Modelling systematic anatomical uncertainties of head and neck cancer patients during fractionated radiotherapy treatment.

Head and neck cancer patients experience systematic anatomical changes as well as random day to day anatomical changes during fractionated radiotherapy treatment. Modelling the expected systematic anatomical changes could aid in creating treatment plans which are more robust against such changes. A patient specific (SM) and population average (AM) model are presented which are able to capture the systematic anatomical changes of some head and neck cancer patients over the course of radiotherapy treatment. Inter- patient correspondence aligned all patients to a model space. Intra- patient correspondence between each planning CT scan and on treatment cone beam CT scans was obtained using diffeomorphic deformable image registration. The stationary velocity fields were then used to develop B-Spline based SMs and AMs. The models were evaluated geometrically and dosimetrically. A leave-one-out method was used to compare the training and testing accuracy of the models. Both SMs and AMs were able to capture systematic changes. The average surface distance between the registration propagated contours and the contours generated by the SM was less than 2mm, showing that the SM are able to capture the anatomical changes which a patient experiences during the course of radiotherapy. The testing accuracy was lower than the training accuracy of the SM, suggesting that the model overfits to the limited data available and therefore also captures some of the random day to day changes. For most patients the AMs were a better estimate of the anatomical changes than assuming there were no changes, but the AMs could not capture the variability in the anatomical changes seen in all patients. No difference was seen in the training and testing accuracy of the AMs. These observations were highlighted in both the geometric and dosimetric evaluations and comparisons. The large patient variability highlights the need for more complex, capable population models.

Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment.

This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications.

Using diffusion MRI to understand white matter damage and the link between brain microstructure and cognitive deficits in paediatric medulloblastoma patients.

PURPOSE: Survivors of medulloblastoma face a range of challenges after treatment, involving behavioural, cognitive, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain resulting from both the tumour and the treatment. Diffusion magnetic resonance imaging (MRI) has been used to investigate the microstructure of the brain. In this review, we aim to summarise the literature on diffusion MRI in patients treated for medulloblastoma and discuss future directions on how diffusion imaging can be used to improve patient quality. METHOD: This review summarises the current literature on medulloblastoma in children, focusing on the impact of both the tumour and its treatment on brain microstructure. We review studies where diffusion MRI has been correlated with either treatment characteristics or cognitive outcomes. We discuss the role diffusion MRI has taken in understanding the relationship between microstructural damage and cognitive and behavioural deficits. RESULTS: We identified 35 studies that analysed diffusion MRI changes in patients treated for medulloblastoma. The majority of these studies found significant group differences in measures of brain microstructure between patients and controls, and some of these studies showed associations between microstructure and neurocognitive outcomes, which could be influenced by patient characteristics (e.g. age), treatment, radiation dose and treatment type. CONCLUSIONS: In future, studies would benefit from being able to separate microstructural white matter damage caused by the tumour, tumour-related complications and treatment. Additionally, advanced diffusion modelling methods can be explored to understand and describe microstructural changes to white matter.

Reproducibility in Radiomics: A Comparison of Feature Extraction Methods and Two Independent Datasets.

Radiomics involves the extraction of information from medical images that are not visible to the human eye. There is evidence that these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations, namely the MATLAB toolkit and Pyradiomics, when applied to independent datasets of CT scans of patients: (i) the open access RIDER dataset containing a set of repeat CT scans taken 15 min apart for 31 patients (RIDER Scan 1 and Scan 2, respectively) treated for lung cancer; and (ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV), manually outlined by an experienced observer available on both datasets, was used. The 43 common radiomics features available in MATLAB and Pyradiomics were calculated using two intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters, and the Spearman's rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset, and vice versa. A total of 29 out of the 43 reported stable features were found to be highly reproducible between MATLAB and Pyradiomics implementations, having a consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in the RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Characterization of Inorganic Scintillator Detectors for Dosimetry in Image-Guided Small Animal Radiotherapy Platforms.

The purpose of the study was to characterize a detection system based on inorganic scintillators and determine its suitability for dosimetry in preclinical radiation research. Dose rate, linearity, and repeatability of the response (among others) were assessed for medium-energy X-ray beam qualities. The response's variation with temperature and beam angle incidence was also evaluated. Absorbed dose quality-dependent calibration coefficients, based on a cross-calibration against air kerma secondary standard ionization chambers, were determined. Relative output factors (ROF) for small, collimated fields (≤10 mm × 10 mm) were measured and compared with Gafchromic film and to a CMOS imaging sensor. Independently of the beam quality, the scintillator signal repeatability was adequate and linear with dose. Compared with EBT3 films and CMOS, ROF was within 5% (except for smaller circular fields). We demonstrated that when the detector is cross-calibrated in the user's beam, it is a useful tool for dosimetry in medium-energy X-rays with small fields delivered by Image-Guided Small Animal Radiotherapy Platforms. It supports the development of procedures for independent "live" dose verification of complex preclinical radiotherapy plans with the possibility to insert the detectors in phantoms.

Enhanced effect of X-rays in the presence of a static magnetic field within a 3D pancreatic cancer model.

OBJECTIVE: To evaluate the impact of static magnetic field (SMF) presence on the radiation response of pancreatic cancer cells in polyurethane-based highly macro-porous scaffolds in hypoxic (1% O2) and normoxic (21% O2) conditions, towards understanding MR-guided radiotherapy, shedding light on the potential interaction phenomenon between SMF and radiation in a three-dimensional (3D) microenvironment. METHODS: Pancreatic cancer cells (PANC-1, ASPC-1) were seeded into fibronectin-coated highly porous polyethene scaffolds for biomimicry and cultured for 4 weeks in in vitro normoxia (21% O2) followed by a 2-day exposure to either in vitro hypoxia (1% O2) or maintenance in in vitro normoxia (21% O2). The samples were then irradiated with 6 MV photons in the presence or absence of a 1.5 T field. Thereafter, in situ post-radiation monitoring (1 and 7 days post-irradiation treatment) took place via quantification of (i) live dead and (ii) apoptotic profiles. RESULTS: We report: (i) pancreatic ductal adenocarcinoma hypoxia-associated radioprotection, in line with our previous findings, (ii) an enhanced effect of radiation in the presence of SMFin in vitro hypoxia (1% O2) for both short- (1 day) and long-term (7 days) post -radiation analysis and (iii) an enhanced effect of radiation in the presence of SMF in in vitro normoxia (21% O2) for long-term (7 days) post-radiation analysis within a 3D pancreatic cancer model. CONCLUSION: With limited understanding of the potential interaction phenomenon between SMF and radiation, this 3D system allows combination evaluation for a cancer in which the role of radiotherapy is still evolving. ADVANCES IN KNOWLEDGE: This study examined the use of a 3D model to investigate MR-guided radiotherapy in a hypoxic microenvironment, indicating that this could be a useful platform to further understanding of SMF influence on radiation.

Improving the quality of head and neck radiotherapy CT images using a second image reconstruction set.

PURPOSE: To improve the quality of radiotherapy head and neck CT images through use of an additional image set reconstructed from the raw data of the primary scan, thus allowing parameters such as reconstruction field-of-view (FOV) and kernel to be optimised without impacting on the images used for treatment planning dose calculations. METHODS: Using a Catphan image quality phantom and a Toshiba Aquilion LB CT scanner, qualitative and quantitative measurements were made for different reconstruction kernels and FOV diameters. The preferred FOV diameter and kernels were selected. Clinical images from six patients were reconstructed using those kernels (FC13, FC41, FC44, FC64) and the chosen FOV, 200 mm. The images were ranked to choose the kernel which gave best image quality for organ delineation. The scanner workflow was adjusted to produce for every scan a second image set using the chosen kernel and FOV. Finally, for 10 patient scans, image quality was compared for the two reconstructed images. RESULTS: The second image set was produced using kernel FC44 and 200 mm FOV. The primary image set using 550 mm FOV and FC13 was unchanged and contours from the second image set merged onto the first. Oncologists reported increased confidence in contouring in all cases using the new procedure. CONCLUSION: Production of a second image set, using a reduced reconstruction FOV and a kernel which optimises contrast and sharpness, significantly improves the quality of head and neck CT images for contouring, and avoids any dose increase.

Volumetric modulated arc therapy (VMAT): a review of clinical outcomes-what is the clinical evidence for the most effective implementation?

Modern conformal radiation therapy using techniques such as modulation, image guidance and motion management have changed the face of radiotherapy today offering superior conformity, efficiency, and reproducibility to clinics worldwide. This review assesses the impact of these advanced radiotherapy techniques on patient toxicity and survival rates reported from January 2017 to September 2020. The main aims are to establish if dosimetric and efficiency gains correlate with improved survival and reduced toxicities and to answer the question 'What is the clinical evidence for the most effective implementation of VMAT?'. Compared with 3DCRT, improvements have been reported with VMAT in prostate, locally advanced cervical carcinoma and various head and neck applications, leading to the shift in technology to VMAT. Other sites such as thoracic neoplasms and nasopharyngeal carcinomas have observed some improvement with VMAT although not in line with improved dosimetric measures, and the burden of toxicity and the incidence of cancer related deaths remain high, signaling the need to further mitigate toxicity and increase survival. As technological advancement continues, large randomised long-term clinical trials are required to determine the way-forward and offer site-specific recommendations. These studies are usually expensive and time consuming, therefore utilising pooled real-world data in a prospective nature can be an alternative solution to comprehensively assess the efficacy of modern radiotherapy techniques.

On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening.

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.

Evaluation of a micro ionization chamber for dosimetric measurements in image-guided preclinical irradiation platforms.

Image-guided small animal irradiation platforms deliver small radiation fields in the medium energy x-ray range. Commissioning of such platforms, followed by dosimetric verification of treatment planning, are mostly performed with radiochromic film. There is a need for independent measurement methods, traceable to primary standards, with the added advantage of immediacy in obtaining results. This investigation characterizes a small volume ionization chamber in medium energy x-rays for reference dosimetry in preclinical irradiation research platforms. The detector was exposed to a set of reference x-ray beams (0.5-4 mm Cu HVL). Leakage, reproducibility, linearity, response to detector's orientation, dose rate, and energy dependence were determined for a 3D PinPoint ionization chamber (PTW 31022). Polarity and ion recombination were also studied. Absorbed doses at 2 cm depth were compared, derived either by applying the experimentally determined cross-calibration coefficient at a typical small animal radiation platform 'user's' quality (0.84 mm Cu HVL) or by interpolation from air kerma calibration coefficients in a set of reference beam qualities. In the range of reference x-ray beams, correction for ion recombination was less than 0.1%. The largest polarity correction was 1.4% (for 4 mm Cu HVL). Calibration and correction factors were experimentally determined. Measurements of absorbed dose with the PTW 31022, in conditions different from reference were successfully compared to measurements with a secondary standard ionization chamber. The implementation of an End-to-End test for delivery of image-targeted small field plans resulted in differences smaller than 3% between measured and treatment planning calculated doses. The investigation of the properties and response of a PTW 31022 small volume ionization chamber in medium energy x-rays and small fields can contribute to improve measurement uncertainties evaluation for reference and relative dosimetry of small fields delivered by preclinical irradiators while maintaining the traceability chain to primary standards.

Novel Anticancer and Treatment Sensitizing Compounds against Pancreatic Cancer.

The isolation of chemical compounds from natural origins for medical application has played an important role in modern medicine with a range of novel treatments having emerged from various natural forms over the past decades. Natural compounds have been exploited for their antioxidant, antimicrobial and antitumor capabilities. Specifically, 60% of today's anticancer drugs originate from natural sources. Moreover, the combination of synthetic and natural treatments has shown applications for (i) reduced side effects, (ii) treatment sensitization and (iii) reduction in treatment resistance. This review aims to collate novel and natural compounds that are being explored for their preclinical anticancer, chemosensitizing and radiosensitizing effects on Pancreatic Ductal Adenocarcinoma (PDAC), which is a lethal disease with current treatments being inefficient and causing serve side effects. Two key points are highlighted by this work: (i) the availability of a range of natural compounds for potentially new therapeutic approaches for PDAC, (ii) potential synergetic impact of natural compounds with advanced chemo- and radio-therapeutic modalities for PDAC.

Quantification of the uncertainties within the radiotherapy dosimetry chain and their impact on tumour control.

BACKGROUND AND PURPOSE: Dose delivered during radiotherapy has uncertainty arising from a number of sources including machine calibration, treatment planning and delivery and can impact outcomes. Any systematic uncertainties will impact all patients and can continue for extended periods. The impact on tumour control probability (TCP) of the uncertainties within the radiotherapy calibration process has been assessed. MATERIALS AND METHODS: The linear-quadratic model was used to simulate the TCP from two prostate cancer and a head and neck (H&N) clinical trial. The uncertainty was separated into four components; 1) initial calibration, 2) systematic shift due to output drift, 3) drift during treatment and 4) daily fluctuations. Simulations were performed for each clinical case to model the variation in TCP present at the end of treatment arising from the different components. RESULTS: Overall uncertainty in delivered dose was +/-2.1% (95% confidence interval (CI)), consisting of uncertainty standard deviations of 0.7% in initial calibration, 0.8% due to subsequent calibration shift due to output drift, 0.1% due to drift during treatment, and 0.2% from daily variations. The overall uncertainty of TCP (95% CI) for a population of patients treated on different machines was +/-3%, +/-5%, and +/-3% for simulations based on the two prostate trials and H&N trial respectively. CONCLUSION: The greatest variation in delivered target volume dose arose from calibration shift due to output drift. Careful monitoring of beam output following initial calibration remains vital and may have a significant impact on clinical outcomes.

Low radiation dose to treat pneumonia and other inflammations.

Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus. While radiotherapy has been most widely used to control malignant tumours, it has also been used for treatment of non-malignant diseases, including acute and chronic inflammation in situations where anti-inflammatory drugs may be ineffective or contraindicated. The present review examines the history and prospects for low-dose anti-inflammatory radiation treatments, the present interest largely being motivated by the increased incidence of pulmonary disease associated Covid-19 infections. Evidence in support of the suggested efficacy are covered, together with an appraisal of one of the number of potential convenient sources that could complement external beam arrangements.

ESTIMATION OF THERMAL & EPITHERMAL NEUTRON FLUX AND GAMMA DOSE DISTRIBUTION IN A MEDICAL CYCLOTRON FACILITY FOR RADIATION PROTECTION PURPOSES USING GOLD FOILS AND GATE 9.

The aim of this study is to characterise the neutron flux generated directly behind targets used in medical cyclotrons. The characterisation process aims at determining the feasibility of using the generated neutrons for research purposes in neutron activation analysis. The study was performed by activating gold foils placed directly behind the cyclotron targets. The thermal and epithermal neutron flux were found to be 4.5E+05 ± 8.78E+04 neutrons cm-2 s-1 and 2.13E+06 ± 8.59E+04 neutrons cm-2 s-1, respectively. The flux value is the same order of magnitude listed in the manual produced by the cyclotron manufacturer. The results are encouraging and show high potential for using the cyclotron facility as a thermal neutron source for research purposes. However, it is important radiation protection procedures be followed to ensure the safety of researchers due to the high gamma dose rate measured directly behind the target at 2.46 Sv/h using an OSL chip during the beam on time.

3d tissue models as tools for radiotherapy screening for pancreatic cancer.

The efficiency of radiotherapy treatment regimes varies from tumour to tumour and from patient to patient but it is generally highly influenced by the tumour microenvironment (TME). The TME can be described as a heterogeneous composition of biological, biophysical, biomechanical and biochemical milieus that influence the tumour survival and its' response to treatment. Preclinical research faces challenges in the replication of these in vivo milieus for predictable treatment response studies. 2D cell culture is a traditional, simplistic and cost-effective approach to culture cells in vitro, however, the nature of the system fails to recapitulate important features of the TME such as structure, cell-cell and cell-matrix interactions. At the same time, the traditional use of animals (Xenografts) in cancer research allows realistic in vivo architecture, however foreign physiology, limited heterogeneity and reduced tumour mutation rates impairs relevance to humans. Furthermore, animal research is very time consuming and costly. Tissue engineering is advancing as a promising biomimetic approach, producing 3D models that capture structural, biophysical, biochemical and biomechanical features, therefore, facilitating more realistic treatment response studies for further clinical application. However, currently, the application of 3D models for radiation response studies is an understudied area of research, especially for pancreatic ductal adenocarcinoma (PDAC), a cancer with a notoriously complex microenvironment. At the same time, specific novel and/or more enhanced radiotherapy tumour-targeting techniques such as MRI-guided radiotherapy and proton therapy are emerging to more effectively target pancreatic cancer cells. However, these emerging technologies may have different biological effectiveness as compared to established photon-based radiotherapy. For example, for MRI-guided radiotherapy, the novel use of static magnetic fields (SMF) during radiation delivery is understudied and not fully understood. Thus, reliable biomimetic platforms to test new radiation delivery strategies are required to more accurately predict in vivo responses. Here, we aim to collate current 3D models for radiation response studies of PDAC, identifying the state of the art and outlines knowledge gaps. Overall, this review paper highlights the need for further research on the use of 3D models for pre-clinical radiotherapy screening including (i) 3D (re)-modeling of the PDAC hypoxic TME to allow for late effects of ionising radiation (ii) the screening of novel radiotherapy approaches and their combinations as well as (iii) a universally accepted 3D-model image quantification method for evaluating TME components in situ that would facilitate accurate post-treatment(s) quantitative comparisons.

In Vitro Evaluation of Notch Inhibition to Enhance Efficacy of Radiation Therapy in Melanoma.

PURPOSE: The scope of radiation therapy is limited in melanoma. Using in vitro melanoma models, we investigated a Notch signaling inhibitor as a radiosensitizer to explore its potential to improve the efficacy of radiation therapy to widen the clinical application of radiation therapy in melanoma. METHODS AND MATERIALS: Melanoma cell lines A375, SKMEL28, and G361 were grown using standard tissue culture methods. Radiation was delivered with a clinical x-ray unit, and a gamma secretase inhibitor RO4929097 was used to inhibit Notch signaling. Cell viability signal was used to calculate Loewe's combination index to assess the interaction between radiation and RO4929097 and also the effect of scheduling of radiation and RO4929097 on synergy. Clonogenic assays were used to assess the clonogenic potential. An in vitro 3-dimensional culture model, γ-H2AX, and notch intracellular domain assays were used to interrogate potential underlying biological mechanisms of this approach. Scratch and transwell migration assays were used to assess cell migration. RESULTS: A375 and SKMEL28 cell lines showed consistent synergy for most single radiation doses examined, with a tendency for better synergy with the radiation-first schedule (irradiation performed 24 hours before RO4929097 exposure). Clonogenic assays showed dose-dependent reduction in colony numbers. Both radiation and RO4929097 reduced the size of melanospheres grown in 3-dimensional culture in vitro, where RO4929097 demonstrated a significant effect on the size of A375 and SKMEL28 melanospheres, indicating potential modulation of stem cell phenotype. Radiation induced γ-H2AX foci signal levels were reduced after exposure to RO4929097 with a tendency toward reduction in notch intracellular domain levels for all 3 cell lines. RO4929097 impaired both de novo and radiation-enhanced cell migration. CONCLUSIONS: We demonstrate Notch signaling inhibition with RO4929097 as a promising strategy to potentially improve the efficacy of radiation therapy in melanoma. This strategy warrants further validation in vivo.

UK adaptive radiotherapy practices for head and neck cancer patients.

OBJECTIVE: To provide evidence on the extent and manner in which adaptive practices have been employed in the UK and identify the main barriers for the clinical implementation of adaptive radiotherapy (ART) in head and neck (HN) cancer cases. METHODS: In December 2019, a Supplementary Material 1, of 23 questions, was sent to all UK radiotherapy centres (67). This covered general information to current ART practices and perceived barriers to implementation. RESULTS: 31 centres responded (46%). 56% responding centres employed ART for between 10 and 20 patients/annum. 96% of respondents were using CBCT either alone or with other modalities for assessing "weight loss" and "shell gap," which were the main reasons for ART. Adaptation usually occurs at week three or four during the radiotherapy treatment. 25 responding centres used an online image-guided radiotherapy (IGRT) approach and 20 used an offline ad hoc ART approach, either with or without protocol level. Nearly 70% of respondents required 2 to 3 days to create an adaptive plan and 95% used 3-5 mm adaptive planning target volume margins. All centres performed pre-treatment QA. "Limited staff resources" and "lack of clinical relevance" were identified as the two main barriers for ART implementation. CONCLUSION: There is no consensus in adaptive practice for HN cancer patients across the UK. For those centres not employing ART, similar clinical implementation barriers were identified. ADVANCES IN KNOWLEDGE: An insight into contemporary UK practices of ART for HN cancer patients indicating national guidance for ART implementation for HN cancer patients may be required.

Can different Catphan phantoms be used in a multi-centre audit of radiotherapy CT image quality?

PURPOSE: To determine the variation between Catphan image quality CT phantoms, specifically for use in a future multi-centre image quality audit. METHOD: 14 Catphan phantoms (models 503, 504 and 604) were scanned on a Canon Aquilion Prime CT scanner using a single scan protocol. Measurements were made of noise in the uniformity section, visibility of low contrast targets and contrast, x-ray attenuation and CT number for 5 materials in the sensitometry section. Scans were also acquired using one phantom and varying reconstruction field of view, image slice thickness, effective tube-current-time product and iterative reconstruction settings to determine how the degree of inter-phantom variability compared with the magnitude of changes from scan parameter alteration. RESULTS: Across all phantoms the mean CT value in the uniformity section was 7.0 (SD 0.9) range: 4.9-8.1 HU. For the different materials the CT numbers were air: -1004 ± 5, Polymethylpentene: -190 ± 2, Polystyrene: -42 ± 2, Delrin: 321 ± 5 and Teflon: 898 ± 8 HU. Consistency of low contrast targets through visual scoring was good. Measured contrast was lower (p < 0.001) with more variability for 504 versus 604 models. All phantoms produced identical tube current settings with x-ray tube current modulation, indicating no x-ray attenuation differences. The degree of change in image quality metrics between phantoms was small compared with results when scan parameters were varied. CONCLUSION: Catphan phantoms model 604 showed minimal differences and will be used for multi-centre inter-comparison work, with the consistency between phantoms appropriate for measuring possible variations in image quality.

IPEM code of practice for high-energy photon therapy dosimetry based on the NPL absorbed dose calibration service.

The 1990 code of practice (COP), produced by the IPSM (now the Institute of Physics and Engineering in Medicine, IPEM) and the UK National Physical Laboratory (NPL), gave instructions for determining absorbed dose to water for megavoltage photon (MV) radiotherapy beams (Lillicrap et al 1990). The simplicity and clarity of the 1990 COP led to widespread uptake and high levels of consistency in external dosimetry audits. An addendum was published in 2014 to include the non-conventional conditions in Tomotherapy units. However, the 1990 COP lacked detailed recommendations for calibration conditions, and the corresponding nomenclature, to account for modern treatment units with different reference fields, including small fields as described in IAEA TRS483 (International Atomic Energy Agency (IAEA) 2017, Vienna). This updated COP recommends the irradiation geometries, the choice of ionisation chambers, appropriate correction factors and the derivation of absorbed dose to water calibration coefficients, for carrying out reference dosimetry measurements on MV external beam radiotherapy machines. It also includes worked examples of application to different conditions. The strengths of the 1990 COP are retained: recommending the NPL2611 chamber type as secondary standard; the use of tissue phantom ratio (TPR) as the beam quality specifier; and NPL-provided direct calibration coefficients for the user's chamber in a range of beam qualities similar to those in clinical use. In addition, the formalism is now extended to units that cannot achieve the standard reference field size of 10 cm × 10 cm, and recommendations are given for measuring dose in non-reference conditions. This COP is designed around the service that NPL provides and thus it does not require the range of different options presented in TRS483, such as generic correction factors for beam quality. This approach results in a significantly simpler, more concise and easier to follow protocol.

A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma-Toward a Better Mimicry of the in vivo Tumor Microenvironment.

With a very low survival rate, pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. This has been primarily attributed to (i) its late diagnosis and (ii) its high resistance to current treatment methods. The latter specifically requires the development of robust, realistic in vitro models of PDAC, capable of accurately mimicking the in vivo tumor niche. Advancements in the field of tissue engineering (TE) have helped the development of such models for PDAC. Herein, we report for the first time a novel hybrid, polyurethane (PU) scaffold-based, long-term, multicellular (tri-culture) model of pancreatic cancer involving cancer cells, endothelial cells, and stellate cells. Recognizing the importance of ECM proteins for optimal growth of different cell types, the model consists of two different zones/compartments: an inner tumor compartment consisting of cancer cells [fibronectin (FN)-coated] and a surrounding stromal compartment consisting of stellate and endothelial cells [collagen I (COL)-coated]. Our developed novel hybrid, tri-culture model supports the proliferation of all different cell types for 35 days (5 weeks), which is the longest reported timeframe in vitro. Furthermore, the hybrid model showed extensive COL production by the cells, mimicking desmoplasia, one of PDAC's hallmark features. Fibril alignment of the stellate cells was observed, which attested to their activated state. All three cell types expressed various cell-specific markers within the scaffolds, throughout the culture period and showed cellular migration between the two zones of the hybrid scaffold. Our novel model has great potential as a low-cost tool for in vitro studies of PDAC, as well as for treatment screening.