Quo vadis radiotherapy? Technological advances and the rising problems in cancer management

Extent: 10p.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.Barry J. Allen, Eva Bezak, and Loredana G. Marc

Physical modelling of proton and heavy ion radiation using Geant4

Protons and heavy ion particles are considered to be ideal particles for use in external beam radiotherapy due to superior properties of the dose distribution that results when these particles are incident externally and due to their relative biological effectiveness. While significant research has been performed into the properties and physical dose characteristics of heavy ions, the nuclear reactions (direct and fragmentation) undergone by He⁴, C¹² and Ne²⁰ nuclei used in radiotherapy in materials other than water is still largely unexplored. In the current project, input code was developed for the Monte Carlo toolkit Geant 4 version 9.3 to simulate the transport of several mono-energetic heavy ions through water. The relative dose contributions from secondary particles and nuclear fragments originating from the primary particles were investigated for each ion in both water and dense bone (ICRU) media. The results indicated that the relative contribution to the total physical dose from nuclear fragments increased with both increasing particle mass and with increasing medium density. In the case of 150 MeV protons, secondary particles were shown to contribute less than 0.5% of the peak dose and as high as 25% when using 10570 MeV neon ions in bone. When water was substituted for a bone medium, the contributions from fragments increased by more than 6% for C¹² and Ne²⁰.M. Douglass, E. Beza

PET-specific parameters and radiotracers in theoretical tumour modelling

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.Matthew Jennings, Loredana G. Marcu, and Eva Beza

In silico modelling of tumour margin diffusion and infiltration: Review of current status

Extent: 16p.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.Fatemeh Leyla Moghaddasi, Eva Bezak, and Loredana Marc

Processing and Interconnections of Finely Segmented Semiconductor Pixel Detectors for Applications in Particle Physics and Photon Detection

Radiation hardness is in the focus of the development of particle tracking and photon imaging detector installations. Semiconductor detectors, widely used in particle physics experiments, have turned into capacitive-coupled (AC-coupled) detectors from the originally developed conductively coupled (DC-coupled) detectors. This is due to the superior isolation of radiation-induced leakage current in AC-coupled detectors. However, some modern detector systems, such as the tracking detectors in the CERN LHC CMS or ATLAS experiments, are still DC-coupled. This originates from the difficulty of implementing AC coupling on very small pixel detector areas. In this report, we describe our advances in the detector processing technology. The first topic is the applications of the atomic layer deposition processing technology, which enables the very high densities of capacitance and resistance that are needed when the dimensions of the physical segmentation of pixel detectors need to be scaled down. The second topic is the flip-chip/bump-bonding interconnection technology, which is necessary in order to manufacture pixel detector modules on a large scale with a more than 99% yield of noise-free and faultless pixels and detector channels.Peer reviewe

Evaluation of current clinical target volume definitions for glioblastoma using cell-based dosimetry stochastic methods

Determination of an optimal clinical target volume (CTV) is complex and remains uncertain. The aim of this study was to develop a glioblastoma multiforme (GBM) model to be used for evaluation of current CTV practices for external radiotherapy.The GBM model was structured as follows: (1) a Geant4 cellular model was developed to calculate the absorbed dose in individual cells represented by cubic voxels of 20 μm sides. The system was irradiated with opposing 6 MV X-ray beams. The beams encompassed planning target volumes corresponding to 2.0- and 2.5-cm CTV margins; (2) microscopic extension probability (MEP) models were developed using MATLAB(®) 2012a (MathWorks(®), Natick, MA), based on clinical studies reporting on GBM clonogenic spread; (3) the cellular dose distribution was convolved with the MEP models to evaluate cellular survival fractions (SFs) for both CTV margins.A CTV margin of 2.5 cm, compared to a 2.0-cm CTV margin, resulted in a reduced total SF from 12.9% ± 0.9% to 3.6% ± 0.2%, 5.5% ± 0.4% to 1.2% ± 0.1% and 11.1% ± 0.7% to 3.0% ± 0.2% for circular, elliptical and irregular MEP distributions, respectively.A Monte Carlo model was developed to quantitatively evaluate the impact of GBM CTV margins on total and penumbral SF. The results suggest that the reduction in total SF ranges from 3.5 to 5, when the CTV is extended by 0.5 cm.The model provides a quantitative tool for evaluation of different CTV margins in terms of cell kill efficacy. Cellular platform of the tool allows future incorporation of cellular properties of GBM.L. Moghaddasi, E. Bezak and W. Harriss-Phillip

Autoradiography imaging in targeted alpha therapy with Timepix detector

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 individual 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 individual 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.Ruqaya AL Darwish, Alexander Hugo Staudacher, Eva Bezak, and Michael Paul Brow

Predictive models of tumour response to treatment using functional imaging techniques

Editorial, abstract not included.Loredana G. Marcu, Eva Bezak, Iuliana Toma-Dasu, and Alexandru Das

Life-cycle assessment of coal mining wastes upcycling

Coal extraction generates coal mining wastes (CMW) that lead to additional environmental burdens. This study assesses the potential environmental benefits of using these CMW as secondary materials in the production of precast concrete cladding panels. Potential environmental impacts are measured using life cycle assessment (LCA). The system under assessment is a multi-functional system, including both the management of CMW and the production of concrete panels. Company data have been used to perform the assessment. Preliminary results show, for the business-as-usual (BAU) scenario, that the main impacts associated with wastes management are due to diesel consumption and direct emissions to groundwater. For the concrete panel production, the impacts are primarily induced by cement production. This BAU scenario will be compared to a recycling scenario where CMW are incorporated into concrete production. Based on this comparative LCA, recommendations as to the use of CMW into construction products will be provided

Modeling the impact of defects on the charge collection efficiency of a Cadmium Telluride detector

Cadmium telluride is a favorable material for X-ray detection as it has an outstanding characteristic for room temperature operation. It is a high-Z material with excellent photon radiation absorption properties. However, CdTe single crystals may include a large number of extended crystallographic defects, such as grain boundaries, twins, and tellurium (Te) inclusions, which can have an impact on detector performance. A Technology Computer Aided Design (TCAD) local defect model has been developed to investigate the effects of local defects on charge collection efficiency (CCE). We studied a 1 mm thick Schottky-type CdTe radiation detector with transient current technique by using a red laser at room temperature. By raster scanning the detector surface we were able to study signal shaping within the bulk, and to locate surface defects by observing their impact on the CCE. In this paper we present our TCAD model with localized defect, and compare the simulation results to TCT measurements. In the model an inclusion with a diameter of 10 mu m was assumed. The center of the defect was positioned at 6 mu m distance from the surface. We show that the defect has a notable effect on current transients, which in turn affect the CCE of the CdTe detector. The simulated charge collection at the position of the defect decreases by 80 % in comparison to the defect-free case. The simulations show that the defects give a characteristic shape to TCT signal. This can further be used to detect defects in CdTe detectors and to estimate the overall defect density in the material.Peer reviewe