ORCID Profile
0000-0002-1315-1735
Current Organisations
Cancer Research Institute, University of South Australia
,
University of South Australia
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Nuclear physics | Nuclear and plasma physics | Law and society and socio-legal research | Mineral processing/beneficiation |
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 09-2010
DOI: 10.1007/S13246-010-0032-6
Abstract: Hypoxic tissues lack adequate oxygenation and it has been long established that tumours commonly exhibit hypoxia and that hypoxia is a factor contributing towards resistance to radiotherapy. To develop computer models and make predictions about the affects of tumour hypoxia on treatment outcome, quantitative tumour oxygenation and reoxygenation data from in vivo systems is required. The aim of this study was to investigate the timing and degree of reoxygenation during radiotherapy in a human head and neck squamous cell carcinoma xenograft mouse model (FaDu). Mice were immobilised using a novel restraining system and exposed unanaesthetised in 3 or 5 Gy fractions, up to a maximum of 40 Gy. Partial pressures of oxygen (pO2) measurements were recorded at six time points throughout the 2 week course of radiotherapy, using a fibre optic system. Tumours receiving 0-30 Gy did not exhibit an increase in pO2. However, the mean pO2 after 2 weeks of accelerated fractionated radiotherapy (40 Gy) was significantly increased (P<0.01) compared to the mean pO2 of tumours not receiving the full schedule (0-30 Gy). These results lead to the conclusion of an average reoxygenation onset time of 2 weeks in this group of xenografts. A relatively large range of pO2 values measured at each dose point in the study indicate a large inter-tumour variation in oxygenation among the tumours. Data from this experimental work will be used to define the range of reoxygenation onset times implemented in a Monte Carlo computer model, simulating hypoxic head and neck cancer growth and radiotherapy.
Publisher: Wiley
Date: 08-07-2021
DOI: 10.1002/HED.26802
Abstract: Superior treatment responses by patients with human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC), compared to patients with HNSCC from other causes, drive biomarker research to optimize treatment. Most HNSCC patients receive radiation therapy delivered as a fractionated course. Changing HPV status in HNSCC from a positive prognostic marker to a predictive one requires biomarkers that capture cellular radiation response to cumulative dose. Nuclear enlargement, γH2AX expression and micronuclei count, were studied in six HNSCC cell lines after 4 Gy fractionated X‐irradiation. All HNSCC cell lines displayed altered cellular responses, indicating increasing inability to repair radiation damage with subsequent radiation fractions. Increases in nuclear area were significantly greater among HPV positive cell lines (207% and 67% for the HPV positive and HPV negative groups, respectively). A different character of DNA repair dysfunction in the HPV positive group suggests greater chromosomal translocation with accumulated radiation dose.
Publisher: IEEE
Date: 1996
Publisher: Elsevier BV
Date: 03-1999
Publisher: Radiation Research Society
Date: 05-01-2014
DOI: 10.1667/RR13460.1
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JACR.2019.05.018
Abstract: Despite the clinical knowledge accumulated over a century about tumor hypoxia, this biologic parameter remains a major challenge in cancer treatment. Patients presenting with hypoxic tumors are more resistant to radiotherapy and often poor responders to chemotherapy. Treatment failure because of hypoxia is, therefore, very common. Several methods have been trialed to measure and quantify tumor hypoxia, with varied success. Over the last couple of decades, hypoxia-specific functional imaging has started to play an important role in personalized treatment planning and delivery. Yet, there are no gold standards in place, owing to inter- and intrapatient phenotypic variations that further complicate the overall picture. The aim of the current article is to analyze, through the review of the literature, the potential role of radiomics and radiogenomics in patient stratification by tumor hypoxia status. Search of literature published in English since 2000 was conducted using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in text and in a tabulated format. Although still an immature area of science, radiomics has shown its potential in the quantification of hypoxia within the heterogeneous tumor, quantification of changes regarding the degree of hypoxia after radiotherapy and drug delivery, monitoring tumor response to anti-angiogenic therapy, and assisting with patient stratification and outcome prediction based on the hypoxic status. The lack of technique standardization to measure and quantify tumor hypoxia presents an opportunity for data mining and machine learning in radiogenomics.
Publisher: MDPI AG
Date: 28-12-2020
Abstract: Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using flow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue s les to identify potential changes in C595-reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5–93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC.
Publisher: Radiation Research Society
Date: 23-08-2013
DOI: 10.1667/RR3381.2
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CRITREVONC.2018.06.014
Abstract: Stereotactic ablative radiation therapy for lung cancer is an advanced technique where tumours are ablated with hypofractionated radiation doses, with a high degree of accuracy. The aim of this paper is to review the available literature and to discuss the SABR-induced toxicities for lung malignancies as a function of radiation delivery technique. A Medline search was conducted to identify the appropriate literature to fulfil the aim of this review and data from all applicable papers were collated and analysed. The most common techniques of SABR delivery employ linear accelerators, CyberKnife robotic radiosurgery system, TomoTherapy and the Novalis beam surgery system. Linear accelerator-based treatments give rise to a variety of toxicities that are strongly dependent on both patient-related factors and planning/dosimetry-related factors. The limited number of studies using CyberKnife reported low grade toxicities. Grade three toxicities mainly include fatigue and chest pain, usually in less than 10% of patients. All treatment techniques presented show efficiency in SABR delivery with various toxicities which, at this stage, cannot render one technique better than the other. For more conclusive results, well-designed phase three randomised clinical trials are required with better patient selection criteria, including dose and fractionation, treatment machine and technique, along with the consistent selection of a common toxicity grading criterion.
Publisher: Future Medicine Ltd
Date: 12-2020
Abstract: Background: The use of gold nanoparticles (AuNPs) as radiosensitizers may offer a new approach in the treatment of head and neck cancers minimizing treatment-associated toxicities and improving patient outcomes. AuNPs promote localized dose deposition permitting improved local control and/or dose reduction. Aim: This work aimed to address the theoretical optimization of radiation doses, fractionation and nanoparticle injection schedules to maximize therapeutic benefits. Materials & methods: Probabilistic nanoparticle sensitization factors were incorporated into the in idual cell-based HYP-RT computer model of tumor growth and radiotherapy. Results: Total dose outcomes across all radiation therapy treatment regimens were found to be significantly reduced with the presence of AuNPs, with bi-weekly injections showing the most decrease. Conclusion: Outcomes suggest the need for regular AuNP administration to permit effective radiosensitization.
Publisher: Informa UK Limited
Date: 04-2017
DOI: 10.2147/HP.S133231
Publisher: Elsevier BV
Date: 07-2021
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/968429
Abstract: The major differences between the physics models in Geant4-DNA and RITRACKS Monte Carlo packages are investigated. Proton and electron ionisation interactions and electron excitation interactions in water are investigated in the current work. While these packages use similar semiempirical physics models for inelastic cross-sections, the implementation of these models is demonstrated to be significantly different. This is demonstrated in a simple Monte Carlo simulation designed to identify differences in interaction cross-sections.
Publisher: MDPI AG
Date: 15-08-2022
Abstract: Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT.
Publisher: Wiley
Date: 27-10-2016
DOI: 10.1118/1.4965805
Abstract: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223 Ra-223) and a Timepix pixelated semiconductor detector. The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM. Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h irradiation, respectively, considering a relative biological effectiveness of alpha particles of 5.5. The study confirmed that the Timepix detector can be used for transmission alpha particle dosimetry. If cross-calibrated using biological dosimetry, this method will give a good indication of the biological effects of alpha particles without the need for repeated biological dosimetry which is costly, time consuming, and not readily available.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2023
DOI: 10.1186/S41181-023-00204-4
Abstract: Pancreatic ductal adenocarcinoma (PDAC) continues to be a malignancy with an unmet clinical demand. Development of radioimmunoconjugates which target cancer-specific receptors provides an opportunity for radioimmunotherapy of both metastatic and primary PDAC. In this study, we characterised the in vitro behaviour of a novel beta-emitting radioimmunoconjugate [ 177 Lu]Lu-DOTA-C595 as a therapeutic agent against PDAC. [ 177 Lu]Lu-DOTA-C595 is designed to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on most epithelial cancers, including PDAC. A series of in vitro experiments were performed on PDAC cell lines (PANC-1, CAPAN-1, BxPC-3 and AsPC-1) exhibiting strong to weak MUC1-CE expression. [ 177 Lu]Lu-DOTA-C595 bound to all cell lines relative to their expression of MUC1-CE. [ 177 Lu]Lu-DOTA-C595 was also rapidly internalised across all cell lines, with a maximum of 75.4% of activity internalised within the PANC-1 cell line at 48 h. The expression of γH2AX foci and clonogenic survival of PANC-1 and AsPC-1 cell lines after exposure to [ 177 Lu]Lu-DOTA-C595 were used to quantify the in vitro cytotoxicity of [ 177 Lu]Lu-DOTA-C595. At 1 h post treatment, the expression of γH2AX foci exceeded 97% in both cell lines. The expression of γH2AX foci continued to increase in PANC-1 cells at 24 h, although expression reduced in AsPC-1. Clonogenic assays showed a high level of cell kill induced by [ 177 Lu]Lu-DOTA-C595. [ 177 Lu]Lu-DOTA-C595 has favourable in vitro characteristics to target and treat MUC1-CE positive PDAC. Further investigations to characterise the in vivo effects and potential value of [ 177 Lu]Lu-DOTA-C595 in other MUC1-CE expressing malignancies such as lung, ovarian and colorectal adenocarcinoma are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
Publisher: MDPI AG
Date: 24-09-2022
Abstract: Mucin 1 is a transmembrane glycoprotein which overexpresses cancer-specific epitopes (MUC1-CE) on pancreatic ductal adenocarcinoma (PDAC) cells. As PDAC is a low survival and highly aggressive malignancy, developing radioimmunoconjugates capable of targeting MUC1-CE could lead to improvements in PDAC outcomes. The aim of this study was to develop and perform preliminary testing of diagnostic and therapeutic radioimmunoconjugates for PDAC using an anti-MUC1 antibody, C595. Firstly, p-SCN-Bn-DOTA was conjugated to the C595 antibody to form a DOTA-C595 immunoconjugate. The stability and binding affinity of the DOTA-C595 conjugate was evaluated using mass spectrometry and ELISA. DOTA-C595 was radiolabelled to Copper-64, Lutetium-177, Gallium-68 and Technetium-99m to form novel radioimmunoconjugates. Cell binding assays were performed in PANC-1 (strong MUC1-CE expression) and AsPC-1 (weak MUC1-CE expression) cell lines using 64Cu-DOTA-C595 and 177Lu-DOTA-C595. An optimal molar ratio of 4:1 DOTA groups per C595 molecule was obtained from the conjugation process. DOTA-C595 labelled to Copper-64, Lutetium-177, and Technetium-99m with high efficiency, although the Gallium-68 labelling was low. 177Lu-DOTA-C595 demonstrated high cellular binding to the PANC-1 cell lines which was significantly greater than AsPC-1 binding at concentrations exceeding 100 nM (p 0.05). 64Cu-DOTA-C595 showed similar binding to the PANC-1 and AsPC-1 cells with no significant differences observed between cell lines (p 0.05). The high cellular binding of 177Lu-DOTA-C595 to MUC1-CE positive cell lines suggests promise as a therapeutic radioimmunoconjugate against PDAC while further work is required to harness the potential of 64Cu-DOTA-C595 as a diagnostic radioimmunoconjugate.
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.CTRV.2011.06.003
Abstract: Despite the large variety of treatment methods available for the management of advanced head and neck carcinomas, these tumours remain highly challenging due to their aggressiveness and complex anatomical location. Among the treatment challenges associated with head and neck cancers, hypoxia and tumour repopulation during treatment are, most likely, the main reason for locoregional treatment failure. Whilst the number of techniques and predictive assays designed to assess the oxygenation status or the proliferative ability of tumours is rather large, they all come with drawbacks which limit their implementation as routine clinical procedures. Latest developments in the field of nuclear medicine have opened the road to new possibilities in functional imaging, thus overcoming some of the confines imposed by the more conventional techniques. The current paper presents the role of PET imaging as a quantitative evaluation tool for hypoxia status and proliferative ability of advanced head and neck tumours. Traditional as well as novel radioisotopes with high affinity towards hypoxia and proliferative tumour activity are presented and their pre-clinical/clinical results analysed. While the number of clinical studies which aimed to validate novel radiotracers for head and neck cancer is limited, a number of results show promising correlation between uptake/marker activity and treatment outcome. There is need for further studies and well designed clinical trials to obtain more conclusive results.
Publisher: Wiley
Date: 02-12-2019
DOI: 10.1002/MP.13923
Abstract: Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy. A two-stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated. A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9-11 was observed for high proton energies however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5-25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement. A large enhancement in dose and radiolysis yield was observed. However, the low-energy secondary electrons produced within the gold for lower energy protons are susceptible to self-absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size however, the yield and dose per gold mass decrease due to self-absorption. Therefore, an intermediate nanoparticle size of approximately 10-25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit the loss of enhancement. For molecular coatings such as PEG, coating density should be maximized as this increases the coating's effectiveness with only a minimal effect on enhancement.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/363564
Abstract: The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO 2 histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical ision probability, while the process of reoxygenation utilises randomised pO 2 increments to the cell population after each treatment fraction. Propagation of 10 8 tumour cells requires 5–30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5–1.0 Gy, in agreement with published reports. The average reoxygenation pO 2 increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2017
DOI: 10.1038/S41598-017-11444-1
Abstract: Tumor oxygenation has been correlated with treatment outcome for radiotherapy. In this work, the dependence of tumor oxygenation on tumor vascularity and blood oxygenation was determined quantitatively in a 4D stochastic computational model of head and neck squamous cell carcinoma (HNSCC) tumor growth and angiogenesis. Additionally, the impacts of the tumor oxygenation and the cancer stem cell (CSC) symmetric ision probability on the tumor volume doubling time and the proportion of CSCs in the tumor were also quantified. Clinically relevant vascularities and blood oxygenations for HNSCC yielded tumor oxygenations in agreement with clinical data for HNSCC. The doubling time varied by a factor of 3 from well oxygenated tumors to the most severely hypoxic tumors of HNSCC. To obtain the doubling times and CSC proportions clinically observed in HNSCC, the model predicts a CSC symmetric ision probability of approximately 2% before treatment. To obtain the doubling times clinically observed during treatment when accelerated repopulation is occurring, the model predicts a CSC symmetric ision probability of approximately 50%, which also results in CSC proportions of 30–35% during this time.
