Kate Ricketts

A quantitative x-ray detection system for gold nanoparticle tumour biomarkers

X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach is being developed that employs x-ray fluorescence with an aim to locate heavy nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles can be functionalized to act as markers for tumour characteristics to map the disease state, with the future aim of imaging them to inform cancer therapy regimes. The uptake of functionalized nanoparticles by cancer cells will also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy-resolving silicon drift detector with high spectral resolution, shows potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A series of synchrotron measurements are presented; a linear relationship between fluorescence intensity and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1), the detection limit of the system. Successful use of a bench-top source, suitable for possible future clinical use, is also demonstrated, and found not to degrade the detection limit or accuracy of the GNP concentration measurement. The achieved system sensitivity suggests possible future clinical usefulness in measuring tumour uptake in vivo, particularly in shallow tumour sites and small animals, in ex vivo tissue and in 3D in vitro research samples.

A 3D In Vitro Cancer Model as a Platform for Nanoparticle Uptake and Imaging Investigations

In order to maximize the potential of nanoparticles (NPs) in cancer imaging and therapy, their mechanisms of interaction with host tissue need to be fully understood. NP uptake is known to be dramatically influenced by the tumor microenvironment, and an imaging platform that could replicate in vivo cellular conditions would make big strides in NP uptake studies. Here, a novel NP uptake platform consisting of a tissue-engineered 3D in vitro cancer model (tumoroid), which mimics the microarchitecture of a solid cancer mass and stroma, is presented. As the tumoroid exhibits fundamental characteristics of solid cancer tissue and its cellular and biochemical parameters are controllable, it provides a real alternative to animal models. Furthermore, an X-ray fluorescence imaging system is developed to demonstrate 3D imaging of GNPs and to determine uptake efficiency within the tumoroid. This platform has implications for optimizing the targeted delivery of NPs to cells to benefit cancer diagnostics and therapy.

Investigation into the effects of high-Z nano materials in proton therapy

Abstract High-Z nano materials have been previously shown to increase the amount of dose deposition within the tumour due to an increase in secondary electrons. This study evaluates the effects of high-Z nano materials in combination with protons, and the impact of proton energy, nanoparticle material and concentration. These effects were studied in silico through Monte Carlo simulation and experimentally through a phantom study, with particular attention to macroscale changes to the Bragg peak in the presence of nanoparticles. Three nanoparticle materials were simulated (gold, silver and platinum) at three concentrations (0.01, 0.1 and 6.5 mg ml−1) at two clinical proton energies (60 and 226 MeV). Simulations were verified experimentally using Gafchromic film measurements of gold nanoparticles suspended in water at two available high concentrations (5.5 mg ml−1 and 1.1 mg ml−1). A significant change to Bragg peak features was evident, where at 226 MeV and 6.5 mg ml−1, simulations of gold showed a 4.7 mm longitudinal shift of the distal edge and experimentally at 5.5 mg ml−1, a shift of 2.2 mm. Simulations showed this effect to be material dependent, where platinum having the highest physical density caused the greatest shift with increasing concentration. A dose enhancement of 6%  ±  0.05 and 5%  ±  0.15 (60 MeV and 226 MeV, respectively) was evident with gold at 6.5 mg ml−1 to water alone, compared to the 21%  ±  0.53 observed experimentally as dose to film with 5.5 mg ml−1 of gold nanoparticles suspended in water at 226 MeV. The introduction of nanoparticles has strong potential to enhance dose in proton therapy, however the changes to the Bragg peak distribution that occur with high concentrations need to be accounted for to ensure tumour coverage.

Automated estimation of disease recurrence in head and neck cancer using routine healthcare data

BACKGROUND Overall survival (OS) and progression free survival (PFS) are key outcome measures for head and neck cancer as they reflect treatment efficacy, and have implications for patients and health services. The UK has recently developed a series of national cancer audits which aim to estimate survival and recurrence by relying on institutions manually submitting interval data on patient status, a labour-intensive method. However, nationally, data are routinely collected on hospital admissions, surgery, radiotherapy and chemotherapy. We have developed a technique to automate the interpretation of these routine datasets, allowing us to derive patterns of treatment in head and neck cancer patients from routinely acquired data. METHODS We identified 122 patients with head and neck cancer and extracted treatment histories from hospital notes to provide a gold standard dataset. We obtained routinely collected local data on inpatient admission and procedures, chemotherapy and radiotherapy for these patients and analysed them with a computer algorithm which identified relevant time points and then calculated OS and PFS. We validated these by comparison with the gold standard dataset. The algorithm was then optimised to maximise correct identification of each timepoint, and minimise false identification of recurrence events. RESULTS Of the 122 patients, 82% had locally advanced disease. OS was 88% at 1 year and 77% at 2 years and PFS was 75% and 66% at 1 and 2 years. 40 patients developed recurrent disease. Our automated method provided an estimated OS of 87% and 77% and PFS of 87% and 78% at 1 and 2 years; 98% and 82% of patients showed good agreement between the automated technique and Gold standard dataset of OS and PFS respectively (ratio of Gold standard to routine intervals of between 0.8 and 1.2). The automated technique correctly assigned recurrence in 101 out of 122 (83%) of the patients: 21 of the 40 patients with recurrent disease were correctly identified, 19 were too unwell to receive further treatment and were missed. Of the 82 patients who did not develop a recurrence, 77 were correctly identified and 2 were incorrectly identified as having recurrent disease when they did not. CONCLUSIONS We have demonstrated that our algorithm can be used to automate the interpretation of routine datasets to extract survival information for this sample of patients. It currently underestimates recurrence rates due to many patients not being well-enough to be treated for recurrent disease. With some further optimisation, this technique could be extended to a national level, providing a new approach to measuring outcomes on a larger scale than is currently possible. This could have implications for healthcare provision and policy for a range of different disease types.

Patient‐reported outcome measures in metastatic prostate cancer

Survival remains a primary aim of treatment in prostate cancer, but quality of life is also an essential benefit of any therapy. Patient‐reported outcome measures, which record quality of life as perceived by the patient, are now widely used in cancer trials and, as discussed in this article, have a place in everyday practice.

Implementation and evaluation of a transit dosimetry system for treatment verification

PURPOSE To evaluate a formalism for transit dosimetry using a phantom study and prospectively evaluate the protocol on a patient population undergoing 3D conformal radiotherapy. METHODS Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. The measured EPID dose map was back-projected using the planning CT images to calculate dose at pre-specified points within the patient using commercially available software, EPIgray (DOSIsoft, France). This software compared computed back-projected dose with treatment planning system dose. A series of tests were performed on solid water phantoms (linearity, field size effects, off-axis effects). 37 patients were enrolled in the prospective study. RESULTS The EPID dose response was stable and linear with dose. For all tested field sizes the agreement was good between EPID-derived and treatment planning system dose in the central axis, with performance stability up to a measured depth of 18cm (agreement within -0.5% at 10cm depth on the central axis and within -1.4% at 2cm off-axis). 126 transit images were analysed of 37 3D-conformal patients. Patient results demonstrated the potential of EPIgray with 91% of all delivered fields achieved the initial set tolerance level of ΔD of 0±5-cGy or %ΔD of 0±5%. CONCLUSIONS The in vivo dose verification method was simple to implement, with very few commissioning measurements needed. The system required no extra dose to the patient, and importantly was able to detect patient position errors that impacted on dose delivery in two of cases.

Recommendations for clinical translation of nanoparticle-enhanced radiotherapy

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. A recent meeting of the group identified barriers to and strategies for accelerated clinical translation. This commentary reports the cooperatives recommendations. Particular emphasis was given to more standardised and cohesive research methods, models and outputs, and reprioritised research drivers including patient quality of life following treatment. Nanoparticle design criteria were outlined to incorporate scalability of manufacture, understanding and optimisation of biological mechanisms of enhancement and in vivo fate of nanoparticles, as well as existing design criteria for physical and chemical enhancement. In addition, the group aims to establish a long-term and widespread international community to disseminate key findings and create a much-needed cohesive body of evidence necessary for commercial and clinical translation.

Advances in external beam radiotherapy for prostate cancer

This article describes some of the advances that have been made in external beam radiotherapy techniques over recent years. These developments mean that modern radiotherapy to the prostate is now highly accurate, maximising the dose to the prostate target whilst minimising radiation to adjacent normal tissues.

MO-F-CAMPUS-I-04: Magnetic Resonance Imaging of An in Vitro 3D Tumor Model

To investigate the use of an in vitro 3D tumor model (tumoroid) as a bio-phantom for repetitive and sequential magnetic resonance imaging (MRI) studies.

Assessment of the dosimetric accuracies of CATPhan 504 and CIRS 062 using kV-CBCT for performing direct calculations

The dosimetric accuracies of CATPhan 504 and CIRS 062 have been evaluated using the kV-CBCT of Varian TrueBeam linac and Eclipse TPS. The assessment was done using the kV-CBCT as a standalone tool for dosimetric calculations towards Adaptive replanning. Dosimetric calculations were made without altering the HU-ED curves of the planning computed tomography (CT) scanner that is used by the Eclipse TPS. All computations were done using the images and dataset from kV-CBCT while maintaining the HU-ED calibration curve of the planning CT (pCT), assuming pCT was used for the initial treatment plan. Results showed that the CIRS phantom produces doses within ±5% of the CT-based plan while CATPhan 504 produces a variation of ±14% of the CT-based plan.