title: Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis.
abstract: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis.
  
  
  
  An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases. Long-term outcomes will be cancer-specific survival, recurrence-free survival and overall survival at 5 years from diagnosis. Beyond routine clinicopathological and anthropometric characteristics and laboratory and biochemistry results, the project allows for additional blood samples and fresh-frozen tumour and normal tissue for investigation of circulating tumour cells (CTCs) and novel biomarkers (e.g. immune cells, microRNAs etc.). Tumour specimens will be investigated by immunohistochemistry in full slides. Extracted DNA/RNA will be analysed for genomic markers using specific PCR techniques and next-generation sequencing (NGS) panels. Flow cytometry will be used to characterise biomarkers in blood. Collaboration is open and welcomed, with particular interest in mutual opportunities for validation studies.
  
  
  
  The project is ongoing and recruiting at an expected rate of 120-150 patients per year, since January 2013. A project on circulating tumour cells (CTCs) has commenced, with analysis being prepared. Investigating molecular classes beyond the TNM staging is under way, including characteristics of microsatellite instability (MSI) and elevated microsatellite alterations in selected tetranucleotides (EMAST). Hot spot panels for known mutations in CRC are being investigated using NGS. Immune-cell characteristics are being performed by IHC and flow cytometry in tumour and peripheral blood samples. The project has ethical approval (REK Helse Vest, #2012/742), is financially supported with a Ph.D.-Grant (EMAST project; Folke Hermansen Cancer Fund) and a CTC-project (Norwegian Research Council; O. Nordgård). The ACROBATICC clinical and molecular biobank repository will serve as a long-term source for novel exploratory analysis and invite collaborators for mutual validation of promising biomarker results. The project aims to generate results that can help better discern prognostic groups in stage II/III cancers; explore prognostic and predictive biomarkers, and help detail the biology of colorectal liver metastasis for better patient selection and tailored treatment. The project is registered at http://www.ClinicalTrials.gov NCT01762813.
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. ksoreide@mac.com.|Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway. ksoreide@mac.com.|Department of Clinical Medicine, University of Bergen, Bergen, Norway. ksoreide@mac.com.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Søreide
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway.|Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Watson
authors.affiliation: Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.|Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dordi
authors.initials: D
authors.lastname: Lea
authors.affiliation: Department of Haematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Oddmund
authors.initials: O
authors.lastname: Nordgård
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Jon Arne
authors.initials: JA
authors.lastname: Søreide
authors.affiliation: Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.|Centre of Organelle Research (CORE), University of Stavanger, Stavanger, Norway.
authors.forename: Hanne R
authors.initials: HR
authors.lastname: Hagland
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D003299:Cooperative Behavior; D023381:Endpoint Determination; D005434:Flow Cytometry; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary*; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D018401:Sample Size; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Cancer; Circulating tumour cells; Colorectal cancer; Genetics; Liver metastasis; Population-based; Translational research