional cell cycle checkpoints, the radiosensitivity of the control and AT cell lines were similar. Analysis of DNA damage in all cell lines, including an additional control cell line, showed elevated γ-H2AX levels for only one AT cell line. Of the 752 miR analyzed, eight miR were upregulated, and six miR were downregulated in the AT cells compared to the control. Upregulated miR-152-3p, miR-24-5p and miR-92-15p and all downregulated miR were indicated as modulators of PTEN and CCDN1. Further measurement of both genes validated their potential role as radiation-response biomarkers. The multi-biomarker approach not only revealed potential candidates for radiation response, but provided additional mechanistic insights into the response in AT-deficient cells.
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Proteínas Mutadas de Ataxia Telangiectasia/deficiência , Ciclina D1/metabolismo , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Biomarcadores/metabolismo , Linhagem Celular , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Linfócitos/citologiaRESUMO
PURPOSE: Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual's response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used not only for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure. MATERIALS AND METHODS: The present study attempts to link the biochemical profile of lymphocytes within PBMCs obtained through Raman spectroscopy to in vitro measures of low-dose (<0.5Gy) DNA damage response and cytogenetic metrics of radiosensitivity in a cohort of healthy controls and prostate cancer patients (from CTRIAL-IE(ICORG) 08-17, NCT00951535). All parallel metrics to the Raman spectra of the cells were obtained ex vivo in cycling peripheral blood lymphocytes, with radiosensitivity estimated using the G2 chromosomal assay and DNA damage assessed using γH2AX fluorescence. Spectra from a total of 26 healthy volunteers and 22 prostate cancer patients were obtained. RESULTS: The links between both measures of cellular response to ionizing radiation and the Raman spectra were modeled using partial least squares regression (PLSR) and support-vector regression (SVR). It was found that neither regression approach could predict radiation-induced G2 score well, but could predict γH2AX MFI with the SVR outperforming PLSR, implying a non-linear relationship between spectral measurements and measures of DNA damage. CONCLUSIONS: Raman spectroscopy of PBMCs represents a label-free approach for prediction of DNA damage levels for either prospective or retrospective analysis.
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Cromossomos Humanos/genética , Cromossomos Humanos/efeitos da radiação , Dano ao DNA , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos da radiação , Tolerância a Radiação/genética , Análise Espectral Raman , Adulto , Aberrações Cromossômicas/efeitos da radiação , Humanos , Masculino , Neoplasias da Próstata/patologia , Adulto JovemRESUMO
On 5 December 2013 the European Council promulgated Directive 2013/59/EURATOM. This Directive is important for Medical Physicists and Medical Physics Experts as it puts the profession on solid foundations and describes it more comprehensively. Much commentary regarding the role and competences has been developed in the context of the European Commission project "European Guidelines on the Medical Physics Expert" published as Radiation Protection Report RP174. The guidelines elaborate on the role and responsibilities under 2013/59/EURATOM in terms of a mission statement and competence profile in the specialty areas of Medical Physics relating to medical radiological services, namely Diagnostic and Interventional Radiology, Radiation Oncology and Nuclear Medicine. The present policy statement summarises the provisions of Directive 2013/59/EURATOM regarding the role and competences, reiterates the results of the European Guidelines on the Medical Physics Expert document relating to role and competences of the profession and provides additional commentary regarding further issues arising following the publication of the RP174 guidelines.
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Física Médica , Políticas , Europa (Continente) , Humanos , Proteção RadiológicaRESUMO
It is now well accepted that radiation induced bystander effects can occur in cells exposed to media from irradiated cells. The aim of this study was to follow the bystander cells in real time following addition of media from irradiated cells and to determine the effect of inhibiting these signals. A human keratinocyte cell line, HaCaT cells, was irradiated (0.005, 0.05 and 0.5 Gy) with γ irradiation, conditioned medium was harvested after one hour and added to recipient bystander cells. Reactive oxygen species, nitric oxide, Glutathione levels, caspase activation, cytotoxicity and cell viability was measured after the addition of irradiated cell conditioned media to bystander cells. Reactive oxygen species and nitric oxide levels in bystander cells treated with 0.5Gy ICCM were analysed in real time using time lapse fluorescence microscopy. The levels of reactive oxygen species were also measured in real time after the addition of extracellular signal-regulated kinase and c-Jun amino-terminal kinase pathway inhibitors. ROS and glutathione levels were observed to increase after the addition of irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). Caspase activation was found to increase 4 hours after irradiated cell conditioned media treatment (0.005, 0.05 and 0.5 Gy ICCM) and this increase was observed up to 8 hours and there after a reduction in caspase activation was observed. A decrease in cell viability was observed but no major change in cytotoxicity was found in HaCaT cells after treatment with irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). This study involved the identification of key signaling molecules such as reactive oxygen species, nitric oxide, glutathione and caspases generated in bystander cells. These results suggest a clear connection between reactive oxygen species and cell survival pathways with persistent production of reactive oxygen species and nitric oxide in bystander cells following exposure to irradiated cell conditioned media.
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Efeito Espectador/fisiologia , Meios de Cultivo Condicionados/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Raios gama , Glutationa/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Transdução de Sinais/efeitos da radiaçãoRESUMO
Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy10. This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Carga Tumoral , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Órgãos em Risco , Probabilidade , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
Multileaf collimators (MLCs) need to be characterized accurately in treatment planning systems to facilitate accurate intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). The aim of this study was to examine the use of MapCHECK 2 and ArcCHECK diode arrays for optimizing MLC parameters in Monaco X-ray voxel Monte Carlo (XVMC) dose calculation algorithm. A series of radiation test beams designed to evaluate MLC model parameters were delivered to MapCHECK 2, ArcCHECK, and EBT3 Gafchromic film for comparison. Initial comparison of the calculated and ArcCHECK-measured dose distributions revealed it was unclear how to change the MLC parameters to gain agreement. This ambiguity arose due to an insufficient sampling of the test field dose distributions and unexpected discrepancies in the open parts of some test fields. Consequently, the XVMC MLC parameters were optimized based on MapCHECK 2 measurements. Gafchromic EBT3 film was used to verify the accuracy of MapCHECK 2 measured dose distributions. It was found that adjustment of the MLC parameters from their default values resulted in improved global gamma analysis pass rates for MapCHECK 2 measurements versus calculated dose. The lowest pass rate of any MLC-modulated test beam improved from 68.5% to 93.5% with 3% and 2 mm gamma criteria. Given the close agreement of the optimized model to both MapCHECK 2 and film, the optimized model was used as a benchmark to highlight the relatively large discrepancies in some of the test field dose distributions found with ArcCHECK. Comparison between the optimized model-calculated dose and ArcCHECK-measured dose resulted in global gamma pass rates which ranged from 70.0%-97.9% for gamma criteria of 3% and 2 mm. The simple square fields yielded high pass rates. The lower gamma pass rates were attributed to the ArcCHECK overestimating the dose in-field for the rectangular test fields whose long axis was parallel to the long axis of the ArcCHECK. Considering ArcCHECK measurement issues and the lower gamma pass rates for the MLC-modulated test beams, it was concluded that MapCHECK 2 was a more suitable detector than ArcCHECK for the optimization process.
Assuntos
Garantia da Qualidade dos Cuidados de Saúde/normas , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/instrumentação , Radioterapia de Intensidade Modulada/métodos , Semicondutores , Algoritmos , Raios gama , Humanos , Método de Monte Carlo , Dosagem Radioterapêutica , SoftwareRESUMO
Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic.