No abstract

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Amplified cellular genes in mammalian cells frequently manifest themselves as double minute chromosomes (DMs) and homogeneously staining regions of chromosomes (HSRs). With few exceptions both karyotypic abnormalities appear to be confined to tumour cells. All vertebrates possess a set of cellular genes homologous to the transforming genes of RNA tumour viruses, and there is circumstantial evidence that these cellular oncogenes are involved in tumorigenesis. We have recently shown that DMs and HSRs in cells of the mouse adrenocortical tumour Y1 and an HSR in the human colon carcinoma COLO320 contain amplified copies of the cellular oncogenes c-Ki-ras and c-myc, respectively. Both DMs and HSRs are found with remarkable frequency in cells of human neuroblastomas. We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification. By in situ hybridization we found that HSRs are the chromosomal sites of the amplified DNA. The frequency with which this amplification appears in cells from neuroblastomas and its apparent specificity raise the possibility that one or more of the genes contained within the amplified domain contribute to tumorigenesis.

No abstract

NA DOC resulted in substantial improvement in responses to DOC.

No abstract

No abstract

The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of b values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications.