Virtual Biopsy in Soft Tissue Sarcoma. How Close Are We?

A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes

Colorado State University, College of Veterinary Medicine and Biomedical Sciences, 11th annual CVMBS research day scientific proceedings

Includes the Pfizer Research Award winner and abstracts only of the oral sessions and posters

Radiogenomics in non-small-cell lung cancer

Ο μη μικροκυτταρικός καρκίνος του πνεύμονα είναι ο πιο συχνά συναντώμενος υποτύπος καρκίνου του πνεύμονα, ο οποίος αποτελείται από ένα φάσμα υποτύπων. Το NSCLC είναι ένας θανατηφόρος, ετερογενής συμπαγής όγκος με μια εκτεταμένη σειρά μοριακών χαρακτηριστικών. Η πάθηση έχει γίνει ένα αξιοσημείωτο παράδειγμα ιατρικής ακριβείας καθώς το ενδιαφέρον για το θέμα συνεχίζει να επεκτείνεται. Ο απώτερος στόχος της τρέχουσας έρευνας είναι να χρησιμοποιήσει συγκεκριμένα γονίδια ως βιοδείκτες για την πρόγνωση, την έγκαιρη διάγνωση και την εξατομικευμένη θεραπεία, τα οποία διευκολύνονται από τη χρήση εξελισσόμενων τεχνικών αλληλούχισης επόμενης γενιάς που επιτρέπουν την ταυτόχρονη ανίχνευση μεγάλου αριθμού γενετικές ανωμαλίες. Γνωστές μεταλλάξεις ενός αριθμού γονιδίων, όπως τα EGFR, ALK και KRAS, επηρεάζουν ήδη τις αποφάσεις θεραπείας και νέα βασικά γονίδια και μοριακές υπογραφές διερευνώνται για την προγνωστική τους αξία καθώς και για την πιθανή συμβολή τους στην ανοσοθεραπεία και τη θεραπεία της υποτροπής στην αντίσταση στις υπάρχουσες θεραπείες. Οι τύποι δειγμάτων που χρησιμοποιούνται για μελέτες NGS, όπως αναρροφήσεις με λεπτή βελόνα, ιστός ενσωματωμένος σε παραφίνη σταθεροποιημένος με φορμαλίνη και DNA χωρίς κύτταρα, έχουν ο καθένας τα δικά του πλεονεκτήματα και μειονεκτήματα που πρέπει να ληφθούν υπόψηNon-small cell lung cancer is the most often encountered subtype of lung cancer, which consists of a spectrum of subtypes. NSCLC is a lethal, heterogeneous solid tumor with an extensive array of molecular features. The condition has become a notable example of precision medicine as interest in the topic continues to expand. The ultimate goal of the current research is to use specific genes as biomarkers for its prognosis, timely diagnosis, and personalized therapy, all of which are facilitated by the use of evolving next-generation sequencing techniques that permit the simultaneous detection of a large number of genetic abnormalities. Known mutations of a number of genes, such as EGFR, ALK, and KRAS, already influence treatment decisions, and new key genes and molecular signatures are being investigated for their prognostic value as well as their potential contribution to immunotherapy and the treatment of recurrence due to resistance to existing therapies. The sample types utilized for NGS studies, such as fine-needle aspirates, formalin-fixed paraffin-embedded tissue, and cell-free DNA, each have their own advantages and disadvantages that must be taken into accoun

The impact of arterial input function determination variations on prostate dynamic contrast-enhanced magnetic resonance imaging pharmacokinetic modeling: a multicenter data analysis challenge, part II

This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate Ktrans (volume transfer rate constant), ve (extravascular, extracellular volume fraction), kep (efflux rate constant), and τi (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T1 values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for Ktrans, ve, kep, and τi, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in Ktrans and ve (wCV = 0.50 and 0.10, respectively), but had smaller effects on kep and τi (wCV = 0.39 and 0.22, respectively). kep is less sensitive to AIF variation than Ktrans, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τi parameter may have advantages over the conventional PK parameters in a longitudinal study

Metastatic Progression and Tumour Heterogeneity

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors

Investigating evolutionary hypotheses of cancer cell motility

Cancer is a disease of evolution. Mutations within a cell lead to the acquisition of cancerous phenotypes. Tumour evolution depends on heritable differences between cells. The extent of heritable variation has not been measured for any trait in cancer cellpopulations. In this thesis techniques have been developed to estimate the broad-sense heritability (H2) of cancer cell traits in vitroand usedto estimate the H2of cell motility. Cell motility is a trait related to the cancer hallmark of metastasis. Results showthat motility is strongly heritable with H2values ranging from 0.77-0.36 across multiple cell generations. H2estimates appeared to decrease slightly between more distantly related cells, a trend that could occur due to a decrease in the genetic contribution to motility or an increase in environmental variation. This was tested by treating cells with epigenetic inhibitors and obtaining H2 estimates.Results showed H2estimates were not significantly affected by the application of epigenetic inhibitorswith values ranging from 0.95-0.18.Quantification of the amount of environmental variation in in vitrocell culture media was attempted using image analysis of fluorescent particles. Variation in particle distribution was found at a range of concentrations, nM –mM. Direct quantitative measures of evolvability in cell traits could have valuable applications to cancer research and tumour treatment.To understand tumour progression, evolutionary theory can be applied to cancer cells in vitroto elucidate the selective pressures driving the evolution of cancer cell traits. In this project experimental evolution techniques have been adapted from microbiology and applied to cancer cell linesin vitro. Adaptation of cell lines to lownutrient environments over 12 weeks showed dispersal theory may play a role in the selection of the cancer cell trait motility. Understanding the selective pressures driving the acquisition of cancer phenotypes will have valuable applications clinically inunderstandingtumour progression

Isolation and Analysis of Characteristic Compounds from Herbal and Plant Extracts

Herbal and plant extracts show diverse activities and have been used for centuries as natural medicines for many health problems and diseases. Through the isolation and analysis of the compounds in the extracts, it is possible to understand why the extracts exhibit those activities, as well as the chemical metabolism of compounds that occur in plants and herbs. Recently, there have been increasing attempts to develop herbal and plant extracts into functional foods and drugs, but the legal requirements are becoming stricter. We need sophisticatedly defined extracts through the isolation and analysis of compounds comprising them in order to meet the legal requirements and to pursue quality control strategies in the production of functional foods and drugs. This Special Issue Book compiled the 15 recent research and review articles that highlight the isolation, profiling, and analysis of compounds in herbal and plant extracts, as well as quality control and standardized processing strategies for extracts with characteristic compounds