Publisher: Informa UK Limited
Date: 05-2020
DOI: 10.2147/RMHP.S247774
Publisher: Elsevier BV
Date: 10-2023
Publisher: Springer Science and Business Media LLC
Date: 09-08-2021
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.EJMP.2009.11.004
Abstract: Advanced head and neck cancers are one of the most challenging cancers facing the oncologists due to their aggressiveness attributable to the high hypoxic content and the tumour's ability to repopulate during radiotherapy. Alterations of radiotherapy fractionation schedules are possible ways to improve tumour control. Clinical trials have shown that both hyperfractionated radiotherapy (multiple fractions a day, over the same treatment time), and accelerated radiotherapy (higher doses per fraction, six days a week, over 5 weeks or less) are more effective than conventional radiotherapy in the management of head and neck cancer. However, the treatment choice between hyperfractionated and accelerated radiotherapy is still debated, due to very similar results obtained regarding tumour control. Furthermore, while radiotherapy alone has an impact on the short-term prognosis of advanced head and neck cancer, the long-term benefits have been moderate. Cisplatin is a chemotherapeutic agent which combined with conventional radiotherapy has shown to improve patient survival. The present paper employs a Monte Carlo modelling approach in assessing the effect of combined cisplatin-altered fractionation schedule on tumour response. The growth of a head and neck carcinoma has been modelled using probabilistic functions s led by computer generated random number sequences, maintaining the biological constitution of a tumour. The tumour growth model has been built to simulate the in vivo processes taking place before and after radiotherapy/chemotherapy. The model has shown that adding cisplatin to radiotherapy improves tumour control in both hyperfractionated and accelerated radiotherapy.
Publisher: MDPI AG
Date: 12-01-2023
DOI: 10.3390/IJMS24021524
Abstract: Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging.
Publisher: Elsevier BV
Date: 08-2021
Publisher: IOP Publishing
Date: 24-05-2006
DOI: 10.1088/0031-9155/51/11/019
Abstract: The use of a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) for two-dimensional transmitted dosimetry was investigated and a calibration method was developed using extended dose range (EDR2) film. In order to convert pixel value to dose, the acquired SLIC-EPID pixel values were calibrated using an ionization chamber on the central axis. The relationship between pixel values, dose rate and absorbed dose was identified for various linac output repetition rates. To correct EPIs for dosimetric purposes, the off-axis ratio of dose profiles measured by EPIDs and EDR2 film was used to derive correction factor matrices (CFMs) for a range of source-to-EPID distances (SEDs). The corrected relative dose maps acquired for different conditions, including open and wedged fields, measured using a SLIC-EPID were compared with EDR2 film images using a gamma function algorithm with distance to agreement (DTA) = 2.5 mm and dose difference (DeltaDmax) = 1% criteria. The results showed that (a) for two-dimensional dosimetric purposes, EPIDs must be calibrated using appropriate two-dimensional correction factors and (b) SLIC-EPIDs can be used to measure the transmitted dose with good accuracy.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.RADONC.2019.02.016
Abstract: Head and neck squamous cell carcinomas (HNSCC) resulting from oncogenic transformations following human papillomavirus (HPV) infection consistently demonstrate better treatment outcomes than HNSCC from other aetiologies. Squamous cell carcinoma of the oropharynx (OPSCC) shows the highest prevalence of HPV involvement at around 70-80%. While strongly prognostic, HPV status alone is not sufficient to predict therapy response or any potential dose de-escalation. Cancer stem cell (CSC) populations within these tumour types represent the most therapy-resistant cells and are the source of recurrence and metastases, setting a benchmark for tumour control. This review examines clinical and preclinical evidence of differences in response to treatment by the HPV statuses of HNSCC and the role played by CSCs in treatment resistance and their repopulation from non-CSCs. Evidence was collated from literature searches of PubMed, Scopus and Ovid for differential treatment response by HPV status and contribution by critical biomarkers including CSC fractions and chemo-radiosensitivity. While HPV and CSC are yet to fulfil promise as biomarkers of treatment response, understanding how HPV positive and negative aetiologies affect CSC response to treatment and tumour plasticity will facilitate their use for greater treatment in idualisation.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2018
DOI: 10.1038/S41598-018-26134-9
Abstract: Head and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative). A novel approach was taken to develop generational cultures of HNC cell lines, UM-SCC-1 (HPV negative) and UM-SCC-47 (HPV positive). MTT assays were used to determine surviving metabolic activity as a function of dose following 6 MV X-ray irradiation. Parallel cultures surviving 4 Gy irradiation (not analysed) were re-cultured and passaged to develop subsequent generations which were re-irradiated and analysed for generational change in radiation response. Second and 3rd generations of UM-SCC-1 showed decreasing metabolic activity with dose but little difference was evident in surviving fractions between these generations. Significantly lower metabolic activity in the 3rd generation at Gy, compared to the 2nd generation, showed UM-SCC-47 becoming progressively more radiosensitive. HPV positive UM-SCC-47 showed generational progression in radiosensitisation not seen in the HPV negative UM-SCC-1.
Publisher: Informa UK Limited
Date: 04-04-2017
Publisher: Wiley
Date: 21-11-2023
DOI: 10.1002/JUM.16129
Abstract: Endometriosis is a common and painful gynaecological condition that takes an average of 6.4years to diagnose. While laparoscopic surgery is the recommend gold standard in diagnosis of endometriosis, transvaginal ultrasound (TVS) is able to assist surgeons in the planning and management of patients, especially when there is limited visualisation in the posterior compartment. Uterosacral ligaments (USL) are located in the posterior compartment and are one of the first and most common places that endometriosis deposits, The International Deep Endometriosis Analysis (IDEA) group consensus, which are the current guidelines for DE imaging, recommends a thorough ultrasound assessment to identify endometriotic disease. This includes an assessment of anatomic structures in the posterior compartment including the USLs. However, IDEA does not explicitly articulate specifics of USL imaging and measurements on ultrasound. The primary aim of this review is to determine is to identify ultrasound techniques and characteristics of USLs in the diagnosis of deep infiltrative endometriosis (DE). The secondary aim is to describe and summarise these findings into normal and pathological findings. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A population, interventions, comparator, and outcome framework was used to define a search strategy. Articles were screened using Covidence review management system, and data was extracted by two authors using a standardised and piolet‐tested form. Quality assessment was conducted using the Critical Appraisal Skills Programme (CASP). Medline, Embase and Scopus and Google Scholar were searched yielding 250 articles, with 22 being included in the review. Analysis of the data demonstrated inconsistent reporting of ultrasound techniques and characteristics of USLs. Most (20/22) papers described abnormal criteria of USLs, only 5/22 papers determined what the normal USL appearance is or what techniques (11/22) were applied. Even though reporting was heterogeneous, there was a high level of tertiary centre participation with gynaecological experienced operators, therefore was a high level of agreement. Through review of the current literature, this study has investigated ultrasound techniques and characteristics of USLs for the diagnosis of DE. All papers included in this review reported presence of pathological sonographic findings of the USLs when DE was presented therefore it is recommended that USL examination become a part of TVS exams when DE is clinically suspected. This study also demonstrated that there was lack of data and no agreement when it comes to measuring USLs with DE. Even so, the current evidence demonstrates that scanning the USLs, and locating, identifying, and describing USL thickening and endometriotic nodules in the various locations using the described techniques and characteristics in this review has clinical value in early diagnosis.
Publisher: MDPI AG
Date: 22-02-2019
Abstract: Background: Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans. Methods: Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others). Results: Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient’s TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R2). Conclusion: The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.EJMP.2019.08.021
Abstract: The purpose of this study was to investigate the potential of real-time optically stimulated luminescence (rtOSL) measurements of a beryllium oxide (BeO) ceramic fibre-coupled luminescence dosimetry system. By pulsing the stimulation laser during the exposure to ionizing radiation, an rtOSL dose-rate measurement can be obtained which could be stem effect free. A portable rtOSL BeO ceramic fibre-coupled dosimetry system is presented and characterized using a constant dose-rate superficial 140 kVp X-ray beam. The rtOSL was measured for dose-rates between 0.29 and 3.88 Gy/min, controlled by varying the source to surface distance. After correcting for OSL decay during the exposure, a linear dose-rate response of the change in rtOSL (ΔrtOSL) was observed. The ΔrtOSL was also observed to be stem effect free.
Publisher: Springer Science and Business Media LLC
Date: 30-12-2022
DOI: 10.1186/S12909-022-03888-5
Abstract: There is limited access to life-saving antenatal ultrasound in low-resource rural and remote settings worldwide, including Australia, mainly due to shortages in skilled staff. Point-of-care ultrasound (PoCUS) offers a viable solution to this service deficit, however, rural clinicians face many barriers accessing training and professional development critical to advancing their clinical practice. Standards for PoCUS training and competency assessment are unclear. Regulation is lacking globally, allowing untrained and inexperienced clinicians to practice PoCUS clinically. This prospective single cohort study aimed to evaluate antenatal PoCUS training workshops for General Practitioners (GPs) and Midwives/Nurses (M/Ns) from rural/remote Australia, assessing the impact of the training on trainees’ knowledge, confidence and translation of PoCUS into clinical practice. Two-day antenatal ultrasound workshops were delivered at the University of South Australia (UniSA) in 2018 and 2019 to 41 rural/remote clinicians . The training was designed and evaluated using the New world Kirkpatrick Evaluation Framework. Sixteen GPs and 25 M/Ns with mixed prior ultrasound experience were funded to attend. The course consisted of lectures interspaced with hands-on training sessions using high-fidelity simulators and live pregnant models. Pre- and post-knowledge assessments were performed. Post-workshop evaluation and follow-up surveys (3- and 6-month post-training) assessed the workshops and changes to trainees’ clinical practice. A 2-day follow-up training session was conducted 12 months after the workshops for 9 trainees. Pre ost knowledge testing demonstrated a 22% mean score improvement (95% CI 17.1 to 27.8, P 0.0001). At 6 months, 62% of trainees were performing PoCUS that had assisted in patient management and clinical diagnosis, and 46% reported earlier diagnosis and changes to patient management. 74% of trainees had increased scanning frequency and 93% reported improved scanning confidence. This study demonstrated intensive 2-day workshops can equip clinicians with valuable antenatal PoCUS skills, offering a viable solution to assist in the assessment and management of pregnant women in the rural/resource-poor setting where access to ultrasound services is limited or non-existent. Geographical isolation and lack of onsite specialist supervision poses an ongoing challenge to the continuing professional development of remote trainees and the implementation of PoCUS.
Publisher: Wiley
Date: 28-04-2021
DOI: 10.1111/GWAO.12690
Abstract: The COVID‐19 pandemic has forced many people, including those in the fields of science and engineering, to work from home. The new working environment caused by the pandemic is assumed to have a different impact on the amount of work that women and men can do from home. Particularly, if the major burden of child and other types of care is still predominantly on the shoulders of women. As such, a survey was conducted to assess the main issues that biomedical engineers, medical physicists (academics and professionals), and other similar professionals have been facing when working from home during the pandemic. A survey was created and disseminated worldwide. It originated from a committee of International Union for Physical and Engineering Sciences in Medicine (IUPESM Women in Medical Physics and Biomedical Engineering Task Group) and supported by the Union. The ethics clearance was received from Carleton University. The survey was deployed on the Survey Monkey platform and the results were analyzed using IBM SPSS software. The analyses mainly consisted of frequency of the demographic parameters and the cross‐tabulation of gender with all relevant variables describing the impact of work at home. A total of 921 responses from biomedical professions in 76 countries were received: 339 males, 573 females, and nine prefer‐not‐to‐say/other. Regarding marital artnership status, 85% of males were married or in partnership, and 15% were single, whereas 72% of females were married or in partnership, and 26% were single. More women were working from home during the pandemic (68%) versus 50% of men. More men had access to an office at home (68%) versus 64% for women. The proportion of men spending more than 3 h on child care and schooling per day was 12%, while for women it was 22% for household duties, 8% of men spent more than 3 h for women, this was 12.5%. It is interesting to note that 44% of men spent between 1 and 3 h per day on household duties, while for women, it was 55%. The high number of survey responses can be considered excellent. It is interesting to note that men participate in childcare and household duties in a relatively high percentage although this corresponds to less hours daily than for women. It is far more than can be found 2 and 3 decades ago. This may reflect the situation in the developed countries only—as majority of responses (75%) was received from these countries. It is evident that the burden of childcare and household duties will have a negative impact on the careers of women if the burden is not more similar for both sexes. It is important to recognize that a change in policies of organizations that hire them may be required to provide accommodation and compensation to minimize the negative impact on the professional status and career of men and women who work in STEM fields.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2014
DOI: 10.1007/S10565-014-9268-3
Abstract: The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.
Publisher: Oxford University Press (OUP)
Date: 09-03-2022
Abstract: Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD. Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: −19.6 ± 0.4, post: −20.1 ± 1.0, CON: pre: −20.0 ± 0.4, post: −20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies. The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.
Publisher: Wiley
Date: 25-12-2019
DOI: 10.1002/MP.13935
Abstract: Protons and heavy ions are considered to be ideal particles for use in external beam radiotherapy due to the superior properties of the dose distribution. While a photon (x-ray) beam delivers considerable dose to healthy tissues around the tumor, a proton beam that is delivered with sufficient energies has: a low entrance dose (the dose in front of the tumor) a high-dose region within the tumor, known as the Bragg peak and, no exit dose beyond the tumor. Proton therapy is the next major step in advancing radiotherapy treatment. The purpose of this project was to adapt an existing radioisotope production cyclotron, a General Electric (GE) PETtrace, to enable radiobiological studies using proton beams. During routine use the PETtrace delivers 16.5 MeV protons to target with beam currents in the range of 10-100 µA resulting in dose rates in the order of kGy/s. To achieve the aim of the project the dose rate had to be reduced to the Gy/min range, without attenuating the proton energy below 5 MeV. This paper covers the design, construction and validation of the beam port. Monte Carlo simulations were performed, using GEANT4, SRIM and PACE4 to design the beam port and optimize its components. Once the beam port was fabricated, validation experiments were performed using EBT3 and HD-V2 Gafchromic™ films, and a Keithley 6485 pico ere meter. The external beam port was successfully modeled, designed and fabricated. By using a 0.25 mm thick gold foil and a brass pin-hole collimator the beam was spread from a narrow full beam diameter of 10 mm to a wide beam with a 5% flatness area in the center of the beam that had a diameter of ~20 mm. In using this system the dose rate was reduced from kGy/s to ~30 Gy/min.
Publisher: Wiley
Date: 31-08-2010
DOI: 10.1118/1.3481514
Abstract: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences in radiation treatment modality and fractionation schedule. Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues.
Publisher: IOP Publishing
Date: 12-07-2006
DOI: 10.1088/0031-9155/51/15/002
Abstract: The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin-radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin-radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the in idual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2020
DOI: 10.1007/S11948-019-00097-0
Abstract: The aim of this article is to offer a view of the current status of women in medical physics and biomedical engineering, while focusing on solutions towards gender balance and providing ex les of current activities carried out at national and international levels. The International Union of Physical and Engineering Scientists in Medicine is committed to advancing women in science and health and has several initiatives overseen by the Women in Medical Physics and Biomedical Engineering Task Group. Some of the main strategies proposed by the Task Group to attain gender balance are: (a) identify and promote female role models that achieve successful work-life balance, (b) establish programs to develop female leaders, (c) create opportunities for females to increase the international visibility within the scientific community, and (d) establish archives and databases of women in STEM.
Publisher: Wiley
Date: 29-05-2012
DOI: 10.1118/1.4719963
Abstract: The objective of the current work was to develop an algorithm for growing a macroscopic tumor volume from in idual randomized quasi-realistic cells. The major physical and chemical components of the cell need to be modeled. It is intended to import the tumor volume into GEANT4 (and potentially other Monte Carlo packages) to simulate ionization events within the cell regions. A MATLAB© code was developed to produce a tumor coordinate system consisting of in idual ellipsoidal cells randomized in their spatial coordinates, sizes, and rotations. An eigenvalue method using a mathematical equation to represent in idual cells was used to detect overlapping cells. GEANT4 code was then developed to import the coordinate system into GEANT4 and populate it with in idual cells of varying sizes and composed of the membrane, cytoplasm, reticulum, nucleus, and nucleolus. Each region is composed of chemically realistic materials. The in-house developed MATLAB© code was able to grow semi-realistic cell distributions (~2 × 10(8) cells in 1 cm(3)) in under 36 h. The cell distribution can be used in any number of Monte Carlo particle tracking toolkits including GEANT4, which has been demonstrated in this work. Using the cell distribution and GEANT4, the authors were able to simulate ionization events in the in idual cell components resulting from 80 keV gamma radiation (the code is applicable to other particles and a wide range of energies). This virtual microdosimetry tool will allow for a more complete picture of cell damage to be developed.
Publisher: Wiley
Date: 07-07-2012
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.IJROBP.2016.03.014
Abstract: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BEDα/β=10 or 3) comparisons. A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO2 histograms were incorporated into the 10(8)-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presented in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Well-oxygenated tumor control BED10 outcomes were not significantly different for high-dose versus conventional radiation therapy (BED10: 79-84 Gy Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy) however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED10) was required, with BED10 increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED10:BED3 of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED10 relatively low and BED3 toxicity to tolerable levels.
Publisher: Springer Science and Business Media LLC
Date: 04-07-2022
Publisher: Springer Science and Business Media LLC
Date: 03-2010
Publisher: Wiley
Date: 12-06-2013
DOI: 10.1118/1.4808150
Abstract: Investigation of increased radiation dose deposition due to gold nanoparticles (GNPs) using a 3D computational cell model during x-ray radiotherapy. Two GNP simulation scenarios were set up in Geant4 a single 400 nm diameter gold cluster randomly positioned in the cytoplasm and a 300 nm gold layer around the nucleus of the cell. Using an 80 kVp photon beam, the effect of GNP on the dose deposition in five modeled regions of the cell including cytoplasm, membrane, and nucleus was simulated. Two Geant4 physics lists were tested: the default Livermore and custom built Livermore/DNA hybrid physics list. 10(6) particles were simulated at 840 cells in the simulation. Each cell was randomly placed with random orientation and a diameter varying between 9 and 13 μm. A mathematical algorithm was used to ensure that none of the 840 cells overlapped. The energy dependence of the GNP physical dose enhancement effect was calculated by simulating the dose deposition in the cells with two energy spectra of 80 kVp and 6 MV. The contribution from Auger electrons was investigated by comparing the two GNP simulation scenarios while activating and deactivating atomic de-excitation processes in Geant4. The physical dose enhancement ratio (DER) of GNP was calculated using the Monte Carlo model. The model has demonstrated that the DER depends on the amount of gold and the position of the gold cluster within the cell. In idual cell regions experienced statistically significant (p < 0.05) change in absorbed dose (DER between 1 and 10) depending on the type of gold geometry used. The DER resulting from gold clusters attached to the cell nucleus had the more significant effect of the two cases (DER ≈ 55). The DER value calculated at 6 MV was shown to be at least an order of magnitude smaller than the DER values calculated for the 80 kVp spectrum. Based on simulations, when 80 kVp photons are used, Auger electrons have a statistically insignificant (p < 0.05) effect on the overall dose increase in the cell. The low energy of the Auger electrons produced prevents them from propagating more than 250-500 nm from the gold cluster and, therefore, has a negligible effect on the overall dose increase due to GNP. The results presented in the current work show that the primary dose enhancement is due to the production of additional photoelectrons.
Publisher: Radiation Research Society
Date: 03-12-2010
DOI: 10.1667/RR2300.1
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.CTRV.2018.10.003
Abstract: The most common solid tumours that develop in children are cancers of the central nervous system. Due to the increased rate of survival over the past decades, greater focus has been placed on the minimisation of long term side effects. In childhood cancer survivors, over 60% report one or more radiation-related late toxicities while half of these adverse events are graded as life-threatening or severe. Proton therapy enables high conformity with the planning target volume and a reduction in dose to areas beyond the target. Owing to the unique nature of dose delivery with proton therapy a reduction of low doses to normal tissues is achievable, and is believed to allow for a decrease in long-term treatment-related side effects. This paper aims to review the published literature around the effectiveness of proton therapy for the treatment of paediatric cancers of the central nervous system, with a focus on treatment outcomes and treatment-related toxicities. A search strategy utilising the Medline database was created with the intent of including all articles reporting on proton therapy, paediatric cancers, CNS tumours and treatment outcomes. The final search strategy included the following limitations: limited to humans, English, published from 2000 onwards. The final article count total was 74. Proton therapy for the treatment of paediatric cancers of the central nervous system was found to provide survival and tumour control outcomes comparable to photon therapy. Reduced incidence of severe acute and late toxicities was also reported with the use of proton therapy. This includes reduced severity of endocrine, neurological, IQ and QoL deficits. Currently, extensive follow-up of proton patient populations still needs to be made to determine incidences of late-onset toxicities and secondary malignancies. Current evidence surrounding proton therapy use in paediatric patients supports its effectiveness and potential benefits in reducing the incidence of severe toxicities in later life.
Publisher: American Chemical Society (ACS)
Date: 16-10-2015
DOI: 10.1021/ACS.ANALCHEM.5B03183
Abstract: Internalized gold nanoparticles were quantified in large numbers of in idual prostate cancer cells using large area synchrotron X-ray fluorescence microscopy. Cells were also irradiated with a 6 MV linear accelerator to assess the biological consequence of radiosensitization with gold nanoparticles. A large degree of heterogeneity in nanoparticle uptake between cells resulted in influenced biological effect.
Publisher: IOP Publishing
Date: 05-04-2016
DOI: 10.1088/0031-9155/61/9/3407
Abstract: Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in in idual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted s le of α/β values. Cellular oxygen pressure was distributed randomly taken from a s le weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6 ± 3.3%, 78.5 ± 3.3%, and 77.7 ± 3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically heterogeneous and hypoxic GBM with two CTV margins and three MEP distributions. The results suggest that photon therapy may not provide cure for hypoxic and genetically heterogeneous GBM. However, the extension of the CTV margin by 0.5 cm could be beneficial to delay the recurrence time for this tumour type due to significant increase in tumour cell irradiation.
Publisher: British Institute of Radiology
Date: 09-2015
DOI: 10.1259/BJR.20150155
Publisher: Springer Science and Business Media LLC
Date: 23-07-2010
DOI: 10.1007/S13246-010-0026-4
Abstract: While repopulation is a clinically observed phenomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radiotherapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed virtual head and neck tumour and to study the effect of cisplatin on tumour regression and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occurring, is a highly potent phenomenon, similar to drug resistance, therefore it should not be neglected during treatment.
Publisher: Informa UK Limited
Date: 24-09-2012
Publisher: Wiley
Date: 05-12-2022
DOI: 10.1002/AJUM.12288
Abstract: This study aimed to determine the additional time needed to perform an endometriosis transvaginal ultrasound (eTVUS) compared to routine transvaginal ultrasound (rTVUS). A retrospective case–control study was performed. The study group included 199 eTVUS performed between September 2019 and September 2020. The control group comprised 105 consecutive rTVUS studies performed in the same time period. The time st s on the ultrasound images of all cases in both groups were reviewed to determine the time taken to perform each study. Mean, median, minimum and maximum scan times for both groups were calculated as was percentage difference between scan times. A two‐tailed, unpaired t‐test of the normalised data and a Mann–Whitney U test assessing time difference of scans between two groups were performed with P value .05 considered statistically significant. Performing eTVUS took significantly longer than rTVUS with increases in the mean (8.4 vs 13.8 min, 64%), median (7 vs 12 min, 71%), minimum (4 vs 7 min, 75%) and maximum (19 vs 42 min, 121%) scan times. The Mann–Whitney U test indicated a statistically significant difference in the median scan times (5.0, CI 4.0–6.0), P 0.001. An independent t‐test of the normalised data revealed a significantly larger mean scan time for eTVUS than rTVUS, Mean = 9.05 95%CI [13.17–4.94], t(302) = 4.327, P 0.001. R 2 = 0.583. Endometriosis transvaginal ultrasound added an average 5.4 min to rTVUS, which is statistically significant. For ultrasound departments wanting to offer this technique, doubling the scan time allocated to perform a transvaginal ultrasound (TVUS) is suggested.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2019
Publisher: Wiley
Date: 29-04-2021
DOI: 10.1002/MP.14872
Abstract: Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitizers could enable total radiation dose reduction and lowered radiation toxicity. AuNP radiosensitization may overcome hypoxia‐induced radioresistance and treatment‐induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. Tumor control was determined by considering in idual cancer cell responses in probabilistic computational simulations using HYP‐RT software for clinical radiotherapy doses and fractionation schedules along with three different nanoparticle administration schedules. Antagonistic tumor hypoxia and rapid tumor regrowth due to accelerated repopulation of cancers cells were taken into consideration. Simulations indicate that tumors that are conventionally uncontrollable can be controlled with AuNP radiosensitization. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation dose reductions below standard clinical dose prescriptions. For ex le, considering a 2 Gy per fraction radiotherapy schedule, tumor control was achieved with 57.2 ± 5.1 Gy ( P = .0001) for weekly AuNP administration and 53.0 ± 4.0 Gy ( P = .0001) for biweekly AuNP administration compared to 69.9 ± 5.8 Gy with no radiosensitization. AuNPs decreased the predicted RT total doses required to achieve tumor control via total stem cell elimination, offering an optimistic prediction and method for which hypoxia‐induced and rapidly growing radioresistant tumors are treated more effectively. Outcomes are also shown to be sensitive to the RT schedule with data for hyperfractionated RT indicating the greatest benefits from radiosensitization.
Publisher: IOP Publishing
Date: 30-05-2012
DOI: 10.1088/0031-9155/57/12/3853
Abstract: Optical CT scanners for a 3D readout of externally irradiated radiosensitive hydrogels currently require the use of a refractive index (RI) matching liquid bath to obtain suitable optical ray paths through the gel s le to the detector. The requirement for a RI matching liquid bath has been negated by the design of a plastic cylindrical gel container that provides parallel beam geometry through the gel s le for the majority of the projection. The design method can be used for various hydrogels. Preliminary test results for the prototype laser beam scanner with ferrous xylenol-orange gel show geometric distortion of 0.2 mm maximum, spatial resolution limited to beam spot size of about 0.4 mm and 0.8% noise (1 SD) for a uniform irradiation. Reconstruction of a star pattern irradiated through the cylinder walls demonstrates the suitability for external beam applications. The extremely simple and cost-effective construction of this optical CT scanner, together with the simplicity of scanning gel s les without RI matching fluid increases the feasibility of using 3D gel dosimetry for clinical external beam dose verifications.
Publisher: Informa UK Limited
Date: 25-04-2014
Publisher: MDPI AG
Date: 06-03-2022
Abstract: (1) Background: This paper aims to present and discuss the most significant challenges encountered by STEM professionals associated with remote working during the COVID-19 lockdowns. (2) Methods: We performed a qualitative analysis of 921 responses from professionals from 76 countries to the open-ended question: “What has been most challenging during the lockdown for you, and/or your family?” (3) Findings: Participants reported challenges within the immediate family to include responsibilities for school, childcare, and children’s wellbeing and the loss of social interactions with family and friends. Participants reported increased domestic duties, blurred lines between home and work, and long workdays. Finding adequate workspace was a problem, and adaptations were necessary, especially when adults shared the same setting for working and childcare. Connectivity issues and concentration difficulties emerged. While some participants reported employers’ expectations did not change, others revealed concerns about efficiency. Mental health issues were expressed as anxiety and depression symptoms, exhaustion and burnout, and no outlets for stress. Fear of becoming infected with COVID-19 and uncertainties about the future also emerged. Pressure points related to gender, relationship status, and ethnicities were also evaluated. Public policies differed substantially across countries, raising concerns about the adherence to unnecessary restrictions, and similarly, restrictions being not tight enough. Beyond challenges, some benefits emerged, such as increased productivity and less time spent getting ready for work and commuting. Confinement resulted in more quality time and stronger relationships with family. (4) Interpretation: Viewpoints on positive and negative aspects of remote working differed by gender. Females were more affected professionally, socially, and personally than males. Mental stress and the feeling of inadequate work efficiency in women were caused by employers’ expectations and lack of flexibility. Working from home turned out to be challenging, primarily due to a lack of preparedness, limited access to a dedicated home-office, and lack of previous experience in multi-layer/multi-scale environments.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/672895
Abstract: As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV) has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME) of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.
