Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Mef Nilbert, Lund University, Sweden
- Second opponent: Professor Torben Frøstrup Hansen, University of Southern Denmark, Vejle
- Third member and chair of the evaluation committee: Professor II Kristin Austlid Taskén, University of Oslo
Chair of the Defence
Professor Emeritus Trond Buanes, University of Oslo
Principal Supervisor
Professor Elin Hegland Kure, Oslo University Hospital
Summary
Colorectal cancer – survival trends and prognostic role of circulating cell-free DNA
Colorectal cancer (CRC) is the third most common cancer worldwide. Survival of patients with CRC has improved throughout the past forty years, but patient outcomes are still heterogeneous which calls for novel tools to facilitate more individualized and dynamic care pathways.
The aims of the thesis were to describe survival trends of colon cancer in Norway throughout the past forty years and investigate the prognostic value of plasma circulating cell-free DNA (cfDNA) and circulating tumor-DNA (ctDNA) in patients with metastatic CRC. Hamfjord and colleagues used a nationwide population-based cohort (Cancer Registry of Norway), a retrospective post hoc cohort based on a prospective multicenter phase III trial (NORDIC-VII; NCT00145314), and a systematic literature review and meta-analysis to address the main research questions.
There was a trend shift in relative survival over the past forty years increasingly disfavoring patients with right-sided colon cancer, particularly those below the age of 75 diagnosed with regional or distant stage cancer. Hamfjord and colleagues further demonstrated, using droplet digital PCR, that having elevated pretreatment cfDNA levels (above a defined upper limit of normal) or high ctDNA RAS/BRAF mutant allele frequencies (≥ 10%) were both associated with inferior overall survival in patients with metastatic CRC. Patients not reaching an early complete/near complete on-treatment ctDNA response during first-line oxaliplatin-based chemotherapy had short progression-free and overall survival. A meta-analysis demonstrated that ctDNA also harbored prognostic information beyond the first-line setting.
cfDNA and ctDNA are biomarkers with the potential of providing relevant prognostic and companion diagnostic information in advanced CRC, which could prove useful in further individualizing treatment and improving outcomes for patients with both right- and left-sided disease.
Additional information
Contact the research support staff.