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Clinicopathological factors associated with tumour-specific mutation detection in plasma of patients with RAS-mutated or BRAF-mutated metastatic colorectal cancer
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- Hamfjord, Julian (author)
- Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.
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- Guren, Tormod Kyrre (author)
- Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway.
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- Glimelius, Bengt (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Sorbye, Halfdan (author)
- Haukeland Hosp, Dept Oncol, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway.
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- Pfeiffer, Per (author)
- Odense Univ Hosp, Dept Oncol, Odense, Denmark.;Univ Southern Denmark, Inst Clin Res, Odense, Denmark.
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- Dajani, Olav (author)
- Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway.
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- Lingjaerde, Ole Christian (author)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.;Univ Oslo, Dept Comp Sci, Oslo, Norway.
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- Tveit, Kjell Magne (author)
- Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway.
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- Pallisgaard, Niels (author)
- Zealand Univ Hosp, Dept Pathol, Roskilde, Denmark.
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- Spindler, Karen-Lise Garm (author)
- Aarhus Univ Hosp, Dept Expt Clin Oncol, Aarhus, Denmark.;Aarhus Univ, Inst Clin Med, Aarhus, Denmark.
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- Kure, Elin H. (author)
- Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.;Univ South Eastern Norway, Fac Technol Nat Sci & Maritime Sci, Campus Bo, Bo, Norway.
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Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway;Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway. Oslo Univ Hosp, Dept Oncol, Ullernchausseen 70, N-0379 Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway. (creator_code:org_t)
- 2021-05-20
- 2021
- English.
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 149:6, s. 1385-1397
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Abstract
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- Detection of tumour-specific circulating cell-free DNA in plasma (ctDNA) fails in a significant number of cases depending on the clinical context. The primary aim was to investigate clinicopathological factors associated with detection of ctDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer (mCRC) prior to first-line therapy. A secondary aim was to evaluate the prognostic impact of ctDNA compared to other biomarkers. Patients were included from the NORDIC-VII study (N = 253). ctDNA was sampled prior to treatment and analysed for hotspot tissue mutations (KRAS, NRAS, and BRAF) using droplet digital PCR. Multivariable regression models were constructed to predict the probability of mutation detection and survival. Increasing radiological size of target lesions by increments of 1 cm (odds ratio [OR] = 1.18; 95% confidence interval [CI] 1.09-1.27; P < .001), intact primary tumour (OR = 3.17; 95% CI 1.22-8.22; P = .018) and more than one metastatic site (OR = 3.08; 95% CI 1.32-7.19; P = .009) were associated with mutation detection in plasma. Metastatic involvement of the lung was associated with non-detection (OR = 0.26; 95% CI 0.12-0.58; P = .001). Preanalytical and analytical factors modulated detection. High allele frequencies of ctDNA indicated poor prognosis independently of CEA and CA19-9 (hazard ratio [HR] = 2.38; 95% CI 1.74-3.26; P < .001; N = 206). Clinicopathological characteristics should be carefully considered when evaluating ctDNA results from mCRC patients, especially when confronted with a plasma negative result. ctDNA may prove to be a clinically useful marker in the evaluation of mCRC treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- blood biomarkers
- carbohydrate antigen 19‐
- 9
- carcinoembryonic antigen
- colorectal cancer
- tumour‐
- specific circulating cell‐
- free DNA
Publication and Content Type
- ref (subject category)
- art (subject category)
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Hamfjord, Julian
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Guren, Tormod Ky ...
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Glimelius, Bengt
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Sorbye, Halfdan
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Pfeiffer, Per
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Dajani, Olav
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Lingjaerde, Ole ...
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Tveit, Kjell Mag ...
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Pallisgaard, Nie ...
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Spindler, Karen- ...
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Kure, Elin H.
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- MEDICAL AND HEALTH SCIENCES
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Uppsala University