Publisher: EDP Sciences
Date: 2012
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.APRADISO.2008.04.024
Abstract: The current work focuses on the verification of transmitted dose maps, measured using a scanning liquid ionization chamber-electronic portal imaging device (SLIC-EPID) for a typical step-and-shoot prostate IMRT treatment using an anthropomorphic phantom at anterior-posterior (A-P), and several non-zero gantry angles. The dose distributions measured using the SLIC-EPID were then compared with those calculated in the modelled EPID for each segment/subfield and also for the corresponding total fields using a gamma function algorithm with a distance to agreement and dose difference criteria of 2.54mm and 3%, respectively.
Publisher: Springer London
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 23-01-2018
DOI: 10.1007/S13246-018-0617-Z
Abstract: Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of in idual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2023
Publisher: MDPI AG
Date: 24-08-2018
DOI: 10.3390/IJMS19092511
Abstract: It is an agreed fact that overall survival among head and neck cancer patients has increased over the last decade. Several factors however, are still held responsible for treatment failure requiring more in-depth evaluation. Among these, hypoxia and proliferation-specific parameters are the main culprits, along with the more recently researched cancer stem cells. This paper aims to present the latest developments in the field of biomarkers for hypoxia, stemness and tumour proliferation, from an imaging perspective that includes both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) as well as functional magnetic resonance imaging (MRI). Quantitative imaging of biomarkers is a prerequisite for accurate treatment response assessment, bringing us closer to the highly needed personalised therapy.
Publisher: Elsevier BV
Date: 2019
Publisher: Informa UK Limited
Date: 05-07-2016
Publisher: Cambridge University Press (CUP)
Date: 02-08-2017
DOI: 10.1017/S0885715617000719
Abstract: A robust analysis script was developed in MATLAB for cross-correlative quantification of internalised gold nanoparticle (AuNP) uptake in a large number of in idual cells with the corresponding number of DNA double-strand breaks (DSBs) in the same cells. The correlation of inorganic NP content with a biological marker at the single-cell level will aid in the elucidation of mechanisms of NP radiosensitisation. PC-3 cells were co-cultured with AuNPs and irradiated using an iridium-192 source. AuNP uptake was measured using synchrotron X-ray fluorescence (XRF) and DSBs imaged via confocal microscopy. MATLAB 2016a was used to develop a script to cross-correlate the two imaging modalities and quantify both DSBs and internalised AuNP content in the same cell. Various user-defined options written into the script give a high degree of versatility, which can account for a large number of variables in experimental parameters and data acquisition. The analysis procedure is flexible and robust, which gives consistent consideration to the wide spectrum of potential input image/data sets. Quantitative correlative microscopy was achieved with a custom MATLAB script used to correlate γH2AX foci (a marker of DNA DSBs) from confocal microscopy with AuNP content acquired using synchrotron XRF at the single-cell level. The script can be extended to a broad range of multi-modality imaging spectroscopies.
Publisher: Radiation Research Society
Date: 31-05-2022
Publisher: MDPI AG
Date: 27-07-2020
DOI: 10.3390/CELLS9081788
Abstract: Head and neck squamous cell carcinomas (HNSCC) resulting from human papillomavirus (HPV) are increasing in incidence but demonstrate significantly better treatment response than HNSCC from other causes such as tobacco and alcohol. This study sought to identify differences in HNSCC, intrinsic to HPV status, in their response to radiation dose. Previously unexamined changes in radio-responsiveness following fractionated X-ray irradiation were compared between HPV positive and negative statuses of HNSCC. Six HNSCC cell lines, 3 of each HPV status, were investigated for radiosensitivity by clonogenic assay and modelled by response as a function of dose. Generational cultures of each cell line were developed to follow changes in radiosensitivity after repeated irradiations simulating fractionated radiation therapy. As a group, the HPV positive cell lines were more radiosensitive, but with changes following repeated fractions of dose, and modelling of response as a function of dose, both statuses displayed large radiobiological heterogeneity. These findings challenge current radiobiological assumptions of head and neck cancers as early responding tissue to radiation and may go some way in explaining difficulties reaching consensus in stratification of treatment by HPV status. Consequently, results from this study do not support stratifying radiation therapy by HPV status.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.EJMP.2019.08.001
Abstract: An investigation into the response of optical fibres to 16.5 MeV protons is presented here. A silica and a poly(methyl methacrylate) (PMMA) optical fibre was exposed to 16.5 MeV protons from a GE PETtrace cyclotron. The optical fibres were exposed to beam currents of 30nA - 270nA and the emission spectrum analysed. The silica fibre was the most sensitive and had two main peaks at 460 nm and 650 nm. The ratio between the peaks was observed to increase as irradiation of the fibres continued, where the 460 nm peak increased at a rate >4 times the 650 nm peak. The rate of increase of the ratio between the peaks was observed to be constant at a constant target current and linear with target current. In the case of the PMMA fibre, significant spectral changes were observed during the exposure to 16.5 MeV protons. A simple method for estimating the effect of photodarkening and activation is presented here and indicated that the changes in the spectrum for the PMMA fibres may be due to photodarkening and activation.
Publisher: Springer Science and Business Media LLC
Date: 11-2005
Publisher: Springer Science and Business Media LLC
Date: 12-1996
DOI: 10.1007/BF02150191
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.CRITREVONC.2017.03.004
Abstract: Oesophageal cancer is a relatively uncommon malignancy, but with poor prognosis. Despite several treatment options that are available, the 5-year survival rates rarely exceed 40%. This review discusses the main challenges of oesophageal cancer, the available treatment options, and the most effective treatment in terms of overall survival. The outcomes of clinical trials show that neo-adjuvant chemo-radiotherapy using cisplatin and 5-fluorouracil followed by oesophagectomy results in the greatest survival. However, the optimal chemotherapy and radiotherapy schedule remains unclear. There is no satisfactory treatment to date, particularly for patients with co-morbidities or advanced tumours.
Publisher: IOP Publishing
Date: 10-04-2007
DOI: 10.1088/0031-9155/52/9/010
Abstract: To measure and verify the dose distribution within a patient during proton therapy, indirect methods must be used. One such method is to use positron emission tomography (PET), which takes advantage of the nuclear reactions that take place between protons and nuclei in the tissue. The dominant nuclear reaction in human muscle tissue involves oxygen nuclei and produces radioactive oxygen-15. Oxygen-15 decays through positron emission, and it is these positrons that go on to annihilate that produce the signal used in the PET technique. Finding the distribution of annihilation points, however, is not analogous to finding the proton dose distribution. The oxygen-15 and positrons travel finite distances within the tissue, blurring the detected PET distribution from the desired proton distribution. Through Monte Carlo modelling, an analysis of the differences between the positron, oxygen-15 and proton distributions has been made. The program SRIM 2003 was used to find the correlation between the three distributions within simulated muscle tissue. Results show that the distal edge of the proton Bragg peak correlates with the detectable positron distribution, which is a section of the dose distribution of interest due to the steep dose gradient and position of adjacent critical structures.
Publisher: British Institute of Radiology
Date: 10-2023
DOI: 10.1259/BJR.20230161
Publisher: Springer Science and Business Media LLC
Date: 09-2010
DOI: 10.1007/S13246-010-0030-8
Abstract: Modern radiobiology is undergoing rapid change due to new discoveries contradicting the target concept which is currently used to predict dose-response relationships. Thus relatively recently discovered radiation-induced bystander effects (RIBEs), that include additional death, mutation and radio-adaptation in non-irradiated cells, change our understanding of the target concept and broadens its boundaries. This can be significant from a radioprotection point of view and also has the potential to reassess radiation damage models currently used in radiotherapy. This article reviews briefly the general concepts of RIBEs such as the proposed underlying mechanisms of signal induction and propagation, experimental approaches and biological end points used to investigate these phenomena. It also summarises several mathematical models currently proposed in an attempt to quantify RIBE. The main emphasis of this article is to review and highlight the potential impact of the bystander phenomena in radiotherapy.
Publisher: Elsevier BV
Date: 04-2000
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.RADONC.2019.01.009
Abstract: Clinical implementation of proton therapy demonstrated its potential to overcome some limitations of the more traditional, photon-based radiotherapy, due to physical and radiobiological advantages of protons. However, questions concerning the long-term effects of protons on paediatric patients need outcome analysis of the reported literature in order to be answered. The current paper has analysed the available clinical trials and comparative studies (protons vs photons) for paediatric cancers of the central nervous system (CNS) analysing the reported outcomes and follow-up times in order to evaluate the safety of proton therapy for this patient group. Based on the literature analysis, proton therapy for treatment of paediatric cancers of the CNS was found to provide survival and tumour control outcomes comparable, and frequently superior, to photon therapy. Furthermore, the use of protons was shown to decrease the incidence of severe acute and late toxicities, including reduced severity of endocrine, neurological, IQ and QoL deficits. Most commonly, the reported median follow-up time was up to 5 years. Only a few studies reported promising, longer follow-up results. Considering that these patients are likely to survive many of the malignancies reported on, the incidence of long term sequellae impacting growth, development and quality of life into adulthood, should be viewed longitudinally for completeness. The evidence surrounding proton therapy in paediatric tumour management supports its effectiveness and potential benefits in reducing the incidence of late-onset toxicities and second malignancies. For stronger evidence, it is highly desired for future studies to improve current reporting by (1) highlighting the paediatric patient cohort's outcome (in mixed patient groups), (2) reporting the follow-up time, (3) clearly indicating the toxicity criteria used in their evaluation, and (4) identifying the risk group. With this suggested clarity of future reporting, meaningful data to support treatment choice may then be available.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 08-2020
Publisher: Public Library of Science (PLoS)
Date: 27-03-2014
Publisher: Springer Science and Business Media LLC
Date: 11-12-2019
DOI: 10.1038/S41598-019-54941-1
Abstract: The repair or misrepair of DNA double-strand breaks (DSBs) largely determines whether a cell will survive radiation insult or die. A new computational model of multicellular, track structure-based and pO 2 -dependent radiation-induced cell death was developed and used to investigate the contribution to cell killing by the mechanism of DNA free-end misrejoining for low-LET radiation. A simulated tumor of 1224 squamous cells was irradiated with 6 MV x-rays using the Monte Carlo toolkit Geant4 with low-energy Geant4-DNA physics and chemistry modules up to a uniform dose of 1 Gy. DNA damage including DSBs were simulated from ionizations, excitations and hydroxyl radical interactions along track segments through cell nuclei, with a higher cellular pO 2 enhancing the conversion of DNA radicals to strand breaks. DNA free-ends produced by complex DSBs (cDSBs) were able to misrejoin and produce exchange-type chromosome aberrations, some of which were asymmetric and lethal. A sensitivity analysis was performed and conditions of full oxia and anoxia were simulated. The linear component of cell killing from misrejoining was consistently small compared to values in the literature for the linear component of cell killing for head and neck squamous cell carcinoma (HNSCC). This indicated that misrejoinings involving DSBs from the same x-ray (including all associated secondary electrons) were rare and that other mechanisms (e.g. unrejoined ends) may be important. Ignoring the contribution by the indirect effect toward DNA damage caused the DSB yield to drop to a third of its original value and the cDSB yield to drop to a tenth of its original value. Track structure-based cell killing was simulated in all 135306 viable cells of a 1 mm 3 hypoxic HNSCC tumor for a uniform dose of 1 Gy.
Publisher: MDPI AG
Date: 19-03-2021
DOI: 10.3390/DIAGNOSTICS11030551
Abstract: Research into machine learning (ML) for clinical vascular analysis, such as those useful for stroke and coronary artery disease, varies greatly between imaging modalities and vascular regions. Limited accessibility to large erse patient imaging datasets, as well as a lack of transparency in specific methods, are obstacles to further development. This paper reviews the current status of quantitative vascular ML, identifying advantages and disadvantages common to all imaging modalities. Literature from the past 8 years was systematically collected from MEDLINE® and Scopus database searches in January 2021. Papers satisfying all search criteria, including a minimum of 50 patients, were further analysed and extracted of relevant data, for a total of 47 publications. Current ML image segmentation, disease risk prediction, and pathology quantitation methods have shown sensitivities and specificities over 70%, compared to expert manual analysis or invasive quantitation. Despite this, inconsistencies in methodology and the reporting of results have prevented inter-model comparison, impeding the identification of approaches with the greatest potential. The clinical potential of this technology has been well demonstrated in Computed Tomography of coronary artery disease, but remains practically limited in other modalities and body regions, particularly due to a lack of routine invasive reference measurements and patient datasets.
Publisher: IOP Publishing
Date: 20-04-2022
Abstract: Objective . A systematic review of dosimetry in Targeted Alpha Therapy (TAT) has been performed, identifying the common issues. Approach . The systematic review was performed in accordance with the PRISMA guidelines, and the literature was searched using the Scopus and PubMed databases. Main results . From the systematic review, three key points should be considered when performing dosimetry in TAT. (1) Biodistribution/Biokinetics: the accuracy of the biodistribution data is a limit to accurate dosimetry in TAT. The biodistribution of alpha-emitting radionuclides throughout the body is difficult to image directly, with surrogate radionuclide imaging, blood/faecal s ling, and animal studies able to provide information. (2) Daughter radionuclides: the decay energy of the alpha-emissions is sufficient to break the bond to the targeting vector, resulting in a release of free daughter radionuclides in the body. Accounting for daughter radionuclide migration is essential. (3) Small-scale dosimetry and microdosimetry: due to the short path length and heterogeneous distribution of alpha-emitters at the target site, small-scale/microdosimetry are important to account for the non-uniform dose distribution in a target region, organ or cell and for assessing the biological effect of alpha-particle radiation. Significance . TAT is a form of cancer treatment capable of delivering a highly localised dose to the tumour environment while sparing the surrounding healthy tissue. Dosimetry is an important part of treatment planning and follow up. Being able to accurately predict the radiation dose to the target region and healthy organs could guide the optimal prescribed activity. Detailed dosimetry models accounting for the three points mentioned above will help give confidence in and guide the clinical application of alpha-emitting radionuclides in targeted cancer therapy.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 04-02-2020
Publisher: Springer Science and Business Media LLC
Date: 02-2012
DOI: 10.1007/S13246-012-0124-6
Abstract: Organ motion is a substantial concern in the treatment of thoracic tumours using radiotherapy. A number of technologies have evolved in order to address this both during computed tomography (CT) imaging and radiation delivery. This review paper investigates the various technologies which have been developed in the field of CT scanning as well as their accuracy, cost and the implications of their clinical implementation. The scanning modalities covered include: slow CT, breath hold CT, gated CT and retrospectively correlated CT (4DCT). It was found that there are advantages and drawbacks to each of the mentioned techniques relating to patient dose, scan time, extra equipment and workload. Also some scanning techniques are only compatible with certain treatment modalities which would further influence the decision as to which technologies to implement.
Publisher: American Chemical Society (ACS)
Date: 22-04-2019
Publisher: MDPI AG
Date: 09-01-2020
Abstract: Introduction: Despite improvements in radiation therapy, chemotherapy and surgical procedures over the last 30 years, pancreatic cancer 5-year survival rate remains at 9%. Reduced stroma permeability and heterogeneous blood supply to the tumour prevent chemoradiation from making a meaningful impact on overall survival. Hypoxia-activated prodrugs are the latest strategy to reintroduce oxygenation to radioresistant cells harbouring in pancreatic cancer. This paper reviews the current status of photon and particle radiation therapy for pancreatic cancer in combination with systemic therapies and hypoxia activators. Methods: The current effectiveness of management of pancreatic cancer was systematically evaluated from MEDLINE® database search in April 2019. Results: Limited published data suggest pancreatic cancer patients undergoing carbon ion therapy and proton therapy achieve a comparable median survival time (25.1 months and 25.6 months, respectively) and 1-year overall survival rate (84% and 77.8%). Inconsistencies in methodology, recording parameters and protocols have prevented the safety and technical aspects of particle therapy to be fully defined yet. Conclusion: There is an increasing requirement to tackle unmet clinical demands of pancreatic cancer, particularly the lack of synergistic therapies in the advancing space of radiation oncology.
Publisher: MDPI AG
Date: 22-06-2020
DOI: 10.3390/IJMS21124431
Abstract: Gold nanoparticle (GNP) enhanced proton therapy is a promising treatment concept offering increased therapeutic effect. It has been demonstrated in experiments which provided indications that reactive species play a major role. Simulations of the radiolysis yield from GNPs within a cell model were performed using the Geant4 toolkit. The effect of GNP cluster size, distribution and number, cell and nuclear membrane absorption and intercellular yields were evaluated. It was found that clusters distributed near the nucleus increased the nucleus yield by 91% while reducing the cytoplasm yield by 7% relative to a disperse distribution. Smaller cluster sizes increased the yield, 200 nm clusters had nucleus and cytoplasm yields 117% and 35% greater than 500 nm clusters. Nuclear membrane absorption reduced the cytoplasm and nucleus yields by 8% and 35% respectively to a permeable membrane. Intercellular enhancement was negligible. Smaller GNP clusters delivered near sub-cellular targets maximise radiosensitisation. Nuclear membrane absorption reduces the nucleus yield, but can damage the membrane providing another potential pathway for biological effect. The minimal effect on adjacent cells demonstrates that GNPs provide a targeted enhancement for proton therapy, only effecting cells with GNPs internalised. The provided quantitative data will aid further experiments and clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 03-2010
DOI: 10.1007/S13246-010-0008-6
Abstract: The MammoSite breast high dose rate brachytherapy is used in treatment of early-stage breast cancer. The tumour bed volume is irradiated with high dose per fraction in a relatively small number of fractions. Uncertainties in the source positioning and MammoSite balloon deformation will alter the prescribed dose within the treated volume. They may also expose the normal tissues in balloon proximity to excessive dose. The purpose of this work is to explore the impact of these two uncertainties on the MammoSite dose distribution in the breast using dose volume histograms and Monte Carlo simulations. The Lyman-Kutcher and relative seriality models were employed to estimate the normal tissues complications associated with the MammoSite dose distributions. The tumour control probability was calculated using the Poisson model. This study gives low probabilities for developing heart and lung complications. The probability of complications of the skin and normal breast tissues depends on the location of the source inside the balloon and the volume receiving high dose. Incorrect source position and balloon deformation had significant effect on the prescribed dose within the treated volume. A 4 mm balloon deformation resulted in reduction of the tumour control probability by 24%. Monte Carlo calculations using EGSnrc showed that a deviation of the source by 1 mm caused approximately 7% dose reduction in the treated target volume at 1 cm from the balloon surface. In conclusion, accurate positioning of the (192)Ir source at the balloon centre and minimal balloon deformation are critical for proper dose delivery with the MammoSite brachytherapy applicator. On the basis of this study, we suggest that the MammoSite treatment protocols should allow for a balloon deformation of < or = 2 mm and a maximum source deviation of < or = 1 mm.
Publisher: MDPI AG
Date: 03-2023
Abstract: Background: Glioblastomas (GBMs) are notorious for their aggressive features, e.g., intrinsic radioresistance, extensive heterogeneity, hypoxia, and highly infiltrative behaviours. The prognosis has remained poor despite recent advances in systemic and modern X-ray radiotherapy. Boron neutron capture therapy (BNCT) represents an alternative radiotherapy technique for GBM. Previously, a Geant4 BNCT modelling framework was developed for a simplified model of GBM. Purpose: The current work expands on the previous model by applying a more realistic in silico GBM model with heterogeneous radiosensitivity and anisotropic microscopic extensions (ME). Methods: Each cell within the GBM model was assigned an α/β value associated with different GBM cell lines and a 10B concentration. Dosimetry matrices corresponding to various MEs were calculated and combined to evaluate cell survival fractions (SF) using clinical target volume (CTV) margins of 2.0 & 2.5 cm. SFs for the BNCT simulation were compared with external X-ray radiotherapy (EBRT) SFs. Results: The SFs within the beam region decreased by more than two times compared to EBRT. It was demonstrated that BNCT results in markedly reduced SFs for both CTV margins compared to EBRT. However, the SF reduction as a result of the CTV margin extension using BNCT was significantly lower than using X-ray EBRT for one MEP distribution, while it remained similar for the other two MEP models. Conclusions: Although the efficiency of BNCT in terms of cell kill is superior to EBRT, the extension of the CTV margin by 0.5 cm may not increase the BNCT treatment outcome significantly.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.CRITREVONC.2018.01.001
Abstract: Targeted therapy for cancer is a rapidly expanding and successful approach to the management of many intractable cancers. However, many immunotherapies fail in the longer term and there continues to be a need for improved targeted cancer cell toxicity, which can be achieved by radiolabelling the targeting vector with a radioisotope. Such constructs are successful in using a gamma ray emitter for imaging. However, traditionally, a beta emitter is used for therapeutic applications. The new approach is to use the short range and highly cytotoxic alpha radiation from alpha emitters to achieve improved efficacy and therapeutic gain. This paper sets out to review all experimental and theoretical comparisons of efficacy and therapeutic gain for alpha and beta emitters labelling the same targeting vector. The overall conclusion is that targeted alpha therapy is superior to targeted beta therapy, such that the use of alpha therapy in clinical settings should be expanded.
Publisher: MDPI AG
Date: 09-2019
DOI: 10.3390/IJMS20174280
Abstract: Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.
Publisher: American Physical Society (APS)
Date: 03-05-1999
Publisher: MDPI AG
Date: 19-02-2020
Abstract: Pancreatic ductal adenocarcinoma (PDAC) has long been associated with low survival rates. A lack of accurate diagnostic tests and limited treatment options contribute to the poor prognosis of PDAC. Radioimmunotherapy using α- or β-emitting radionuclides has been identified as a potential treatment for PDAC. By harnessing the cytotoxicity of α or β particles, radioimmunotherapy may overcome the anatomic and physiological factors which traditionally make PDAC resistant to most conventional treatments. Appropriate selection of target receptors and the development of selective and cytotoxic radioimmunoconjugates are needed to achieve the desired results of radioimmunotherapy. The aim of this review is to examine the growing preclinical and clinical trial evidence regarding the application of α and β radioimmunotherapy for the treatment of PDAC. A systematic search of MEDLINE® and Scopus databases was performed to identify 34 relevant studies conducted on α or β radioimmunotherapy of PDAC. Preclinical results demonstrated α and β radioimmunotherapy provided effective tumour control. Clinical studies were limited to investigating β radioimmunotherapy only. Phase I and II trials observed disease control rates of 11.2%–57.9%, with synergistic effects noted for combination therapies. Further developments and optimisation of treatment regimens are needed to improve the clinical relevance of α and β radioimmunotherapy in PDAC.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/702675
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/02841860802537916
Abstract: The MammoSite radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of > or =7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5-25%). Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer providing good local control, minimal complication rate and excellent cosmesis.
Publisher: Oxford University Press (OUP)
Date: 27-08-2012
DOI: 10.1093/RPD/NCR359
Abstract: (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescent dosemeters (TLDs) were used for measurements of out-of-field photon and neutron doses produced by Varian iX linear accelerator. Both TLDs were calibrated using 18-MV X-ray beam to investigate their dose-response sensitivity and linearity. CR-39 etch-track detectors (Luxel+, Landauer) were employed to provide neutron dose data to calibrate (6)LiF:Mg,Cu,P TLDs at various distances from the isocentre. With cadmium filters employed, slow neutrons (<0.5 eV) were distinguished from fast neutrons. The average in-air photon dose equivalents per monitor unit (MU) ranged from 1.5±0.4 to 215.5±94.6 μSv at 100 and 15 cm from the isocentre, respectively. Based on the cross-calibration factors obtained with CR-39 etch-track detectors, the average in-air fast neutron dose equivalents per MU range from 10.6±3.8 to 59.1±49.9 μSv at 100 and 15 cm from the isocentre, respectively. Contribution of thermal neutrons to total neutron dose equivalent was small: 3.1±7.2 μSv per MU at 15 cm from the isocentre.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.EJMP.2016.09.007
Abstract: Emerging radiotherapy treatments including targeted particle therapy, hadron therapy or radiosensitisation of cells by high-Z nanoparticles demand the theoretical determination of radiation track structure at the nanoscale. This is essential in order to evaluate radiation damage at the cellular and DNA level. Since 2007, Geant4 offers physics models to describe particle interactions in liquid water at the nanometre level through the Geant4-DNA Package. This package currently provides a complete set of models describing the event-by-event electromagnetic interactions of particles with liquid water, as well as developments for the modelling of water radiolysis. Since its release, Geant4-DNA has been adopted as an investigational tool in kV and MV external beam radiotherapy, hadron therapies using protons and heavy ions, targeted therapies and radiobiology studies. It has been benchmarked with respect to other track structure Monte Carlo codes and, where available, against reference experimental measurements. While Geant4-DNA physics models and radiolysis modelling functionalities have already been described in detail in the literature, this review paper summarises and discusses a selection of representative papers with the aim of providing an overview of a) geometrical descriptions of biological targets down to the DNA size, and b) the full spectrum of current micro- and nano-scale applications of Geant4-DNA.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JACR.2019.05.045
Abstract: Head and neck carcinomas are clinically challenging malignancies because of tumor heterogeneities and resilient tumor subvolumes that require in idualized treatment planning and delivery for an improved outcome. Although current approaches to diagnosis and therapy have boosted locoregional control, the long-term survival in this patient group remains unchanged over the last decades. A new approach to head and neck cancer management is therefore needed to better identify patient subgroups that are responsive to specific therapies. The aim of this article is to review the current status of knowledge and practice utilizing big data toward personalized therapy in head and neck cancers based on CT and PET imaging modalities. Literature published in English since 2000 was searched using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in tabulated format. Studies based on big data in head and neck cancer are limited however, the field of radiomics is under continuous development and provides valuable input for personalized treatment. Using PET/PET CT biomarkers for patient treatment in idualization and response prediction seems promising, especially in regard to detection of hypoxia and clonogenic cancer stem cells. Literature shows that macroscopic changes in medical images (whether structural or functional) are correlated with biologic and biochemical changes within a tumor. Current trends in data science suggest that the ideal model for decision support in head and neck cancers should be based on human-machine collaboration, namely, on (1) software-based algorithms, (2) physician innovation collaboratives, and (3) clinician mix optimization.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.JTBI.2011.12.001
Abstract: Current clinical studies support the role of neoadjuvant cisplatin administration prior to curative radiotherapy or radio-chemotherapy for advanced head and neck cancer. Nevertheless, based on locoregional control rates the studies indicate that there is need to redesign cisplatin-based schedules for induction chemotherapy, thus the ideal treatment regimen is yet to be established. While the pharmacokinetics/dynamics of daily cisplatin regimens correspond better with the cell cycle properties of head and neck cancers, weekly regimens are more commonly employed in clinics due to lower complications. Yet, the high rates of adverse events induced by current cisplatin schedules often represent a limiting factor in the overall success of the treatment. The aim of the present paper was to model the pharmacodynamic properties of cisplatin and to simulate and compare various neoadjuvant treatment regimens in regards to their effect on tumour control. Treatment simulation was undertaken on a virtual squamous cell carcinoma of the head and neck, previously grown by computer-based probabilistic methods. The model suggests that a novel cisplatin treatment, given every three days is comparable, in regards to tumour control, with the daily administration and more effective than the weekly regimen in neoadjuvant settings. Endpoints were assessed in terms of cell population regrowth after treatment cessation followed by two weeks of unperturbed growth. Simulation of two weeks low-dose daily cisplatin followed by two weeks 'free growth' lead to 15% population regrowth, while weekly high-dose cisplatin over three weeks, followed by two weeks unperturbed growth resulted in 52% tumour cell regrowth. The proposed novel schedule of low-dose third-daily cisplatin gives closer tumour regrowth to daily administration (27% versus 15%) than to the weekly regimen (52%) and also similar cell distribution along the cell cycle as the daily one, suggesting therefore comparable response to subsequent treatment. The advantage of using a third-daily drug regimen would be a decrease in normal tissue complication rates compared to daily administration and possibly an increase in tumour control when compared to the 'conventional' weekly cisplatin delivery.
Publisher: Elsevier BV
Date: 1999
Publisher: Springer Science and Business Media LLC
Date: 16-03-2022
DOI: 10.1007/S00421-022-04931-5
Abstract: Exercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre–post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59 95% CI 0.16–1.02 p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2023
Publisher: Radiation Research Society
Date: 28-06-2018
DOI: 10.1667/RR15050.1
Publisher: Radiation Research Society
Date: 05-2017
DOI: 10.1667/RR14710.1
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.EJMP.2017.02.018
Abstract: Out-of-field organs can be affected by secondary radiations originating from high energy linear accelerators, leading to an increased risk of carcinogenesis. The aim of this work was to determine the risk of second primary cancers (SPC) in the organs distal to the prostate during 3D conformal radiotherapy. Based on previously measured peripheral photon and neutron doses in a Rando phantom using an 18MV photon beam, SPC risks in the out-of-field organs were estimated using the linear-no-threshold and the competitive risk models. Whole body as well as organ specific risk coefficients were used to calculate the SPC risks in order to estimate upper and lower risk limits, given the uncertainties associated with the coefficients. The corresponding estimated average SPC risks ranged from 1.5±0.3% for thyroid to 4.5±4.2% for colon using whole body risk coefficients and 0.12±0.03% and 1.45±1.34%, respectively, using organ specific risk coefficients. The linear-no-threshold and the competitive risk models resulted in the same risk estimates (within the estimated errors) in the dose range received by out-of-field organs (≤1Gy). Distally located organs such as lungs, oesophagus, and thyroid received higher neutron versus photon dose. The findings have important radiation protection implications when using high energy linear accelerators, as radiation protective measures could be employed to minimize the secondary out-of-field radiation for patients undergoing high energy external beam irradiation of the prostate.
Publisher: Elsevier BV
Date: 09-2005
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/02841860510029815
Abstract: That three dimensional (3D) planning for radiation therapy (RT) of carcinoma of the prostate (CaP) improves radiation dosimetry to the tumour and reduces dose to the rectum and bladder compared with 2D planning, has not been properly evaluated. We addressed this by downloading the CT data files of twenty-two patients who had completed 2D planned RT for CaP onto a 3D planning system and re-planning RT using the same four field technique and dose prescription as the 2D technique. The radiation dose at 100%, 90%, 50% and 0% volumes (D100, D90, D50 and D0) of the Dose Volume Histograms (DVH's) of the GTV, PTV, rectum and bladder, the area under the curves of each DVH and the field sizes were evaluated and compared between the two sets of plans. Repeated measured t-tests were used to compare the means of the different measurements. The D100, D90 and D50 of the GTV, PTV and rectum were increased for the 3D versus the 2D plans (p < 0.05 for each parameter). The area under the rectal DVH was also greater for the 3D plans (p < 0.05). These changes are attributable to the larger field sizes, particularly the length in the 3D compared with the 2D plans.
Publisher: Hindawi Limited
Date: 04-10-2018
DOI: 10.1155/2018/6483626
Abstract: Introduction. Lung cancer is a disease which, despite the advancements in treatment, still has a very poor 5-year survival rate. Stereotactic ablative radiation therapy (SABR) is a highly advanced, sophisticated, and safe treatment which allows patients with early stage lung cancer to be treated effectively without invasive procedures and with excellent clinical outcomes. Avoiding surgery minimises morbidity and recovery time, bettering patients’ quality of life. Furthermore, SABR allows patients unsuitable for surgery to still undergo curative treatment. Methods. We aimed to review SABR-related normal tissue toxicities reported in the literature. While many studies assess safety, clinical efficacy, and disease control of SABR for lung cancer, the number of comprehensive reviews that analyse SABR-related side-effects is scarce. This integrative review summarises the toxicities reported in literature based on published clinical trials and tumour location (central or peripheral tumours) for available SABR techniques. Given that the majority of the clinical studies did not report on the statistical significance (e.g., p -values and confidence intervals) of the toxicities experienced by patients, statistical analyses cannot be performed. As a result, adverse events are compiled from clinical reports however, due to various techniques and nonstandard toxicity reports, no meta-analysis is possible at the current stage of reported data. Results. When comparing lobectomy and SABR in phase III trials, surgery resulted in increased procedure-related morbidity. In phase II trials, very few studies showed high grade toxicities/fatalities as a result of SABR for lung cancer. Gross target volume size was a significant predictor of toxicity. An ipsilateral mean lung dose larger than 9 Gy was significantly associated with radiation pneumonitis. Conclusions. Based on the studies reviewed SABR is a safe treatment technique for lung cancer however, further well-designed phase III randomised clinical trials are required to produce timely conclusive results and to enable their comparison and statistical analysis.
Publisher: Elsevier BV
Date: 07-2022
Publisher: IOP Publishing
Date: 06-01-2009
DOI: 10.1088/0031-9155/54/3/009
Abstract: This study aimed to estimate the risk of developing second primary cancer (SPC) corresponding to various radiation treatment techniques for prostate cancer. Estimation of SPC was done by analysing differential dose-volume histograms (DDVH) of normal tissues such as rectum, bladder and urethra with the competitive risk model. Differential DVHs were obtained from treatment planning systems for external beam radiotherapy (EBRT), low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy techniques. The average risk of developing SPC was no greater than 0.6% for all treatment techniques but was lower with either LDR or HDR brachytherapy alone compared with any EBRT technique. For LDR and HDR brachytherapy alone, the risk of SPC for the rectum was 2.0 x 10(-4)% and 8.3 x 10(-5)% respectively compared with 0.2% for EBRT using five-field 3D-CRT to a total dose of 74 Gy. Overall, the risk of developing SPC for urethra following all radiation treatment techniques was very low compared with the rectum and bladder. Treatment plans which deliver equivalent doses of around 3-5 Gy to normal tissues were associated with higher risks of development of SPC.
Publisher: Wiley
Date: 23-06-2017
DOI: 10.1002/HED.24848
Abstract: Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose. This is shown to be not just as a result of preferential killing, but also their capacity to alter isional dynamics and enlist the support of a complicit microenvironment in therapy resistance and proliferation. The CSCs represent the apex of a hierarchy in the heterogeneity of cancer cells and may be seen as the agents of treatment failure, metastasis, and tumor recurrence, the principal cause of mortality in head and neck cancers. Greater than 90% of head and neck cancers are squamous cell carcinomas (HNSCCs), and among these an increasing incidence of the involvement of the human papillomavirus (HPV) is reported. Chemoradiotherapy along with surgical resection are the interventions of choice for control and cure of HNSCC, but given CSCs therapy resistance and proliferative responses to radiation, the identification and understanding of the radiobiology of this subpopulation is critical to their targeted elimination. This article reviews the current evidence on CSC generally and in HNSCC specifically to identify their phenotype, evaluate their responses to radiotherapy, and evaluate the defensive mechanisms used to resist therapeutic control.
Publisher: Wiley
Date: 19-11-2022
DOI: 10.1111/AJR.12811
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/571351
Publisher: Wiley
Date: 26-12-2019
DOI: 10.1002/MP.13332
Abstract: Indirect biological damage due to reactive species produced in water radiolysis reactions is responsible for the majority of biological effect for low linear energy transfer (LET) radiation. Modeling water radiolysis and the subsequent interactions of reactive species, as well as track structures, is essential to model radiobiology on the microscale. Recently, chemistry models have been developed for Geant4-DNA to be used in combination with the comprehensive existing physics models. In the current work, the first detailed, independent, in silico validation of all species yields with published experimental observations and comparison with other radiobiological simulations is presented. Additionally, the effect of LET of protons and heavier ions on reactive species yield in the model was examined, as well as the completeness of the chemical reactions following the radiolysis within the time after physical interactions simulated in the model. Yields over time of reactive species were simulated for water radiolysis by incident electrons, protons, alpha particles, and ions with various LETs using Geant4 and RITRACKS simulation tools. Water dissociation and recombination was simulated using Geant4 to determine the completeness of chemical reactions at the end of the simulation. Yield validation was performed by comparing yields simulated using Geant4 with experimental observations and other simulations. Validation was performed for all species for low LET radiation and the solvated electron and hydroxyl radical for high LET ions. It was found that the Geant4-DNA chemistry yields were generally in good agreement with experimental observations and other simulations. However, the Geant4-DNA yields for the hydroxyl radical and hydrogen peroxide at the end of the chemistry stage were found to be respectively considerably higher and lower than the experimentally observed yields. Increasing the LET of incident hadrons increased the yield of secondary species and decreased the yield of primary species. The effect of LET on the yield of the hydroxyl radical at 100 ns simulated with Geant4 was in good agreement with experimental measurements. Additionally, by the end of the simulation only 40% of dissociated water molecules had been recombined and the rate of recombination was slowing. The yields simulated using Geant4 are within reasonable agreement with experimental observations. Higher LET radiation corresponds with increased yields of secondary species and decreased yields of primary species. These trends combined with the LET having similar effects on the 100 ns hydroxyl radical yield for Geant4 and experimental measurements indicate that Geant4 accurately models the effect of LET on radiolysis yields. The limited recombination within the modeled chemistry stage and the slowing rate of recombination at the end of the stage indicate potential long-range indirect biological damage.
Publisher: AIP Publishing
Date: 27-09-1999
DOI: 10.1063/1.124872
Abstract: The perturbed angular correlation (PAC) technique has been used to characterize the implantation-induced crystalline-to-amorphous transformation in InP. Radioactive In111 probes were first introduced in InP substrates which were then irradiated with Ge ions over an ion-dose range extending 2 orders of magnitude beyond that required for amorphization. Crystalline, disordered and amorphous probe environments were subsequently identified with PAC. The dose dependence of the relative fractions of the in idual probe environments were determined, a direct amorphization process consistent with the overlap model was quantified and evidence for a second amorphization process via the overlap of disordered regions was observed. Given the ability to differentiate disordered and amorphous probe environments, a greater effective resolution was achieved with the PAC technique compared with other common analytical methodologies.
Publisher: Radiation Research Society
Date: 10-2011
DOI: 10.1667/RR2606.1
Abstract: Determination and understanding of out-of-field neutron and photon doses in accelerator-based radiotherapy is an important issue since linear accelerators operating at high energies (>10 MV) produce secondary radiations that irradiate parts of the patient's anatomy distal to the target region, potentially resulting in detrimental health effects. This paper provides a compilation of data (technical and clinical) reported in the literature on the measurement and Monte Carlo simulations of peripheral neutron and photon doses produced from high-energy medical linear accelerators and the reported risk and/or incidence of second primary cancer of tissues distal to the target volume. Information in the tables facilitates easier identification of (1) the various methods and measurement techniques used to determine the out-of-field neutron and photon radiations, (2) reported linac-dependent out-of-field doses, and (3) the risk/incidence of second cancers after radiotherapy due to classic and modern treatment methods. Regardless of the measurement technique and type of accelerator, the neutron dose equivalent per unit photon dose ranges from as low as 0.1 mSv/Gy to as high as 20.4 mSv/Gy. This radiation dose potentially contributes to the induction of second primary cancer in normal tissues outside the treated area.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/415923
Abstract: The innovation of computational techniques serves as an important step toward optimized, patient-specific management of cancer. In particular, in silico simulation of tumour growth and treatment response may eventually yield accurate information on disease progression, enhance the quality of cancer treatment, and explain why certain therapies are effective where others are not. In silico modelling is demonstrated to considerably benefit from information obtainable with PET and PET/CT. In particular, models have successfully integrated tumour glucose metabolism, cell proliferation, and cell oxygenation from multiple tracers in order to simulate tumour behaviour. With the development of novel radiotracers to image additional tumour phenomena, such as pH and gene expression, the value of PET and PET/CT data for use in tumour models will continue to grow. In this work, the use of PET and PET/CT information in in silico tumour models is reviewed. The various parameters that can be obtained using PET and PET/CT are detailed, as well as the radiotracers that may be used for this purpose, their utility, and limitations. The biophysical measures used to quantify PET and PET/CT data are also described. Finally, a list of in silico models that incorporate PET and/or PET/CT data is provided and reviewed.
Publisher: Informa UK Limited
Date: 23-04-2012
Publisher: Public Library of Science (PLoS)
Date: 13-10-2017
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/612580
Abstract: There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of in idual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that in idual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.
Publisher: Elsevier BV
Date: 03-2006
Publisher: MDPI AG
Date: 20-03-2022
DOI: 10.3390/IJMS23063366
Abstract: The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.
Publisher: Oxford University Press (OUP)
Date: 05-01-2015
DOI: 10.1093/RPD/NCU362
Abstract: Peripheral photon and neutron doses from external beam radiotherapy (EBRT) are associated with increased risk of carcinogenesis in the out-of-field organs thus, dose estimations of secondary radiation are imperative. Peripheral photon and neutron doses from EBRT of prostate carcinoma were measured in Rando phantom. (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescence dosemeters (TLDs) were inserted in slices of a Rando phantom followed by exposure to 80 Gy with 18-MV photon four-field 3D-CRT technique. The TLDs were calibrated using 6- and 18-MV X-ray beam. Neutron dose equivalents measured with CR-39 etch-track detectors were used to derive readout-to-neutron dose conversion factor for (6)LiF:Mg,Cu,P TLDs. Average neutron dose equivalents per 1 Gy of isocentre dose were 3.8±0.9 mSv Gy(-1) for thyroid and 7.0±5.4 mSv Gy(-1) for colon. For photons, the average dose equivalents per 1 Gy of isocentre dose were 0.2±0.1 mSv Gy(-1) for thyroid and 8.1±9.7 mSv Gy(-1) for colon. Paired (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P TLDs can be used to measure photon and neutron doses simultaneously. Organs in close proximity to target received larger doses from photons than those from neutrons whereas distally located organs received higher neutron versus photon dose.
