Publications by authors named "Gary Royle"

Mitotic activity is an important feature for grading several cancer types. However, counting mitotic figures (cells in division) is a time-consuming and laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment.

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Article Synopsis
  • - The study introduces the SPRINTER algorithm, which analyzes single-cell DNA sequencing to identify and classify the proliferation rates of different cancer cell clones within tumors, shedding light on the variability of cell growth among these clones.
  • - Applying SPRINTER to nearly 15,000 non-small cell lung cancer cells showed significant differences in clone proliferation, which was corroborated by various imaging techniques and indicated that more proliferative clones also had a higher likelihood of metastasis and altered genetic replication patterns.
  • - The algorithm's effectiveness was further demonstrated in breast and ovarian cancer datasets, where it uncovered higher proliferation rates and genetic variations in specific, more rapidly growing cell clones.
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Background: Motion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.

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Article Synopsis
  • Integrated-mode proton radiography can effectively create water equivalent thickness (WET) maps, which are useful for managing patient motion and verifying treatment ranges in proton therapy.
  • The study introduces a novel reconstruction method that utilizes 2D information from two lateral view cameras, significantly enhancing image quality compared to traditional methods that use a single camera.
  • Experimental results show this new method achieves higher resolution and contrast in radiographs, leading to improved accuracy in WET measurements, which is crucial for optimizing clinical proton therapy applications.
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 Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past.

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Objectives: Glioblastoma (GBM) is the most common malignant primary brain tumor with local recurrence after radiotherapy (RT), the most common mode of failure. Standard RT practice applies the prescription dose uniformly across tumor volume disregarding radiological tumor heterogeneity. We present a novel strategy using diffusion-weighted (DW-) MRI to calculate the cellular density within the gross tumor volume (GTV) in order to facilitate dose escalation to a biological target volume (BTV) to improve tumor control probability (TCP).

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Background: Particle imaging can increase precision in proton and ion therapy. Interactions with nuclei in the imaged object increase image noise and reduce image quality, especially for multinucleon ions that can fragment, such as helium.

Purpose: This work proposes a particle imaging filter, referred to as the Prior Filter, based on using prior information in the form of an estimated relative stopping power (RSP) map and the principles of electromagnetic interaction, to identify particles that have undergone nuclear interaction.

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Develop an anatomical model based on the statistics of the population data and evaluate the model for anatomical robust optimisation in head and neck cancer proton therapy.Deformable image registration was used to build the probability model (PM) that captured the major deformation from patient population data and quantified the probability of each deformation. A cohort of 20 nasopharynx patients was included in this retrospective study.

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Purpose: To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans.

Methods: A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs).

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Purpose: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer.

Methods: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model.

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. We proposed two anatomical models for head and neck patients to predict anatomical changes during the course of radiotherapy..

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Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe.

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Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life.

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Purpose: Relative stopping powers (RSPs) for proton therapy are estimated using single-energy computed tomography (SECT), calibrated with standardized tissues of the adult male. It is assumed that those tissues are representative of tissues of all age and sex. Female, male, and pediatric tissues differ from one another in density and composition.

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Article Synopsis
  • Nasopharyngeal cancer (NPC) has poor treatment options and survival rates, particularly in advanced stages, even in wealthy countries.* -
  • Research shows that the Epstein-Barr virus (EBV) promotes high levels of somatostatin receptor 2 (SSTR2) in NPC, which can be targeted for therapy.* -
  • Targeting SSTR2 with a new drug, PEN-221, could improve treatment outcomes and is linked to better survival rates, with successful imaging results in clinical trials.*
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Materials with a high atomic number (Z) are shown to cause an increase in the level of cell kill by ionizing radiation when introduced into tumor cells. This study uses in vitro experiments to investigate the differences in radiosensitization between two cell lines (MCF-7 and U87) and three commercially available nanoparticles (gold, gadolinium, and iron oxide) irradiated by 6 MV X-rays. To assess cell survival, clonogenic assays are carried out for all variables considered, with a concentration of 0.

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Proton imaging is a promising technology for proton radiotherapy as it can be used for: (1) direct sampling of the tissue stopping power, (2) input information for multi-modality RSP reconstruction, (3) gold-standard calibration against concurrent techniques, (4) tracking motion and (5) pre-treatment positioning. However, no end-to-end characterization of the image quality (signal-to-noise ratio and spatial resolution, blurring uncertainty) against the dose has been done. This work aims to establish a model relating these characteristics and to describe their relationship with proton energy and object size.

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Purpose: In pencil beam scanning proton therapy, target coverage is achieved by scanning the pencil beam laterally in the x- and y-directions and delivering spots of dose to positions at a given radiological depth (layer). Dose is delivered to the spots on different layers by pencil beams of different energy until the entire volume has been irradiated. The aim of this study is to investigate the implementation of proton planning parameters (spot spacing, layer spacing and margins) in four commercial proton treatment planning systems (TPSs): Eclipse, Pinnacle , RayStation and XiO.

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Purpose: In all recent protocols for the reference dosimetry of clinical proton beams, ionization chamber perturbation factors are assumed to be unity. In this work, such factors were computed using the FLUKA Monte Carlo code for three ionization chamber types, with particular attention to the influence of nuclear interactions.

Methods: The accuracy of the transport algorithms implemented in FLUKA was first evaluated by performing a Fano cavity test.

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Background: To quantify the geometrical changes of each neck nodal level (NNL) and estimate the geometric planning target volume (PTV) margin during image-guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC).

Methods: Twenty patients with locally advanced NPC underwent one planning computed tomography (CT) and 6 weekly repeat CT (CT) scans during chemoradiotherapy. Each CT was rigidly registered to the CT.

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A multi-disciplinary cooperative for nanoparticle-enhanced radiotherapy (NERT) has been formed to review the current status of the field and identify key stages towards translation. Supported by the Colorectal Cancer Healthcare Technologies Cooperative, the cooperative comprises a diverse cohort of key contributors along the translation pathway including academics of physics, cancer and radio-biology, chemistry, nanotechnology and clinical trials, clinicians, manufacturers, industry, standards laboratories, policy makers and patients. Our aim was to leverage our combined expertise to devise solutions towards a roadmap for translation and commercialisation of NERT, in order to focus research in the direction of clinical implementation, and streamline the critical pathway from basic science to the clinic.

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Novel imaging modalities can improve the estimation of patient elemental compositions for particle treatment planning. The mean excitation energy (I-value) is a main contributor to the proton range uncertainty. To minimize their impact on beam range errors and quantify their uncertainties, the currently used I-values proposed in 1982 are revisited.

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Background: Outcomes for patients in UK with locally advanced non-small cell lung cancer (LA NSCLC) are amongst the worst in Europe. Assessing outcomes is important for analysing the effectiveness of current practice. However, data quality is inconsistent and regular large scale analysis is challenging.

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Purpose: The purpose of this work is to evaluate the performance of dual-energy CT (DECT) for determining proton stopping power ratios (SPRs) in an experimental environment and to demonstrate its potential advantages over conventional single-energy CT (SECT) in clinical conditions.

Methods: Water equivalent range (WER) measurements of 12 tissue-equivalent plastic materials and 12 fresh animal tissue samples are performed in a 195 MeV broad proton beam using the dose extinction method. SECT and DECT scans of the samples are performed with a dual-source CT scanner (Siemens SOMATOM Definition Flash).

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Purpose: Dual-energy CT (DECT) promises improvements in estimating stopping power ratios (SPRs) for proton therapy treatment planning. Although several comparable mathematical formalisms have been proposed in literature, the optimal techniques to characterize human tissue SPRs with DECT in a clinical environment are not fully established. The aim of this work is to compare the most robust DECT methods against conventional single-energy CT (SECT) in conditions reproducing a clinical environment, where CT artifacts and noise play a major role on the accuracy of these techniques.

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