Haukeland University Hospital

About: Haukeland University Hospital is a healthcare organization based out in Bergen, Norway. It is known for research contribution in the topics: Population & Cancer. The organization has 3833 authors who have published 11617 publications receiving 396135 citations. The organization is also known as: Haukeland universitetssykehus.

Genome-wide analysis of DNA copy number variation in breast cancer using DNA microarrays

Abstract: Gene amplifications and deletions frequently have pathogenetic roles in cancer. 30,000 radiation-hybrid mapped cDNAs provide a genomic resource to map these lesions with high resolution. We developed a cDNA microarray-based comparative genomic hybridisation method for analysing DNA copy number changes across thousands of genes simultaneously. Using this procedure, we could reliably detect DNA copy number alterations of twofold or less. In breast cancer cell lines, we have mapped regions of DNA copy number variation at high resolution, revealing previously unrecognised genomic amplifications and deletions, and new complexities of amplicon structure. Recurrent regions of DNA amplification, which may harbour novel oncogenes, were readily identified. Alterations of DNA copy number and gene expression could be compared and correlated in parallel analyses. We have now collected genome-wide DNA copy number information on a set of 9 breast cancer cell lines and over 35 primary breast tumours. For the breast tumours, DNA copy number information is being compared and correlated with data already collected on p53 status, microarray gene expression profiles, and treatment response and clinical outcome. The results of this analysis will be presented.

An overview of deep learning in medical imaging focusing on MRI

Abstract: What has happened in machine learning lately, and what does it mean for the future of medical image analysis? Machine learning has witnessed a tremendous amount of attention over the last few years. The current boom started around 2009 when so-called deep artificial neural networks began outperforming other established models on a number of important benchmarks. Deep neural networks are now the state-of-the-art machine learning models across a variety of areas, from image analysis to natural language processing, and widely deployed in academia and industry. These developments have a huge potential for medical imaging technology, medical data analysis, medical diagnostics and healthcare in general, slowly being realized. We provide a short overview of recent advances and some associated challenges in machine learning applied to medical image processing and image analysis. As this has become a very broad and fast expanding field we will not survey the entire landscape of applications, but put particular focus on deep learning in MRI. Our aim is threefold: (i) give a brief introduction to deep learning with pointers to core references; (ii) indicate how deep learning has been applied to the entire MRI processing chain, from acquisition to image retrieval, from segmentation to disease prediction; (iii) provide a starting point for people interested in experimenting and perhaps contributing to the field of deep learning for medical imaging by pointing out good educational resources, state-of-the-art open-source code, and interesting sources of data and problems related medical imaging.

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

Abstract: Summary Background The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy. Methods Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (≥5 cm, Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052. Findings 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20–67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0·58, 95% CI 0·41–0·83; p=0·003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6–26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0·70 (95% CI 0·54–0·92, p=0·011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28·8%, compared with 12·7% in the group who received chemotherapy alone (p=0·002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0·66, 95% CI 0·45–0·98, p=0·038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0·005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40·5%), 43 (26·4%), and 29 patients (17·8%), and severe in seven (4·3%), eight (4·9%), and one patient (0·6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group. Interpretation To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location. Funding Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).

Influence of Letrozole and Anastrozole on Total Body Aromatization and Plasma Estrogen Levels in Postmenopausal Breast Cancer Patients Evaluated in a Randomized, Cross-Over Study

Abstract: PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels. PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor–positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E1), estradiol (E2), and estrone sulfate (E1S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays. RESULTS: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibit...