Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan-cancer setting. Int J Cancer 2020 Jan 15;146(2):566-576
Date
06/15/2019Pubmed ID
31199507Pubmed Central ID
PMC6874714DOI
10.1002/ijc.32510Scopus ID
2-s2.0-85068474243 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
We investigated the impact of time interval, primary vs. metastatic biopsy site, variant allele fraction (VAF) and histology on concordance of KRAS alterations in tissue vs. circulating tumor DNA (ctDNA), and association of concordance with survival. Blood and tissue were evaluated by next-generation sequencing in 433 patients with diverse cancers. Altogether, 101 patients (23.3%) had KRAS alterations: 56, ctDNA (12.9%); 81, tissue (18.7%); and 36, both (8.3%). The overall blood and tissue concordance rate for KRAS alterations was 85%, but was mainly driven by the large negative/negative subset. Therefore, specificity of one test for the other was high (88.1-94.3%), while sensitivity was not high (44.4-64.3%) and was lower still in patients with >6 vs. ≤2 months between blood and tissue sampling (31.0-40.9% vs. 51.2-84.0%; p = 0.14 time interval-dependent sensitivity of blood for tissue; p = 0.003, tissue for blood). Positive concordance rate for KRAS alterations was 57.1% vs. 27.4% (colorectal vs. noncolorectal cancer; p = 0.01), but site of biopsy (primary vs. metastatic) and VAF (%ctDNA) was not impactful. The presence of KRAS alterations in both tests was independently associated with shorter survival from diagnosis (hazard ratio, 1.72; 95% confidence interval, 1.04-2.86) and from recurrent/metastatic disease (1.70; 1.03-2.81). Positive concordance of KRAS alterations between ctDNA and tissue was negatively affected by a longer time period between blood and tissue sampling and was higher in colorectal cancer than in other malignancies. The presence of KRAS alterations in both tests was an independent prognostic factor for poor survival.
Author List
Mardinian K, Okamura R, Kato S, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Biomarkers, Tumor
Biopsy
Child
Child, Preschool
Circulating Tumor DNA
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasms
Prognosis
Proto-Oncogene Proteins p21(ras)
Spatio-Temporal Analysis
Survival Analysis
Time Factors
Young Adult