Publisher: British Institute of Radiology
Date: 10-2011
DOI: 10.1259/BJR/25012212
Publisher: Wiley
Date: 13-12-2021
DOI: 10.1002/MP.15360
Abstract: Proton therapy (PT) is broadly accepted as the gold standard of care for pediatric patients with cranial cancer. The superior dose distribution of PT compared to photon radiotherapy reduces normal tissue complication probability (NTCP) for organs at risk. As NTCPs for pediatric organs are not well understood, clinics generally base radiation response on adult data. However, there is evidence that radiation response strongly depends on the age and even sex of a patient. Furthermore, questions surround the influence of in idual intrinsic radiosensitivity (α/β ratio) on pediatric NTCP. While the clinical pediatric NTCP data is scarce, radiobiological modeling and sensitivity analyses can be used to investigate the NTCP trends and its dependence on in idual modeling parameters. The purpose of this study was to perform sensitivity analyses of NTCP models to ascertain the dependence of radiosensitivity, sex, and age of a child and predict cranial side‐effects following intensity‐modulated proton therapy (IMPT) and intensity‐modulated radiotherapy (IMRT). Previously, six sex‐matched pediatric cranial datasets (5, 9, and 13 years old) were planned in Varian Eclipse treatment planning system (13.7). Up to 108 scanning beam IMPT plans and 108 IMRT plans were retrospectively optimized for a range of simulated target volumes and locations. In this work, dose‐volume histograms were extracted and imported into BioSuite Software for radiobiological modeling. Relative‐Seriality and Lyman‐Kutcher‐Burman models were used to calculate NTCP values for toxicity endpoints, where TD50, (based on reported adult clinical data) was varied to simulate sex dependence of NTCP. Plausible parameter ranges, based on published literature for adults, were used in modeling. In addition to sensitivity analyses, a 20% difference in TD50 was used to represent the radiosensitivity between the sexes (with females considered more radiosensitive) for ease of data comparison as a function of parameters such as α/β ratio. IMPT plans resulted in lower NTCP compared to IMRT across all models ( p 0.0001). For medulloblastoma treatment, the risk of brainstem necrosis ( 10%) and cochlea tinnitus ( 20%) among females could potentially be underestimated considering a lower TD50 value for females. Sensitivity analyses show that the difference in NTCP between sexes was significant ( p 0.0001). Similarly, both brainstem necrosis and cochlea tinnitus NTCP varied significantly ( p 0.0001) across tested α/β as a function of TD50 values (assumption being that TD50 values are 20% lower in females). If the true α/β of these pediatric tissues is higher than expected (α/β ∼ 3), the risk of tinnitus for IMRT can significantly increase ( p 0.0001). Due to the scarcity of pediatric NTCP data available, sensitivity analyses were performed using plausible ranges based on published adult data. In the clinical scenario where, if female pediatric patients were 20% more radiosensitive (lower TD50 value), they could be up to twice as likely to experience side‐effects of brainstem necrosis and cochlea tinnitus compared to males, highlighting the need for considering the sex in NTCP models. Based on our sensitivity analyses, age and sex of a pediatric patient could significantly affect the resultant NTCP from cranial radiotherapy, especially at higher α/β values.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.CRITREVONC.2020.102881
Abstract: In iduals do not react to radiation in a homogeneous manner. Recent radiogenomic research has proven that in idual polymorphisms can correlate with treatment response most likely due to variation in the ability to recognise and repair DNA breaks. The difference in radiosensitivity between genders has been well documented, yet most radiotherapeutic guidelines are based solely on population averages rather than demographic subgroups such as age, race and gender. This paper is a review of the burgeoning literature available on the differences in efficacy and outcome of radiotherapy between genders. The work examines the effect of radiation on gender both from a tumour control as well as normal tissue toxicity perspective. While the literature reporting such findings is limited, the results show a small but significant difference in response to radiotherapy between sexes. Prospective and retrospective studies for evaluating these gender-specific differences are encouraged as a next step in personalised medicine.
Publisher: British Institute of Radiology
Date: 04-2013
DOI: 10.1259/BJR.20120443
Publisher: BMJ
Date: 06-2023
DOI: 10.1136/BMJOPEN-2022-071203
Abstract: There is a growing need for interventions to improve well-being in healthcare workers, particularly since the onset of COVID-19. To synthesise evidence since 2015 on the impact of interventions designed to address well-being and burnout in physicians, nurses and allied healthcare professionals. Systematic literature review. Medline, Embase, Emcare, CINAHL, PsycInfo and Google Scholar were searched in May–October 2022. Studies that primarily investigated burnout and/or well-being and reported quantifiable preintervention and postintervention outcomes using validated well-being measures were included. Full-text articles in English were independently screened and quality assessed by two researchers using the Medical Education Research Study Quality Instrument. Results were synthesised and presented in both quantitative and narrative formats. Meta-analysis was not possible due to variations in study designs and outcomes. A total of 1663 articles were screened for eligibility, with 33 meeting inclusion criterium. Thirty studies used in idually focused interventions, while three were organisationally focused. Thirty-one studies used secondary level interventions (managed stress in in iduals) and two were primary level (eliminated stress causes). Mindfulness-based practices were adopted in 20 studies the remainder used meditation, yoga and acupuncture. Other interventions promoted a positive mindset (gratitude journaling, choirs, coaching) while organisational interventions centred on workload reduction, job crafting and peer networks. Effective outcomes were reported in 29 studies, with significant improvements in well-being, work engagement, quality of life and resilience, and reductions in burnout, perceived stress, anxiety and depression. The review found that interventions benefitted healthcare workers by increasing well-being, engagement and resilience, and reducing burnout. It is noted that the outcomes of numerous studies were impacted by design limitations that is, no control/waitlist control, and/or no post intervention follow-up. Suggestions are made for future research.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Medknow
Date: 2009
Publisher: Informa UK Limited
Date: 05-03-2020
Publisher: Springer Science and Business Media LLC
Date: 02-11-2019
DOI: 10.1007/S13246-018-0706-Z
Abstract: A survey was designed to determine aspirations, motivations and workplace experiences of both female and male members of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM). The survey collected both quantitate and qualitative data, including open ended questions. This paper reports the survey's qualitative results. The research was approved by Ethics at University of South Australia and endorsed by ACPSEM. All 205 women (30% of total membership) and 440 men were invited to complete the survey online. The data for the qualitative analysis were responses to open-ended questions within the survey. 102 women and 150 men completed surveys were received, with 66 surveys analysed, before data saturation was reached. The survey revealed a number of themes that reflect concerns and opportunities identifying the direction for improving work-life balance and gender equity within the medical physics profession in Australasia. Issues around managing challenging workloads and professional development were lified for women with children and child-rearing responsibilities, directly contributing to a reduction in work capacity and a reorientation of work-life priorities. The survey provides direction for strategies to improve work-life balance and enable equitable engagement in the profession. The first is to identify and develop role models that actively model successful work-life balance and flexibility in gender roles and in professional conduct. The second is to improve the management skills of current and emerging administrators, advocating for improved work conditions for medical physics professionals at an organisation level. Finally, efforts need to be made to establish flexible professional development and career progression opportunities amongst those that are unable to commit to large workloads, which is common for those with child-rearing responsibilities. The realisation of these strategic goals will reduce the identified barriers to full female participation in the workforce, and shift gender-based subcultures within the workplace.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.IJROBP.2018.04.055
Abstract: Improvements in personalized therapy are made possible by the advances in molecular biology that led to developments in molecular imaging, allowing highly specific in vivo imaging of biological processes. Positron emission tomography (PET) is the most specific and sensitive imaging technique for in vivo molecular targets and pathways, offering quantification and evaluation of functional properties of the targeted anatomy. This work is an integrative research review that summarizes and evaluates the accumulated current status of knowledge of recent advances in PET imaging for cancer diagnosis and treatment, concentrating on novel radiotracers and evaluating their advantages and disadvantages in cancer characterization. Medline search was conducted, limited to English publications from 2007 onward. Identified manuscripts were evaluated for most recent developments in PET imaging of cancer hypoxia, angiogenesis, proliferation, and clonogenic cancer stem cells (CSC). There is an expansion observed from purely metabolic-based PET imaging toward antibody-based PET to achieve more information on cancer characteristics to identify hypoxia, proangiogenic factors, CSC, and others. Progress in the field of functional imaging will possibly lead to more specific tumor targeting and personalized treatment, increasing tumor control and improving quality of life.
Publisher: IOP Publishing
Date: 08-2008
DOI: 10.1088/0031-9155/53/17/002
Abstract: A Monte Carlo tumour model has been developed to simulate tumour cell propagation for head and neck squamous cell carcinoma. The model aims to eventually provide a radiobiological tool for radiation oncology clinicians to plan patient treatment schedules based on properties of the in idual tumour. The inclusion of an oxygen distribution amongst the tumour cells enables the model to incorporate hypoxia and other associated parameters, which affect tumour growth. The object oriented program FORTRAN 95 has been used to create the model algorithm, with Monte Carlo methods being employed to randomly assign many of the cell parameters from probability distributions. Hypoxia has been implemented through random assignment of partial oxygen pressure values to in idual cells during tumour growth, based on in vivo Eppendorf probe experimental data. The accumulation of up to 10 million virtual tumour cells in 15 min of computer running time has been achieved. The stem cell percentage and the degree of hypoxia are the parameters which most influence the final tumour growth rate. For a tumour with a doubling time of 40 days, the final stem cell percentage is approximately 1% of the total cell population. The effect of hypoxia on the tumour growth rate is significant. Using a hypoxia induced cell quiescence limit which affects 50% of cells with and oxygen levels less than 1 mm Hg, the tumour doubling time increases to over 200 days and the time of tumour growth for a clinically detectable tumour (10(9) cells) increases from 3 to 8 years. A biologically plausible Monte Carlo model of hypoxic head and neck squamous cell carcinoma tumour growth has been developed for real time assessment of the effects of multiple biological parameters which impact upon the response of the in idual patient to fractionated radiotherapy.
Publisher: Springer Science and Business Media LLC
Date: 08-2017
DOI: 10.1038/S41598-017-07302-9
Abstract: Glioblastomas (GBM) are notorious for their high fatality rate. Boron Neutron Capture Therapy (BNCT) being a biochemically targeted type of radiotherapy is a potent modality for GBM. In the current work, a BNCT treatment modelling framework for GBM was developed. Optimal Clinical Target Volume (CTV) margins for GBM-BNCT and the BNCT efficacy have been investigated. The model integrated a cell-based dosimetry model, an in-house-developed epithermal neutron beam model and previously-developed Microscopic Extension Probability (MEP) model. The system was defined as a cubic ICRP-brain phantom ided into 20 μ m side voxels. The corresponding 10 B concentrations in GBM and normal brain cells were applied. The in-silico model was irradiated with the epithermal neutron beam using 2 and 2.5 cm CTV margins. Results from the cell-based dosimetry and the MEP models were combined to calculate GBM cell survival fractions (SF) post BNCT and compared to x-ray radiotherapy (XRT) SFs. Compared to XRT, the SF within the beam decreased by five orders of magnitudes and the total SF was reduced three times following BNCT. CTV extension by 0.5 cm reduced the SF by additional (53.8 ± 0.3)%. In conclusion, BNCT results in a more efficient cell kill. The extension of the CTV margin, however, may not increase the treatment outcome significantly.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/749203
Abstract: Purpose . Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. Methods . The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Results . Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. Conclusion . The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.EJMP.2018.03.004
Abstract: The use of gold nanoparticle (GNP) and other metal nanoparticle (MNP) radiosensitisers to enhance radiotherapy offers the potential of improved treatment outcomes. Originally intended for use with X-ray therapy, the possibility of enhanced hadron therapy is desirable due to the superior sparing of healthy tissue in hadron therapy compared to conventional X-ray therapy. While MNPs were not expected to be effective radiosensitisers for hadron therapy due to the limited Z dependence of interactions, recent experimental measurements have contradicted this expectation. Key experimental measurements and Monte Carlo simulations of MNP radiosensitisation for hadron irradiation are reviewed in the current work. Numerous experimental measurements have found a large radiosensitisation effect due to MNPs for proton and carbon ion irradiation. Experiments have also indicated that the radiosensitisation is due in large part to enhanced reactive oxygen species (ROS) production. Simulations have found a large radial dose and ROS enhancement on the nanoscale around a single MNP. However, the short range of the dose enhancement is insufficient for a large macroscale dose enhancement or enhanced biological effect in a cell model considering dose to the nucleus from GNPs in the cytoplasm (a distribution observed in most experiments).
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.RADONC.2022.04.027
Abstract: Proton therapy (PT) can reduce side effects for paediatric cranial malignancies. Despite the high number of paediatric patients treated with PT, radiation induced risk factors for second primary cancer (SPC) in out-of-field organs are unknown. This study estimated lifetime attributable risk (LAR) of SPC as a function of age and sex for out-of-field organs following passive scattering and scanning beam PT in paediatric brain tumours. Measured neutron dose equivalent spectra for scattered and scanning PT were sourced from literature. The physical distance of 12 measured organs from paediatric CT dataset-based phantoms (5, 9 and 13 years-of-age) were applied to Schneider et al.'s analytical model using MATLAB (R2020B) to calculate the organ-specific LAR of SPC. Scanning beam PT demonstrated smaller LAR (per 10,000 person years) of SPC compared to scattering. This was prominent for more radiosensitive organs, including the lung (320 vs 50), breast (1000 vs 150) and thyroid (350 vs 75), but not for all (i.e., rectum and reproductive organs were <10). For most organs, LAR was highest for 5-year-old females (i.e., breast LAR was 1,000 higher than for 13-year-olds), however, outliers existed for distal organs (i.e., stomach and lung). There was large variation in LAR estimates of out-of-field organs based on measured neutron dose equivalents. Younger female cranial paediatric patients were found at higher risk compared to males, especially for passive scattering PT. Not all organs had improved LAR using scanning beam PT for younger age groups.
Publisher: Radiation Research Society
Date: 06-2016
DOI: 10.1667/RR14390.1
Publisher: Inderscience Publishers
Date: 2009
Publisher: IOP Publishing
Date: 20-12-2007
Publisher: Elsevier BV
Date: 03-2006
Publisher: Wiley
Date: 22-03-2017
DOI: 10.1002/MP.12130
Abstract: A stochastic computer model of tumour growth with spatial and temporal components that includes tumour angiogenesis was developed. In the current work it was used to simulate head and neck tumour growth. The model also provides the foundation for a 4D cellular radiotherapy simulation tool. The model, developed in Matlab, contains cell positions randomised in 3D space without overlap. Blood vessels are represented by strings of blood vessel units which branch outwards to achieve the desired tumour relative vascular volume. Hypoxic cells have an increased cell cycle time and become quiescent at oxygen tensions less than 1 mmHg. Necrotic cells are resorbed. A hierarchy of stem cells, transit cells and differentiated cells is considered along with differentiated cell loss. Model parameters include the relative vascular volume (2-10%), blood oxygenation (20-100 mmHg), distance from vessels to the onset of necrosis (80-300 μm) and probability for stem cells to undergo symmetric ision (2%). Simulations were performed to observe the effects of hypoxia on tumour growth rate for head and neck cancers. Simulations were run on a supercomputer with eligible parts running in parallel on 12 cores. Using biologically plausible model parameters for head and neck cancers, the tumour volume doubling time varied from 45 ± 5 days (n = 3) for well oxygenated tumours to 87 ± 5 days (n = 3) for severely hypoxic tumours. The main achievements of the current model were randomised cell positions and the connected vasculature structure between the cells. These developments will also be beneficial when irradiating the simulated tumours using Monte Carlo track structure methods.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.APRADISO.2014.03.006
Abstract: Radio-resistant hypoxic tumor cells are significant contributors to the locoregional recurrences and distant metastases that mark failure of radiotherapy. Due to restricted tissue oxygenation, chronically hypoxic tumor cells frequently become necrotic and thus there is often an association between chronically hypoxic and necrotic tumor regions. This simulation study is the first in a series to determine the feasibility of hypoxic cell killing after first targeting adjacent areas of necrosis with either an α- or β-emitting radioimmunoconjugate.
Publisher: MDPI AG
Date: 11-02-2021
DOI: 10.3390/BIOMEDICINES9020181
Abstract: FLASH radiotherapy, or the administration of ultra-high dose rate radiotherapy, is a new radiation delivery method that aims to widen the therapeutic window in radiotherapy. Thus far, most in vitro and in vivo results show a real potential of FLASH to offer superior normal tissue sparing compared to conventionally delivered radiation. While there are several postulations behind the differential behaviour among normal and cancer cells under FLASH, the full spectra of radiobiological mechanisms are yet to be clarified. Currently the number of devices delivering FLASH dose rate is few and is mainly limited to experimental and modified linear accelerators. Nevertheless, FLASH research is increasing with new developments in all the main areas: radiobiology, technology and clinical research. This paper presents the current status of FLASH radiotherapy with the aforementioned aspects in mind, but also to highlight the existing challenges and future prospects to overcome them.
Publisher: Hindawi Limited
Date: 16-08-2013
DOI: 10.1111/ECC.12109
Abstract: Technological advances in both diagnosis and treatment of breast cancer lead to early detection and better treatment management. Consequently, the population of long-term survivors is on the rise. The risk of developing second cancers among breast cancer survivors was shown to be higher than that for the general population. The aim of this work was to review the literature on the risk of second primary cancer (SPC) after breast irradiation. Pubmed search of population-based studies on SPC after breast irradiation was conducted and the findings (in terms of Standardised Incidence Ratio) were collated and discussed. Several studies confirmed the link between breast tumour irradiation and risk of SPC, showing a small, but valid risk. There are, however, confounding factors that can either underestimate or overestimate risks: misclassification of tumour status, genetic inheritance, smoking, environmental factors, and the lack of accurate data in cancer registries. While isolating these potential triggers might be difficult, this approach would allow better discernability between radiotherapy-related risks and those generated by other factors. It is also important to evaluate the current status of treatment-related late effects and to lower such risks by minimising the dose delivered to normal tissues.
Publisher: MDPI AG
Date: 25-08-2023
Abstract: The well-known clinical benefits of proton therapy are achieved through higher target-conformality and normal tissue sparing than conventional radiotherapy. However, there is an increased sensitivity to uncertainties in patient motion/setup, proton range and radiobiological effect. Although recent efforts have mitigated some uncertainties, radiobiological effect remains unresolved due to a lack of clinical data for relevant endpoints. Therefore, RBE optimisations may be currently unsuitable for clinical treatment planning. LET optimisation is a novel method that substitutes RBE with LET, shifting LET hotspots outside critical structures. This review outlines the current status of LET optimisation in proton therapy, highlighting knowledge gaps and possible future research. Following the PRISMA 2020 guidelines, a search of the MEDLINE® and Scopus databases was performed in July 2023, identifying 70 relevant articles. Generally, LET optimisation methods achieved their treatment objectives however, clinical benefit is patient-dependent. Inconsistencies in the reported data suggest further testing is required to identify therapeutically favourable methods. We discuss the methods which are suitable for near-future clinical deployment, with fast computation times and compatibility with existing treatment protocols. Although there is some clinical evidence of a correlation between high LET and adverse effects, further developments are needed to inform future patient selection protocols for widespread application of LET optimisation in proton therapy.
Publisher: Medknow
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1007/S13246-012-0178-5
Abstract: Organ motion is a substantial concern in the treatment of thoracic tumours using radiotherapy. A number of technologies have evolved in order to address this concern in both the fields of CT imaging and radiation delivery. This review paper investigates the technologies which have been developed for the delivery of radiotherapy as well as the accuracy and workload implications of their use. Treatment techniques investigated include: breath hold, breath gating, robotic compensation and MLC manipulation. Each technique has its own advantages and drawbacks in regards to accuracy, treatment time, linac alterations and workload. Further, some treatment techniques have specific requirements for what kind of CT scans needs to be used in the planning process. This, along with the aforementioned considerations, could influence the decision as to implement some of these treatment techniques in the clinic.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Informa UK Limited
Date: 05-04-2022
DOI: 10.1080/10872981.2022.2041366
Abstract: There is limited access to life-saving antenatal ultrasound in rural and low-resource settings largely due to shortages in skilled staff. Studies have shown healthcare practitioners can be upskilled in PoCUS through focused training, offering a viable solution to this deficit. However, standards for training and competency assessment are unclear and regulation surrounding practice is lacking. We aimed to review published literature examining antenatal PoCUS training programs, comparing teaching approaches and study methodologies. A search of electronic databases EMBASE, MEDLINE and Google Scholar was conducted. Original research articles evaluating antenatal PoCUS training of healthcare professionals worldwide were identified for analysis. Articles with limited detail on the PoCUS training intervention and those describing comprehensive diagnostic training programs were excluded. Evaluations were compared against the Kirkpatrick Evaluation Framework (KEF). Twenty-seven studies were included from an initial search result of 484 articles. There was considerable heterogeneity between the PoCUS training programs described. Course duration ranged from 3 hours to 2 years, with 11 of the 27 studies delivering obstetric-exclusive content. 44% trained multidisciplinary groups of health professionals. Long-term follow-up training and skills assessments were lacking in over half of the reviewed studies. Study quality and reporting detail varied, but overall beneficial outcomes were reported with 3/4s of the studies reaching upper KEF levels 3 and 4. PoCUS performed by upskilled healthcare professionals offers an attractive solution to the problem of inequitable access to antenatal ultrasound. A review of available literature highlighted a paucity of comparable high-quality studies needed to establish a stronger evidence base for antenatal PoCUS, and a need to standardise training and competency assessment. This review may inform educators, researchers and policy-makers on existing training formats and methodologies to assist in establishing best practice antenatal PoCUS training methods for safe service delivery by remote healthcare professionals.
Publisher: Springer Science and Business Media LLC
Date: 05-04-2022
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.EJMP.2019.07.006
Abstract: The negative impact of tumour hypoxia on cancer treatment outcome has been long-known, yet there has been little success combating it. This paper investigates the potential role of in silico modelling to help test emerging hypoxia-targeting treatments in cancer therapy. A Medline search was undertaken on the current landscape of in silico models that simulate cancer therapy and evaluate their ability to test hypoxia-targeting treatments. Techniques and treatments to combat tumour hypoxia and their current challenges are also presented. Hypoxia-targeting treatments include tumour reoxygenation, hypoxic cell radiosensitization with nitroimidazoles, hypoxia-activated prodrugs and molecular targeting. Their main challenges are toxicity and not achieving adequate delivery to hypoxic regions of the tumour. There is promising research toward combining two or more of these techniques. Different types of in silico therapy models have been developed ranging from temporal to spatial and from stochastic to deterministic models. Numerous models have compared the effectiveness of different radiotherapy fractionation schedules for controlling hypoxic tumours. Similarly, models could help identify and optimize new treatments for overcoming hypoxia that utilize novel hypoxia-targeting technology. Current therapy models should attempt to incorporate more sophisticated modelling of tumour angiogenesis/vasculature and vessel perfusion in order to become more useful for testing hypoxia-targeting treatments, which typically rely upon the tumour vasculature for delivery of additional oxygen, (pro)drugs and nanoparticles.
Publisher: MDPI AG
Date: 10-09-2020
Abstract: Background: Proton radiotherapy produces superior dose distributions compared to photon radiotherapy, reducing side effects. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Our aim was to compare intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) radiation doses for select paediatric intracranial tumours. Methods: IMPT and IMRT dose distributions for gender-matched paediatric cranial CT-datasets (ages 5, 9 and 13 years) were retrospectively calculated to simulate irradiation of supratentorial (ependymoma) and infratentorial (medulloblastoma) target volumes diameters (1–3 cm) and position (central and 1–2 cm shifts). Results: Clinical dosimetric objectives were achieved for all 216 treatment plans. Whilst infratentorial IMPT plans achieved greater maximum dose sparing to optic structures (4.8–12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Mean dose difference for optic chiasm was associated with medulloblastoma target position (p 0.0197). Supratentorial IMPT plans demonstrated greater dose reduction for the youngest patients (pituitary gland p 0.001). Conclusions: Normal tissue sparing was achieved regardless of patient age for infratentorial tumours. However, for supratentorial tumours, there was a dosimetric advantage of IMPT across 9 vs. 13-year-old patients.
Publisher: IOP Publishing
Date: 17-12-2005
DOI: 10.1088/0031-9155/50/1/008
Abstract: Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2023
DOI: 10.1007/S13246-023-01266-Z
Abstract: Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume mechanistic understanding is still in its infancy stringent verification of dosimetry is rarely provided biological assays are prone to limitations which need greater acknowledgement.
Publisher: IOP Publishing
Date: 27-03-2015
DOI: 10.1088/0031-9155/60/8/3217
Abstract: The preliminary framework of a combined radiobiological model is developed and calibrated in the current work. The model simulates the production of in idual cells forming a tumour, the spatial distribution of in idual ionization events (using Geant4-DNA) and the stochastic biochemical repair of DNA double strand breaks (DSBs) leading to the prediction of survival or death of in idual cells. In the current work, we expand upon a previously developed tumour generation and irradiation model to include a stochastic ionization damage clustering and DNA lesion repair model. The Geant4 code enabled the positions of each ionization event in the cells to be simulated and recorded for analysis. An algorithm was developed to cluster the ionization events in each cell into simple and complex double strand breaks. The two lesion kinetic (TLK) model was then adapted to predict DSB repair kinetics and the resultant cell survival curve. The parameters in the cell survival model were then calibrated using experimental cell survival data of V79 cells after low energy proton irradiation. A monolayer of V79 cells was simulated using the tumour generation code developed previously. The cells were then irradiated by protons with mean energies of 0.76 MeV and 1.9 MeV using a customized version of Geant4. By replicating the experimental parameters of a low energy proton irradiation experiment and calibrating the model with two sets of data, the model is now capable of predicting V79 cell survival after low energy (<2 MeV) proton irradiation for a custom set of input parameters. The novelty of this model is the realistic cellular geometry which can be irradiated using Geant4-DNA and the method in which the double strand breaks are predicted from clustering the spatial distribution of ionisation events. Unlike the original TLK model which calculates a tumour average cell survival probability, the cell survival probability is calculated for each cell in the geometric tumour model developed in the current work. This model uses fundamental measurable microscopic quantities such as genome length rather than macroscopic radiobiological quantities such as alpha/beta ratios. This means that the model can be theoretically used under a wide range of conditions with a single set of input parameters once calibrated for a given cell line.
Publisher: Wiley
Date: 27-07-2023
Abstract: This study aimed to assess the accuracy of transvaginal ultrasound (TVUS) for the mapping of endometriosis before surgery when performed by sonographers in an outpatient women's imaging centre. A prospective longitudinal cohort study was performed. The study group comprised of 201 women who underwent a comprehensive TVUS assessment, performed by a sonographer. Laparoscopy was performed as the reference standard. Complete TVUS and surgical data were available for 53 women who were included in the final analysis. Endometriosis was confirmed at a surgery in 50/53 (94.3%) participants, with 25/53 (47.2%) having deep endometriosis (DE) nodules and/or endometriomas present. TVUS for mapping of DE had an overall sensitivity of 84.0%, specificity of 89.3%, PPV of 87.5%, NPV of 86.2%, LR+ of 7.85, LR− of 0.18, and accuracy of 86.8% ( P 0.001). Ovarian immobility had poor sensitivity for detecting localised superficial endometriosis, DE, adhesions, and/or endometriomas (Left = 61.9% and right = 13.3%) but high specificities (left = 87.5% and right = 94.7%). Site‐specific tenderness had low sensitivities and moderate specificities for the same. All soft markers of endometriosis failed to reach statistical significance except for left ovarian immobility ( P = .001). Sonographers well experienced in obstetric and gynaecological imaging, working in an outpatient women's imaging setting can accurately map DE however, the performance of soft markers for detection of SE was poor.
Location: Australia
Start Date: 2023
End Date: 12-2027
Amount: $4,999,600.00
Funder: Australian Research Council
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