127 research outputs found
Targeted radiotherapy of neuroblastoma: future directions
No abstract available
Commentary: Opportunities for research in molecular radiotherapy
Cancer has been treated with radiopharmaceuticals for 80 years. A recent National Cancer Research Institute report from the Clinical and Translational Radiotherapy Research Working Group reviews the current status of molecular radiotherapy and has highlighted the barriers to and opportunities for increased research activities. The report recommends a number of actions to promote this field, which in the dawning age of personalized medicine and theragnostics is of increasing importance, particularly with the clinical introduction of a range of new commercial radiotherapeutics at costs in line with those seen for conventional chemotherapeutics. These recommendations recognize the importance of a multidisciplinary approach to the development of molecular radiotherapy and the particular need for investment in radiopharmacies and personalized dosimetry. There are many areas to be investigated including adaptive treatment planning, the use of radiosensitizers and translational radiation biology. Progress in these areas will result in significant patient benefit and more cost-effective use of increasingly expensive therapeutic radiopharmaceuticals. A concerted effort from the community, from funding bodies and from health service providers is now needed to address the scientific and logistical changes necessary to realize the potential offered by this currently underused treatment modality
Inhibition of Poly(ADP-Ribose) polymerase enhances the toxicity of 131I-Metaiodobenzylguanidine/Topotecan combination therapy to cells and xenografts that express the noradrenaline transporter
Targeted radiotherapy using [131I]meta-iodobenzylguanidine ([131I]MIBG) has produced remissions in some neuroblastoma patients. We previously reported that combining [131I]MIBG with the topoisomerase I (Topo-I) inhibitor topotecan induced long-term DNA damage and supra-additive toxicity to NAT-expressing cells and xenografts. This combination treatment is undergoing clinical evaluation. This present study investigated the potential of PARP-1 inhibition, in vitro and in vivo, to further enhance [131I]MIBG/topotecan efficacy
Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.
Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens
Image guidance and inter-fractional anatomical variation in paediatric abdominal radiotherapy
OBJECTIVES: To identify variables predicting inter fractional anatomical variationsmeasured with cone-beam CT (CBCT) throughout abdominal paediatric radiotherapy, and to assess the potential of surface-guided radiotherapy (SGRT) to monitor these changes. METHODS: Metrics of variation in gastrointestinal (GI) gas volume andseparation of the body contour and abdominal wallwere calculated from 21 planning CTs and 77 weekly CBCTs for 21 abdominal neuroblastoma patients (median 4y, range: 2 -19y). Age, sex, feeding tubes, and general anaesthesia (GA) were explored as predictive variables for anatomical variation. Furthermore,GI gas variationwas correlated with changes in body and abdominal wall separation, as well as simulated SGRT metrics of translational and rotationalcorrections between CT/CBCT. RESULTS: GI gas volumes varied 74 ± 54âml across all scans, while body and abdominal wall separationvaried 2.0 ± 0.7âmm and4.1±1.5mmfrom planning, respectively. Patients < 3.5y (p = 0.04) and treated under GA (p < 0.01) experienced greater GI gas variation; GA was the strongest predictor in multivariate analysis (p < 0.01). Absence of feeding tubes was linked to greater body contour variation (p = 0.03). GI gas variation correlated with body (R = 0.53) and abdominal wall (R = 0.63) changes. The strongest correlations with SGRT metrics were found for anteroposterior translation (R = 0.65) androtation of the left-right axis (R = -0.36). CONCLUSIONS: Young age, GA, and absence of feeding tubes were linked to stronger inter fractional anatomical variation and are likely indicative of patients benefiting from adaptive/robust planning pathways.Our data suggests a role for SGRT toinformthe need for CBCT at each treatment fractionin this patient group. ADVANCES IN KNOWLEDGE: This is the first study to suggest the potential role of SGRT for the management of internal inter fractional anatomical variation in paediatric abdominal radiotherapy
Developing a framework for CBCT-to-CT synthesis in paediatric abdominal radiotherapy
We proposed a CBCT-to-CT synthesis framework tailored for
paediatric abdominal patients. Our approach was based on the cycle-consistent
generative adversarial network (cycleGAN) modified to preserve structural
consistency. To adjust for differences in field-of-view and body size from
different patient groups, our training data was spatially co-registered to a
common field-of-view and normalised to a fixed size. The proposed framework
showed improvements in generating synthetic CTs from CBCTs compared to the
original implementation of cycleGAN without field-of-view adjustments and
structural consistency constrain
Deep learning based synthetic CT from cone beam CT generation for abdominal paediatric radiotherapy
Objective: Adaptive radiotherapy workflows require images with the quality of computed tomography
(CT) for re-calculation and re-optimisation of radiation doses. In this work we aim to improve quality of
cone beam CT (CBCT) images for dose calculation using deep learning. /
Approach: We propose a novel framework for CBCT-to-CT synthesis using cycle-consistent Generative
10 Adversarial Networks (cycleGANs). The framework was tailored for paediatric abdominal patients, a
challenging application due to the inter-fractional variability in bowel filling and smaller patient numbers.
We introduced the concept of global residuals only learning to the networks and modified the cycleGAN
loss function to explicitly promote structural consistency between source and synthetic images. Finally, to
compensate for the anatomical variability and address the difficulties in collecting large datasets in the
15 paediatric population, we applied a smart 2D slice selection based on the common field-of-view across
the dataset (abdomen). This acted as a weakly paired data approach that allowed us to take advantage of
scans from patients treated for a variety of malignancies (thoracic-abdominal-pelvic) for training
purposes. We first optimised the proposed framework and benchmarked its performance on a
development dataset. Later, a comprehensive quantitative evaluation was performed on an unseen
20 dataset, which included calculating global image similarity metrics, segmentation-based measures and
proton therapy-specific metrics.
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Main results: We found improved performance, compared to a baseline implementation, on imagesimilarity metrics such as Mean Absolute Error calculated for a matched virtual CT (55.0±16.6 proposed
vs 58.9±16.8 baseline). There was also a higher level of structural agreement for gastrointestinal gas
25 between source and synthetic images measured through dice similarity overlap (0.872±0.053 proposed
vs 0.846±0.052 baseline). Differences found in water-equivalent thickness metrics were also smaller for
our method (3.3±2.4% proposed vs 3.7±2.8% baseline). /
Significance: Our findings indicate that our innovations to the cycleGAN framework improved the quality
and structure consistency of the synthetic CTs generated
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